bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of decellularized extracellular matrix derived from Jagged1-treated human dental pulp stem cells on biological responses of stem cells isolated from apical papilla
Authors: Phothichailert Suphalak , Nowwarote Nunthawan , Fournier Benjamin P.J. , Trachoo Vorapat , Roytrakul Sittiruk , Namangkalakul Worachat , Osathanon Thanaphum
Published: August 2022

Objective: Indirect Jagged1 immobilization efficiently activates canonical Notch signaling in human dental pulp stem cells (hDPSCs). This study aimed to investigate the characteristics of the Jagged1-treated hDPSC-derived decellularized extracellular matrix (dECM) and its biological activity on odonto/osteogenic differentiation of stem cells isolated from apical papilla (SCAPs).

Methods: Bioinformatic database of Jagged1-treated hDPSCs was analyzed using NetworkAnalyst. hDPSCs seeded on the Jagged1 immobilized surface were maintained with normal or osteogenic induction medium (OM) followed by decellularization procedure, dECM-N, or dECM-OM, respectively. SCAPs were reseeded on each dECM with either the normal medium or the OM. Cell viability was determined by MTT assay. Characteristics of dECMs and SCAPs were evaluated by SEM, EDX, immunofluorescent staining, and alcian blue staining. Mineralization was assessed by alizarin red S, Von Kossa, and alkaline phosphatase staining. Statistical significance was considered at p < 0.05.

Results: RNA-seq database revealed upregulation of several genes involved in ECM organization, ECM–receptor interaction, and focal adhesion in Jagged1-treated hDPSCs. Immobilized Jagged1 increased the osteogenesis of the hDPSC culture with OM. dECMs showed fibrillar-like network structure and maintained major ECM proteins, fibronectin, type I-collagen, and glycosaminoglycans. A decrease in calcium and phosphate components was observed in dECMs after the decellularized process. Cell viability on dECMs did not alter by 7 days. Cell attachment and f-actin cytoskeletal organization of SCAPs proliferated on Jagged1-treated dECMs were comparable to those of the control dECMs. SCAPs exhibited significantly higher mineralization on dECM-N in OM and markedly enhanced on dECM-OM with normal medium or OM conditions.

Conclusion: Jagged1-treated hDPSC-derived dECMs are biocompatible and increase odonto/osteogenic differentiation of SCAPs. The results suggested the potential of Jagged1 dECMs, which could be further developed into ECM scaffolds for application in regenerative medicine.
Inactivated vaccine injection and immunoglobulin G levels related to severe coronavirus disease 2019 (Delta) pneumonia in Xi’an, China: A single-centered, retrospective, observational study
Authors: Yang Han , Ma Jinbao , Li Aifang , Lei Jing , Shang Fenqing , Cheng Yue , Han Bei , Li Hongbo , Chen Yuee , Yang Yuanli , Xu You
Published: August 2022

The World Health Organization declared a public health emergency of international concern in January 2020. The Delta variant became the main epidemic strain on 11 May 2021. Vaccines were proven highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 infections. Real data on vaccine efficacy against B.1.617.2 infection in the Chinese population were currently limited. This study aimed to evaluate the protective effect of inactivated vaccine injection and immunoglobulin (Ig) G levels in coronavirus disease 2019 (COVID-19) severity. This retrospective study included patients with COVID-19 in Xi’an Chest Hospital from December 2021 to January 2022. The protective effect of inactivated vaccine injection and IgG levels on COVID-19 severity was analyzed using multiple logistic regressions. A total of 580 patients were included in the study, of whom 158 (27.24%) were mild, 412 (71.03%) were moderate, 5 (0.9%) were severe, and 5 (0.86%) were critical. Severe case (including severe and critical) rates were 1.72% (10/580). Compared with the unvaccinated group, the vac+IgG− group had a 0.21 (0.02–2.05)-fold risk of suffering from severe cases, and the vac+IgG+ group had a 0.05 (0–0.63)-fold risk of suffering from severe cases. Of the 10 severe cases, 8 were older than 60 years, 8 were men, 8 had underlying diseases, 6 were in the unvaccinated group, and 2 were in the vac+IgG− group. Vaccination and sufficient IgG antibody production can protect patients with COVID-19 from severe cases. Booster vaccine injection can produce a stronger immune response and protection.
Leptolysin, a Leptospira secreted metalloprotease of the pappalysin family with broad-spectrum activity
Authors: Courrol Daniella dos Santos , Silva Cristiane Castilho Fernandes da , Prado Luan Gavião , Chura-Chambi Rosa Maria , Morganti Ligia , de Souza Gisele Oliveira , Heinemann Marcos Bryan , Isaac Lourdes , Conte Fernando Paiva , Portaro Fernanda Calheta Vieira , Rodrigues-da-Silva Rodrigo Nunes , Barbosa Angela Silva
Published: August 2022

Extracellular proteolytic enzymes are produced by a variety of pathogenic microorganisms, and contribute to host colonization by modulating virulence. Here, we present a first characterization of leptolysin, a Leptospira metalloprotease of the pappalysin family identified in a previous exoproteomic study. Comparative molecular analysis of leptolysin with two other pappalysins from prokaryotes, ulilysin and mirolysin, reveals similarities regarding calcium, zinc, and arginine -binding sites conservation within the catalytic domain, but also discloses peculiarities. Variations observed in the primary and tertiary structures may reflect differences in primary specificities. Purified recombinant leptolysin of L. interrogans was obtained as a ~50 kDa protein. The protease exhibited maximal activity at pH 8.0 and 37°C, and hydrolytic activity was observed in the presence of different salts with maximum efficiency in NaCl. Substrate specificity was assessed using a small number of FRET peptides, and showed a marked preference for arginine residues at the P1 position. L. interrogans leptolysin proteolytic activity on proteinaceous substrates such as proteoglycans and plasma fibronectin was also evaluated. All proteins tested were efficiently degraded over time, confirming the protease´s broad-spectrum activity in vitro. In addition, leptolysin induced morphological alterations on HK-2 cells, which may be partially attributed to extracellular matrix (ECM) degradation. Hemorrhagic foci were observed in the dorsal skin of mice intradermally injected with leptolysin, as a plausible consequence of ECM disarray and vascular endothelium glycocalyx damage. Assuming that leptospiral proteases play an important role in all stages of the infectious process, characterizing their functional properties, substrates and mechanisms of action is of great importance for therapeutic purposes.
The activity of BcsZ of Salmonella Typhimurium and its role in Salmonella-plants interactions
Authors: Fratty Ilana S. , Shachar Dina , Katsman Marina , Yaron Sima
Published: August 2022

Salmonella enterica is one of the most common human pathogens associated with fresh produce outbreaks. The present study suggests that expression of BcsZ, one of the proteins in the bcs complex, enhances the survival of Salmonella Typhimurium on parsley. BcsZ demonstrated glucanase activity with the substrates carboxymethylcellulose and crystalline cellulose, and was responsible for a major part of the S. Typhimurium CMCase activity. Moreover, there was constitutive expression of BcsZ, which was also manifested after exposure to plant polysaccharides and parsley-leaf extract. In an in-planta model, overexpression of BcsZ significantly improved the epiphytic and endophytic survival of S. Typhimurium on/in parsley leaves compared with the wild-type strain and bcsZ null mutant. Interestingly, necrotic lesions appeared on the parsley leaf after infiltration of Salmonella overexpressing BcsZ, while infiltration of the wild-type S. Typhimurium did not cause any visible symptoms. Infiltration of purified BcsZ enzyme, or its degradation products also caused symptoms on parsley leaves. We suggest that the BcsZ degradation products trigger the plant’s defense response, causing local necrotic symptoms. These results indicate that BcsZ plays an important role in the Salmonella-plant interactions, and imply that injured bacteria may take part in these interactions.
Making a mark: Transforming everyday work of city arborists into dance
Authors: Ingram Matthew Bruce , Wallace Ian Mitchell
Published: August 2022

This article expands on previous scholarship on the choreographic practice of marking by studying two disparate communities—community-based dance makers and arborists—who collaborate to create a large-scale, public dance performance. With the dance company's goal being to bring public awareness to the embodied skillfulness of the city's urban forestry department and the impacts these city workers have on the community green spaces they service, the dancers for the performance are the foresters themselves who enact dancerly versions of their professional movements. We analyzed 21 h of videotaped data of dance rehearsals, proffering up an interaction-based approach to the study of marking, analyzing the moment-to-moment way, both groups mark out dance phrases for a sub-section of the final performance: the brush truck routine. In doing so, we develop the termmarking togetherto denote how dance ideas are built, transformed, and enacted through group idea formation and revision. Ultimately, we provide insights into how to study dance marking in its full, interactional complexity.
Coronary functional assessment in non-obstructive coronary artery disease: Present situation and future direction
Authors: Zhai Changlin , Fan Hongyan , Zhu Yujuan , Chen Yunqing , Shen Liang
Published: August 2022

Non-obstructive coronary artery disease (CAD), which is defined as coronary stenosis <50%, has been increasingly recognized as an emerging entity in clinical practice. Vasomotion abnormality and coronary microvascular dysfunction are two major mechanisms contributing to the occur of angina with non-obstructive CAD. Although routine coronary functional assessment is limited due to several disadvantages, functional evaluation can help to understand the pathophysiological mechanism and/or to exclude specific etiologies. In this review, we summarized the potential mechanisms involved in ischemia with non-obstructive coronary arteries (INOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA), the two major form of non-obstructive CAD. Additionally, we reviewed currently available functional assessment indices and their use in non-obstructive CAD. Furthermore, we speculated that novel technique combined anatomic and physiologic parameters might provide more individualized therapeutic choice for patients with non-obstructive CAD.
Machine learning for predicting acute hypotension: A systematic review
Authors: Zhao Anxing , Elgendi Mohamed , Menon Carlo
Published: August 2022

An acute hypotensive episode (AHE) can lead to severe consequences and complications that threaten patients' lives within a short period of time. How to accurately and non-invasively predict AHE in advance has become a hot clinical topic that has attracted a lot of attention in the medical and engineering communities. In the last 20 years, with rapid advancements in machine learning methodology, this topic has been viewed from a different perspective. This review paper examines studies published from 2008 to 2021 that evaluated the performance of various machine learning algorithms developed to predict AHE. A total of 437 articles were found in four databases that were searched, and 35 full-text articles were included in this review. Fourteen machine learning algorithms were assessed in these 35 articles; the Support Vector Machine algorithm was studied in 12 articles, followed by Logistic Regression (six articles) and Artificial Neural Network (six articles). The accuracy of the algorithms ranged from 70 to 96%. The size of the study sample varied from small (12 subjects) to very large (3,825 subjects). Recommendations for future work are also discussed in this review.
Clinical features and outcomes of patients with stable or unstable chest pain and no-obstructive coronary artery disease
Authors: Cambise Nello , Telesca Alessandro , Tremamunno Saverio , Felici Tamara , De Vita Antonio , Filice Monica , Ingrasciotta Gessica , Ruscio Eleonora , Crea Filippo , Lanza Gaetano A.
Published: August 2022

Background

Coronary microvascular dysfunction can be responsible for both stable angina and acute coronary syndrome (ACS). There are scarce data, however, about comparisons of clinical characteristics and outcomes of these 2 groups of patients.

Materials and methods

We studied 47 consecutive patients who underwent coronary angiography for angina syndromes and showed no obstructive stenosis. Patients were divided in 2 groups, according to their clinical presentation, i.e., stable angina (n = 21) or non-ST segment elevation ACS (NSTE-ACS; n = 26). An intracoronary acetylcholine (Ach) test was performed in 12 and 17 patients of the 2 groups, respectively. Angina status, assessed by Seattle Angina Questionnaire (SAQ), and clinical events were assessed after 1, 6, and 30 months. An exercise stress test was performed 1 month after discharge.

Results

Clinical characteristics and exercise test results of the 2 groups were largely similar. Ach testing induced epicardial or microvascular spasm in 6 (50.0%) and 10 (58.8%) stable and NSTE-ACS patients, respectively (p = 0.72). Stable patients reported higher rates of angina, compared to NSTE-ACS patients, both at 1 (p = 0.04) and 30 months (81 vs. 50%, p = 0.036) of follow-up. SAQ scores were also lower in stable vs. NSTE-ACS patients. Ach testing results showed no association with clinical outcomes.

Conclusion

Clinical characteristics and exercise and Ach testing results are similar in angina patients with no-obstructive coronary artery disease with a stable or NSTE-ACS presentation. Stable patients show a worse symptomatic outcome irrespective of Ach test results.
Comparison of mid-term clinical outcome in heart transplantation patients using mycophenolate mofetil vs. enteric-coated mycophenolate sodium
Authors: Jeon Kina , Kim Darae , Choi Jin-Oh , Cho Yang Hyun , Sung Kiick , Oh Jaewon , Cho Hyun Jai , Jung Sung-Ho , Lee Hae-Young , Park Jin Joo , Choi Dong-Ju , Kang Seok-Min , Kim Jae-Joong , Jeon Eun-Seok
Published: August 2022

Background

Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and a key immunosuppressant for improving graft survival in patients with heart transplantation (HTx). However, dose reduction or interruption is occasionally needed due to gastrointestinal (GI) side effects. Enteric-coated mycophenolate sodium (EC-MPS) is an alternative form of MPA delivery to improve GI tolerability. In the present study, the efficacy of EC-MPS compared with MMF in HTx patients was investigated.

Methods

In this retrospective study, the Korean Organ Transplant Registry (KOTRY) data were used to analyze the efficacy and rejection rate of MMF and EC-MPS. A total of 611 patients was enrolled from 2014 to February of 2021. Patients were divided based on the use of MMF or EC-MPS at 6 months post-HTx. Patients who were not prescribed MMF or EC-MPS were excluded. Graft survival, all-cause mortality, and treated rejection were compared between the two groups. All statistical analyses were performed using SPSS; characteristics were compared using Pearson chi-square test and survival rate with Kaplan-Meier plot and log-rank test.

Results

A total of 510 HTx patients was analyzed (mean age: 51.74 ± 13.16 years, males: 68.2%). At 6 months after HTx, 78 patients were taking EC-MPA (12.8%) and 432 patients were taking MMF (70.7%). The median follow-up was 42.0 months (IQR: 21.7–61.0 months). Post-HTx outcomes including overall survival, all cause mortality, acute cell mediated rejection (ACR), acute antibody mediated rejection (AMR), treated rejection, and cardiac allograft vasculopathy (CAV) were comparable between the two groups during follow-up.

Conclusion

Notable differences were not observed in overall survival, all cause mortality, ACR, AMR, treated rejection, and CAV between MMF and EC-MPS groups. Efficacy of EC-MPS was similar to that of MMF in HTx patients during mid-term follow up after HTx.
Revealing the Impacts of Banking Sector Development on Renewable Energy Consumption, Green Growth, and Environmental Quality in China: Does Financial Inclusion Matter?
Authors: Khan Muhammad Asghar , Rehan Raja
Published: August 2022

China aims to reduce its carbon dioxide emissions and promote green growth. This study aims to examine the effect of banking sector performance indicators (banks assets and return on asset) and financial inclusion on renewable energy consumption, green growth, and carbon emissions for China from 1995 to 2020 using the ARDL approach. The long-run results suggest that bank assets increase renewable energy consumption and green growth. While return on assets also increases green growth and decreases carbon emission in the long run. Financial inclusion enhances renewable energy consumption and green growth, curbing CO2 emissions. Banking sector performance and financial inclusion have short-run effects on renewable energy consumption, green growth, and carbon dixoside emissions. The findings thus point to the need for policies that promote banking sector performance and financial inclusion to boost green growth and alleviate CO2 emissions.
Evaluation of T-Shaped Fins With a Novel Layout for Improved Melting in a Triple-Tube Heat Storage System
Authors: Ebrahimnataj Tiji Mohammadreza , Mohammed Hayder I. , Ibrahem Raed Khalid , Dulaimi Anmar , Mahdi Jasim M. , Sh. Majdi Hasan , Keshtkar Mohammad Mehdi , Talebizadehsardari Pouyan
Published: August 2022

The effects of T-shaped fins on the improvement of phase change materials (PCM) melting are numerically investigated in vertical triple-tube storage containment. The PCM is held in the middle pipe of a triple-pipe heat exchanger while the heat transfer fluid flows through the internal and external pipes. The dimension effects of the T-shaped fins on the melting process of the PCM are investigated to determine the optimum case. Results indicate that while using T-shaped fins improves the melting performance of the PCM, the improvement potential is mainly governed by the fin’s body rather than the head. Hence, the proposed T-shaped fin did not noticeably improve melting at the bottom of the PCM domain; additionally, a flat fin is added to the optimal case (Added-Fin case) and compared to the No-Fin, Uniform-Fin, and Optimum T-shaped Fin cases (no added fin). The analysis shows that the total heat storage rate of the Added-Fin case increased by 141.7%, 58.8%, and 47.6% compared with the No-Fin, Uniform-Fin, and the Optimum T-shaped Fin cases, respectively. Furthermore, the total melting time for the Added-Fin case was 1882 s and decreased by 59.6%, 38.4%, and 33.6% compared with those of the No-Fin, Uniform-Fin, and the Optimum T-shaped Fin (Optimum) cases, respectively.
Future crop risk estimation due to drought, extreme temperature, hail, lightning, and tornado at the census tract level in Louisiana
Authors: Mostafiz Rubayet Bin , Rohli Robert V. , Friedland Carol J. , Gall Melanie , Bushra Nazla
Published: August 2022

Louisiana is one of the most hazard-prone states in the U.S., and many of its people are engaged directly or indirectly in agricultural activities that are impacted by an array of weather hazards. However, most hazard impact research on agriculture to date, for Louisiana and elsewhere, has focused on floods and hurricanes. This research develops a method of future crop loss risk assessment due to droughts, extreme low and high temperatures, hail, lightning, and tornadoes, using Louisiana as a case study. This approach improves future crop risk assessment by incorporating historical crop loss, historical and modeled future hazard intensity, cropland extent, population, consumer demand, cropping intensity, and technological development as predictors of future risk. The majority of crop activities occurred and will continue to occur in south-central and northeastern Louisiana along the river basins. Despite the fact that cropland is decreasing across most of the state, weather impacts to cropland are anticipated to increase substantially by 2050. Drought is by far the costliest among the six hazards, accounting for $56.1 million of $59.2 million (∼95%) in 2050-projected crop loss, followed by extreme cold ($1.4 million), extreme heat ($1.0 million), tornadoes ($0.4 million), hail ($0.2 million), and lightning ($0.05 million), respectively. These findings will assist decision-makers to minimize risk and enhance agricultural resilience to future weather hazards, thereby strengthening this economically-important industry in Louisiana and enhancing food security.
Macroeconomics of decarbonization strategies of selected global south countries: A systematic review
Authors: Emenekwe Chukwuemeka Chinonso , Okereke Chukwumerije , Nnamani Uchenna Alexander , Emodi Nnaemeka Vincent , Diemuodeke Ogheneruona Endurance , Anieze Ethelbert Elochukwu
Published: August 2022

Global concerns over increasing carbon emissions, climate change, decreasing environmental quality, limited and uneven endowments of fossil fuels, rising energy demand, and volatile oil prices have inspired the move toward global energy system decarbonization. The challenges of achieving ambitious climate targets and sustainable development cannot be solved without the significant efforts of the Global South. Regarding net-zero emissions, the main issue for developing countries is avoiding future emissions from industrialization and lock-in into fossil fuel-intensive technologies. However, achieving strategic and ambitious climate targets in the Global South will require understanding the economic implications of decarbonization. This study’s objective and key contribution are to systematically review and provide a detailed assessment of the literature on decarbonization in the Global South to understand the multi-level economic implications of achieving net-zero emissions in the Global South. The assessment considers four broad themes–investment costs, employment impacts, economic growth, and other macroeconomic impacts (such as consumption, debt level, net savings, income and welfare, and trade balance, among others). Overall, the review finds that energy system decarbonization requires substantial investment outlay. Also, it is linked with job displacement in fossil energy sectors and job creation in green sectors. However, there is no unanimous evidence on net job creation in developing countries. Additionally, the GDP impacts are ambiguous; some studies find future GDP growth impacts, while others find GDP decline impacts of decarbonization scenarios. This paper also provides directions for future research.
Early-Life Exposure of Pigs to Topsoil Alters miRNA and mRNA Expression in Peripheral Blood Mononuclear Cells
Authors: De Souza M. M. , Koltes D. A. , Beiki H. , Sales M. A. , Tsai T. , Maxwell C. V. , Zhao J. , Koltes J. E.
Published: August 2022

Exposure to less-hygienic conditions during early childhood has been associated with stimulation and development of the immune system. A recent study indicated that exposure of piglets to soil-borne microbes during lactation was related with modulation of gut microbiota and immune function. To identify the potential molecular mechanisms and pathways impacted by early-life topsoil exposure, we analyzed the messenger RNA (mRNA) and micro-RNA (miRNA) expression in peripheral blood mononuclear cells (PBMCs) from these piglets. Total RNA was extracted from the PBMCs of piglets exposed to topsoil only from d 4–d 21 of life (mRNA n = 6; miRNA n = 5) or unexposed control pigs (mRNA n = 6; miRNA n = 8) at 11, 20, and 56 days of age. Small RNA and mRNA were sequenced with 50-bp single-end reads using Illumina chemistry. Sequence data were quality checked with FASTQC software and aligned to the Sscrofa 11.1 genome with the STAR aligner for mRNA and mirDeep2 for miRNA. Differential expression (DE) analysis was performed using PROC Glimmix of SAS to evaluate changes in expression due to topsoil exposure over time with genes declared DE at a false discovery rate (FDR) of q < 0.10. A total of 138 mRNA and 21 miRNAs were identified as DE for the treatment by age interaction. Ontology enrichment analysis of DE mRNA revealed Gene ontology (GO) terms directly involved in the connection between T-cell and antigen-presenting cells that are associated with T-cell activation. Key regulatory genes identified include PTPRJ, ITGB3, TRBV30, CD3D, mir-143, mir-29, and mir-148a. While these results require validation, this study provides data supporting the hypothesis that less-hygienic environments during early life may contribute to the development of the immune system.
The role and mechanism of histone lactylation in health and diseases
Authors: Xie Yumei , Hu Hongxia , Liu Maoting , Zhou Tingting , Cheng Xi , Huang Wei , Cao Ling
Published: August 2022

Whether under anaerobic or aerobic conditions, glycolysis results in production of lactate. Increasing evidence suggests that lactate serves as a multifunctional signaling molecule that develops non-metabolic activities in addition to serving as a key metabolite to link glycolysis and oxidative phosphorylation. Histone posttranslational modification patterns (HPTMs) are essential epigenetic processes controlling a variety of biological activities. Proteomics based on mass spectrometry (MS) has been used to progressively reveal new HPTMs. Recent discoveries of histone lactylation modification mediated by lactate and subsequent research demonstrating its involvement in cancer, inflammation, lung fibrosis, and other conditions suggest that it plays a significant role in immune regulation and homeostasis maintenance. This review provides a brief overview of the complicated control of histone lactylation modification in both pathological and physiological conditions.
Construction of a prognostic model related to copper dependence in breast cancer by single-cell sequencing analysis
Authors: Guan Xiao , Lu Na , Zhang Jianping
Published: August 2022

Purpose: To explore the clinical significance of copper-dependent-related genes (CDRG) in female breast cancer (BC).

Methods: CDRG were obtained by single-cell analysis of the GSE168410 dataset in the Gene Expression Omnibus (GEO) database. According to a 1:1 ratio, the Cancer Genome Atlas (TCGA) cohort was separated into a training and a test cohort randomly. Based on the training cohort, the prognostic model was built using COX and Lasso regression. The test cohort was used to validate the model. The GSE20685 dataset and GSE20711 dataset were used as two external validation cohorts to further validate the prognostic model. According to the median risk score, patients were classified as high-risk or low-risk. Survival analysis, immune microenvironment analysis, drug sensitivity analysis, and nomogram analysis were used to evaluate the clinical importance of this prognostic model.

Results: 384 CDRG were obtained by single-cell analysis. According to the prognostic model, patients were classified as high-risk or low-risk in both cohorts. The high-risk group had a significantly worse prognosis. The area under the curve (AUC) of the model was around 0.7 in the four cohorts. The immunological microenvironment was examined for a possible link between risk score and immune cell infiltration. Veliparib, Selumetinib, Entinostat, and Palbociclib were found to be more sensitive medications for the high-risk group after drug sensitivity analysis.

Conclusion: Our CDRG-based prognostic model can aid in the prediction of prognosis and treatment of BC patients.
Immune effector cell associated neurotoxicity syndrome in chimeric antigen receptor-T cell therapy
Authors: Sterner Robert C. , Sterner Rosalie M.
Published: August 2022

Chimeric antigen receptor (CAR)-T cell therapy is an emerging staple in the treatment of certain hematological malignancies. While CAR-T cells have produced robust responses in certain hematological malignancies, toxicities associated with the therapy have limited their use. Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) is a potentially life-threatening neurotoxicity that commonly occurs with CAR-T cell therapy. Here we will discuss ICANS, its treatment, possible mechanisms, and potential solutions to this critical limitation of CAR-T cell therapy. As the field of CAR-T cell therapy evolves, improved treatments and methods to circumvent or overcome ICANS are necessary to improve morbidity, mortality, and decrease the cost of CAR-T cell therapy. This serious, life-threatening side effect needs to be studied to better understand its mechanisms and develop treatments and alternative strategies.
Potential biomarkers for retinopathy of prematurity identified by circular RNA profiling in peripheral blood mononuclear cells
Authors: Li Yun , Zhou Haixiang , Huang Qian , Tan Wei , Cai Yuting , Wang Zicong , Zou Jingling , Li Bingyan , Yoshida Shigeo , Zhou Yedi
Published: August 2022

Purpose

This study aims to reveal the altered expression profiles of circular RNAs (circRNAs) in the peripheral blood mononuclear cells (PBMCs) of patients with retinopathy of prematurity (ROP), and to identify potential biomarkers for ROP diagnosis.

Methods

Differentially expressed circRNAs in PBMCs of five infants with ROP and five controls were identified using microarray analysis. Twelve altered circRNAs were validated using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatic analyses were conducted to predict the circRNA/miRNA interactions, competing endogenous RNA (ceRNA) network, related biological functions, and signaling pathways. Four selected circRNAs in PBMCs were verified using RT-qPCR in another cohort, including 24 infants with ROP and 23 premature controls, and receiver operating characteristic (ROC) curves were used to estimate their potential as diagnostic biomarkers of ROP.

Results

A total of 54 and 143 circRNAs were significantly up- and down-regulated, respectively, in the PBMCs of patients with ROP compared with controls. Twelve of the significantly altered circRNAs were preliminarily validated by RT-qPCR, which confirmed the reliability of the microarray analysis. The circRNA/miRNA interactions and ceRNA network were displayed according to the altered circRNAs. Three circRNAs (hsa_circRNA_061346, hsa_circRNA_092369, and hsa_circRNA_103554) were identified as potential diagnostic biomarkers for ROP with certain clinical values.

Conclusions

CircRNAs were significantly altered in PBMCs of treatment-requiring ROP patients. CircRNAs may be used as potential biomarkers and possible therapeutic targets for ROP.
Novel insight on marker genes and pathogenic peripheral neutrophil subtypes in acute pancreatitis
Authors: Zhang Deyu , Wang Meiqi , Zhang Yang , Xia Chuanchao , Peng Lisi , Li Keliang , Yin Hua , Li Shiyu , Yang Xiaoli , Su Xiaoju , Huang Haojie
Published: August 2022

Acute pancreatitis is a common critical and acute gastrointestinal disease worldwide, with an increasing percentage of morbidity. However, the gene expression pattern in peripheral blood has not been fully analyzed. In addition, the mechanism of coronavirus disease 2019 (COVID-19)-induced acute pancreatitis has not been investigated. Here, after bioinformatic analysis with machine-learning methods of the expression data of peripheral blood cells and validation in local patients, two functional gene modules in peripheral blood cells of acute pancreatitis were identified, and S100A6, S100A9, and S100A12 were validated as predictors of severe pancreatitis. Additionally, through a combination analysis of bulk sequencing and single-cell sequencing data of COVID-19 patients, a pivotal subtype of neutrophils with strong activation of the interferon-related pathway was identified as a pivotal peripheral blood cell subtype for COVID-19-induced acute pancreatitis. These results could facilitate the prognostic prediction of acute pancreatitis and research on COVID-19-induced acute pancreatitis.
Exploration of PDCoV-induced apoptosis through mitochondrial dynamics imbalance and the antagonistic effect of SeNPs
Authors: Ren Zhihua , Yu Yueru , Zhang Xiaojie , Wang Qiuxiang , Deng Junliang , Chen Chaoxi , Shi Riyi , Wei Zhanyong , Hu Hui
Published: August 2022

Porcine Deltacoronavirus (PDCoV), an enveloped positive-strand RNA virus that causes respiratory and gastrointestinal diseases, is widely spread worldwide, but there is no effective drug or vaccine against it. This study investigated the optimal Selenium Nano-Particles (SeNPs) addition concentration (2 - 10 μg/mL) and the mechanism of PDCoV effect on ST (Swine Testis) cell apoptosis, the antagonistic effect of SeNPs on PDCoV. The results indicated that 4 μg/mL SeNPs significantly decreased PDCoV replication on ST cells. SeNPs relieved PDCoV-induced mitochondrial division and antagonized PDCoV-induced apoptosis via decreasing Cyt C release and Caspase 9 and Caspase 3 activation. The above results provided an idea and experimental basis associated with anti-PDCoV drug development and clinical use.
Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma
Authors: Lu Juan , Yu Chengbo , Bao Qiongling , Zhang Xiaoqian , Wang Jie
Published: August 2022

Background

Hepatocellular carcinoma remains the third most common cause of cancer-related deaths worldwide. Although great achievements have been made in resection, chemical therapies and immunotherapies, the pathogenesis and mechanism of HCC initiation and progression still need further exploration. Necroptosis genes have been reported to play an important role in HCC malignant activities, thus it is of great importance to comprehensively explore necroptosis-associated genes in HCC.

Methods

We chose the LIHC cohort from the TCGA, ICGC and GEO databases for this study. ConsensusClusterPlus was adopted to identify the necroptosis genes-based clusters, and LASSO cox regression was applied to construct the prognostic model based on necroptosis signatures. The GSEA and CIBERSORT algorithms were applied to evaluate the immune cell infiltration level. QPCR was also applied in this study to evaluate the expression level of genes in HCC.

Results

We identified three clusters, C1, C2 and C3. Compared with C2 and C3, the C1 cluster had the shortest overall survival time and highest immune score. The C1 was samples were significantly enriched in cell cycle pathways, some tumor epithelial-mesenchymal transition related signaling pathways, among others. The DEGs between the 3 clusters showed that C1 was enriched in cell cycle, DNA replication, cellular senescence, and p53 signaling pathways. The LASSO cox regression identified KPNA2, SLC1A5 and RAMP3 as prognostic model hub genes. The high risk-score subgroup had an elevated expression level of immune checkpoint genes and a higher TIDE score, which suggested that the high risk-score subgroup had a lower efficiency of immunotherapies. We also validated that the necroptosis signatures-based risk-score model had powerful prognosis prediction ability.

Conclusion

Based on necroptosis-related genes, we classified patients into 3 clusters, among which C1 had significantly shorter overall survival times. The proposed necroptosis signatures-based prognosis prediction model provides a novel approach in HCC survival prediction and clinical evaluation.
Impacts of ocean warming on a reef-building coralline alga Amphiroa cf. fragilissima under high irradiance
Authors: Yang Fangfang , Wei Zhangliang , Long Lijuan
Published: August 2022

Coralline algae, an important calcifying group, play vital roles in the primary productivity, reef frameworks construction, and carbon store. In this study, we investigated the responses of an articulated coralline alga Amphiroa cf. fragilissima to ocean warming under various light intensities. The relative growth rate significantly decreased under light or heat stress. When A. cf. fragilissima was exposed to high light intensity (120 μmol photons m−2 s−1) at 32°C, the relative growth rate was lowest, which reduced by 87% compared with that of group A1 (60 μmol photons m−2 s−1, 26°C). Meanwhile, a higher level of algal bleaching occurred when light intensity was 120 μmol photons m−2 s−1. Similarly, Fv/Fm and Chl-a content were negatively affected by light and heat stress, but they were more affected by light. Furthermore, the mineralogical responses to temperature and light were investigated. The net calcification rate declined from 92.27 (60 μmol photons m−2 s−1, 26°C) to 10.92 μmol CaCO3 g−1 DW day−1 (120 μmol photons m−2 s−1, 32°C). High temperature significantly decreased Ca content in live algal pigmented layer, whereas there were no significant differences in Ca content in the skeleton layer, implying that the pigmented layer could protect skeleton layer from mineral changes under ocean warming. The results revealed that A. cf. fragilissima was impaired by high light or thermal stress from various aspects, including growth, survival, photosynthesis, reproduction, and calcification. This study contributes to understand the effects of warming and light on coralline algae and provides a theoretical basis to protect the richness and diversity of calcified macroalgae.
Relationship between knowledge, attitudes, and practices and COVID-19 vaccine hesitancy: A cross-sectional study in Taizhou, China
Authors: Lin Xiao-Qing , Zhang Mei-Xian , Chen Yan , Xue Ji-Ji , Chen He-Dan , Tung Tao-Hsin , Zhu Jian-Sheng
Published: August 2022

Objective

This study aimed to explore COVID-19 vaccine hesitancy in Chinese adults and analyzed the relationship between knowledge, attitudes, practices (KAP), and COVID-19 vaccine hesitancy.

Methods

A population-based self-administered online survey was conducted in Taizhou, China to evaluate the population's hesitancy to receive COVID-19 vaccination. A total of 2.463 adults received the invitation for the survey through WeChat (A Chinese app that is used for chat, social media, and mobile payment), and 1.788 interviewees answered the structured questionnaire. The overall response rate was 72.6%.

Results

Total 45.2% of people were hesitant about the COVID-19 vaccination. Using binary logistic regression analysis, we found low perception of safety (Model 3: Odds ratio = 2.977, Confidence interval: 2.237–3.963) and efficacy (Model 3: OR = 1.904, 95%CI: 1.462–2.479) of the COVID-19 vaccine in adults is the most important risk factor for COVID-19 vaccine hesitation. People who know more about COVID-19 vaccination are less hesitant (Model 2: OR = 0.967, 95% CI: 0.951–0.983). People who did not seek information independently about the COVID-19 vaccine are more likely to be skeptical (Model 4: OR = 1.300, 95% CI: 1.058–1.598, P = 0.013).

Conclusion

In China, the population had higher levels of COVID-19 vaccine hesitation, and their knowledge of the COVID-19 vaccine, perceptions of safety and efficacy, and physical health status were significantly associated with vaccine hesitation. These results provide ideas for promoting COVID-19 vaccination and intervention and have far-reaching implications for further strengthening research on vaccine hesitancy in COVID-19 and exploring strategies for COVID-19 vaccine promotion.
Emerging role of neutrophil extracellular traps in the complications of diabetes mellitus
Authors: Shafqat Areez , Abdul Rab Saleha , Ammar Osama , Al Salameh Sulaiman , Alkhudairi Anas , Kashir Junaid , Alkattan Khaled , Yaqinuddin Ahmed
Published: August 2022

Immune dysfunction is widely regarded as one of the central tenants underpinning the pathophysiology of diabetes mellitus (DM) and its complications. When discussing immunity, the role of neutrophils must be accounted for: neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation, where they contribute to host defense via phagocytosis, degranulation, and extrusion of neutrophil extracellular traps (NETs). NETs are composed of DNA associated with nuclear and cytosolic neutrophil proteins. Although originally reported as an antimicrobial strategy to prevent microbial dissemination, a growing body of evidence has implicated NETs in the pathophysiology of various autoimmune and metabolic disorders. In these disorders, NETs propagate a pathologic inflammatory response with consequent tissue injury and thrombosis. Many diabetic complications—such as stroke, retinopathy, impaired wound healing, and coronary artery disease—involve these mechanisms. Therefore, in this review, we discuss laboratory and clinical data informing our understanding of the role of NETs in the development of these complications. NET markers, including myeloperoxidase, citrullinated histone H3, neutrophil elastase, and cell-free double-stranded DNA, can easily be measured in serum or be detected via immunohistochemical/immunocytochemical staining of tissue specimens. Therefore, NET constituents potentially constitute reliable biomarkers for use in the management of diabetic patients. However, no NET-targeting drug is currently approved for the treatment of diabetic complications; a candidate drug will require the outcomes of well-designed, robust clinical trials assessing whether NET inhibition can benefit patients in terms of morbidity, quality of life, health expenditures, and mortality. Therefore, much work remains to be done in translating these encouraging pieces of data into clinical trials for NET-targeting medications to be used in the clinic.
A novel SAR reduction technique for implantable antenna using conformal absorber metasurface
Authors: Das Soumyadeep , Mitra Debasis , Chezhian Arvind S. , Mandal Bappaditya , Augustine Robin
Published: August 2022

In this paper, a conformal absorber metasurface has been designed and used for reducing the specific absorption rate (SAR) of an implantable antenna. SAR reduction of implantable antennas is one of the significant design aspects to be considered for their use in modern-day healthcare applications. The introduction of the absorber metasurface restricts the back radiation of the antenna to control the SAR value. This technique decreases the maximum SAR value by 24% and also reduces the average SAR distribution significantly without affecting the desired antenna gain. A reduction in SAR value indicates the decrease in radiation absorption by human tissue, and thus, decreases the possibility of health hazards due to EM radiation. Later, this antenna-absorber system is designed as a capsule module for increased mobility and less-invasiveness. The redundancy of invasive surgery increases acceptance of the capsule module designs of implantable antennas and devices for various biomedical usages. In vitro testing of the fabricated prototype has been carried out inside a multi-layer porcine slab to verify the effectiveness of this unique SAR reduction technique.
The territorial nature of aggression in biofilms
Authors: Hashem Ihab , Van Impe Jan F. M.
Published: August 2022

Microbial conflicts have a particularly aggressive nature. In addition to other chemical, mechanical, and biological weapons in their repertoire, bacteria have evolved bacteriocins, which are narrow-spectrum toxins that kill closely related strains. Bacterial cells are known to frequently use their arsenal while competing against each other for nutrients and space. This stands in contrast with the animal world, where conflicts over resources and mating opportunities are far less lethal, and get commonly resolvedviaritualized fighting or “limited war” tactics. Prevalence of aggression in microbial communities is usually explained as due to their limited ability to resolve conflictsviasignaling as well as their limited ability to pull out from conflicts due to the sessile nature of their life within biofilms. We use an approach that combines Evolutionary Game Theory (EGT) and Individual-based Modeling (IbM) to investigate the origins of aggression in microbial conflicts. In order to understand how the spatial mode of growth affects the cost of a fight, we compare the growth dynamics emerging from engaging in aggression in a well-mixed system to a spatially structured system. To this end, a mathematical model is constructed for the competition between two bacterial strains where each strain produces a diffusible toxin to which the other strain is sensitive. It is observed that in the biofilm growth mode, starting from a mixed layer of two strains, mutual aggression gives rise to an exceedingly high level of spatial segregation, which in turn reduces the cost of aggression on both strains compared to when the same competition occurs in a well-mixed culture. Another observation is that the transition from a mixed layer to segregated growth is characterized by a switch in the overall growth dynamics. An increased “lag time” is observed in the overall population growth curve that is associated with the earlier stages of growth, when each strain is still experiencing the inhibiting effect of the toxin produced by its competitor. Afterwards, an exponential phase of growth kicks in once the competing strains start segregating from each other. The emerging “lag time” arises from the spiteful interactions between the two strains rather than acclimation of cells' internal physiology. Our analysis highlights the territorial nature of microbial conflicts as the key driver to their elevated levels of aggression as it increases the benefit-to-cost ratio of participating in antagonistic interactions.
Prevalence, distribution, enterotoxin profiles, antimicrobial resistance, and genetic diversity of Bacillus cereus group isolates from lettuce farms in Korea
Authors: Rajalingam Nagendran , Jung Jieun , Seo Seung-Mi , Jin Hyun-Sook , Kim Bo-Eun , Jeong Myeong-In , Kim Dawoon , Ryu Jae-Gee , Ryu Kyoung-Yul , Oh Kwang Kyo
Published: August 2022

Lettuce wraps are popular in Korean cuisine for their high nutritional value and versatility as healthy additions to multiple dishes. Microbial contamination of lettuce is a major concern, as lettuce is consumed fresh without cooking. Among foodborne pathogens, the spore-forming, facultative anaerobic bacterium, Bacillus cereus is one of the frequently detected pathogen in lettuce in Korea. In this study, we investigated the prevalence and distribution of Bacillus cereus strains in lettuce production farms and further evaluated the enterotoxin gene profiles, antibiotic susceptibility, multidrug resistance pattern, and genetic differences among the B. cereus group isolates. Of the 140 samples isolated from 10 lettuce production farms, 30 samples (21.42%) were positive for B. cereus in which 19 (31.6%) and 10 (23.25%) were from soil and lettuce, respectively. The enterotoxin patterns A (hblCDA, nheABC, entFM, and cytK genes) and B (hblCDA, nheABC, and entFM genes) accounted for 50% and 20% of all the isolates, whereas the emetic gene cesB was not detected in any of the B. cereus group isolates. Antibiotic susceptibility testing of the B. cereus group isolates revealed that all the strains were predominantly resistant to β-lactam antibiotics except imipenem and generally susceptible to most of the non β-lactam antibiotics, including gentamycin, streptomycin, chloramphenicol, and tetracycline. ERIC-PCR and MLST analysis revealed high genetic diversity among the 30 B. cereus group isolates, which belonged to 26 different sequence types (STs) and seven new STs. Moreover, isolates with identical STs exhibited similar patterns of antibiotic resistance and enterotoxin profiles. Results of this study indicate a high prevalence of B. cereus group isolates in lettuce production farms in the Republic of Korea.