bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Renewable Energy Distribution Between Gasifier and Electrolyzer for Syngas Generation in a Power and Biomass-to-Liquid Fuel Process
Authors: Putta Koteswara R. , Pandey Umesh , Gavrilovic Ljubisa , Rout Kumar R. , Rytter Erling , Blekkan Edd A. , Hillestad Magne
Published: January 2022

By adding energy as hydrogen to the biomass-to-liquid (BtL) process, several published studies have shown that carbon efficiency can be increased substantially. Hydrogen can be produced from renewable electrical energy through the electrolysis of water or steam. Adding high-temperature thermal energy to the gasifier will also increase the overall carbon efficiency. Here, an economic criterion is applied to find the optimal distribution of adding electrical energy directly to the gasifier as opposed to the electrolysis unit. Three different technologies for electrolysis are applied: solid oxide steam electrolysis (SOEC), alkaline water electrolysis (AEL), and proton exchange membrane (PEM). It is shown that the addition of part of the renewable energy to the gasifier using electric heaters is always beneficial and that the electrolysis unit operating costs are a significant portion of the costs. With renewable electricity supplied at a cost of 50 USD/MWh and a capital cost of 1,500 USD/kW installed SOEC, the operating costs of electric heaters and SOEC account for more than 70% of the total costs. The energy efficiency of the electrolyzer is found to be more important than the capital cost. The optimal amount of energy added to the gasifier is about 37–39% of the energy in the biomass feed. A BtL process using renewable hydrogen imports at 2.5 USD/kg H2 or SOEC for hydrogen production at reduced electricity prices gives the best values for the economic objective.
Regulation Effect of Smart Grid on Green Transformation of Electric Power Enterprises: Based on the Investigation of “Leader” Trap
Authors: Li Chengyu , Zhang Yanbing , Pratap Saurabh , Zhou Li , Liu Baoquan , Zhou Guangliang
Published: January 2022

The 2060 carbon neutral target reflects the long-term equilibrium and stability of production activities and the natural environment. As an important part of Chinese energy structure, the operation and transformation of power enterprises will face higher requirements. Although the rapid development of smart grids provides necessary technical support for power enterprises to build a modern energy system with green power as the core, whether power enterprises can use smart grids to improve their operating performance and environmental performance has yet to be discussed. The differences caused by the heterogeneity of property rights will also have an impact on the green transformation and development of enterprises. This paper selects 25 Chinese power enterprises as the research objects and uses the 2011–2019 enterprise panel data and the data envelopment analysis model to evaluate the operating performance and environmental performance of power enterprises. The results show that the overall fluctuation trend of the total factor productivity index and green total factor productivity index of power enterprises are W-shaped, and technological progress is the main driving force for the improvement of power operating performance and environmental performance; Compared with enterprises with a single power generation method, enterprises with diversified power generation methods performed better in their overall total factor productivity index. After that, text mining and machine learning methods are used to classify the text of the enterprise’s annual report to determine whether the enterprise applies smart grid technology for production and operation activities. Finally, using feasible generalized least squares method (FLGS) and dynamic panel system generalized moment estimation (SYS-GMM) to analyze the impact of smart grid on the operating performance and environmental performance of power enterprises, and the nature of corporate property rights in this process. It is found that smart grids can improve the operating performance and environmental performance of power enterprises; compared with state-owned enterprises, non-state-owned enterprises can achieve better performance in the application of smart grids to improve operating performance and environmental performance. Finally, this study provides corresponding policy recommendations for power enterprises to achieve performance improvement and green transformation development.
Assessing the Effects of Market Power on Electricity Reliability in China: Toward a Green and Reliable Market
Authors: Liu Minghui , Ju Chunhua , Huang Ruting
Published: January 2022

The transition to a low-carbon power system is among the measures to forge green energy transition and carbon neutrality, where grid firms have a crucial role. In this context, this paper uses the provincial data from 2004 to 2017 to evaluate the impact of market power of grid companies on service quality in China. Panel dynamic ordinary least square (DOLS) and fully modified ordinary least square (FMOLS) models are employed. The findings indicate that higher market power has indeed reduced reliability measured by average outage duration. Renewable energy integration also has negative effects and reduces electricity reliability. Finally, the effects are also heterogeneous across the different regions. The results may also provide useful lessons for other developing countries aiming to improve the electricity supply chain.
Research on the Unstable Branch Screening Method for Power System With High-Proportion Wind Power
Authors: Tang Fei , Wei Xiaoqing , Guo Yuhan , Qi Junfeng , Xie Jiarui , Li Xinang
Published: January 2022

The sooner the system instability is predicted and the unstable branches are screened, the timelier emergency control can be implemented for a wind power system. In this paper, aiming at the problem that the existing unstable branch screening methods are lack prejudgment, an unstable branch screening method for power system with high-proportion wind power is proposed. Firstly, the equivalent external characteristics model of the wind farm was deduced. And based on this, the out-of-step oscillation characteristics of the power system with high proportion wind power was analyzed. Secondly, based on the oscillation characteristics, line weak-connection index (LWcI) was proposed to quantify the stability margin of a branch. Then an instability prediction method and an unstable branch screening method were proposed based on LWcI and voltage phase angle difference. Finally, the rapidity and effectiveness of the proposed method are verified through the simulation analysis of IEEE-118 system.
YOLOv4-Lite–Based Urban Plantation Tree Detection and Positioning With High-Resolution Remote Sensing Imagery
Authors: Zheng Yueyuan , Wu Gang
Published: January 2022

Automatic tree identification and position using high-resolution remote sensing images are critical for ecological garden planning, management, and large-scale environmental quality detection. However, existing single-tree detection methods have a high rate of misdetection in forests not only due to the similarity of background and crown colors but also because light and shadow caused abnormal crown shapes, resulting in a high rate of misdetections and missed detection. This article uses urban plantations as the primary research sample. In conjunction with the most recent deep learning method for object detection, a single-tree detection method based on the lite fourth edition of you only look once (YOLOv4-Lite) was proposed. YOLOv4’s object detection framework has been simplified, and the MobileNetv3 convolutional neural network is used as the primary feature extractor to reduce the number of parameters. Data enhancement is performed for categories with fewer single-tree samples, and the loss function is optimized using focal loss. The YOLOv4-Lite method is used to detect single trees on campus, in an orchard, and an economic plantation. Not only is the YOLOv4-Lite method compared to traditional methods such as the local maximum value method and the watershed method, where it outperforms them by nearly 46.1%, but also to novel methods such as the Chan-Vese model and the template matching method, where it outperforms them by nearly 26.4%. The experimental results for single-tree detection demonstrate that the YOLOv4-Lite method improves accuracy and robustness by nearly 36.2%. Our work establishes a reference for the application of YOLOv4-Lite in additional agricultural and plantation products.
Free and Immobilized Microbial Culture–Mediated Crude Oil Degradation and Microbial Diversity Changes Through Taxonomic and Functional Markers in a Sandy Loam Soil
Authors: Khandelwal Ashish , Sugavanam Ramya , Ramakrishnan B. , Dutta Anirban , Varghese Eldho , Nain Lata , Banerjee Tirthankar , Singh Neera
Published: January 2022

Crude oil contamination of soil and water resources is a widespread issue. The present study evaluated the degradation of aliphatic hydrocarbons (C11–C36) in crude oil by 17 bacteria isolated from a crude oil–contaminated soil. The results suggested that Pseudomonas sp. and Bacillus amyloliquefaciens were the best hydrocarbon-degrading bacteria in the presence of surfactant Tween-80 (0.1% w/v). Based on the present investigation and a previous study, Pseudomonas sp. + B. amyloliquefaciens and fungus Aspergillus sydowii were identified as best oil degraders and were immobilized in alginate–bentonite beads, guargum–nanobenonite water dispersible granules (WDGs), and carboxy methyl cellulose (CMC)–bentonite composite. Sandy loam soil was fortified with 1, 2, and 5% crude oil, and total petroleum hydrocarbon (TPH) degradation efficiency of free cultures and bio-formulations was evaluated in sandy loam soils. Compared to a half-life (t1/2) of 69.7 days in the control soil (1% oil), free cultures of Pseudomonas sp. + B. amyloliquefaciens and A. sydowii degraded TPH with t1/2 of 10.8 and 19.4 days, respectively. Increasing the oil content slowed down degradation, and the t1/2 in the control and soils inoculated with Pseudomonas sp. + B. amyloliquefaciens and A. sydowii was 72.9, 14.7, and 22.2 days (2%) and 87.0, 23.4, and 30.8 days (5%), respectively. Supplementing soil with ammonium sulfate (1%) enhanced TPH degradation by Pseudomonas sp. + B. amyloliquefaciens (t1/2–10 days) and A. sydowii (t1/2–12.7 days). All three bio-formulations were effective in degrading TPH (1%), and the t1/2 was 10.7–11.9 days (Pseudomonas sp. + B. amyloliquefaciens and 14–20.2 days (A. sydowii) and were at par with free cultures. Microbial diversity analysis based on taxonomic markers and functional markers suggested that the bioaugmentation process helped keep soil in the active stage and restored the original microbial population to some extent. The present study concluded that bio-formulations of crude oil–degrading microbes can be exploited for its degradation in the contaminated environment.
Key Issues for Realizing Open Ecoacoustic Monitoring in Australia
Authors: Vella Kellie , Capel Tara , Gonzalez Ashleigh , Truskinger Anthony , Fuller Susan , Roe Paul
Published: January 2022

Many organizations are attempting to scale ecoacoustic monitoring for conservation but are hampered at the stages of data management and analysis. We reviewed current ecoacoustic hardware, software, and standards, and conducted workshops with 23 participants across 10 organizations in Australia to learn about their current practices, and to identify key trends and challenges in their use of ecoacoustics data. We found no existing metadata schemas that contain enough ecoacoustics terms for current practice, and no standard approaches to annotation. There was a strong need for free acoustics data storage, discoverable learning resources, and interoperability with other ecological modeling tools. In parallel, there were tensions regarding intellectual property management, and siloed approaches to studying species within organizations across different regions and between organizations doing similar work. This research contributes directly to the development of an open ecoacoustics platform to enable the sharing of data, analyses, and tools for environmental conservation.
Clinical Utility of the Prenatal BACs-on-Beads™ Assay in Invasive Prenatal Diagnosis
Authors: Jiang Yu , Wu Lili , Ge Yunshen , Zhang Jian , Huang Yanru , Wu Qichang , Zhang Yanhong , Zhou Yulin
Published: January 2022

Background: The prenatal BACs-on-Beads™ (PNBoBs™) assay has been applied worldwide for prenatal diagnosis. However, there are neither guidelines nor consensus on choosing patients, sample types, or clinical pathways for using this technique. Moreover, different perspectives have emerged regarding its clinical value. This study aimed to evaluate its clinical utility in the context of clinical practice located in a prenatal diagnostic center in Xiamen, a city in southeast China.

Methods: We tested 2,368 prenatal samples with multiple referral indications using both conventional karyotyping and PNBoBs™. Positive results from PNBoBs™ were verified using current gold-standard approaches.

Results: The overall rates for the detection of pathogenic copy number variation (pCNV) by karyotyping and PNBoBs™ were 1.9% (46/2,368) and 2.0% (48/2,368), respectively. The overall detection rate of karyotyping combined with PNBoBs™ for pCNV was 2.3% (54/2,368). A total of 13 cases of copy number variation (CNV)with a normal karyotype were detected by PNBoBs™. Another case with a normal karyotype that was detected as a CNV of sex chromosomes by PNBoBs™ was validated to be maternal cell contamination by short tandem repeat analysis.

Conclusion: Karyotyping combined with PNBoBs™ can improve both the yield and efficiency of prenatal diagnosis and is appropriate in the second trimester in all patients without fetal ultrasound anomalies who undergo invasive prenatal diagnosis.
Construction of the Classification Model Using Key Genes Identified Between Benign and Malignant Thyroid Nodules From Comprehensive Transcriptomic Data
Authors: Yang Qingxia , Gong Yaguo
Published: January 2022

Thyroid nodules are present in upto 50% of the population worldwide, and thyroid malignancy occurs in only 5–15% of nodules. Until now, fine-needle biopsy with cytologic evaluation remains the diagnostic choice to determine the risk of malignancy, yet it fails to discriminate as benign or malignant in one-third of cases. In order to improve the diagnostic accuracy and reliability, molecular testing based on transcriptomic data has developed rapidly. However, gene signatures of thyroid nodules identified in a plenty of transcriptomic studies are highly inconsistent and extremely difficult to be applied in clinical application. Therefore, it is highly necessary to identify consistent signatures to discriminate benign or malignant thyroid nodules. In this study, five independent transcriptomic studies were combined to discover the gene signature between benign and malignant thyroid nodules. This combined dataset comprises 150 malignant and 93 benign thyroid samples. Then, there were 279 differentially expressed genes (DEGs) discovered by the feature selection method (Student’s t test and fold change). And the weighted gene co-expression network analysis (WGCNA) was performed to identify the modules of highly co-expressed genes, and 454 genes in the gray module were discovered as the hub genes. The intersection between DEGs by the feature selection method and hub genes in the WGCNA model was identified as the key genes for thyroid nodules. Finally, four key genes (ST3GAL5, NRCAM, MT1F, and PROS1) participated in the pathogenesis of malignant thyroid nodules were validated using an independent dataset. Moreover, a high-performance classification model for discriminating thyroid nodules was constructed using these key genes. All in all, this study might provide a new insight into the key differentiation of benign and malignant thyroid nodules.
In-Silico Multi-Omics Analysis of the Functional Significance of Calmodulin 1 in Multiple Cancers
Authors: Yao Maolin , Fu Lanyi , Liu Xuedong , Zheng Dong
Published: January 2022

Aberrant activation of calmodulin 1 (CALM1) has been reported in human cancers. However, comprehensive understanding of the role of CALM1 in most cancer types has remained unclear. We systematically analyzed the expression landscape, DNA methylation, gene alteration, immune infiltration, clinical relevance, and molecular pathway of CALM1 in multiple cancers using various online tools, including The Cancer Genome Atlas, cBioPortal and the Human Protein Atlas databases. Kaplan–Meier and receiver operating characteristic (ROC) curves were plotted to explore the prognostic and diagnostic potential of CALM1 expression. Multivariate analyses were used to evaluate whether the CALM1 expression could be an independent risk factor. A nomogram predicting the overall survival (OS) of patients was developed, evaluated, and compared with the traditional Tumor-Node-Metastasis (TNM) model using decision curve analysis. R language was employed as the main tool for analysis and visualization. Results revealed CALM1 to be highly expressed in most cancers, its expression being regulated by DNA methylation in multiple cancers. CALM1 had a low mutation frequency (within 3%) and was associated with immune infiltration. We observed a substantial positive correlation between CALM1 expression and macrophage and neutrophil infiltration levels in multiple cancers. Different mutational forms of CALM1 hampered immune cell infiltration. Additionally, CALM1 expression had high diagnostic and prognostic potential. Multivariate analyses revealed CALM1 expression to be an independent risk factor for OS. Therefore, our newly developed nomogram had a higher clinical value than the TNM model. The concordance index, calibration curve, and time-dependent ROC curves of the nomogram exhibited excellent performance in terms of predicting the survival rate of patients. Moreover, elevated CALM1 expression contributes to the activation of cancer-related pathways, such as the WNT and MAPK pathways. Overall, our findings improved our understanding of the function of CALM1 in human cancers.
Episodes of Rapid Recovery of the Functional Activity of the ras85D Gene in the Evolutionary History of Phylogenetically Distant Drosophila Species
Authors: Chekunova A. I. , Sorokina S. Yu. , Sivoplyas E. A. , Bakhtoyarov G. N. , Proshakov P. A. , Fokin A. V. , Melnikov A. I. , Kulikov A. M.
Published: January 2022

As assemblies of genomes of new species with varying degrees of relationship appear, it becomes obvious that structural rearrangements of the genome, such as inversions, translocations, and transposon movements, are an essential and often the main source of evolutionary variation. In this regard, the following questions arise. How conserved are the regulatory regions of genes? Do they have a common evolutionary origin? And how and at what rate is the functional activity of genes restored during structural changes in the promoter region? In this article, we analyze the evolutionary history of the formation of the regulatory region of the ras85D gene in different lineages of the genus Drosophila, as well as the participation of mobile elements in structural rearrangements and in the replacement of specific areas of the promoter region with those of independent evolutionary origin. In the process, we substantiate hypotheses about the selection of promoter elements from a number of frequently repeated motifs with different degrees of degeneracy in the ancestral sequence, as well as about the restoration of the minimum required set of regulatory sequences using a conversion mechanism or similar.
The Role of Alternative Polyadenylation in the Regulation of Subcellular RNA Localization
Authors: Arora Ankita , Goering Raeann , Lo Hei Yong G. , Lo Joelle , Moffatt Charlie , Taliaferro J. Matthew
Published: January 2022

Alternative polyadenylation (APA) is a widespread and conserved regulatory mechanism that generates diverse 3′ ends on mRNA. APA patterns are often tissue specific and play an important role in cellular processes such as cell proliferation, differentiation, and response to stress. Many APA sites are found in 3′ UTRs, generating mRNA isoforms with different 3′ UTR contents. These alternate 3′ UTR isoforms can change how the transcript is regulated, affecting its stability and translation. Since the subcellular localization of a transcript is often regulated by 3′ UTR sequences, this implies that APA can also change transcript location. However, this connection between APA and RNA localization has only recently been explored. In this review, we discuss the role of APA in mRNA localization across distinct subcellular compartments. We also discuss current challenges and future advancements that will aid our understanding of how APA affects RNA localization and molecular mechanisms that drive these processes.
DNA Double Strand Break Repair and Its Control by Nucleosome Remodeling
Authors: Karl Leonhard Andreas , Peritore Martina , Galanti Lorenzo , Pfander Boris
Published: January 2022

DNA double strand breaks (DSBs) are repaired in eukaryotes by one of several cellular mechanisms. The decision-making process controlling DSB repair takes place at the step of DNA end resection, the nucleolytic processing of DNA ends, which generates single-stranded DNA overhangs. Dependent on the length of the overhang, a corresponding DSB repair mechanism is engaged. Interestingly, nucleosomes—the fundamental unit of chromatin—influence the activity of resection nucleases and nucleosome remodelers have emerged as key regulators of DSB repair. Nucleosome remodelers share a common enzymatic mechanism, but for global genome organization specific remodelers have been shown to exert distinct activities. Specifically, different remodelers have been found to slide and evict, position or edit nucleosomes. It is an open question whether the same remodelers exert the same function also in the context of DSBs. Here, we will review recent advances in our understanding of nucleosome remodelers at DSBs: to what extent nucleosome sliding, eviction, positioning and editing can be observed at DSBs and how these activities affect the DSB repair decision.
STING Signaling Drives Production of Innate Cytokines, Generation of CD8+ T Cells and Enhanced Protection Against Trypanosoma cruzi Infection
Authors: Vieira Raquel de Souza , Nascimento Marilda Savoia , Noronha Isaú Henrique , Vasconcelos José Ronnie Carvalho , Benvenuti Luiz Alberto , Barber Glen N. , Câmara Niels Olsen Saraiva , Kalil Jorge , Cunha-Neto Edecio , Almeida Rafael Ribeiro
Published: January 2022

A variety of signaling pathways are involved in the induction of innate cytokines and CD8+T cells, which are major players in protection against acuteTrypanosoma cruziinfection. Previous data have demonstrated that a TBK-1/IRF3-dependent signaling pathway promotes IFN-β production in response toTrypanosoma cruzi, but the role for STING, a main interactor of these proteins, remained to be addressed. Here, we demonstrated that STING signaling is required for production of IFN-β, IL-6, and IL-12 in response toTrypanosoma cruziinfection and that STING absence negatively impacts activation of IRF-dependent pathways in response to the parasite. We reported no significant activation of IRF-dependent pathways and cytokine expression in RAW264.7 macrophages in response to heat-killed trypomastigotes. In addition, we showed that STING is essential forT. cruziDNA-mediated induction of IFN-β, IL-6, and IL-12 gene expression in RAW264.7 macrophages. We demonstrated that STING-knockout mice have significantly higher parasitemia from days 5 to 8 of infection and higher heart parasitism at day 13 after infection. Although we observed similar heart inflammatory infiltrates at day 13 after infection, IFN-β, IL-12, CXCL9, IFN-γ, and perforin gene expression were lower in the absence of STING. We also showed an inverse correlation between parasite DNA and the expression of CXCL9, IFN-γ, and perforin genes in the hearts of infected animals at day 13 after infection. Finally, we reported that STING signaling is required for splenic IFN-β and IL-6 expression early after infection and that STING deficiency results in lower numbers of splenic parasite-specific IFN-γ and IFN-γ/perforin-producing CD8+T cells, indicating a pivotal role for STING signaling in immunity toTrypanosoma cruzi.
Therapeutic Management of Ocular Ischemia in Takayasu’s Arteritis: A Case-Based Systematic Review
Authors: Zeng Yue , Duan Jianan , Ge Ge , Zhang Meixia
Published: January 2022

Background

Takayasu’s arteritis (TA) is a rare, chronic granulomatous large-vessel vasculitis that can lead to ocular ischemia. Ocular outcomes after therapeutic management in TA remain largely unknown. We herein conduct a case-based systematic review to address the current treatment options in this particular cohort.

Methods

PubMed, Medline, and EMBASE databases were searched pertaining to ocular outcomes after systemic treatment in TA. Studies reporting ocular examinations before and after treatment in TA patients with ocular ischemia were included. Clinical characteristics, therapies, ocular outcomes, and complications were recorded.

Results

A 29-year-old woman with newly diagnosed TA showed dramatic regression of Takayasu’s retinopathy (TR) following balloon angioplasty. Optical coherence tomography angiography (OCTA) was used as a novel strategy for subsequent follow-up. A total of 117 eyes of 66 patients with a median age of 27 years were included for systematic review. TR was the most common ocular manifestation. Oral steroids were prescribed in nearly all patients (n = 65), followed by the use of methotrexate and antiplatelet therapy. Of the patients, 65.8% and 34.2% underwent open surgery and endovascular procedure, respectively. The median follow-up period was 12 weeks (interquartile range 8–33.5). Surgical therapy showed better ocular improvement (including visual and imaging responses) in both acute and chronic vision loss, along with fewer complications than medical therapy alone. In the surgical group, the visual prognosis was significantly better in patients with initial visual acuity better than 20/200 (p = 0.03) and those who underwent surgery before stage III TR (p = 0.01). Ocular outcomes were equivalent in the two surgical approaches.

Conclusion

Clinicians should be familiar with ophthalmic manifestations of this potentially treatable complication in TA. Compared with medical therapy alone, surgical intervention might be a better choice for both acute and chronic vision loss. Surgery is best recommended before the onset of irreversible ischemia to the globe. A combined regimen (oral steroids, immunosuppressants, and antiplatelet drugs) might be effective for those with surgical contradictions or reluctance to an invasive procedure. Physicians should be aware of the importance of ocular examinations, including OCTA, during the diagnosis and follow-up in TA.
Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells
Authors: Yan Shuping , Ye Pingsheng , Aleem Muhammad Tahir , Chen Xi , Xie Nana , Zhang Yuanshu
Published: January 2022

Mesenchymal stem cells (MSCs) are capable of homing injury sites to exert anti-inflammatory as well as anti-damage effects and can be used as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2) plays an important role in numerous inflammatory diseases, but fewer studies have been reported in animal mastitis. We hypothesized that MSCs overexpressing ACE2 is more effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory injury in mammary epithelial cells compared to MSCs alone. The results showed that MSC-ACE2 inhibited the LPS induction by upregulation of TNF-α, IL-Iβ, IL-6, and iNOS mRNA expression levels in EpH4-Ev cells compared with MSCs. Furthermore, results showed that both MSC and MSC-ACE2 were significantly activated IL-10/STAT3/SOCS3 signaling pathway as well as inhibited TLR4/NF-κB and MAPK signaling pathways, but MSC-ACE2 had more significant effects. Meanwhile, MSC-ACE2 promoted the expression of proliferation-associated proteins and inhibited the expression of the apoptosis-associated proteins in EpH4-Ev cells. In addition, MSC and MSC-ACE2 reversed the LPS-induced downregulation expression levels of the tight junction proteins in mammary epithelial cells, indicating that both MSC as well as MSC-ACE2 could promote blood-milk barrier repair, and MSC-ACE2 was more effective. These results suggested that MSCs overexpressing ACE2 were more anti-inflammatory as well as anti-injurious action into LPS-induced inflammatory injury in the EpH4-Ev cells. Thus, MSCs overexpressing ACE2 is expected to serve as a potential strategy for mastitis treatment.
Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy
Authors: Ye Zu , Shi Yin , Lees-Miller Susan P. , Tainer John A.
Published: January 2022

The DNA damage response (DDR) is an organized network of multiple interwoven components evolved to repair damaged DNA and maintain genome fidelity. Conceptually the DDR includes damage sensors, transducer kinases, and effectors to maintain genomic stability and accurate transmission of genetic information. We have recently gained a substantially improved molecular and mechanistic understanding of how DDR components are interconnected to inflammatory and immune responses to stress. DDR shapes both innate and adaptive immune pathways: (i) in the context of innate immunity, DDR components mainly enhance cytosolic DNA sensing and its downstream STimulator of INterferon Genes (STING)-dependent signaling; (ii) in the context of adaptive immunity, the DDR is needed for the assembly and diversification of antigen receptor genes that is requisite for T and B lymphocyte development. Imbalances between DNA damage and repair impair tissue homeostasis and lead to replication and transcription stress, mutation accumulation, and even cell death. These impacts from DDR defects can then drive tumorigenesis, secretion of inflammatory cytokines, and aberrant immune responses. Yet, DDR deficiency or inhibition can also directly enhance innate immune responses. Furthermore, DDR defects plus the higher mutation load in tumor cells synergistically produce primarily tumor-specific neoantigens, which are powerfully targeted in cancer immunotherapy by employing immune checkpoint inhibitors to amplify immune responses. Thus, elucidating DDR-immune response interplay may provide critical connections for harnessing immunomodulatory effects plus targeted inhibition to improve efficacy of radiation and chemotherapies, of immune checkpoint blockade, and of combined therapeutic strategies.
The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer
Authors: Liu Chen , Huang Yuhan , Cui Yaoyuan , Zhou Jun , Qin Xu , Zhang Li , Li Xi , Li Yuan , Guo Ensong , Yang Bin , Li Xi , Fan Junpeng , Li Xiong , Fu Yu , Liu Si , Hu Dianxing , Xiao Rourou , Wang Zizhuo , Dou Yingyu , Wang Wei , Li Wenting , Yang Xiaohang , Liu Jingbo , Peng Wenju , Qin Tianyu , You Lixin , Lu Funian , Sun Chaoyang
Published: January 2022

Background

Ovarian cancer (OC) is one of the most lethal gynecologic cancers. Growing evidence has proven that CDK4/6 plays a key role in tumor immunity and the prognosis of many cancers. However, the expression and function of CDK4/6 in OC remain unclear. Therefore, we aimed to explore the influence of CDK4/6 in OC, especially on immunity.

Methods

We analyzed CDK4/6 expression and prognosis using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype Tissue Expression (GTEx) data. Subsequently, we used the cytoHubba plug-in of Cytoscape software and starBase to identify the noncoding RNAs (ncRNAs) regulating CDK4/6. Finally, we verified the effect of CDK4/6 on immunity in OC cell lines and animal models.

Results

CDK4/6 expression was higher in OC tissues than in normal ovarian tissues, and the high expression levels of CDK4/6 contributed to the immunosuppressive state of OC and were thus related to the poor prognosis of OC patients. This was also in general agreement with the results of OC cell line and animal experiments. Mechanistically, the CDK4/6 inhibitor palbociclib increased the secretion of interferon (IFN)-γ and the interferon-stimulated gene (ISG) response, thereby upregulating the expression of antigen-presenting molecules; this effect was partly dependent on the STING pathway and thus activated immunity in OC. Additionally, according to public data, the LRRC75A-AS1-hsa-miR-330-5p axis could inhibit the immune response of OC patients by upregulating CDK4/6, leading to a poor prognosis.

Conclusion

CDK4/6 affects the immune microenvironment of OC and correlates with the prognosis of OC patients.
Persistent Oxidative Stress and Inflammasome Activation in CD14highCD16− Monocytes From COVID-19 Patients
Authors: Lage Silvia Lucena , Amaral Eduardo Pinheiro , Hilligan Kerry L. , Laidlaw Elizabeth , Rupert Adam , Namasivayan Sivaranjani , Rocco Joseph , Galindo Frances , Kellogg Anela , Kumar Princy , Poon Rita , Wortmann Glenn W. , Shannon John P. , Hickman Heather D. , Lisco Andrea , Manion Maura , Sher Alan , Sereti Irini
Published: January 2022

The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome and oxidative stress have independently been implicated in COVID-19, it is poorly understood whether these two pathways cooperatively contribute to disease severity. Herein, we found an enrichment of CD14highCD16− monocytes displaying inflammasome activation evidenced by caspase-1/ASC-speck formation in severe COVID-19 patients when compared to mild ones and healthy controls, respectively. Those cells also showed aberrant levels of mitochondrial superoxide and lipid peroxidation, both hallmarks of the oxidative stress response, which strongly correlated with caspase-1 activity. In addition, we found that NLRP3 inflammasome-derived IL-1β secretion by SARS-CoV-2-exposed monocytes in vitro was partially dependent on lipid peroxidation. Importantly, altered inflammasome and stress responses persisted after short-term patient recovery. Collectively, our findings suggest oxidative stress/NLRP3 signaling pathway as a potential target for host-directed therapy to mitigate early COVID-19 hyperinflammation and also its long-term outcomes.
Role of Lactate in Inflammatory Processes: Friend or Foe
Authors: Manosalva Carolina , Quiroga John , Hidalgo Alejandra I. , Alarcón Pablo , Ansoleaga Nicolás , Hidalgo María Angélica , Burgos Rafael Agustín
Published: January 2022

During an inflammatory process, shift in the cellular metabolism associated with an increase in extracellular acidification are well-known features. This pH drop in the inflamed tissue is largely attributed to the presence of lactate by an increase in glycolysis. In recent years, evidence has accumulated describing the role of lactate in inflammatory processes; however, there are differences as to whether lactate can currently be considered a pro- or anti-inflammatory mediator. Herein, we review these recent advances on the pleiotropic effects of lactate on the inflammatory process. Taken together, the evidence suggests that lactate could exert differential effects depending on the metabolic status, cell type in which the effects of lactate are studied, and the pathological process analyzed. Additionally, various targets, including post-translational modifications, G-protein coupled receptor and transcription factor activation such as NF-κB and HIF-1, allow lactate to modulate signaling pathways that control the expression of cytokines, chemokines, adhesion molecules, and several enzymes associated with immune response and metabolism. Altogether, this would explain its varied effects on inflammatory processes beyond its well-known role as a waste product of metabolism.
The Transient IFN Response and the Delay of Adaptive Immunity Feature the Severity of COVID-19
Authors: Xu Gang , Qi Furong , Wang Haiyan , Liu Yu , Wang Xin , Zou Rongrong , Yuan Jing , Liao Xuejiao , Liu Yang , Zhang Shuye , Zhang Zheng
Published: January 2022

COVID-19 patients show heterogeneous and dynamic immune features which determine the clinical outcome. Here, we built a single-cell RNA sequencing (scRNA-seq) dataset for dissecting these complicated immune responses through a longitudinal survey of COVID-19 patients with various categories of outcomes. The data reveals a highly fluctuating peripheral immune landscape in severe COVID-19, whereas the one in asymptomatic/mild COVID-19 is relatively steady. Then, the perturbed immune landscape in peripheral blood returned to normal state in those recovered from severe COVID-19. Importantly, the imbalance of the excessively strong innate immune response and delayed adaptive immunity in the early stage of viral infection accelerates the progression of the disease, indicated by a transient strong IFN response and weak T/B-cell specific response. The proportion of abnormal monocytes appeared early and rose further throughout the severe disease. Our data indicate that a dynamic immune landscape is associated with the progression and recovery of severe COVID-19, and have provided multiple immune biomarkers for early warning of severe COVID-19.
Generation of High Quality Memory B Cells
Authors: Inoue Takeshi , Shinnakasu Ryo , Kurosaki Tomohiro
Published: January 2022

Protection against pathogen re-infection is mediated, in large part, by two humoral cellular compartments, namely, long-lived plasma cells and memory B cells. Recent data have reinforced the importance of memory B cells, particularly in response to re-infection of different viral subtypes or in response with viral escape mutants. In regard to memory B cell generation, considerable advancements have been made in recent years in elucidating its basic mechanism, which seems to well explain why the memory B cells pool can deal with variant viruses. Despite such progress, efforts to develop vaccines that induce broadly protective memory B cells to fight against rapidly mutating pathogens such as influenza virus and HIV have not yet been successful. Here, we discuss recent advances regarding the key signals and factors regulating germinal center-derived memory B cell development and activation and highlight the challenges for successful vaccine development.
Toward a Solution of the “Peruvian Puzzle”: Pelagic Food-Web Structure and Trophic Interactions in the Northern Humboldt Current Upwelling System Off Peru
Authors: Massing Jana C. , Schukat Anna , Auel Holger , Auch Dominik , Kittu Leila , Pinedo Arteaga Elda Luz , Correa Acosta Jonathan , Hagen Wilhelm
Published: January 2022

The northern Humboldt Current upwelling system (HCS) belongs to the most productive marine ecosystems, providing five to eight times higher fisheries landings per unit area than other coastal upwelling systems. To solve this “Peruvian puzzle”, to elucidate the pelagic food-web structure and to better understand trophic interactions in the HCS, a combined stable isotope and fatty acid trophic biomarker approach was adopted for key zooplankton taxa and higher trophic positions with an extensive spatial coverage from 8.5 to 16°S and a vertical range down to 1,000 m depth. A pronounced regional shift by up to ∼5‰ in the δ15N baseline of the food web occurred from North to South. Besides regional shifts, δ15N ratios of particulate organic matter (POM) also tended to increase with depth, with differences of up to 3.8‰ between surface waters and the oxygen minimum zone. In consequence, suspension-feeding zooplankton permanently residing at depth had up to ∼6‰ higher δ15N signals than surface-living species or diel vertical migrants. The comprehensive data set covered over 20 zooplankton taxa and indicated that three crustacean species usually are key in the zooplankton community, i.e., the copepods Calanus chilensis at the surface and Eucalanus inermis in the pronounced OMZ and the krill Euphausia mucronata, resulting in an overall low number of major trophic pathways toward anchovies. In addition, the semi-pelagic squat lobster Pleuroncodes monodon appears to play a key role in the benthic-pelagic coupling, as indicated by highest δ13C’ ratios of −14.7‰. If feeding on benthic resources and by diel vertical migration, they provide a unique pathway for returning carbon and energy from the seafloor to the epipelagic layer, increasing the food supply for pelagic fish. Overall, these mechanisms result in a very efficient food chain, channeling energy toward higher trophic positions and partially explaining the “Peruvian puzzle” of enormous fish production in the HCS.
Framing Cutting-Edge Integrative Deep-Sea Biodiversity Monitoring via Environmental DNA and Optoacoustic Augmented Infrastructures
Authors: Stefanni Sergio , Mirimin Luca , Stanković David , Chatzievangelou Damianos , Bongiorni Lucia , Marini Simone , Modica Maria Vittoria , Manea Elisabetta , Bonofiglio Federico , del Rio Fernandez Joaquin , Cukrov Neven , Gavrilović Ana , De Leo Fabio C. , Aguzzi Jacopo
Published: January 2022

Deep-sea ecosystems are reservoirs of biodiversity that are largely unexplored, but their exploration and biodiscovery are becoming a reality thanks to biotechnological advances (e.g., omics technologies) and their integration in an expanding network of marine infrastructures for the exploration of the seas, such as cabled observatories. While still in its infancy, the application of environmental DNA (eDNA) metabarcoding approaches is revolutionizing marine biodiversity monitoring capability. Indeed, the analysis of eDNA in conjunction with the collection of multidisciplinary optoacoustic and environmental data, can provide a more comprehensive monitoring of deep-sea biodiversity. Here, we describe the potential for acquiring eDNA as a core component for the expanding ecological monitoring capabilities through cabled observatories and their docked Internet Operated Vehicles (IOVs), such as crawlers. Furthermore, we provide a critical overview of four areas of development: (i) Integrating eDNA with optoacoustic imaging; (ii) Development of eDNA repositories and cross-linking with other biodiversity databases; (iii) Artificial Intelligence for eDNA analyses and integration with imaging data; and (iv) Benefits of eDNA augmented observatories for the conservation and sustainable management of deep-sea biodiversity. Finally, we discuss the technical limitations and recommendations for future eDNA monitoring of the deep-sea. It is hoped that this review will frame the future direction of an exciting journey of biodiscovery in remote and yet vulnerable areas of our planet, with the overall aim to understand deep-sea biodiversity and hence manage and protect vital marine resources.
Molecular Imaging of Lower Extremity Peripheral Arterial Disease: An Emerging Field in Nuclear Medicine
Authors: Stacy Mitchel R.
Published: January 2022

Peripheral arterial disease (PAD) is an atherosclerotic disorder of non-coronary arteries that is associated with vascular stenosis and/or occlusion. PAD affecting the lower extremities is characterized by a variety of health-related consequences, including lifestyle-limiting intermittent claudication, ulceration of the limbs and/or feet, increased risk for lower extremity amputation, and increased mortality. The diagnosis of lower extremity PAD is typically established by using non-invasive tests such as the ankle-brachial index, toe-brachial index, duplex ultrasound, and/or angiography imaging studies. While these common diagnostic tools provide hemodynamic and anatomical vascular assessments, the potential for non-invasive physiological assessment of the lower extremities has more recently emerged through the use of magnetic resonance- and nuclear medicine-based approaches, which can provide insight into the functional consequences of PAD-related limb ischemia. This perspectives article specifically highlights and discusses the emerging applications of clinical nuclear medicine techniques for molecular imaging investigations in the setting of lower extremity PAD.
Nanomaterials-Based Urinary Extracellular Vesicles Isolation and Detection for Non-invasive Auxiliary Diagnosis of Prostate Cancer
Authors: Wang Na , Yuan Shuai , Fang Cheng , Hu Xiao , Zhang Yu-Sen , Zhang Ling-Ling , Zeng Xian-Tao
Published: January 2022

Extracellular vesicles (EVs) are natural nanoparticles secreted by cells in the body and released into the extracellular environment. They are associated with various physiological or pathological processes, and considered as carriers in intercellular information transmission, so that EVs can be used as an important marker of liquid biopsy for disease diagnosis and prognosis. EVs are widely present in various body fluids, among which, urine is easy to obtain in large amount through non-invasive methods and has a small dynamic range of proteins, so it is a good object for studying EVs. However, most of the current isolation and detection of EVs still use traditional methods, which are of low purity, time consuming, and poor efficiency; therefore, more efficient and highly selective techniques are urgently needed. Recently, inspired by the nanoscale of EVs, platforms based on nanomaterials have been innovatively explored for isolation and detection of EVs from body fluids. These newly developed nanotechnologies, with higher selectivity and sensitivity, greatly improve the precision of isolation target EVs from urine. This review focuses on the nanomaterials used in isolation and detection of urinary EVs, discusses the advantages and disadvantages between traditional methods and nanomaterials-based platforms, and presents urinary EV-derived biomarkers for prostate cancer (PCa) diagnosis. We aim to provide a reference for researchers who want to carry out studies about nanomaterial-based platforms to identify urinary EVs, and we hope to summarize the biomarkers in downstream analysis of urinary EVs for auxiliary diagnosis of PCa disease in detail.