bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Distinct Etiologies of Gastric Cancer: Infection and Autoimmunity
Authors: Hoft Stella G. , Noto Christine N. , DiPaolo Richard J.
Published: December 2021

Gastric cancer is a leading cause of mortality worldwide. The risk of developing gastric adenocarcinoma, which comprises >90% of gastric cancers, is multifactorial, but most associated withHelicobacter pyloriinfection. Autoimmune gastritis is a chronic autoinflammatory syndrome where self-reactive immune cells are activated by gastric epithelial cell autoantigens. This cause of gastritis is more so associated with the development of neuroendocrine tumors. However, in both autoimmune and infection-induced gastritis, high risk metaplastic lesions develop within the gastric mucosa. This warrants concern for carcinogenesis in both inflammatory settings. There are many similarities and differences in disease progression between these two etiologies of chronic gastritis. Both diseases have an increased risk of gastric adenocarcinoma development, but each have their own unique comorbidities. Autoimmune gastritis is a primary cause of pernicious anemia, whereas chronic infection typically causes gastrointestinal ulceration. Both immune responses are driven by T cells, primarily CD4+T cells of the IFN-γ producing, Th1 phenotype. Neutrophilic infiltrates help clearH. pyloriinfection, but neutrophils are not necessarily recruited in the autoimmune setting. There have also been hypotheses that infection withH. pyloriinitiates autoimmune gastritis, but the literature is far from definitive with evidence of infection-independent autoimmune gastric disease. Gastric cancer incidence is increasing among young women in the United States, a population at higher risk of developing autoimmune disease, andH. pyloriinfection rates are falling. Therefore, a better understanding of these two chronic inflammatory diseases is needed to identify their roles in initiating gastric cancer.
TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
Authors: Zhang Ziwen , Hao Ran , Guo Qiusheng , Zhang Sheyu , Wang Xiaojia
Published: December 2021

Background: This study aimed to investigate the TP53 mutation, its potential immune features, its prognostic value, and its impact on immune infiltration in patients with breast cancer (BC).

Methods: We downloaded the somatic mutation data and clinicopathologic features of BC patients from the TCGA GDC database, UCSC Xena platform, and International Cancer Genome Consortium (ICGC) database. The association between the TP53 mutation, clinicopathology features, and overall survival (OS) in BC patients was analyzed. We evaluated the potential role of the TP53 mutation in the immune therapy response, including the tumor mutation burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion (TIDE). Moreover, ESTIMATE was employed to assess the ImmuneScore and StromalScore in BC patients. We also explored immunocyte infiltration related to the TP53 mutation and its potential mechanism. Immunohistochemistry (IHC) was performed to validate the association between the expression of CXCL1, CXCL10, and CCL20 and TP53 status.

Results: We found that the TP53 mutation was significantly associated with the shorter OS (p = 0.038) and was also an independent predictive factor of OS for BC patients (p < 0.001). Compared to that in the wild type group, the TP53-mutant group showed a higher TMB value (P< 0.001), MSI value (p = 0.077), and TIDE value (p < 0.001) with respect to BC patient immunotherapy. In addition, the ImmuneScore and StromalScore were both significantly increased in the TP53-mutant group (ImmuneScore: p < 0.001; StromalScore: p = 0.003). The results of CIBERSORT suggested that the TP53 mutation significantly promoted the infiltration of Tregs, T helper cells, and M0-type macrophages. KEGG and GSEA enrichment results suggested that the IL-17 signaling pathway and antigen processing and presentation pathways were significantly enriched in the TP53-mutant group. Importantly, based on IHC results of immune-related hub-genes, the chemokines CXCL1, CXCL10, and CCL20 were significantly upregulated in the TP53-mutant group in BC patients.

Conclusion: These results indicate that a TP53 mutation might serve as a biomarker for BC prognosis and is related to immunocyte infiltration in the tumor microenvironment.
TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease
Authors: He Xin , Xie Yue , Zheng Qiongping , Zhang Zeyu , Ma Shanshan , Li Junyu , Li Mingtao , Huang Qiaoying
Published: December 2021

Impairment of autophagy has been strongly implicated in the progressive loss of nigral dopaminergic neurons in Parkinson’s disease (PD). Transcription factor E3 (TFE3), an MiTF/TFE family transcription factor, has been identified as a master regulator of the genes that are associated with lysosomal biogenesis and autophagy. However, whether TFE3 is involved in parkinsonian neurodegeneration remains to be determined. In this study, we found decreased TFE3 expression in the nuclei of the dopaminergic neurons of postmortem human PD brains. Next, we demonstrated that TFE3 knockdown led to autophagy dysfunction and neurodegeneration of dopaminergic neurons in mice, implying that reduction of nuclear TFE3 may contribute to autophagy dysfunction-mediated cell death in PD. Further, we showed that enhancement of autophagy by TFE3 overexpression dramatically reversed autophagy downregulation and dopaminergic neurons loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Taken together, these findings demonstrate that TFE3 plays an essential role in maintaining autophagy and the survival of dopaminergic neurons, suggesting TFE3 activation may serve as a promising strategy for PD therapy.
Ferroptosis: The Silver Lining of Cancer Therapy
Authors: Tang Zhengming , Huang Zhijie , Huang Yisheng , Chen Yuanxin , Huang Mingshu , Liu Hongyu , Ye Q. Adam , Zhao Jianjiang , Jia Bo
Published: December 2021

Regulatory cell death has been a major focus area of cancer therapy research to improve conventional clinical cancer treatment (e.g. chemotherapy and radiotherapy). Ferroptosis, a novel form of regulated cell death mediated by iron-dependent lipid peroxidation, has been receiving increasing attention since its discovery in 2012. Owing to the highly iron-dependent physiological properties of cancer cells, targeting ferroptosis is a promising approach in cancer therapy. In this review, we summarised the characteristics of ferroptotic cells, associated mechanisms of ferroptosis occurrence and regulation and application of the ferroptotic pathway in cancer therapy, including the use of ferroptosis in combination with other therapeutic modalities. In addition, we presented the challenges of using ferroptosis in cancer therapy and future perspectives that may provide a basis for further research.
ER-Phagy and Microbial Infection
Authors: Li Jiahui , Gao Enfeng , Xu Chenguang , Wang Hongna , Wei Yongjie
Published: December 2021

The endoplasmic reticulum (ER) is an essential organelle in cells that synthesizes, folds and modifies membrane and secretory proteins. It has a crucial role in cell survival and growth, thus requiring strict control of its quality and homeostasis. Autophagy of the ER fragments, termed ER-phagy or reticulophagy, is an essential mechanism responsible for ER quality control. It transports stress-damaged ER fragments as cargo into the lysosome for degradation to eliminate unfolded or misfolded protein aggregates and membrane lipids. ER-phagy can also function as a host defense mechanism when pathogens infect cells, and its deficiency facilitates viral infection. This review briefly describes the process and regulatory mechanisms of ER-phagy, and its function in host anti-microbial defense during infection.
Epithelial-Mesenchymal Transition Induces GSDME Transcriptional Activation for Inflammatory Pyroptosis
Authors: Jia Chenqiang , Zhang Zhuqing , Tang Jun , Cai Mei-Chun , Zang Jingyu , Shi Kaixuan , Sun Yunheng , Wu Jie , Shi Hailei , Shi Weiping , Ma Pengfei , Zhao Xiaojing , Yu Zhuang , Fu Yujie , Zhuang Guanglei
Published: December 2021

GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.
ISGylation in Innate Antiviral Immunity and Pathogen Defense Responses: A Review
Authors: Zhang Mengdi , Li Jingxian , Yan Haiyan , Huang Jun , Wang Fangwei , Liu Ting , Zeng Linghui , Zhou Fangfang
Published: December 2021

The interferon-stimulating gene 15 (ISG15) protein is a ubiquitin-like protein induced by interferons or pathogens. ISG15 can exist in free form or covalently bind to the target protein through an enzymatic cascade reaction, which is called ISGylation. ISGylation has been found to play an important role in the innate immune responses induced by type I interferon, and is, thus, critical for the defense of host cells against RNA, DNA, and retroviruses. Through covalent binding with the host and viral target proteins, ISG15 inhibits the release of viral particles, hinder viral replication, and regulates the incubation period of viruses, thereby exerting strong antiviral effects. The SARS-CoV-2 papain-like protease, a virus-encoded deubiquitinating enzyme, has demonstrated activity on both ubiquitin and ISG15 chain conjugations, thus playing a suppressive role against the host antiviral innate immune response. Here we review the recent research progress in understanding ISG15-type ubiquitin-like modifications, with an emphasis on the underlying molecular mechanisms. We provide comprehensive references for further studies on the role of ISG15 in antiviral immunity, which may enable development of new antiviral drugs.
Publication Trends on Mitophagy in the World and China: A 16-Year Bibliometric Analysis
Authors: Chen Jingli , Li Xin , Jia Yifan , Xia Zhongyuan , Ye Jishi
Published: December 2021

In the past 16 years, research on mitophagy has increasingly expanded to a wider range of subjects. Therefore, comprehensively analyzing the relevant progress and development trends on mitophagy research requires specific methods. To assess the hotspots, directions, and quality of results in this field worldwide, we used multiple tools to examine research progress and growing trends in research on the matter during the last 16 years (from 2005 to 2020). We also compared the quantity and quality of the literature records on mitophagy published by research institutions in China and other developed countries, reviewed China’s contribution, and examined the gap between China and these developed countries. According to the results of our bibliometric analysis, the United States and its research institutes published the most papers. We identified cell biology as the most commonly researched subject on mitophagy and AUTOPHAGY as the most popular journal for research on mitophagy. We also listed the most cited documents from around the world and China. With gradually increased funding, China is progressively becoming prominent in the field of mitophagy; nevertheless, the gap between her and major countries in the world must be closed.
Programmed Cell Death: Complex Regulatory Networks in Cardiovascular Disease
Authors: Zhou Liuhua , Sun Jiateng , Gu Lingfeng , Wang Sibo , Yang Tongtong , Wei Tianwen , Shan Tiankai , Wang Hao , Wang Liansheng
Published: December 2021

Abnormalities in programmed cell death (PCD) signaling cascades can be observed in the development and progression of various cardiovascular diseases, such as apoptosis, necrosis, pyroptosis, ferroptosis, and cell death associated with autophagy. Aberrant activation of PCD pathways is a common feature leading to excessive cardiac remodeling and heart failure, involved in the pathogenesis of various cardiovascular diseases. Conversely, timely activation of PCD remodels cardiac structure and function after injury in a spatially or temporally restricted manner and corrects cardiac development similarly. As many cardiovascular diseases exhibit abnormalities in PCD pathways, drugs that can inhibit or modulate PCD may be critical in future therapeutic strategies. In this review, we briefly describe the process of various types of PCD and their roles in the occurrence and development of cardiovascular diseases. We also discuss the interplay between different cell death signaling cascades and summarize pharmaceutical agents targeting key players in cell death signaling pathways that have progressed to clinical trials. Ultimately a better understanding of PCD involved in cardiovascular diseases may lead to new avenues for therapy.
Historical Perspective of the Addition of Magnetic Nanoparticles Into Anaerobic Digesters (2014-2021)
Authors: Casals Eudald , Barrena Raquel , Gonzalez Edgar , Font Xavier , Sánchez Antoni , Puntes Victor
Published: December 2021

The addition of magnetic nanoparticles to batch anaerobic digestion was first reported in 2014. Afterwards, the number of works dealing with this subject has been increasing year by year. The discovery of the enhancement of anaerobic digestion by adding iron-based nanoparticles has created a multidisciplinary emerging research field. As a consequence, in the last years, great efforts have been made to understand the enhancement mechanisms by which magnetic nanoparticles (NPs) addition enhances the anaerobic digestion process of numerous organic wastes. Some hypotheses point to the dissolution of iron as essential iron for anaerobic digestion development, and the state of oxidation of iron NPs that can reduce organic matter to methane. The evolution and trends of this novel topic are discussed in this manuscript. Perspectives on the needed works on this topic are also presented.
First Study on Nihonium (Nh, Element 113) Chemistry at TASCA
Authors: Yakushev A. , Lens L. , Düllmann Ch. E. , Block M. , Brand H. , Calverley T. , Dasgupta M. , Di Nitto A. , Götz M. , Götz S. , Haba H. , Harkness-Brennan L. , Herzberg R-D. , Heßberger F. P. , Hinde D. , Hübner A. , Jäger E. , Judson D. , Khuyagbaatar J. , Kindler B. , Komori Y. , Konki J. , Kratz J.V. , Krier J. , Kurz N. , Laatiaoui M. , Lommel B. , Lorenz Christian , Maiti M. , Mistry A.K. , Mokry Ch. , Nagame Y. , Papadakis P. , Såmark-Roth A. , Rudolph D. , Runke J. , Sarmiento L.G. , Sato T.K. , Schädel M. , Scharrer P. , Schausten B. , Steiner J. , Thörle-Pospiech P. , Toyoshima A. , Trautmann N. , Uusitalo J. , Ward A. , Wegrzecki M. , Yakusheva V.
Published: December 2021

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p1/2 and 7p3/2 orbitals. One unpaired electron in the outermost 7p1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.
Cross-Linking With Diamine Monomers to Prepare Graphene Oxide Composite Membranes With Varying D-Spacing for Enhanced Desalination Properties
Authors: Ju Hong , Duan Jinzhuo , Lu Haitong , Xu Weihui
Published: December 2021

As a new type of membrane material, graphene oxide (GO) can easily form sub-nanometer interlayer channels, which can effectively screen salt ions. The composite membrane and structure with a high water flux and good ion rejection rate were compared by the cross-linking of GO with three different diamine monomers: ethylenediamine (EDA), urea (UR), and p-phenylenediamine (PPD). X-ray photoelectron spectroscopy (XPS) results showed that unmodified GO mainly comprises π-π interactions and hydrogen bonds, but after crosslinking with diamine, both GO and mixed cellulose (MCE) membranes are chemically bonded to the diamine. The GO-UR/MCE membrane achieved a water flux similar to the original GO membrane, while the water flux of GO-PPD/MCE and GO-EDA/MCE dropped. X-ray diffraction results demonstrated that the covalent bond between GO and diamine can effectively inhibit the extension of d-spacing during the transition between dry and wet states. The separation performance of the GO-UR/MCE membrane was the best. GO-PPD/MCE had the largest contact angle and the worst hydrophilicity, but its water flux was still greater than GO-EDA/MCE. This result indicated that the introduction of different functional groups during the diamine monomer cross-linking of GO caused some changes in the performance structure of the membrane.
Advances in the Total Synthesis of Aflatoxins
Authors: Yang Liyan , Wang Zhonglei
Published: December 2021

Abstract: Aflatoxins, which are produced by Aspergillus flavus, Aspergillus nomius, and Aspergillus parasiticus, are a group of pentacyclic natural products with difuran and coumarin skeletons. They mainly include aflatoxin B1, B2, G1, G2, M1, and M2. Biologically, aflatoxins are of concern to human health as they can be present as contaminants in food products. The unique skeletons of aflatoxins and their risk to human health have led to the publication of nine remarkable total syntheses (including three asymmetric syntheses) and ten formal total syntheses (including four asymmetric formal syntheses) of aflatoxins in the past 55 years. To better understand the mechanism of the biological activity of aflatoxins and their presence in samples from the food industry, this review summarizes progress in the total synthesis of aflatoxins.
In Situ Synthesis of Surface-Mounted Novel Nickel(II) Trimer-Based MOF on Nickel Oxide Hydroxide Heterostructures for Enhanced Methanol Electro-Oxidation
Authors: Sun Ya-Ya , Wang Yan-Jiang , Pi Qiu , Wu Ya-Pan , Wu Xue-Qian , Li Shuang , Lan Ya-Qian , Zhang Qichun , Li Dong-Sheng
Published: December 2021

Engineering the heterogeneous interface fusing MOFs and inorganic active component is an effective strategy to improve the electrochemical performance. Herein, we report a new Ni3-based MOF (denoted as CTGU-24) with an infrequent two-fold interpenetrating 3D (3,8)-connected network constructed from Ni(II) trimer and mixed tripodal tectonics for the electrocatalytic methanol oxidation reaction (MOR). In order to improve its stability and activities, the heterogeneous hybrid CTGU-24@NiOOH has been fabricated successfully via the first preparation of the NiOOH nanosphere and then in situ formation of CTGU-24 decorated on the NiOOH surface. Moreover, the integration of CTGU-24@NiOOH and different additives [acetylene black (AB) and ketjen black (KB)], resulting in the optimized hybrid sample AB&CTGU-24@NiOOH (4:4). It attains better MOR performance with an area-specific peak current density of 34.53 mA·cm−2 than pure CTGU-24 (14.99 mA·cm−2) and improved durability in an alkali medium. The new findings indicate that the CTGU-24@NiOOH heterostructure formed in situ and the integration of moderate additives are critical to optimizing and improving electrocatalytic activity of pure MOF crystalline material.
A Mini-Review: Recent Advances in Coumarin-Metal Complexes With Biological Properties
Authors: Balewski Łukasz , Szulta Sylwia , Jalińska Aleksandra , Kornicka Anita
Published: December 2021

The coumarin nucleus is a recurring motif in both natural and synthetic compounds that exhibit a broad spectrum of biological properties including anticoagulant, anti-inflammatory, antioxidant, antiviral, antimicrobial and anticancer agents as well as enzyme inhibitors. On the other hand, it has been reported that the incorporation of a metal ion into coumarin derivatives can increase the activity of such complexes compared to coumarin-based ligands. Accordingly, some of them have been found to display promising antioxidant, antitumor or antibacterial activities. This mini-review briefly summarizes the recent development of coumarin-metal complexes with proven biological properties. The attention is also paid to agents for which practical applications in the detection of biologically important species may be found.
Lighting up Individual Organelles With Fluorescent Carbon Dots
Authors: Liu Haifang , Guo Jiancheng , Aryee Aaron Albert , Hua Linlin , Sun Yuanqiang , Li Zhaohui , Liu Jianbo , Tang Wenxue
Published: December 2021

Cell organelles play crucial roles in the normal functioning of an organism, therefore the disruption of their operation is associated with diseases and in some cases death. Thus, the detection and monitoring of the activities within these organelles are of great importance. Several probes based on graphene oxide, small molecules, and other nanomaterials have been developed for targeting specific organelles. Among these materials, organelle-targeted fluorescent probes based on carbon dots have attracted substantial attention in recent years owing to their superior characteristics, which include facile synthesis, good photostability, low cytotoxicity, and high selectivity. The ability of these probes to target specific organelles enables researchers to obtain valuable information for understanding the processes involved in their functions and/or malfunctions and may also aid in effective targeted drug delivery. This review highlights recently reported organelle-specific fluorescent probes based on carbon dots. The precursors of these carbon dots are also discussed because studies have shown that many of the intrinsic properties of these probes originate from the precursor used. An overview of the functions of the discussed organelles, the types of probes used, and their advantages and limitations are also provided. Organelles such as the mitochondria, nucleus, lysosomes, and endoplasmic reticulum have been the central focus of research to date, whereas the Golgi body, centrosome, vesicles, and others have received comparatively little attention. It is therefore the hope of the authors that further studies will be conducted in an effort to design probes with the ability to localize within these less studied organelles so as to fully elucidate the mechanisms underlying their function.
Active Smoking Induces Aberrations in Digestive Tract Microbiota of Rats
Authors: Wang Xiang , Ye Pei , Fang Li , Ge Sheng , Huang Fan , Polverini Peter J. , Heng Weiwei , Zheng Lichun , Hu Qingang , Yan Fuhua , Wang Wenmei
Published: December 2021

Cigarette smoking could have certain effects on gut microbiota. Some pioneering studies have investigated effects of active smoking on the microbiome in local segments of the digestive tract, while active smoking-induced microbiome alterations in the whole digestive tract have not been fully investigated. Here, we developed a rat model of active smoking and characterized the effects of active smoking on the microbiota within multiple regions along the digestive tract. Blood glucose and some metabolic factors levels, the microbial diversity and composition, relative abundances of taxa, bacterial network correlations and predictive functional profiles were compared between the control group and active smoking group. We found that active smoking induced hyperglycemia and significant reductions in serum insulin and leptin levels. Active smoking induced region-specific shifts in microbiota structure, composition, network correlation and metabolism function along the digestive tract. Our results demonstrated that active smoking resulted in a reduced abundance of some potentially beneficial genera (i.e. Clostridium, Turicibacter) and increased abundance of potentially harmful genera (i.e. Desulfovibrio, Bilophila). Functional prediction suggested that amino acid, lipid, propanoate metabolism function could be impaired and antioxidant activity may be triggered. Active smoking may be an overlooked risk to health through its potential effects on the digestive tract microbiota, which is involved in the cause and severity of an array of chronic diseases.
Early Immune Response Elicited by Different Trypanosoma cruzi Infective Stages
Authors: Gutierrez Brenda Celeste , Lammel Estela , González-Cappa Stella Maris , Poncini Carolina Verónica
Published: December 2021

Trypanosoma cruzi is a protozoan parasite that affects millions of people in Latin America. Infection occurs by vectorial transmission or by transfusion or transplacental route. Immune events occurring immediately after the parasite entrance are poorly explored. Dendritic cells (DCs) are target for the parasite immune evasion mechanisms. Recently, we have demonstrated that two different populations of DCs display variable activation after interaction with the two infective forms of the parasite: metacyclic or blood trypomastigotes (mTp or bTp) in vitro. The skin constitutes a complex network with several populations of antigen-presenting cells. Previously, we have demonstrated T. cruzi conditioning the repertoire of cells recruited into the site of infection. In the present work, we observed that mTp and bTp inoculation displayed differences in cell recruitment to the site of infection and in the activation status of APCs in draining lymph nodes and spleen during acute infection. Animals inoculated with mTp exhibited 100% of survival with no detectable parasitemia, in contrast with those injected with bTp that displayed high mortality and high parasite load. Animals infected with mTp and challenged with a lethal dose of bTp 15 days after primary infection showed no mortality and incremented DC activation in secondary lymphoid organs compared with controls injected only with bTp or non-infected mice. These animals also displayed a smaller number of amastigote nests in cardiac tissue and more CD8 T cells than mice infected with bTp. All the results suggest that both Tp infective stages induce an unequal immune response since the beginning of the infection.
The Protective Role of TLR2 Mediates Impaired Autophagic Flux by Activating the mTOR Pathway During Neospora caninum Infection in Mice
Authors: Wang Jielin , Wang Xiaocen , Gong Pengtao , Ren Fu , Li Xin , Zhang Nan , Zhang Xu , Zhang Xichen , Li Jianhua
Published: December 2021

Autophagy has been shown to play an essential role in defending against intracellular bacteria, viruses, and parasites. Mounting evidence suggests that autophagy plays different roles in the infection process of different pathogens. Until now, there has been no conclusive evidence regarding whether host autophagy is involved in Neospora caninum infection. In the current study, we first monitored the activation of autophagy by N. caninum, which occurred mainly in the early stages of infection, and examined the role of host autophagy in N. caninum infection. Here, we presented evidence that N. caninum induced an increase in autophagic vesicles with double-membrane structures in macrophages at the early stage of infection. LC3-II expression peaked and decreased as infection continued. However, the expression of P62/SQSTM1 showed significant accumulation within 12 h of infection, indicating that autophagic flux was blocked. A tandem fluorescence protein mCherry-GFP-LC3 construct was used to corroborate the impaired autophagic flux. Subsequently, we found that N. caninum infection induced the activation of the TLR2–AKT–mTOR pathways. Further investigation revealed that TLR2–mTOR, accompanied by the blockade of autophagic flux, was responsible for impaired autophagy but was not associated with AKT. In vitro and in vivo, N. caninum replication was strongly blocked by the kinase inhibitor 3-methyladenine (3-MA, autophagy inhibitor). In contrast, rapamycin (Rapa, an autophagy inducer) was able to promote intracellular proliferation and reduce the survival rate of N. caninum-infected mice. On the other hand, the accumulation of autophagosomes facilitated the proliferation of N. caninum. Collectively, our findings suggest that activation of host autophagy facilitates N. caninum replication and may counteract the innate immune response of the host. In short, inhibition of the early stages of autophagy could potentially be a strategy for neosporosis control.
The Politics of Pulpit Religiosity in the Era of Covid-19 in Kenya
Authors: Kilonzo Susan M. , Omwalo Bryson O.
Published: December 2021

This essay centres on the role of religion in the era of Covid-19. We juxtapose social media and religious practices in a way that challenges the conventional religion of the pulpit to deconstruct the myths and misconceptions around spirituality in the era of Covid-19. We show the transformation of worship from physical worship places, particularly churches, to virtual engagements through social media. Through observation, close relations’ accounts, personal experiences and media perspectives, we analyze the politics that surrounded religious observances in the first 7 months of Covid-19 pandemic in Kenya. We make a case that, discoveries made in these seven and other months to come, will most likely influenced the myths and misconceptions about religion and religious practices in the Country. From these accounts, we project a future that is likely to reap from the benefits of technology, and especially social media, which has revolutionized exchange of ideas, sermons, prayers and music. We challenge the very notion of pulpit religiosity, and the myths and misconceptions that religion cannot be without physical fellowships.
“All this Regulatory Uncertainty in the Air”: The Indispensability of Public Hearings in Guarding and Guiding Public Deliberation
Authors: Carroll Jaclyn , Bsumek Pete
Published: December 2021

The field of Environmental Communication has often critiqued the shortcomings of public hearings, noting their limitations in bringing about effective and equitable public decision making. While this work has been significant, it has tended to limit the deliberative field to public hearings themselves, sometimes going so far as to assume that public hearings are the only spaces in which significant deliberations occur. Using a field analysis of the “No Coal Plant” campaign in Surry County, Virginia (2008–2013), the authors illuminate some limitations of existing literature. Their analysis suggests that while public hearings can be extremely limiting, even “failed” public hearings can play a critical role in constituting, organizing, and pacing formal and informal deliberative spaces, which are necessary for communities as they manage the stresses and strains of the decision-making process.
Iron in Cardiovascular Disease: Challenges and Potentials
Authors: Li Shizhen , Zhang Xiangyu
Published: December 2021

Iron is essential for many biological processes. Inadequate or excess amount of body iron can result in various pathological consequences. The pathological roles of iron in cardiovascular disease (CVD) have been intensively studied for decades. Convincing data demonstrated a detrimental effect of iron deficiency in patients with heart failure and pulmonary arterial hypertension, but it remains unclear for the pathological roles of iron in other cardiovascular diseases. Meanwhile, ferroptosis is an iron-dependent cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been reported in several CVDs, namely, cardiomyopathy, atherosclerotic cardiovascular disease, and myocardial ischemia/reperfusion injury. Iron chelation therapy seems to be an available strategy to ameliorate iron overload-related disorders. It is still a challenge to accurately clarify the pathological roles of iron in CVD and search for effective medical intervention. In this review, we aim to summarize the pathological roles of iron in CVD, and especially highlight the potential mechanism of ferroptosis in these diseases.
Role of Multimodal Imaging in Patients With Suspected Infections After the Bentall Procedure
Authors: Sollini Martina , Bartoli Francesco , Boni Roberto , Zanca Roberta , Colli Andrea , Levantino Maurizio , Menichetti Francesco , Ferrari Mauro , Berchiolli Raffaella , Lazzeri Elena , Erba Paola A.
Published: December 2021

Purpose: This study aimed to assess the diagnostic performances of multimodal imaging [i.e., white blood cell single-photon emission computed tomography/CT (99mTc-HMPAO-WBC SPECT/CT) and 18-fluoride-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG PET/CT)] in patients with suspected infection after the Bentall procedure, proposing new specific diagnostic criteria for the diagnosis.

Methods: Between January 2009 and December 2019, we selected within a cardiovascular infections registry, 76 surgically treated patients (27 women and 49 men, median 66 years, and range 29–83 years). All the patients underwent molecular imaging for a suspected infection after the replacement of the aortic valve and ascending aorta according to the Bentall procedure. We analyzed 98 scans including 49 99mTc-WBC and 49 [18F]FDG PET/CT. A total of 22 patients with very early/early suspected infection (<3 months after surgery) were imaged with both the techniques. Positive imaging was classified according to the anatomical site of increased uptake: to the aortic valve (AV), to both the AV and AV tube graft (AVTG) or to the TG, to surrounding tissue, and/or to extracardiac sites (embolic events or other sites of concomitant infection). Standard clinical workup included in all the patients having echocardiography/CT, blood culture, and the Duke criteria. Pretest probability and positive/negative likelihood ratio were calculated. Sensitivity and specificity of 99mTc labeled hexamethylpropylene amine oxime-WBC SPECT/CT (99mTc-HMPAO-WBC SPECT/CT) and [18F]FDG PET/CT imaging were calculated by using microbiology (n = 35) or clinical follow-up (n = 41) as final diagnosis. 99mTc-HMPAO-WBC scintigraphy and [18F]FDG PET/CT findings were compared with 95% CIs by using the McNemar test to those of echocardiography/CT, blood culture, and the Duke criteria.

Results: Sensitivity, specificity, and accuracy of 99mTc-HMPAO-WBC were 86, 92, and 88%, respectively, with a slightly higher sensitivity for tube graft infection (TGI) as compared to isolated AV and combined AVTG. Overall, sensitivity, specificity, and accuracy of [18F]FDG PET/CT were 97, 73, and 90%, respectively. In 22 patients with suspected very early and early postsurgical infections, the two imaging modalities were concordant in 17 cases [10 true positive (TP) and 7 true negative (TN)]. [18F]FDG PET/CT presented a higher sensitivity than 99mTc-HMPAO-WBC scan. 99mTc-HMPAO-WBC scan correctly classified as negative three false-positive (FP) PET/CT findings.

Conclusion: Our findings supported the use of 99mTc-HMPAO-WBC SPECT/CT and [18F]FDG PET/CT in patients with suspicion infection after the Bentall procedure early in the course of the disease onset to confirm the diagnosis and provide a comprehensive assessment of disease burden through the proposed criteria.
Cardiovascular Biomarkers and Diastolic Dysfunction in Patients With Chronic Chagas Cardiomyopathy
Authors: Echeverría Luis E. , Gómez-Ochoa Sergio Alejandro , Rojas Lyda Z. , García-Rueda Karen Andrea , López-Aldana Pedro , Muka Taulant , Morillo Carlos A.
Published: December 2021

Background: Chronic Chagas Cardiomyopathy is a unique form of cardiomyopathy, with a significantly higher mortality risk than other heart failure etiologies. Diastolic dysfunction (DD) plays an important role in the prognosis of CCM; however, the value of serum biomarkers in identifying and stratifying DD has been poorly studied in this context. We aimed to analyze the correlation of six biochemical markers with diastolic function echocardiographic markers and DD diagnosis in patients with CCM.

Methods: Cross-sectional study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high-sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Tissue Doppler imaging was used to measure echocardiographic parameters indicating DD. Multivariate logistic regression models adjusted by age, sex, BMI, and NYHA classification were used to evaluate the association between the biomarkers and DD.

Results: From the total patients included (55% male with a median age of 62 years), 38% had a preserved LVEF, but only 14% had a normal global longitudinal strain. Moreover, 64% had a diagnosis of diastolic dysfunction, with most of the patients showing a restrictive pattern (n = 28). The median levels of all biomarkers (except for sST2) were significantly higher in the group of patients with DD. Higher levels of natural log-transformed NTproBNP (per 1-unit increase, OR = 3.41, p < 0.001), Hs-cTnT (per 1-unit increase, OR = 3.24, p = 0.001), NGAL (per 1-unit increase, OR = 5.24, p =0.003), and Cys-C (per 1-unit increase, OR = 22.26, p = 0.008) were associated with increased odds of having diastolic dysfunction in the multivariate analyses. Finally, NT-proBNP had the highest AUC value (88.54) for discriminating DD presence.

Conclusion: Cardiovascular biomarkers represent valuable tools for diastolic dysfunction assessment in the context of CCM. Additional studies focusing mainly on patients with HFpEF are required to validate the performance of these cardiovascular biomarkers in CCM, allowing for an optimal assessment of this unique population.
Cellular and Molecular Mechanism of Traditional Chinese Medicine on Ventricular Remodeling
Authors: Zhu Yong-Chun , Liang Bo , Gu Ning
Published: December 2021

Ventricular remodeling is related to the renin-angiotensin-aldosterone system, immune system, and various cytokines involved in inflammation, apoptosis, and cell signal regulation. Accumulated studies have shown that traditional Chinese medicine can significantly inhibit the process of ventricular remodeling, which may be related to the mechanism mentioned above. Here, we conducted a system overview to critically review the cellular and molecular mechanism of traditional Chinese medicine on ventricular remodeling. We mainly searched PubMed for basic research about the anti-ventricular remodeling of traditional Chinese medicine in 5 recent years, and then objectively summarized these researches. We included more than 25 kinds of Chinese herbal medicines including Qi-Li-Qian-Xin, Qi-Shen-Yi-Qi Pill, Xin-Ji-Er-Kang Formula, and Yi-Qi-Wen-Yang Decoction, and found that they can inhibit ventricular remodeling effectively through multi-components and multi-action targets, which are promoting the clinical application of traditional Chinese medicine.
The Predictors of Conduction Disturbances Following Transcatheter Aortic Valve Replacement in Patients With Bicuspid Aortic Valve: A Multicenter Study
Authors: Guo Yuchao , Zhou Dao , Dang Mengqiu , He Yuxing , Zhang Shenwei , Fang Jun , Wu Shili , Huang Qiong , Chen Lianglong , Yuan Yiqiang , Fan Jiaqi , Jilaihawi Hasan , Liu Xianbao , Wang Jian'an
Published: December 2021

Objective: To evaluate the predictors of new-onset conduction disturbances in bicuspid aortic valve patients using self-expanding valve and identify modifiable technical factors.

Background: New-onset conduction disturbances (NOCDs), including complete left bundle branch block and high-grade atrioventricular block, remain the most common complication after transcatheter aortic valve replacement (TAVR).

Methods: A total of 209 consecutive bicuspid patients who underwent self-expanding TAVR in 5 centers in China were enrolled from February 2016 to September 2020. The optimal cut-offs in this study were generated from receiver operator characteristic curve analyses. The infra-annular and coronal membranous septum (MS) length was measured in preoperative computed tomography. MSID was calculated by subtracting implantation depth measure on postoperative computed tomography from infra-annular MS or coronal MS length.

Results: Forty-two (20.1%) patients developed complete left bundle branch block and 21 (10.0%) patients developed high-grade atrioventricular block after TAVR, while 61 (29.2%) patients developed NOCDs. Coronal MS <4.9 mm (OR: 3.08, 95% CI: 1.63–5.82, p = 0.001) or infra-annular MS <3.7 mm (OR: 2.18, 95% CI: 1.04–4.56, p = 0.038) and left ventricular outflow tract perimeter <66.8 mm (OR: 4.95 95% CI: 1.59–15.45, p = 0.006) were powerful predictors of NOCDs. The multivariate model including age >73 years (OR: 2.26, 95% CI: 1.17–4.36, p = 0.015), Δcoronal MSID <1.8 mm (OR: 7.87, 95% CI: 2.84–21.77, p < 0.001) and prosthesis oversizing ratio on left ventricular outflow tract >3.2% (OR: 3.42, 95% CI: 1.74–6.72, p < 0.001) showed best predictive value of NOCDs, with c-statistic = 0.768 (95% CI: 0.699–0.837, p < 0.001). The incidence of NOCDs was much lower (7.5 vs. 55.2%, p < 0.001) in patients without Δcoronal MSID <1.8 mm and prosthesis oversizing ratio on left ventricular outflow tract >3.2% compared with patients who had these two risk factors.

Conclusion: The risk of NOCDs in bicuspid aortic stenosis patients could be evaluated based on MS length and prosthesis oversizing ratio. Implantation depth guided by MS length and reducing the oversizing ratio might be a feasible strategy for heavily calcified bicuspid patients with short MS.
Prevalence and Prognosis of HFimpEF Developed From Patients With Heart Failure With Reduced Ejection Fraction: Systematic Review and Meta-Analysis
Authors: He Yibo , Ling Yihang , Guo Wei , Li Qiang , Yu Sijia , Huang Haozhang , Zhang Rongting , Gong Zhiwen , Liu Jiaxuan , Mo Liyi , Yi Shixin , Lai Disheng , Yao Younan , Liu Jin , Chen Jiyan , Liu Yong , Chen Shiqun
Published: December 2021

Background: Heart failure with improved ejection fraction (HFimpEF) is classified as a new type of heart failure, and its prevalence and prognosis are not consistent in previous studies. There is no systematic review and meta-analysis regarding the prevalence and prognosis of the HFimpEF.

Method: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library from inception to May 22, 2021 (PROSPERO registration: CRD42021260422). Studies were included for analysis if the prognosis of mortality or hospitalization were reported in HFimpEF or in patients with heart failure with recovered ejection fraction (HFrecEF). The primary outcome was all-cause mortality. Cardiac hospitalization, all-cause hospitalization, and composite events of mortality and hospitalization were considered as secondary outcomes.

Result: Nine studies consisting of 9,491 heart failure patients were eventually included. During an average follow-up of 3.8 years, the pooled prevalence of HFimpEF was 22.64%. HFimpEF had a lower risk of mortality compared with heart failure patients with reduced ejection fraction (HFrEF) (adjusted HR: 0.44, 95% CI: 0.33–0.60). HFimpEF was also associated with a lower risk of cardiac hospitalization (HR: 0.40, 95% CI: 0.20–0.82) and the composite endpoint of mortality and hospitalization (HR: 0.56, 95% CI: 0.44–0.73). Compared with patients with preserved ejection fraction (HFpEF), HFimpEF was associated with a moderately lower risk of mortality (HR: 0.42, 95% CI: 0.32–0.55) and hospitalization (HR: 0.73, 95% CI: 0.58–0.92).

Conclusion: Around 22.64% of patients with HFrEF would be treated to become HFimpEF, who would then obtain a 56% decrease in mortality risk. Meanwhile, HFimpEF is associated with lower heart failure hospitalization. Further studies are required to explore how to promote left ventricular ejection fraction improvement and improve the prognosis of persistent HFrEF in patients.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021260422, identifier: CRD42021260422.
Increase in Right Temporal Cortex Thickness Is Related to Decline of Overall Cognitive Function in Patients With Hypertension
Authors: Li Wei , Yue Ling , Xiao Shifu
Published: December 2021

Background: Hypertension is associated with poorer cognitive functions, but the mechanisms are unclear.

Objective: This research aims to explore the cognitive status of elderly patients with hypertension and the possible mechanisms of hypertension affecting cognitive function.

Methods: Data were obtained from the China Longitudinal Aging Study (CLAS), and a total of 128 residents, aged 60 years and above, were recruited in this study. Based on whether they had hypertension, these 128 people were divided into the hypertension (n = 64) and non-hypertension groups (n = 64). The Beijing version of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess the overall cognitive function of the subjects, while digit span, language fluency, Wechsler mapping, and Wechsler wood block were used to assess their domain-specific cognitive function (both at baseline and follow-up stages). At the same time, we also examined baseline blood biochemical indicators (such as total protein, fasting plasma glucose (FPG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, and triglyceride) and baseline MRI data of hippocampus and amygdala volume and temporal polar cortex thickness.

Results: The total protein and thickness of temporal polar cortex in patients with hypertension were significantly higher than those in normal controls, but the scores on MMSE, MoCA, digit span, Wechsler mapping and Wechsler wood block at baseline were significantly lower than those in normal controls (p < 0.05). By linear regression analysis and correlation analysis (age and education were controlled), we found that baseline Wechsler mapping scores were negatively correlated with total protein (B = −0.243, t = −3,735, p < 0.001, 95% confidence interval (CI): −0.371 to −0.114); and both the follow-up MMSE score (B = 2.657, t = 2.002, p = 0.049, 95% CI: 0.009~5.306) and the change score of MMSE (r = −0.025, p = 0.047) were related to the thickness of the right temporal pole cortex. Then, by linear regression analysis (mediating model), we found that hypertension may influence follow-up MMSE scores by influencing the cortical thickness of the right temporal pole (B = 1.727, p = 0.022, 95% CI: 0.261–3.193).

Conclusions: Elderly patients with hypertension exhibit poorer overall cognitive function and executive function, and the mechanism may be related to the effect of hypertension on the cortical thickness of the right temporal pole.