bluuebunny/crossref_metadata_2025 huggingface dataset:
PRC1 and RACGAP1 are Diagnostic Biomarkers of Early HCC and PRC1 Drives Self-Renewal of Liver Cancer Stem Cells
Authors: Liao Shixin , Wang Kaili , Zhang Lulu , Shi Gaoli , Wang Zhiwei , Chen Zhenzhen , Zhu Pingping , He Qiankun
Published: April 2022

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths across the world. Due to the lack of reliable markers for early HCC detection, most HCC patients are diagnosed in middle/late stages. Liver cancer stem cells (CSCs), which are drivers of liver tumorigenesis, usually emerge in the early HCC stage and are also termed as liver tumor initiation cells (TIC). Liver CSCs contribute to initiation, propagation, and metastasis of HCC and also play a key role in tumor therapy. Taking advantage of online-available data sets, bioinformatic analyses, and experimental confirmation, here we have screened out PRC1 and RACGAP1 as reliable markers for early HCC detection. PRC1 or RACGAP1 knockdown dramatically inhibited the proliferation, migration, and invasion capacities of HCC cells, conferring PRC1 and RACGAP1 as predominant modulators for HCC propagation and metastasis. Moreover, the sphere formation capacity of HCC cells was impaired after PRC1 knockdown, revealing the function of PRC1 as a modulator for liver CSC self-renewal. Furthermore, the inhibitor of PRC1 had same phenotypes as PRC1 knockdown in HCC cells. Altogether, PRC1 and RACGAP1 are identified both as prognosis markers for early HCC detection and therapeutic targets for liver cancer and liver CSCs, adding additional layers for the early prognosis and therapy of HCC.
Zebrafish Establish Female Germ Cell Identity by Advancing Cell Proliferation and Meiosis
Authors: Pan You-Jiun , Tong Sok-Keng , Hsu Chen-wei , Weng Jui-Hsia , Chung Bon-chu
Published: April 2022

Zebrafish is a popular research model; but its mechanism of sex determination is unclear and the sex of juvenile fish cannot be distinguished. To obtain fish with defined sex, we crossed domesticated zebrafish with the Nadia strain that has a female-dominant W segment. These fish were placed on a ziwi:GFP background to facilitate sorting of fluorescent germ cells for transcriptomic analysis. We analyzed the transcriptomes of germ cells at 10–14 days postfertilization (dpf), when sex dimorphic changes started to appear. Gene ontology showed that genes upregulated in the 10-dpf presumptive females are involved in cell cycles. This correlates with our detection of increased germ cell numbers and proliferation. We also detected upregulation of meiotic genes in the presumptive females at 14 dpf. Disruption of a meiotic gene, sycp3, resulted in sex reversal to infertile males. The germ cells of sycp3 mutants could not reach diplotene and underwent apoptosis. Preventing apoptosis by disrupting tp53 restored female characteristics in sycp3 mutants, demonstrating that adequate germ cells are required for female development. Thus, our transcriptome and gene mutation demonstrate that initial germ cell proliferation followed by meiosis is the hallmark of female differentiation in zebrafish.
News and Views on Polysialic Acid: From Tumor Progression and Brain Development to Psychiatric Disorders, Neurodegeneration, Myelin Repair and Immunomodulation
Authors: Thiesler Hauke , Küçükerden Melike , Gretenkort Lina , Röckle Iris , Hildebrandt Herbert
Published: April 2022

Polysialic acid (polySia) is a sugar homopolymer consisting of at least eight glycosidically linked sialic acid units. It is a posttranslational modification of a limited number of proteins with the neural cell adhesion molecule NCAM being the most prominent. As extensively reviewed before, polySia-NCAM is crucial for brain development and synaptic plasticity but also modulates tumor growth and malignancy. Functions of polySia have been attributed to its polyanionic character, its spatial expansion into the extracellular space, and its modulation of NCAM interactions. In this mini-review, we first summarize briefly, how the modulation of NCAM functions by polySia impacts tumor cell growth and leads to malformations during brain development of polySia-deficient mice, with a focus on how the latter may be linked to altered behaviors in the mouse model and to neurodevelopmental predispositions to psychiatric disorders. We then elaborate on the implications of polySia functions in hippocampal plasticity, learning and memory of mice in light of recently described polySia changes related to altered neurogenesis in the aging human brain and in neurodegenerative disease. Furthermore, we highlight recent progress that extends the range of polySia functions across diverse fields of neurobiology such as cortical interneuron development and connectivity, myelination and myelin repair, or the regulation of microglia activity. We discuss possible common and distinct mechanisms that may underlie these seemingly divergent roles of polySia, and provide prospects for new therapeutic approaches building on our improved understanding of polySia functions.
The Role of microRNAs in the Drosophila Melanogaster Visual System
Authors: Colaianni Davide , De Pittà Cristiano
Published: April 2022

MicroRNAs (miRNAs) are a class of small non-coding RNAs (∼22 nucleotides in length) that negatively regulate protein-coding gene expression post-transcriptionally by targeting mRNAs and triggering either translational repression or RNA degradation. MiRNA genes represent approximately 1% of the genome of different species and it has been estimated that every miRNA can interact with an average of 200 mRNA transcripts, with peaks of 1,500 mRNA targets per miRNA molecule. As a result, miRNAs potentially play a fundamental role in several biological processes including development, metabolism, proliferation, and apoptotic cell death, both in physiological and pathological conditions. Since miRNAs were discovered, Drosophila melanogaster has been used as a model organism to shed light on their functions and their molecular mechanisms in the regulation of many biological and behavioral processes. In this review we focus on the roles of miRNAs in the fruit fly brain, at the level of the visual system that is composed by the compound eyes, each containing ∼800 independent unit eyes called ommatidia, and each ommatidium is composed of eight photoreceptor neurons that project into the optic lobes. We describe the roles of a set of miRNAs in the development and in the proper function of the optic lobes (bantam, miR-7, miR-8, miR-210) and of the compound eyes (bantam, miR-7, miR-9a, miR-210, miR-263a/b, miR-279/996), summarizing also the pleiotropic effects that some miRNAs exert on circadian behavior.
Gut Microbiota Targeted Approach in the Management of Chronic Liver Diseases
Authors: Liu Jing , Yang Dakai , Wang Xiaojing , Asare Paul Tetteh , Zhang Qingwen , Na Lixin , Shao Lei
Published: April 2022

The liver is directly connected to the intestines through the portal vein, which enables the gut microbiota and gut-derived products to influence liver health. There is accumulating evidence of decreased gut flora diversity and alcohol sensitivity in patients with various chronic liver diseases, including non-alcoholic/alcoholic liver disease, chronic hepatitis virus infection, primary sclerosing cholangitis and liver cirrhosis. Increased intestinal mucosal permeability and decline in barrier function were also found in these patients. Followed by bacteria translocation and endotoxin uptake, these will lead to systemic inflammation. Specific microbiota and microbiota-derived metabolites are altered in various chronic liver diseases studies, but the complex interaction between the gut microbiota and liver is missing. This review article discussed the bidirectional relationship between the gut and the liver, and explained the mechanisms of how the gut microbiota ecosystem alteration affects the pathogenesis of chronic liver diseases. We presented gut-microbiota targeted interventions that could be the new promising method to manage chronic liver diseases.
Clinical Feature, Therapy, Antimicrobial Resistance Gene Distribution, and Outcome of Nosocomial Meningitis Induced by Multidrug-Resistant Enterobacteriaceae—A Longitudinal Cohort Study From Two Neurosurgical Centers in Northern China
Authors: Zheng Guanghui , Shi Yijun , Cao Yanfei , Qian Lingye , Lv Hong , Zhang Lina , Zhang Guojun
Published: April 2022

Objectives

This is a comparative cohort study aiming to evaluate the mortality risk factors for patients with nosocomial meningitis (NM) induced by multidrug-resistant Enterobacteriaceae (MDRE) in China. The clinical features and therapies of patients and the resistance mechanisms of MDRE pathogens were also assessed.

Methods

MDRE-NM patients from two neurosurgical centers in China from 2014 to 2019 were included in this study. Clinical features were extracted from the medical record databases of the two centers. The molecular mechanisms underlying the microbiological resistance mechanisms of each MDRE pathogen were determined, Kaplan–Meier survival analysis was conducted, and multivariable analyses were performed using a Cox proportional hazard model.

Results

Ninety MDRE-NM patients were included in this study. Klebsiella pneumoniae accounted for the highest proportion of causative pathogens (46/90, 51.1%), and 40 causative pathogens (44.4%) were meropenem-resistant. blaKPC (27/40, 67.5%) was the predominant carbapenem resistance gene. Multivariate Cox analysis showed that external ventricular drainage (EVD) [hazard ratio (HR) = 2.524, 95% confidence interval (CI) = 1.101–5.787, p = 0.029] and a Glasgow Coma Scale (GCS) score ≤;8 (HR = 4.033, 95% CI = 1.526–10.645, p = 0.005) were mortality risk factors for patients with MDRE-NM. A total of 90.0%, 94.4%, and 97.8% of MDRE-NM patients received antibiotic prophylaxis (AP), antibiotic empirical therapy (AET), and antibiotic definitive therapy (ADT), respectively.

Conclusions

NM caused by MDRE is an important sign of the failure of neurosurgery. MDRE possesses multiple drug resistance genotypes, and EVD and a GCS score ≤;8 are independent mortality risk factors for patients with MDRE-NM, which deserve the attention of microbiologists and neurosurgical clinicians.
AMOC Recent and Future Trends: A Crucial Role for Oceanic Resolution and Greenland Melting?
Authors: Swingedouw Didier , Houssais Marie-Noëlle , Herbaut Christophe , Blaizot Anne-Cecile , Devilliers Marion , Deshayes Julie
Published: April 2022

The Atlantic Meridional Overturning Circulation (AMOC) is a crucial element of the Earth climate. It is a complex circulation system difficult to monitor and to model. There is considerable debate regarding its evolution over the last century as well as large uncertainty about its fate at the end of this century. We depict here the progress since the IPCC SROCC report, offering an update of its chapter 6.7. We also show new results from a high-resolution ocean model and a CMIP6 model to investigate the impact of Greenland Ice Sheet (GrIS) melting, a key uncertainty for past and future AMOC changes. The ocean-only simulation at 1/24° resolution in the Arctic-North Atlantic Ocean performed over the period 2004–2016 indicates that the spread of the Greenland freshwater runoff toward the center of the Labrador Sea, where oceanic convection occurs, seems larger in this model than in a CMIP6 model. Potential explanations are related to the model spatial resolution and the representation of mesoscale processes, which more realistically transport the freshwater released around the shelves and, through eddies, provides strong lateral exchanges between the fine-scale boundary current and the convective basin in the Labrador Sea. The larger freshening of the Labrador Sea in the high-resolution model then strongly affects deep convection activity. In the simulation including GrIS melting, the AMOC weakens by about 2 Sv after only 13 years, far more strongly than what is found in the CMIP6 model. This difference raises serious concerns on the ability of CMIP6 models to correctly assess the potential impact of GrIS melting on the AMOC changes over the last few decades as well as on its future fate. To gain confidence in the GrIS freshwater impacts on climate simulations and therefore in AMOC projections, urgent progress should be made on the parameterization of mesoscale processes in ocean models.
Comparative Efficacy of Dapagliflozin and Empagliflozin of a Fixed Dose in Heart Failure: A Network Meta-Analysis
Authors: Shi Zepeng , Gao Feng , Liu Wei , He Xuezhi
Published: April 2022

Background

The efficacy of dapagliflozin and empagliflozin in sodium-glucose cotransport-2 inhibitors (SGLT-2i) in patients with heart failure (HF) has been discovered. However, which drug could improve varied prognostic outcomes has not been elucidated. Hence, we compared their efficacies on the prognostic improvement of HF.

Methods

Databases including PubMed, EMBASE, Scopus, Google Scholars, and the Cochrane Library were searched for all related randomized controlled trials (RCTs) published from inception to 13 October 2021. Network meta-analyses were performed to generate matrices to show the effect size for pairwise comparison regarding all the interventions.

Results

Eventually a total of 11 RCTs were included in this study. For the primary endpoints, dapagliflozin was comparable with empagliflozin in hospitalization for HF, and empagliflozin (OR=0.70, 95%CI: 0.59–0.84) decreased the risk of exacerbation of HF over dapagliflozin. For the secondary endpoints, dapagliflozin was comparable with empagliflozin in cardiovascular (CV) death /hospitalization for HF, and for CV death, dapagliflozin (OR=0.78, 95%CI: 0.65–0.92) significantly reduced mortality over the placebo. For the tertiary endpoints, dapagliflozin (OR=0.80, 95%CI: 0.66–0.98) significantly decreased the mortality over empagliflozin in all-cause death, and neither drug significantly increased the risk of hypoglycemia.

Recommendations

Overall, 10 mg/day dapagliflozin may be the optimal recommendation for its premium and comprehensive effect on improving the prognosis of patients with HF compared to 10 mg/day empagliflozin.
Deep Learning Approach for Assessing Air Quality During COVID-19 Lockdown in Quito
Authors: Chau Phuong N. , Zalakeviciute Rasa , Thomas Ilias , Rybarczyk Yves
Published: April 2022

Weather Normalized Models (WNMs) are modeling methods used for assessing air contaminants under a business-as-usual (BAU) assumption. Therefore, WNMs are used to assess the impact of many events on urban pollution. Recently, different approaches have been implemented to develop WNMs and quantify the lockdown effects of COVID-19 on air quality, including Machine Learning (ML). However, more advanced methods, such as Deep Learning (DL), have never been applied for developing WNMs. In this study, we proposed WNMs based on DL algorithms, aiming to test five DL architectures and compare their performances to a recent ML approach, namely Gradient Boosting Machine (GBM). The concentrations of five air pollutants (CO, NO2, PM2.5, SO2, and O3) are studied in the city of Quito, Ecuador. The results show that Long-Short Term Memory (LSTM) and Bidirectional Recurrent Neural Network (BiRNN) outperform the other algorithms and, consequently, are recommended as appropriate WNMs to quantify the effects of the lockdowns on air pollution. Furthermore, examining the variable importance in the LSTM and BiRNN models, we identify that the most relevant temporal and meteorological features for predicting air quality are Hours (time of day), Index (1 is the first collected data and increases by one after each instance), Julian Day (day of the year), Relative Humidity, Wind Speed, and Solar Radiation. During the full lockdown, the concentration of most pollutants has decreased drastically: −48.75%, for CO, −45.76%, for SO2, −42.17%, for PM2.5, and −63.98%, for NO2. The reduction of this latter gas has induced an increase of O3 by +26.54%.
Predicting Severity of Huntington's Disease With Wearable Sensors
Authors: Scheid Brittany H. , Aradi Stephen , Pierson Robert M. , Baldassano Steven , Tivon Inbar , Litt Brian , Gonzalez-Alegre Pedro
Published: April 2022

The Unified Huntington's Disease Rating Scale (UHDRS) is the primary clinical assessment tool for rating motor function in patients with Huntington's disease (HD). However, the UHDRS and similar rating scales (e.g., UPDRS) are both subjective and limited to in-office assessments that must be administered by a trained and experienced rater. An objective, automated method of quantifying disease severity would facilitate superior patient care and could be used to better track severity over time. We conducted the present study to evaluate the feasibility of using wearable sensors, coupled with machine learning algorithms, to rate motor function in patients with HD. Fourteen participants with symptomatic HD and 14 healthy controls participated in the study. Each participant wore five adhesive biometric sensors applied to the trunk and each limb while completing brief walking, sitting, and standing tasks during a single office visit. A two-stage machine learning method was employed to classify participants by HD status and to predict UHDRS motor subscores. Linear discriminant analysis correctly classified all participants' HD status except for one control subject with abnormal gait (96.4% accuracy, 92.9% sensitivity, and 100% specificity in leave-one-out cross-validation). Two regression models accurately predicted individual UHDRS subscores for gait, and dystonia within a 10% margin of error. Our regression models also predicted a composite UHDRS score–a sum of left and right arm rigidity, total chorea, total dystonia, bradykinesia, gait, and tandem gait subscores–with an average error below 15%. Machine learning classifiers trained on brief in-office datasets discriminated between controls and participants with HD, and could accurately predict selected motor UHDRS subscores. Our results could enable the future use of biosensors for objective HD assessment in the clinic or remotely and could inform future studies for the use of this technology as a potential endpoint in clinical trials.
Quantifying Geodetic Mass Balance of the Northern and Southern Patagonian Icefields Since 1976
Authors: McDonnell Morgan , Rupper Summer , Forster Richard
Published: April 2022

Southern Andean glaciers contribute substantially to global sea-level rise. Unfortunately, mass balance estimates prior to 2000 are limited, hindering our understanding of the evolution of glacier mass changes over time. Elevation changes over 1976/1979 to 2000 derived from historical KH-9 Hexagon imagery and NASADEM provide the basis for geodetic mass balance estimates for subsets of the Northern Patagonian Icefield (NPI) and the Southern Patagonian Icefield (SPI), extending current mass balance observations by ∼20 years. Geodetic mass balances were −0.63 ± 0.03 m w.e. yr−1 for 63% of the NPI and −0.33 ± 0.05 m w.e. yr−1 for 52% of the SPI glacierized areas for this historical period. We also extend previous estimates temporally by 25% using NASADEM and ASTER elevation trends for the period 2000 to 2020, and find geodetic mass balances of −0.86 ± 0.03 m w.e. yr−1 for 100% of the NPI and −1.23 ± 0.04 m w.e. yr−1 for 97% of the SPI glacierized areas. 2000–2020 aggregations for the same areas represented in the 1976/1979 to 2000 estimates are −0.78 ± 0.03 m w.e. yr−1 in the NPI and −0.80 ± 0.04 m w.e. yr−1 on the SPI. The significant difference in SPI geodetic mass balance in the modern period for 100% vs. 52% of the glacierized area suggests subsampling leads to significant biases in regional mass balance estimates. When we compare the same areas in each time period, the results highlight an acceleration of ice loss by a factor of 1.2 on the NPI and 2.4 on the SPI in the 21st century as compared to the 1976/1979 to 2000 period. While lake-terminating glaciers show the most significant increase in mass loss rate from 1976/1979–2000 to 2000–2020, mass balance trends are highly variable within glaciers of all terminus environments, which suggests that individual glacier sensitivity to climate change is dependent on a multitude of morphological and climatological factors.
Resiliency Estimation of Synchrophasor Communication Networks in a Wide Area Measurement System
Authors: Appasani Bhargav , Jha Amitkumar V. , Swain Kunjabihari , Cherukuri Murthy , Mohanta Dusmanta Kumar
Published: April 2022

The power grid is evolving into a smart grid due to the diverse energy generation and distribution. This complex grid has to be continuously monitored in real-time for its safe operation. Sensors known as phasor measurement units (PMUs) are used for obtaining health information pertaining to the grid in terms of time-synchronized voltage and current phasors. Measurements from several PMUs are sent through a synchrophasor communication network (SCN) to the phasor data concentrator (PDC). The PMUs, the PDC and the SCN together constitute the wide area measurement system (WAMS). Being an important constituent of the WAMS, the resiliency estimation of SCNs is paramount for their proper design. Resilience is a measure of the systems resistance to the disturbances or a measure of its ability to bounce back to a functional state in the event of failure. This paper presents a quantitative metric for estimating the resiliency of SCNs. Monte Carlo simulation (MCS) models are used to simulate random component failures, and the data is used for measuring the resiliency of the SCNs. A multi-objective genetic algorithm (GA) is used for optimizing the placement of PMUs and the PDC, to observe the power system with the minimum number of PMUs, and to simultaneously maximize the resilience. The practical power grid of West Bengal, India, is analyzed as a case study. This work can be a significant contribution to the power sector as it assists in the proper planning and placement of the communication infrastructure in a WAMS.
Integrated Optimal Planning of Distribution Network With Geographical-Zone-Restricted Renewable Energy Sources
Authors: Qing Ke , Huang Qi , Du Yuefang
Published: April 2022

Recently, a lot of renewable energy sources have been integrated into the distribution network. In consideration of economy and construction feasibility, some renewable energy sources are required to be installed in specific areas. In this paper, a bi-layer distribution network planning optimization model that considers the geographical restrictions of the installation locations of the substation, pumped storage plant, photovoltaic (PV) and wind power, as well as the impact of operation on planning, is proposed. In the planning optimization layer, the optimal distribution network topology with minimal total cost is obtained. The locations of the renewable energy sources and the substation are determined by the particle swarm optimization (PSO), and then all the components are interconnected using the dynamic minimum spanning tree (DMST) method. In the operation optimization layer, the economic operation strategy of the hybrid energy system with uncertainty is obtained by the scenario-based stochastic optimal power flow (OPF). The forecast error of the uncertain variable is represented by the probability distribution function, and the roulette wheel mechanism (RWM) is used to generate the stochastic scenarios. A modified 103-bus system is used to test the effectiveness of the proposed method, and the simulation results show that the proposed method can effectively reduce the total cost of the distribution network.
Experimental Study on the Working Characteristics of a Pre-combustion AC Plasma Jet Igniter
Authors: Cheng Weida , Yu Jinlu , Jiang Luyun , Miao Qinyu , Zhang Lei , Zhao Bingbing
Published: April 2022

A new pre-combustion AC plasma jet igniter has been designed. The pre-combustion plasma jet igniter can widen the ignition envelope for the aeroengine and reduce the power consumption of the igniter. To fully exploit the ignition efficiency of the plasma jet, experimental studies concerning the operational parameters and the discharge and arc motion characteristics have been performed. The results showed that three discharge modes were formed in the new igniter, namely, the Intermittent Breakdown Mode (IBM), the Stable Breakdown Mode (SBM) and the Stable-Intermittent Breakdown mode (S-IBM), the three different discharge modes corresponding to different arc shapes and movement processes. Moreover, the addition of kerosene readily changed the discharge state from the SBM to the IBM. The discharge state and discharge power of the igniter were affected by the working parameters. The discharge power increased with increase of the output voltage of the regulator, and an increase in the air supply affected the discharge power when the output voltage of the regulator was varied. After the addition of kerosene, the discharge power of the igniter was reduced to a certain extent, the maximum reduction being up to 47.7%.
Calmodulin Activity Affects the Function of the Odorant Receptor AcerOr2 in Honeybees
Authors: Guo Lina , Xu Bing , Zhao Huiting , Guo Yuan , Jiang Yusuo
Published: April 2022

Bees rely on their sensitive olfactory system to perform foraging activities in the surrounding environment. This ability is associated with the existence of olfactory receptors (ORs). In this study, we identified the AcerOr2 (ortholog to the Orco) protein in Apis cerana cerana, which contains a conserved, putative calmodulin (CaM)-binding site (CBS) indicating that CaM is involved in its function. We used immunofluorescence, Western blot, and Ca2 + imaging to monitor changes in the expression and activation of the signaling pathway associated with Ca2 + and Ca2 +/CaM-dependent protein kinase II (CaMKII) in Sf9 cells heterologously expressing AcerOr2 and a CaM-binding mutant. We used the synthetic Orco agonist VUAA1 to stimulate the cells or the antagonist W7 to inhibit CaM activity. The AcerOr2 CaM-binding mutant has a point mutation in the putative CBS (K331N). When heterologously expressed in Sf9 cells, the mutant should have less CaM activity. When the cells expressing AcerOr2 were treated with W7, the Ca2 + response of AceOr2 was similar to that of the mutant stimulated by VUAA1, and the expression of the CaM, CaMKII, and p-CaMKII has similar effects. Our results suggest that CaM activity affects the function of AceOr2 in vitro and can be used to further study the interaction between the AcerOr2 and calcium/CaM signaling pathway in the pollen collection behavior of bees.
Small RNA Sequencing Revealed that miR4415, a Legume-Specific miRNA, was Involved in the Cold Acclimation of Ammopiptanthus nanus by Targeting an L-Ascorbate Oxidase Gene and Regulating the Redox State of Apoplast
Authors: Zhu Ming , Wang Xue , Zhou Yanqiu , Tan Jinhua , Zhou Yijun , Gao Fei
Published: April 2022

MicroRNAs (miRNAs) are small endogenous single-stranded RNAs that regulate plant growth, development, and environmental stress response posttranscriptionally. Ammopiptanthus nanus, a rare evergreen broad-leaved shrub in the temperate area of Central Asia, can tolerate freezing stress as low as –30 degrees centigrade in winter, and miRNA might be involved in the cold acclimation which enables A. nanus to obtain tolerance to freezing stress. Systematic identification and functional analysis of the miRNAs involved in the cold acclimation in A. nanus may promote understanding of the miRNA-mediated gene regulation network underlying cold acclimation. Here, based on small RNA and degradome sequencing, 256 miRNAs and 1,808 miRNA-target pairs were identified in A. nanus. A total of 39 cold-responsive miRNAs were identified, of which 29 were upregulated and ten were downregulated. These cold-responsive miRNAs may participate in the cold acclimation by regulating redox homeostasis (miR398, miR4415, and miR408), calcium signaling (miR5225 and miR5211), growth and development (miR159 and miR390), and small RNA–mediated gene silencing (miR168 and miR1515). We found that miR4415, a legume-specific miRNA, is involved in the cold acclimation of A. nanus by targeting an L-ascorbate oxidase gene and then regulating the redox state of the apoplast. Our study provides important data for understanding the regulatory role of miRNA in the cold acclimation of A. nanus.
Notch-Signaling Deregulation Induces Myeloid-Derived Suppressor Cells in T-Cell Acute Lymphoblastic Leukemia
Authors: Grazioli Paola , Orlando Andrea , Giordano Nike , Noce Claudia , Peruzzi Giovanna , Abdollahzadeh Behnaz , Screpanti Isabella , Campese Antonio Francesco
Published: April 2022

Notch receptors deeply influence T-cell development and differentiation, and their dysregulation represents a frequent causative event in “T-cell acute lymphoblastic leukemia” (T-ALL). “Myeloid-derived suppressor cells” (MDSCs) inhibit host immune responses in the tumor environment, favoring cancer progression, as reported in solid and hematologic tumors, with the notable exception of T-ALL. Here, we prove that Notch-signaling deregulation in immature T cells promotes CD11b+Gr-1+ MDSCs in the Notch3-transgenic murine model of T-ALL. Indeed, aberrant T cells from these mice can induce MDSCs in vitro, as well as in immunodeficient hosts. Conversely, anti-Gr1-mediated depletion of MDSCs in T-ALL-bearing mice reduces proliferation and expansion of malignant T cells. Interestingly, the coculture with Notch-dependent T-ALL cell lines, sustains the induction of human CD14+HLA-DRlow/neg MDSCs from healthy-donor PBMCs that are impaired upon exposure to gamma-secretase inhibitors. Notch-independent T-ALL cells do not induce MDSCs, suggesting that Notch-signaling activation is crucial for this process. Finally, in both murine and human models, IL-6 mediates MDSC induction, which is significantly reversed by treatment with neutralizing antibodies. Overall, our results unveil a novel role of Notch-deregulated T cells in modifying the T-ALL environment and represent a strong premise for the clinical assessment of MDSCs in T-ALL patients.
Circular RNAs Involve in Immunity of Digestive Cancers From Bench to Bedside: A Review
Authors: Chen Chunyue , Xia Congcong , Tang Hao , Jiang Yirun , Wang Shan , Zhang Xin , Huang Tao , Yuan Xiaoqing , Wang Junpu , Peng Li
Published: April 2022

The immune system plays a complex role in tumor formation and development. On the one hand, immune surveillance can inhibit the growth of tumors; on the other hand, immune evasion of tumors can create conditions conducive for tumor development and growth. CircRNAs are endogenous non-coding RNAs with a covalently closed loop structure that are abundantly expressed in eukaryotic organisms. They are characterized by stable structure, rich diversity, and high evolutionary conservation. In particular, circRNAs play a vital role in the occurrence, development, and treatment of tumors through their unique functions. Recently, the incidence and mortality of digestive cancers, especially those of gastric cancer, colorectal cancer, and liver cancer, have remained high. However, the functions of circRNAs in digestive cancers immunity are less known. The relationship between circRNAs and digestive tumor immunity is systematically discussed in our paper for the first time. CircRNA can influence the immune microenvironment of gastrointestinal tumors to promote their occurrence and development by acting as a miRNA molecular sponge, interacting with proteins, and regulating selective splicing. The circRNA vaccine even provides a new idea for tumor immunotherapy. Future studies should be focused on the location, transportation, and degradation mechanisms of circRNA in living cells and the relationship between circRNA and tumor immunity. This paper provides a new idea for the diagnosis and treatment of gastrointestinal tumors.
Apoptosis, Pyroptosis, and Ferroptosis Conspiringly Induce Immunosuppressive Hepatocellular Carcinoma Microenvironment and γδ T-Cell Imbalance
Authors: Hu Yi , Chen Dan , Hong Minjing , Liu Jing , Li Yijia , Hao Jianlei , Lu Ligong , Yin Zhinan , Wu Yangzhe
Published: April 2022

Hepatocellular carcinoma (HCC) is highly malignant and prone to metastasize due to the heterogeneous and immunosuppressive tumor microenvironment (TME). Programmed cell deaths (PCDs) including apoptosis, ferroptosis, and pyroptosis routinely occur in the HCC TME and participate in tumorigenesis. However, how apoptosis, ferroptosis, and pyroptosis are involved in constructions of the immunosuppressive TME and their underlying cross-talk remains to be further unveiled. In this work, we deciphered the immunosuppressive landscape of HCC TME, which demonstrated high expressions of inhibitory checkpoint molecules and infiltration of protumor immune cells but low infiltration of antitumor effector immune cells. Further investigations unequivocally revealed that marker genes of apoptosis, ferroptosis, and pyroptosis are closely correlated with expressions and infiltrations of inhibitory checkpoint molecules and immune cells and that higher “-optosis” links to poorer patient prognosis. Notably, such three types of “-optosis” interact with each other at both the gene and protein levels, suggesting that they conspiringly induce the establishment of the immunosuppressive HCC TME. Interestingly, examinations of circulating γδ T cells in HCC patients revealed a noticeable dysfunction phenotype. The strikingly elevated ratio of the Vδ1+ versus the Vδ2+ subset suggested that the Vδ1+/Vδ2+ ratio would be a potential biomarker for the diagnosis and prognosis in HCC patients. Altogether, this work thoroughly decrypted the underlying correlations between apoptosis, ferroptosis, and pyroptosis and the formation of immunosuppressive HCC TME and, meanwhile, indicated that allogeneic Vδ2+ γδ T-cell transfer would be a promising adjuvant strategy for renormalizing circulating γδ T cell and thus achieving sound clinical efficacy against HCC.
Risk Factors of Silicosis Progression: A Retrospective Cohort Study in China
Authors: Quan Hua , Wu Wenhong , Yang Guanghong , Wu Yunlin , Yang Wenlan , Min Chunyan , Shi Jinyun , Qin Lianhua , Huang Jin , Wang Jie , Huang Xiaochen , Mao Ling , Feng Yonghong
Published: April 2022

Background

Silicosis poses a threat to workers’ health due to the irreversible lung lesions.

Design

A retrospective cohort study.

Methods

A total of 259 patients [80 worked with artificial stone (AS), 179 with non-artificial stone (non-AS)] with confirmed silicosis were included in this study. Forty-one of AS and 91 of non-AS had approximately 2 years’ follow-up records [lung function tests and high-resolution computer tomography (HRCT)]. Compared with the first records, increased, densified, or newly emerging lesions in lung HRCT images were judged as progression of the disease. Cox proportional hazards models were used to determine the risk factors. Kaplan–Meier survival curve and log-rank test were used to compare prognostic factors for cumulative risk of progression.

Results

In 132 patients with median follow-up of 24.0 months (IQR, 13.8, 24.9), 66 patients showed progression, in them, 36 (87.8%) were from AS group and 30 (32.9%) from non-AS group. Working experience of AS processing (hazard ratio, 5.671; 95% CI, 3.048–10.550) and complicated silicosis in CT images (hazard ratio, 2.373; 95% CI, 1.379–4.082) were the main risk factors associated with progression. Forced vital capacity decreased after 1-year (241.5 vs. 55.2 mL) and 2-year (328.1 vs. 68.8 mL) follow-up in the two groups (AS vs. non-AS). History of anti-tuberculosis medication, chest oppression and pain, ground-glass opacity, pleural abnormalities, and restrictive pulmonary dysfunction were more frequently found on HRCT images in the AS group than non-AS group. Lung functions (DLCO, %) were lower in the current/former smokers than the non-smokers (P < 0.05) in AS patients.

Conclusion

Prevention and protection rules are needed to be enforced in the occupation involving AS processing; smoking may be associated with declined lung function in AS patients.
Transcriptome Analysis of Otodectes cynotis in Different Developmental Stages
Authors: He Ran , Zhang Qian , Gu Xiaobin , Xie Yue , Xu Jing , Peng Xuerong , Yang Guangyou
Published: April 2022

The mite Otodectes cynotis is distributed worldwide and parasitism the ear canals of cats and dogs, causing otitis externa. Molecular biology of O. cynotis is poorly understood, with only a few genes being deposited in public databases. In the present study, we aimed to perform transcriptome analysis of O. cynotis using SMRT and Illumina sequencing of RNA from different development stages. SMRT-Seq of O. cynotis demonstrated 5,431 final transcripts, including 406 long non-coding RNAs and 2,698 differentially expressed genes (DEGs), including 1,357 up-regulated genes and 1,341 down-regulated genes between adult mites and nymph/larva. A total of 397 putative allergen genes were detected, 231 of which were DEGs. Among them, 77 were homologous of known mite allergens. The expression level of allergen genes hints at the pathogenicity of mites in different life stages, and the protein interaction network analysis could identify possible key genes in the pathogenic mechanism. Intriguingly, Gene Ontology analysis showed that most of the (DEGs) were associated with the terms hydrolase activity and proteolysis. Kyoto Encyclopedia of genes and genomes (KEGG) analysis identified drug metabolism-cytochrome P450 signal pathway as one of the top pathways. SMRT-Seq of the full-length transcriptome of O. cynotis was performed first, and a valuable resource was acquired through the combination analysis with the Illumina sequencing data. The results of our analyses provide new information for further research into Otodectes cynotis.
Cover Plants-Mediated Suppression of Fusarium Wilt and Root-Knot Incidence of Cucumber is Associated With the Changes of Rhizosphere Fungal Microbiome Structure-Under Plastic Shed System of North China
Authors: Ali Ahmad , Elrys Ahmed S. , Liu Liangliang , Iqbal Muhammad , Zhao Jun , Huang Xinqi , Cai Zucong
Published: April 2022

Cover crops are known to alleviate the adverse effects of continuous cropping by influencing plant health and changing host fungal-microbiome structures. However, insight into the shift of rhizomicrobiota composition and their effects on plant growth performance and resistance mechanism is still limited under plastic shed cultivation (PSC). Four leafy vegetable rotations namely spinach rotation (SR), non-heading Chinese cabbage rotation (NCCR), coriander rotation (CR), and leafy lettuce rotation (LLR) were used as cover crops in 7-years of continuous cucumber planted soil (CC). Their ecological impacts were studied for plant growth performance, replant diseases incidence rate, and rhizosphere fungal microbiome. Compared to CC, SR showed a highly suppressive effect on fusarium wilt, i.e., by 13.2% in the spring season, while NCCR decreased the root-knot nematode incidence rate by 8.9% in the autumn season. Such protective effects caused a significant increase of shoot and fruit biomass and thus sustained the fruit quality of cucumber. High-throughput sequencing revealed that the CR, SR, and NCCR treatments altered the fungal community composition by increasing the abundance of the beneficial fungal genera, decreasing pathogenic taxa, and fostering the saprotrophic and symbiotic functions. However, the relative abundance of most of the potentially pathogenic fungal genera increased in CC and LLR cropping. There were 8 potential pathogens and 10 beneficial or biocontrol fungi characterized. It was found that Paecilomyces, Chaetomium, Cladorrhinum, Zopfiella, Purpureocillium, and Metarhizium were the putative biocontrol microbes that positively affected plant growth and replanted diseases inhibition. The characterized Fusarium, Dactylonectria, Alternaria, Gibberella, and Aspergillus were the key pathogenic fungal agents found to be negatively associated with plant growth characters, suggesting that rhizomicrobiome may play an important role in the occurrence of disease incidence of cucumber plants. Considering the ecological potential of some cover plants, this study suggested that rotation with spinach, non-heading Chinese cabbage, or coriander can enhance rhizosphere immunity by triggering the development of plant-protective fungal microbiomes under plastic shed cucumber cultivation.
Synergism Among the Four Tobacco Bushy Top Disease Casual Agents in Symptom Induction and Aphid Transmission
Authors: Chen Xiaojiao , Luo Hengming , Zhang Jingyi , Ma Yan , Li Kehua , Xiong Feng , Yang Yahui , Yang Jiazhen , Lan Pingxiu , Wei Taiyun , Xu Yi , Chen Hairu , Li Fan
Published: April 2022

Tobacco bushy top disease (TBTD), caused by multiple pathogens including tobacco bushy top virus (TBTV), tobacco vein distorting virus (TVDV), TBTV satellite RNA (TBTVsatRNA), and TVDV-associated RNA (TVDVaRNA), is a destructive disease in tobacco fields. To date, how these causal agents are co-transmitted by aphid vectors in field and their roles in disease symptom induction remain largely unknown, due mainly to the lack of purified causal agents. In this study, we have constructed four full-length infectious clones, representing the Yunnan Kunming isolates of TVDV, TBTV, TBTVsatRNA, and TVDVaRNA (TVDV-YK, TBTV-YK, TBTVsatRNA-YK, and TVDVaRNA-YK), respectively. Co-inoculation of these four causal agents to tobacco K326 plants caused typical TBTD symptoms, including smaller leaves, necrosis, and plant stunting. In addition, inoculation of tobacco K326 plants with TBTV alone caused necrosis in systemic leaves by 7 dpi. Tobacco K326 and Nicotiana benthamiana plants infected by single virus or multiple viruses showed very different disease symptoms at various dpi. RT-PCR results indicated that co-infection of TVDVaRNA-YK could increase TVDV-YK or TBTV-YK accumulation in N. benthamiana plants, suggesting that TVDVaRNA-YK can facilitate TVDV-YK and TBTV-YK replication and/or movement in the infected plants. Aphid transmission assays showed that the successful transmission of TBTV-YK, TBTVsatRNA-YK, and TVDVaRNA-YK by Myzus persicae depended on the presence of TVDV-YK, while the presence of TBTVsatRNA-YK increased the aphid transmission efficiency of TBTV and TVDV. We consider that these four new infectious clones will allow us to further dissect the roles of these four causal agents in TBTD induction as well as aphid transmission.
Full-Length Genome of an Ogataea polymorpha Strain CBS4732 ura3Δ Reveals Large Duplicated Segments in Subtelomeric Regions
Authors: Chang Jia , Bei Jinlong , Shao Qi , Wang Hemu , Fan Huan , Yau Tung On , Bu Wenjun , Ruan Jishou , Wei Dongsheng , Gao Shan
Published: April 2022

Background

Currently, methylotrophic yeasts (e.g., Pichia pastoris, Ogataea polymorpha, and Candida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genus Ogataea, most research is focused on three basic O. polymorpha strains-CBS4732, NCYC495, and DL-1. However, the relationship between CBS4732, NCYC495, and DL-1 remains unclear, as the genomic differences between them have not be exactly determined without their high-quality complete genomes. As a nutritionally deficient mutant derived from CBS4732, the O. polymorpha strain CBS4732 ura3Δ (named HU-11) is being used for high-yield production of several important proteins or peptides. HU-11 has the same reference genome as CBS4732 (noted as HU-11/CBS4732), because the only genomic difference between them is a 5-bp insertion.

Results

In the present study, we have assembled the full-length genome of O. polymorpha HU-11/CBS4732 using high-depth PacBio and Illumina data. Long terminal repeat retrotransposons (LTR-rts), rDNA, 5′ and 3′ telomeric, subtelomeric, low complexity and other repeat regions were exactly determined to improve the genome quality. In brief, the main findings include complete rDNAs, complete LTR-rts, three large duplicated segments in subtelomeric regions and three structural variations between the HU-11/CBS4732 and NCYC495 genomes. These findings are very important for the assembly of full-length genomes of yeast and the correction of assembly errors in the published genomes of Ogataea spp. HU-11/CBS4732 is so phylogenetically close to NCYC495 that the syntenic regions cover nearly 100% of their genomes. Moreover, HU-11/CBS4732 and NCYC495 share a nucleotide identity of 99.5% through their whole genomes. CBS4732 and NCYC495 can be regarded as the same strain in basic research and industrial applications.

Conclusion

The present study preliminarily revealed the relationship between CBS4732, NCYC495, and DL-1. Our findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications of O. polymorpha CBS4732, NCYC495, DL-1, and their derivative strains. The full-length genome of O. polymorpha HU-11/CBS4732 should be included into the NCBI RefSeq database for future studies of Ogataea spp.
Gold In-and-Out: A Toolkit for Analyzing Subcellular Distribution of Immunogold-Labeled Membrane Proteins in Freeze-Fracture Replica Images
Authors: Guerrero-Given Debbie , Goldin Seth L. , Thomas Connon I. , Anthony Skylar A. , Jerez Diego , Kamasawa Naomi
Published: April 2022

Integral membrane proteins such as ion channels, transporters, and receptors shape cell activity and mediate cell-to-cell communication in the brain. The distribution, quantity, and clustering arrangement of those proteins contribute to the physiological properties of the cell; therefore, precise quantification of their state can be used to gain insight into cellular function. Using a highly sensitive immunoelectron microscopy technique called sodium dodecyl sulfate-digested freeze-fracture replica immunogold labeling (SDS-FRL), multiple membrane proteins can be tagged with different sizes of immunogold particles at once and visualized two-dimensionally. For quantification, gold particles in the images must be annotated, and then different mathematical and statistical methods must be applied to characterize the distribution states of proteins of interest. To perform such analyses in a user-friendly manner, we developed a program with a simple graphical user interface called Gold In-and-Out (GIO), which integrates several classical and novel analysis methods for immunogold labeled replicas into one self-contained package. GIO takes an input of particle coordinates, then allows users to implement analysis methods such as nearest neighbor distance (NND) and particle clustering. The program not only performs the selected analysis but also automatically compares the results of the real distribution to a random distribution of the same number of particles on the membrane region of interest. In addition to classical approaches for analyzing protein distribution, GIO includes new tools to analyze the positional bias of a target protein relative to a morphological landmark such as dendritic spines, and can also be applied for synaptic protein analysis. Gold Rippler provides a normalized metric of particle density that is resistant to differences in labeling efficiency among samples, while Gold Star is useful for quantifying distances between a protein and landmark. This package aims to help standardize analysis methods for subcellular and synaptic protein localization with a user-friendly interface while increasing the efficiency of these time-consuming analyses.