Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of long noncoding RNAs in Neuro-2a cells.

Paraquat (PQ) is a ubiquitously applied herbicide. Long-term PQ exposure with low dose has been reported to induce abnormal expression of long non-coding RNAs (lncRNAs) in brain nerve cells, which could further lead to Parkinson's disease (PD). N6-methyladenosine (m6A) modification has recently been identified as having an important role in regulating the function of lncRNAs. However, how m6A modification regulates lncRNAs following PQ exposure remains largely unknown. Herein, this study reported m6A modification of lncRNAs in mouse neuroblastoma cells (Neuro-2a) following PQ induced reactive oxide species (ROS). M6A sequencing was performed to explore the m6A modificated pattern of lncRNAs in Neuro-2a cells which were treated with 200 µM PQ for 3 h. It was found that PQ hypermethylated total RNA and changed the expression of m6A methyltransferase and demethylase proteins, which leading to the alteration of m6A modification of lncRNAs. Furthermore, the functional analysis further revealed that N-acetyl-L-cysteine (NAC)，a ROS scavengers, partly reversed PQ-induced distinct m6A modificated pattern of lncRNAs. In addition, tow specific m6A modified lncRNAs were identified: cell division cycle 5-like (lncRNA CDC5L) and signal transducer and activator of transcription 3 (lncRNA STAT3), which could influence downstream autophagy related biological function. In summary, this work could potentially contribute to the new insight of lncRNAs m6A modification mechanism in the field of environmental toxicology.

In Situ Modulation of A-Site Vacancies in LaMnO3.15 Perovskite for Surface Lattice Oxygen Activation and Boosted Redox Reactions.

Modulation of A-site defects is crucial to the redox reactions on ABO3 perovskites for both clean air application and electrochemical energy storage. Herein we report a scalable one-pot strategy for in situ regulation of La vacancies (VLa ) in LaMnO3.15 by simply introducing urea in the traditional citrate process, and further reveal the fundamental relationship between VLa creation and surface lattice oxygen (Olatt ) activation. The underlying mechanism is shortened Mn-O bonds, decreased orbital ordering, promoted MnO6 bending vibration and weakened Jahn-Teller distortion, ultimately realizing enhanced Mn-3d and O-2p orbital hybridization. The LaMnO3.15 with optimized VLa exhibits order of magnitude increase in toluene oxidation and ca. 0.05 V versus RHE (reversible hydrogen electrode) increase of half-wave potential in oxygen reduction reaction (ORR). The reported strategy can benefit the development of novel defect-meditated perovskites in both heterocatalysis and electrocatalysis.

Preparation of 4-Flexible Amino-2-Arylethenyl-Quinoline Derivatives as Multi-target Agents for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder of aged people. The development of multitarget-directed ligands (MTDLs) to act as multifunctional agents to treat this disease is the mainstream of current research. As a continuation of our previous studies, a series of 4-flexible amino-2-arylethenylquinoline derivatives as multi-target agents was efficiently synthesized and evaluated for the treatment of AD. Among these synthesized derivatives, some compounds exhibited strong self-induced Aß1⁻42 aggregation inhibition and antioxidant activity. The structure-activity relationship was summarized, which confirmed that the introduction of a flexible amino group featuring a N,N-dimethylaminoalkylamino moiety at the 4-position increased the Aß1⁻42 aggregation inhibition activity, with an inhibition ratio of 95.3% at 20 µM concentration. Compound 6b1, the optimal compound, was able to selectively chelate copper (II), and inhibit Cu2+-induced Aß aggregation effectively. It also could disassemble the self-induced Aß1⁻42 aggregation fibrils with a ratio of 64.3% at 20 µM concentration. Moreover, compound 6b1 showed low toxicity and a good neuroprotective effect against Aß1⁻42-induced toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated compound 6b1 significantly reversed scopolamine-induced memory deficit in mice. Taken together, these results suggested that compound 6b1 was a promising multi-target compound worthy of further study for AD.

Design, Synthesis and Antibacterial Evaluation of Some New 2-Phenyl-quinoline-4-carboxylic Acid Derivatives.

A series of new 2-phenyl-quinoline-4-carboxylic acid derivatives was synthesized starting from aniline, 2-nitrobenzaldehyde, pyruvic acid followed by Doebner reaction, amidation, reduction, acylation and amination. All of the newly-synthesized compounds were characterized by ¹H-NMR, (13)C-NMR and HRMS. The antibacterial activities of these compounds against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis), as well as one strain of methicillin-resistant Staphylococcus aureus (MRSA) bacteria were evaluated by the agar diffusion method (zone of inhibition) and a broth dilution method (minimum inhibitory concentration (MIC)), and their structure-activity relationships were obtained and discussed. The results revealed that some compounds displayed good antibacterial activity against Staphylococcus aureus, and Compounds 5a4 and 5a7 showed the best inhibition with an MIC value of 64 µg/mL against Staphylococcus aureus and with an MIC value of 128 µg/mL against Escherichia coli, respectively. The results of the MTT assay illustrated the low cytotoxicity of Compound 5a4.

Current and future of immunotherapy for thyroid cancer based on bibliometrics and clinical trials.

BACKGROUND: Thyroid cancer is a leading endocrine malignancy, with anaplastic and medullary subtypes posing treatment challenges. Existing therapies have limited efficacy, highlighting a need for innovative approaches. METHODS: We analyzed 658 articles and 87 eligible clinical trials using bibliometric tools and database searches, including annual publication and citation trends, were executed using Web of Science, CiteSpace, and VOS Viewer. RESULTS: Post-2018, there is a surge in thyroid cancer immunotherapy research, primarily from China and the University of Pisa. Of the 87 trials, 32 were Phase I and 55 were Phase II, mostly exploring combination therapies involving immune checkpoint inhibitors. CONCLUSION: The study's dual approach verifies the swift advancement of thyroid cancer immunotherapy from diverse perspectives. Immune checkpoint inhibitors have become the preferred regimen for advanced MTC and ATC in late therapeutic lines. However, since ICB plays a pivotal role in ATC, current clinical trial data show that ATC patients account for more and the curative effect is more accurate. Anticipated future developments are inclined toward combination regimens integrating immunotherapy with chemotherapy or targeted therapies. Emerging approaches, such as bispecific antibodies, cytokine-based therapies, and adoptive cell therapies like CAR-T and TCR-T, are exhibiting considerable potential. Upcoming research is expected to concentrate on refining the tumor immune milieu and discovering novel biomarkers germane to immunotherapeutic interventions.

Advancements and current trends in tumor treating fields: a scientometric analysis.

Tumor treating fields (TTFields) therapy is a novel and effective noninvasive cancer therapy, and it has been approved by FDA in the treatment of recurrent and newly diagnosed glioblastoma, and malignant pleural mesothelioma. Moreover, TTFields therapy has been widely studied in both clinical trials and preclinical studies in recent years. Based on its high efficacy, research on TTFields therapy has been a hot topic. Thus, the authors made this scientometric analysis of TTfields to reveal the scientometric distributions such as annual publications and citations, countries and institutions, authors, journals, references, and more importantly, research status and hot topics of the field. In recent years, publication numbers have been stable at high values, and citation numbers have been increasing greatly. The United States and Israel were the top two countries with the highest publication numbers, followed by Germany and Switzerland. Scientometric analyses of keywords indicated that clinical applications and antitumor mechanisms are probably the two main parts of current research on TTfields. Most clinical trials of TTfields focus on the treatment of glioblastoma. And a variety of other cancers such as lung cancer especially nonsmall cell lung cancer, hepatic cancer, other brain tumors, etc. have also been studied in both clinical trials and preclinical studies.

A scientometric analysis of immunotherapies for gliomas: Focus on GBM.

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. The standard therapy for GBM has remained unchanged for nearly two decades, with no significant improvement in survival outcomes. Despite several barriers such as the tumor microenvironment (TME) and blood-brain barrier, immunotherapies bring new hope for the treatment of GBM. To better understand the development and progress of immunotherapies in GBM, we made this scientometric analysis of this field. A total of 3753 documents were obtained from the Web of Science Core Collection, with publication years ranging from 1999 to 2022. The Web of Science platform, CiteSpace, and VOS viewer were used to conduct the scientometric analysis. The results of scientometric analysis showed that this field has recently become a popular topic of interest. The United States had the most publications among 89 countries or regions. Keyword analysis indicated significant areas in the field of immunotherapies for GBM, especially TME, immune checkpoint blockades (ICBs), chimeric antigen receptor T (CAR-T) cells, vaccines, and oncolytic viruses (OVs). Overall, we hope that this scientometric analysis can provide insights for researchers and promote the development of this field.

Advances and key focus areas in gastric cancer immunotherapy: A comprehensive scientometric and clinical trial review (1999-2023).

BACKGROUND: Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease. AIM: To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy. METHODS: We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented. RESULTS: Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability". CONCLUSION: Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Immunotherapy in cervical cancer: From the view of scientometric analysis and clinical trials.

Background: Cervical cancer is the fourth most cancer and the fourth leading cause of cancer-related deaths in women worldwide. Current treatment for patients with advanced cervical cancer is limited. And in the urgent demand for novel effective therapies both as the first and the second line treatment for these patients, immunotherapy is developing fast and has made some achievements. Methods: This study incorporated 1,255 topic-related articles and reviews from 1999 to 2022 in the Web of Science Core Collection (WoSCC). The WoS platform, Citespace, and VOS viewer provided the annual distribution of publications and citations, the analysis of researching countries and institutions, references, keywords (co-occurrence analysis, burst analysis, and timeline view analysis), and researching authors, respectively. For clinical trials, 720 trials and 114 trials from ClinicalTrials.gov and ICTRP were retrieved, respectively. And 296 trials were finally incorporated into the analysis. Results: The scientometric analysis showed that the study of immunotherapies in cervical cancer developed fast in recent years. Most publications were from the United States, followed by China. Seven of the top 10 co-cited references belong to clinical trials, and five of them were published in recent five years. There are lots of clinical trials us specific treatment patterns, some of which have represented excellent effects. Conclusions: Both the scientometric analysis of the 1,255 publications and the analysis of clinical trials showed that the field of immunotherapies in cervical cancer developed so fast in recent years. It was found that a lot of clinical trials using various immunotherapies (mainly vaccine therapy, adoptive cell therapy, immune checkpoint blockade, and antibody-drug conjugate) for advanced cervical cancer are currently ongoing or have represented considerable effect. Centered in immunotherapies, immune checkpoint blockades have represented great efficacy and huge potential, especially combined with other therapies such as chemotherapy, targeted therapy, and other immunotherapies.

Emerging trends and research foci of epithelial-mesenchymal transition in gliomas: A scientometric analysis and review.

Background: Epithelial-mesenchymal transition (EMT) is a key factor in the invasion and migration of glioma cells, and the study of EMT in gliomas has become a hot topic over the past decade. Scientometric analysis is gaining more attention since it can obtain hot topics and emerging trends in a research field. This article analyzed the research related to EMT in gliomas for the first time, including descriptions of research situations, evaluations of research foci, and predictions of emerging trends. Methods: We searched the topic-related original articles from January 2012 to December 2021 in the Web of Science Core Collection (WoSCC) by using a specific strategy, and a total of 1,217 publications were obtained. The WoS platform, VOS viewer, and CiteSpace were used to analyze the annual distribution of publications and citations, authors and density of keywords, and other analyses including countries, institutions, references, clustering, burst analysis, and the timeline view of keywords. Results: Scientometric analysis identified that the study of EMT in gliomas has developed fast and received continuous attention in the last decade. Based on the results of data analysis, most publications on the topic came from China, and the United States had the highest betweenness centrality. The top 10 co-cited references revealed the landmark documents that had greatly promoted the development of this field. The major focus is on the cellular and molecular mechanisms of EMT in gliomas, and the therapy related to EMT target and non-coding RNAs has been developing fast in recent years. Conclusions: This study revealed the intimate connections between EMT and gliomas, and the complex mechanisms regulating EMT in gliomas had been studied widely in the last decade. Exploring the deep mechanisms of EMT in gliomas is the foundation of the targeted inhibitions, which can promote the development of therapies for gliomas.

Theoretical Study on P-coordinated Metal Atoms Embedded in Arsenene for the Conversion of Nitrogen to Ammonia.

The conversion of gaseous N2 to ammonia under mild conditions by artificial methods has become one of the hot topics and challenges in the field of energy research today. Accordingly, based on density function theory calculations, we comprehensively explored the d-block of metal atoms (Ti, V, Cr, Mn, Fe, Co, Ni, Nb, Mo, Ru, Rh, W, and Pt) embedded in arsenene (Ars) for different transition systems of phosphorus (P) coordination as potential electrocatalysts for N2 reduction reaction (NRR). By adopting a "two-step" strategy with stringent NRR catalyst screening criteria, we eventually selected Nb@P3-Ars as a research object for a further in-depth NRR mechanism study. Our results show that Nb@P3-Ars not only maintains the thermodynamic stability at mild temperatures but also dominates the competition with the hydrogen evolution reaction when used as the electrochemical NRR (e-NRR) catalyst. In particular, while the NRR process occurs by the distal mechanism, Nb@P3-Ars has a low overpotential (0.36 V), which facilitates the efficient reduction of N2. Therefore, this work predicts the possibility of Nb@P3-Ars as an e-NRR catalyst for reducing N2 from a theoretical perspective and provides significant insights and theoretical guidance for future experimental research.