bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling the Tumor Microenvironment: Recapitulating Nano- and Micro-Scale Properties that Regulate Tumor Progression
Authors: Vahala Danielle , Choi Yu Suk
Published: June 2022

Breast cancer remains a significant burden with 1 in 8 women affected and metastasis posing a significant challenge for patient survival. Disease progression involves remodeling of the extracellular matrix (ECM). In breast cancer, tissue stiffness increases owing to an increase in collagen production by recruited cancer-associated fibroblasts (CAFs). These stromal modifications are notable during primary tumor growth and have a dualistic action by creating a hard capsule to prevent penetration of anti-cancer therapies and forming a favorable environment for tumor progression. Remodeling of the tumor microenvironment immediately presented to cells can include changes in protein composition, concentration and structural arrangement and provides the first mechanical stimuli in the metastatic cascade. Not surprisingly, metastatic cancer cells possess the ability to mechanically adapt, and their adaptability ensures not only survival but successful invasion within altered environments. In the past decade, the importance of the microenvironment and its regulatory role in diseases have gained traction and this is evident in the shift from plastic culture to the development of novel biomaterials that mimic in vivo tissue. With these advances, elucidations can be made into how ECM remodeling and more specifically, altered cell-ECM adhesions, regulate tumor growth and cancer cell plasticity. Such enabling tools in mechanobiology will identify fundamental mechanisms in cancer progression that eventually help develop preventative and therapeutic treatment from a clinical perspective. This review will focus on current platforms engineered to mimic the micro and nano-properties of the tumor microenvironment and subsequent understanding of mechanically regulated pathways in cancer.
Impact of Riverine Fresh Water on Indian Summer Monsoon: Coupling a Runoff Routing Model to a Global Seasonal Forecast Model
Authors: Srivastava Ankur , Rao Suryachandra A. , Ghosh Subimal
Published: June 2022

Rivers form an essential component of the earth system, with ~36,000 km3 of riverine freshwater being dumped into the global oceans every year. The role of rivers in controlling the sea-surface salinity and ensuing air-sea interactions in the Bay of Bengal (BoB) is well-known from observational studies; however, attempts to include rivers in coupled models used for seasonal prediction have been limited. This study reports the benefits of river routing in coupled models over prescribing observational river discharge and the impact on the Indian Summer Monsoon (ISM) simulation. Seasonal hindcasts are carried out using a state-of-the-art global coupled ocean-atmosphere-land-sea ice model, Climate Forecast System version 2, coupled to a runoff routing model. It is demonstrated that such a coupling leads to a better representation of the upper ocean stratification in northern BoB, causes mixed layer warming during July-August, and imparts a significant inter-annual variability to the mixed layer heat budget. The rainfall-runoff coupled feedback associated with ISM is captured better, and remote teleconnections with the equatorial Pacific are enhanced. Improved seasonal mean temperature and salinity profiles in the northern BoB lead to the formation of a thicker barrier layer, which is closely tied to the freshwater from rivers. These processes result in an overall enhancement of the ISM rainfall simulation skill, which stems from scale interactions between the sub-seasonal and seasonal variability of ISM. A significant community effort is required to reduce biases in land-surface processes to improve streamflow simulations, along with better parameterization of mixing of river water with the ocean.
Significance of Low Muscle Mass on Arterial Stiffness as Measured by Cardio-Ankle Vascular Index
Authors: Park Hyo Eun , Chung Goh Eun , Lee Heesun , Kim Min Joo , Choi Su-Yeon , Lee Wonjae , Yoon Ji Won
Published: June 2022

Aim

A link between low muscle mass and arterial stiffness is not always consistent. In this study, we aimed to evaluate the clinical significance of low skeletal muscle mass in relation to arterial stiffness measured by the cardio-ankle vascular index (CAVI).

Methods

A total of 2,561 asymptomatic Korean subjects who underwent bioelectrical impedance analysis (BIA) and CAVI were included for analysis. Using appendicular skeletal muscle mass (ASM), classes I and II sarcopenia were defined as ASM% greater than 1 standard deviation (SD) and 2 SDs below the gender-specific mean of healthy young Korean adults.

Results

Compared to normal, CAVI was significantly higher, but the number of patients with a low ankle-brachial index (ABI) was not significantly different (p < 0.001 for CAVI, p = 0.078 for ABI). Classes I and II sarcopenia showed an independent and significant association with CAVI (estimate 0.148, standard error (SE) 0.043, p < 0.001 and estimate 0.304, SE 0.073, p < 0.001 for classes I and II sarcopenia, respectively, adjusted for age groups, gender, body mass index (BMI) ≥25, hypertension, diabetes, hypercholesterolemia, and smoking).

Conclusion

Low muscle mass is independently and significantly associated with increased CAVI, and should be considered when managing asymptomatic subjects to assess the risk of atherosclerosis.
A Methodology for Evaluating Operator Usage of Machine Learning Recommendations for Power Grid Contingency Analysis
Authors: Wenskovitch John , Jefferson Brett , Anderson Alexander , Baweja Jessica , Ciesielski Danielle , Fallon Corey
Published: June 2022

This work presents the application of a methodology to measure domain expert trust and workload, elicit feedback, and understand the technological usability and impact when a machine learning assistant is introduced into contingency analysis for real-time power grid simulation. The goal of this framework is to rapidly collect and analyze a broad variety of human factors data in order to accelerate the development and evaluation loop for deploying machine learning applications. We describe our methodology and analysis, and we discuss insights gained from a pilot participant about the current usability state of an early technology readiness level (TRL) artificial neural network (ANN) recommender.
Stability Analysis of a Landslide Scarp by Means of Virtual Outcrops: The Mt. Peron Niche Area (Masiere di Vedana Rock Avalanche, Eastern Southern Alps)
Authors: Livio Franz A. , Bovo Francesco , Gabrieli Fabio , Gambillara Roberto , Rossato Sandro , Martin Silvana , Michetti Alessandro M.
Published: June 2022

We investigated the Mt. Peron niche area of the Masiere di Vedana rock avalanche (BL), one of the major mass movements that affected the Eastern Southern Alps in historical times. So far, a geomechanical characterization and a stability analysis of the niche area, where potential rockfall sources are present, are lacking. The Mt. Peron niche area is a rocky cliff almost inaccessible to field-based measurements. In order to overcome this issue, we performed a geo-structural characterization of a sector of the cliff by means of a UAV-based photogrammetric survey. From the virtual outcrop, we extracted the orientation of 159 fractures that were divided into sets based on a K-means clustering algorithm and field-checked with some measurements collected along a rappelling descent route down to the cliff. Finally, with the aim of evaluating the stability of the volume under investigation, we performed a stability analysis of three rock pillars included in our survey by means of a distinct element numerical simulation. Our results indicate that two out of the three pillars are characterized by a stable state, under the simulation assumptions, whereas the third is close to failure, and for this reason, its condition needs further investigation.
Sharing Experiences in Designing Professional Learning to Support Hydrology and Water Resources Instructors to Create High-Quality Curricular Materials
Authors: Gallagher Melissa A. , Habib Emad H. , Williams Douglas , Lane Belize , Byrd Jenny L. , Tarboton David
Published: June 2022

The creation of high-quality curricular materials requires knowledge of curriculum design and a considerable time commitment. Instructors often have limited time to dedicate to the creation of curricular materials. Additionally, the knowledge and skills needed to develop high-quality materials are often not taught to instructors. Furthermore, similar learning material is often prepared by multiple instructors working at separate institutions, leading to unnecessary duplication of effort and inefficiency that can impact quality. To address these problems, we established the HydroLearn platform and associated professional learning experiences for hydrology and water resources instructors. HydroLearn is an online platform for developing and sharing high-quality curricular materials, or learning modules, focused on hydrology and water resources. The HydroLearn team has worked with three cohorts of instructors from around the world who were dedicated to creating high-quality curricular materials to support both their students and the broader community. In order to overcome some of the aforementioned barriers, we tested and revised several different models of professional learning with these cohorts. These models ranged from (a) instructors working individually with periodic guidance from the HydroLearn team, to (b) small groups of instructors collaborating on topics of shared interests guided through an intensive HydroLearn training workshop. We found the following factors to contribute to the success of instructors in creating modules: (1) instructor pairs co-creating modules enhanced the usability and transferability of modules between universities and courses, (2) dedicating an intensive block of time (∼63 h over 9 days) to both learning about and implementing curriculum design principles, (3) implementing structures for continuous feedback throughout that time, (4) designing modules for use in one’s own course, and (5) instituting a peer-review process to refine modules. A comprehensive set of learning modules were produced covering a wide range of topics that target undergraduate and early graduate students, such as: floodplain analysis, hydrologic droughts, remote sensing applications in hydrology, urbanization and stormwater runoff, evapotranspiration, snow and climate, groundwater flow, saltwater intrusion in coastal regions, and stream solute tracers. We share specifics regarding how we structured the professional learning models, as well as lessons learned and challenges faced.
A New Perspective for Predicting the Therapeutic Success of RFA in Solid BTNs: Quantitative Initial RFA Ratio by Contrast-Enhanced Ultrasound
Authors: Zhu Yaqiong , Jiao Ziyu , Zhu Lianhua , Xie Fang , Song Qing , Yan Lin , Luo Yukun , Zhang Mingbo
Published: June 2022

Objective

The short-term therapeutic success of radiofrequency ablation (RFA) in solid benign thyroid nodules is of great concern. The aim of this study was to investigate a new method, initial radiofrequency ablative ratio (IRAR) using contrast-enhanced ultrasound (CEUS), for predicting therapeutic success of RFA in solid benign thyroid nodules (BTNs) immediately and effectively after RFA.

Methods

A total of 813 nodules in 776 patients with benign thyroid nodules were treated with RFA from January 2014 to August 2018, among which 120 patients (M:F=41:79) with 120 solid BTNs (small: ≤10ml, n=57; medium: 10-30ml, n=42; large: >30ml, n=21) were enrolled in our study according to the inclusion criteria. The IRAR was defined as the ablative volume ratio immediately after RFA displayed by CEUS. The therapeutic success was evaluated at the 6-month follow-up. The relationship between the IRAR and volume reduction ratio (VRR) at 6-month was analyzed. The marginal regrowth of solid BTNs was also examined by CEUS at the 6 and 12 months of follow-up.

Results

In medium and large nodules, the IRAR was significantly and positively correlated with VRR (r= 0.69, P < 0.001) at 6 months after RFA. There was a tendency to achieve therapeutic success (50% VRR: 55/63, 87.3%) when the IRAR exceeded 75%, and marginal regrowth was also relatively slow within 12 months after a single session treatment. No significant correlation between IRAR and VRR of small nodules was found. In conclusion, IRAR is significantly and positively correlated with VRR, which may indicate therapeutic success when it exceeds 75%.

Conclusions

CEUS can be used to accurately quantify the IRAR, which is positively correlated with the VRR. Moreover, the IRAR may be used as a parameter to predict the short-term therapeutic success of RFA in solid BTNs.
Operation of Conventional Power Plants During the German Energy Transition: A Mini Review
Authors: Hanel Andreas , Fendt Sebastian , Spliethoff Hartmut
Published: June 2022

Several unforeseen events have affected the energy market in recent years, both on the consumer side and on the primary energy supply side. Once again, the question is being asked, which impact conventional power plants can have on Germany’s energy transition. In this work various energy system studies from the last 4 years are evaluated, covering a time span of 30 years. Summarized, most studies expect an increasing use of natural gas, peaking in the years between 2030 and 2035. While the overall gross electricity generation from conventional power plants decreases, the share of synthetic energy carries will increase from around zero until 2040 to 100% in 2050. Hereby the technologically openness of the used energy system model strongly influences the final installed capacities. While more open simulations lead to a median of about 50 GW in 2050, more restrictive ones expect roughly 30 GW. However, the full load hours will decrease significantly in both cases. Since the synthesis of synthetic energy carriers requires large amounts of renewable electricity, this development is linked to a national electricity demand of over 200 TWh for power-to-x applications and an additional import of 350 TWh of power-to-x products.
Transient Protection Schemes for Transmission Lines Used in Offshore Wind Farm: A State-of-the-Art Review
Authors: Sun Xiangfei , Yang Xiao , Cai Jingfei , Jiang Xiaohan
Published: June 2022

The weak feeder and high harmonic characteristics of wind farms connected to the grid have an impact on the safe operation of the system, especially on the action selectivity and reliability of the traditional work-frequency quantity protection, which makes the transient protection of wind farms become a hot direction of wind power development and research. In this article, the key technologies of transient protection for offshore wind farm transmission lines are reviewed, including the analysis of the fault characteristics of wind farm transmission lines based on two types of wind turbines (i.e., doubly fed asynchronous wind turbines and direct-drive permanent magnet synchronous generators), while the comparison with the characteristics of ground faults and short-circuit faults in traditional synchronous power systems as well as the current status of research on transient protection for offshore wind farm transmission lines, upon which the protection of wind farm transmission lines is also discussed.
Compact and Versatile QEPAS-Based Sensor Box for Simultaneous Detection of Methane and Infrared Absorber Gas Molecules in Ambient Air
Authors: Zifarelli Andrea , Menduni Giansergio , Giglio Marilena , Elefante Arianna , Sukhinets Anton , Sampaolo Angelo , Patimisco Pietro , Fangyuan Sun , Chongwu Wang , Wang Qi Jie , Spagnolo Vincenzo
Published: June 2022

In this work we report on an innovative sensor box employing two acoustic detection modules connected in series for quartz-enhanced photoacoustic multi-gas detection. One detection module is coupled with an internal distributed-feedback quantum cascade laser (DFB-QCL) emitting at ∼7.719 µm for methane (CH4) sensing, while the second module has been designed to be coupled with an external laser source targeting the absorption features of a specific gas molecule Mx in the infrared spectral range. The sensor box can thus be employed for any application, depending on the CH4/Mx gas combination to be detected. The ∼7.719 µm DFB-QCL also allowed water vapor monitoring. To demonstrate the sensor versatility, we report on the QEPAS-box environmental monitoring application by simultaneously detecting in air methane, which is a greenhouse gas, nitric oxide (NO), an ozone depleting substance, and water vapor. Sensitivity levels of 4.30 mV ppm−1 and 17.51 mV ppm−1 and minimum detection limits of 48 ppb and 11 ppb for methane and nitric oxide detection were achieved, respectively. The sensor box operation was tested by analysing ambient air. Average concentrations of ∼1.73 ppm of CH4, ∼0.134 ppm of NO and 1.8% of H2O were measured.
Penalties vs. Subsidies: A Study on Which Is Better to Promote Corporate Environmental Governance
Authors: He Ling , Zhong Tingyong , Gan Shengdao , Liu Jiamin , Xu Chaoya
Published: June 2022

To reverse the trend of ecological environment deterioration, the government tries to stimulate firms to participate in environmental governance through environmental regulation. Then, which environmental regulation tools can better drive firms to carry out environmental governance activities needs to be corroborated by empirical studies. Using a sample consisting of Chinese A-shares listed firms from 2015 to 2019, this article investigated the effects of two heterogeneous environmental regulation tools (environmental penalties and environmental subsidies) and their interactions on corporate environmental investment. The results showed that environmental penalties have a positive impact on corporate environmental investment. Furthermore, the heavier the penalty or the higher the administrative level of the penalty subject, the more pronounced is the impact of environmental penalties on corporate environmental investment. Firms that receive environmental subsidies do not increase their investment in environmental governance. A series of robustness tests further verify that penalties have a greater impact on the environment than subsidies. In addition, it is found that environmental penalties have an environmental deterrent effect on other firms in the same industry. Our work presents evidence for the economic consequences of environmental regulation and supplements the mechanism of environmental regulation affecting corporate environmental governance. Meanwhile, this article also provides essential guidance for the positive role of environmental penalties in driving corporate environmental governance and has important practical significance for emerging market countries to choose appropriate environmental regulation tools to promote corporate green development.
The Influence and Continuance Intention of the E-Government System: A Case Study of Community Water Supply Business
Authors: Sukma Narongsak , Leelasantitham Adisorn
Published: June 2022

The e-Service system is utilized in government administration to help achieve efficiency and provide people with services that meet their needs. This service is also known as e-Government. This article discovers the actual impacts and examines the paper to identify the underlying factors affecting the government’s e-service system. The Administration created it to help achieve efficiency and provide people with services that meet their needs, also known as e-government. In addition, it leads to an increase in participation in the equity of the distribution of social benefits. This research examines the essential aspects that influence a community’s perception of E-Government Continuance Intentions Toward E-Services. A questionnaire with a five-point Likert scale was issued to 1,000 community water consumers, and the researcher received 627 valid responses. Data were collected using a simple random sampling technique with a sampling ratio of 14 villages. Subsequently, descriptive statistics characterize the data (frequency distributions, percentages, averages, medians, and standard deviation). Furthermore, PLS-SEM was utilized to study the interactions between variables and launch the conceptual model via partial least squares (PLS) path modeling. This research demonstrates that digital technologies are critical to boosting community expectations and satisfaction with e-Services. Numerous factors contribute to its growth. Moreover, this paper presents an excellent case study approach based on expectation confirmation theory for examining people’s community participation behaviors regarding e-services. In addition, community water consumers participate in electronic services by confirming their expectations with satisfaction.
Estimation of the Surface Net Radiation Under Clear-Sky Conditions in Areas With Complex Terrain: A Case Study in Haihe River Basin
Authors: Liu Xingran , Zhang Jing , Yan Haiming , Yang Huicai
Published: June 2022

The surface net radiation as an important component of the surface radiation budget has attracted wide attention; however, it is still an enormous challenge to carry out an accurate estimation of the surface net radiation in areas with complex terrain due to the scarcity of radiation observation sites and high-spatial heterogeneity of the influencing factors of the surface net radiation. Taking the Haihe River Basin as the study area, this study estimated the surface net radiation under clear-sky conditions from 2001∼2019 based on an improved algorithm of the net long-wave radiation, and the solar short-wave radiation in terms of direct radiation, diffuse sky radiation, and reflected radiation from the surrounding terrain. In this study, the regional meteorological factors were inverted based on remote sensing data to make up for the deficiency of meteorological factor interpolation. The solar short-wave radiation was corrected by considering the comprehensive influence of the atmosphere, underlying surface, and terrain, and the net long-wave radiation was optimized by localizing the algorithm coefficients. The results showed the correlation coefficient between the estimated and observed surface net radiation reached approximately 0.9, indicating the accuracy of this improved method is acceptable. Besides, the results suggested the surface net radiation was significantly influenced by the terrain, the highest value of which occurred on the south slope, followed by that on the southwest slope, west or southeast slopes, and the lowest value occurred on the north slope. In addition, there was the highest surface net radiation in summer, and there was the lowest and most frequently negative surface net radiation in winter. This study makes up for the shortcomings of the traditional spatial interpolation of meteorological factors and previous empirical formulas, and can therefore provide an important methodological foundation for the research on the surface radiation, climate, and hydrology in the areas with complex terrain.
A Novel Defined Super-Enhancer Associated Gene Signature to Predict Prognosis in Patients With Diffuse Large B-Cell Lymphoma
Authors: Xu Hong , Li Yuhang , Jiang Yanan , Wang Jinhuan , Sun Huimeng , Wu Wenqi , LV Yangyang , Liu Su , Zhai Yixin , Tian LinYan , Li Lanfang , Zhao Zhigang
Published: June 2022

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease that can have profound differences in survival outcomes. A variety of powerful prognostic factors and models have been constructed; however, the development of more accurate prognosis prediction and targeted treatment for DLBCL still faces challenges. An explosion of research on super-enhancer (SE)–associated genes provide the possibility to use in prognostication for cancer patients. Here, we aimed to establish a novel effective prognostic model using SE-associated genes from DLBCL.

Methods: A total of 1,105 DLBCL patients from the Gene Expression Omnibus database were included in this study and were divided into a training set and a validation set. A total of 11 SE-associated genes (BCL2, SPAG16, PXK, BTG1, LRRC37A2, EXT1, TGFBR2, ANKRD12, MYCBP2, PAX5, and MYC) were initially screened and identified by the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, univariate and multivariate Cox regression analysis. Finally, a risk score model based on these 11 genes was constructed.

Results: Kaplan–Meier (K–M) curves showed that the low-risk group appeared to have better clinical survival outcomes. The excellent performance of the model was determined via time-dependent receiver operating characteristic (ROC) curves. A nomogram based on the polygenic risk score was further established to promote reliable prognostic prediction. This study proposed that the SE-associated-gene risk signature can effectively predict the response to chemotherapy in DLBCL patients.

Conclusion: A novel and reliable SE-associated-gene signature that can effectively classify DLBCL patients into high-risk and low-risk groups in terms of overall survival was developed, which may assist clinicians in the treatment of DLBCL.
The Key Network of mRNAs and miRNAs Regulated by HIF1A in Hypoxic Hepatocellular Carcinoma Cells
Authors: Liu Tong , Tang Jing , Li Xiaoyu , Lin Yuan , Yang Yuma , Ma Kai , Hui Zhaoyuan , Ma Hong , Qin Yanyan , Lei Hetian , Yang Yanhui
Published: June 2022

Purpose: Hypoxia plays an essential role in the progression of hepatocellular carcinoma (HCC), whereas hypoxia inducible factor-1 (HIF-1) is the key transcription factor allowing HCC to survive hypoxia. The aim of this study was to define the essential mRNAs and miRNAs regulated by HIF1A and dissect their functions, interactions, and tumor-infiltrating immune cells in HCC.

Methods: A human HCC cell line HepG2 was used as a cell model of HCC. The CRISPR/Cas9 system was used to knock out HIF1A in HepG2 cells, and RNA sequencing was utilized to characterize differentially expressed mRNAs and miRNAs in the HIF1A-knockout HepG2 cells; the identified candidates were then analyzed by GO annotation and KEGG pathway enrichment to study their function and establish a PPI network. Quantitative (q) PCR was used to verify if there were significant differences in the expression of mRNAs, and the association of the selected mRNAs expression with immune cell infiltration levels was further analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data.

Results: Using RNA-sequencing, we discovered that there were 1535 mRNAs differentially expressed (adjusted p < 0.05, |fold change|>1.5) in the HIF1A-knockout HepG2 cells, among which there were 644 mRNAs upregulated and 891 mRNAs downregulated. GO annotation and KEGG pathway enrichment showed that these mRNAs were involved in glycolysis/gluconeogenesis, PI3K-Akt signaling pathways, and HIF-1 signaling pathways. In addition, we found that there were 309 miRNAs differentially expressed (adjusted p < 0.05, |fold change|>1.5) in the HIF1A-knockout HepG2 cells, of which there were 213 miRNAs upregulated and 96 miRNAs downregulated. Our further analyses uncovered that these miRNA putative targets were involved in the hippo signaling pathway, axon guidance, and tight junction. Moreover, the construction and analysis of the PPI network showed that OASL, IL6, and TAF1 were recognized as hub genes with the highest connectivity degrees. Importantly, in the HIF1A-knockout HepG2 cells, our qRT-PCR data confirmed the selected mRNA changes revealed by RNA-sequencing, and with TCGA pan-cancer data, we revealed that the expressional levels of these three genes, LUM, SCOC, and CCL2, were associated with immune cell infiltration levels.

Conclusion: The identified potential key network of mRNAs and miRNAs regulated by HIF1A in the HCC cells suggests a key role of HIF1A in the tumorigenesis of HCC.
Transcriptome Profiling and Identification of the Candidate Genes Involved in Early Ripening in Ziziphus Jujuba
Authors: Li Baiyun , Li Hui , Xu Zehua , Guo Xinnian , Zhou Tao , Shi Jiangli
Published: June 2022

The early ripening jujube is an immensely popular fresh fruit due to its high commercial value as well as rich nutrition. However, little is known about the mechanism of jujube fruit’s ripening. In this study, the transcriptome profiles were comprehensively analyzed between the ‘Lingwu Changzao’ jujube and its early-ripening mutant during the fruit development and maturity. A total of 5,376 and 762 differentially expressed genes (DEGs) were presented at 80 and 90 days after the flowering of the jujube fruit, respectively. Furthermore, 521 common DEGs were identified as candidate genes that might be associated with the fruit’s early ripening. Our findings demonstrated that in a non-climacteric jujube fruit, abscisic acid (ABA) was more greatly involved in fruit ripening than ethylene. Meanwhile, the fruit ripening of the early-ripening mutant was regulated by eight promotors of DEGs related to glucose and fructose, seven repressors of DEGs related to brassinosteroid signal transduction, and a series of transcription factor genes (MYB, Bhlh, and ERF). Additionally, the expression of 20 candidate DEGs was further validated by real-time PCR during the late fruit maturation stage. Collectively, the present study sheds light on the metabolic mechanism of the fruit’s early ripening and provides valuable candidate genes for the early-ripening mutant’s breeding.
BSA-seq Identifies a Major Locus on Chromosome 6 for Root-Knot Nematode (Meloidogyne graminicola) Resistance From Oryza glaberrima
Authors: Kaur Gurwinder , Yadav Inderjit Singh , Bhatia Dharminder , Vikal Yogesh , Neelam Kumari , Dhillon Narpinderjeet Kaur , Praba Umesh Preethi , Mangat Gurjit Singh , Singh Kuldeep
Published: June 2022

Root-knot nematode (Meloidogyne graminicola) is one of the emerging threats to rice production worldwide that causes substantial yield reductions. There is a progressive shift of the cropping system from traditional transplanting to direct-seeded water-saving rice production that favored the development of M. graminicola. Scouting and deploying new resistance genes is an economical approach to managing the root-knot nematodes. Here, we report that the inheritance of root-knot nematode resistance in Oryza glaberrima acc. IRGC102206 is governed by a single dominant gene. Traditional mapping coupled with BSA-seq is used to map nematode resistance gene(s) using the BC1F1 population derived from a cross of O. sativa cv. PR121 (S) and O. glaberrima acc. IRGC102206 (R). One major novel genomic region spanning a 3.0-Mb interval on chromosome 6 and two minor QTLs on chromosomes 2 and 4 are the potential genomic regions associated with rice root-knot nematode resistance. Within the QTL regions, 19 putative candidate genes contain 81 non-synonymous variants. The detected major candidate region could be fine mapped to accelerate marker-assisted breeding for root-knot nematode resistance in rice.
Differentially Expressed Bone Marrow microRNAs Are Associated With Soluble HLA-G Bone Marrow Levels in Childhood Leukemia
Authors: Almeida Renata Santos , Gomes Thailany Thays , Araújo Felipe Souza , Oliveira Sávio Augusto Vieira de , Santos Jair Figueredo , Donadi Eduardo Antônio , Lucena-Silva Norma
Published: June 2022

HLA-G is a nonclassical histocompatibility class I molecule that plays a role in immune vigilance in cancer and infectious diseases. We previously reported that highly soluble HLA-G (sHLA-G) levels in the bone marrow were associated with a high blood cell count in T-acute lymphoblastic leukemia, a marker associated with a poor prognosis. To understand the posttranscriptionalHLA-Ggene regulation in leukemia, we evaluated the bone marrow microRNA profile associated with the HLA-G bone marrow mRNA expression and sHLA-G bone marrow levels in children exhibiting acute leukemia (B-ALL, T-ALL, and AML) using massively parallel sequencing. Ten differentially expressed miRNAs were associated with high sHLA-G bone marrow levels, and four of them (hsa-miR-4516, hsa-miR-486-5p, hsa-miR-4488, and hsa-miR-5096) targetedHLA-G, acting at distinctHLA-Ggene segments. For qPCR validation, these miRNA expression levels (ΔCt) were correlated withHLA-G5andRREB1mRNA expressions and sHLA-G bone marrow levels according to the leukemia subtype. The hsa-miR-4488 and hsa-miR-5096 expression levels were lower in B-ALL than in AML, while that of hsa-miR-486-5p was lower in T-ALL than in AML. In T-ALL, hsa-miR-5096 correlated positively withHLA-G5and negatively with sHLA-G. In addition, hsa-miR-4516 correlated negatively with sHLA-G levels. In AML, hsa-miR-4516 and hsa-miR-4488 correlated positively withHLA-G5mRNA, but theHLA-G5negatively correlated with sHLA-G. Our findings highlight the need to validate the findings of massively parallel sequencing since the experiment generally uses few individuals, and the same type of leukemia can be molecularly quite variable. We showed that miRNA’s milieu in leukemia’s bone marrow environment varies according to the type of leukemia and that the regulation of sHLA-G expression exerted by the same miRNA may act by a distinct mechanism in different types of leukemia.
Transcriptome Analysis Reveals that Exogenous Melatonin Confers Lilium Disease Resistance to Botrytis elliptica
Authors: Xie Xuehua , Han Yu , Yuan Xi , Zhang Man , Li Ping , Ding Aiqin , Wang Jia , Cheng Tangren , Zhang Qixiang
Published: June 2022

Leaf blight, caused by Botrytis elliptica (Berk.) Cooke, is a devastating disease that limits the production of Lilium in China and in other countries worldwide. Numerous studies have indicated that plants have evolved sophisticated and effective signal transduction and defense-related pathways in response to pathogen invasion. Recently, particular attention has been given to the action(s) of melatonin in plants in response to biotic stress, and the role of melatonin in plant–pathogen interactions has also been discussed. In this study, RNA-seq was applied to analyze the transcriptomic changes in Lilium leaves that were pre-treated and post-treated with melatonin after B. elliptica infection for 0, 12, 24, 36, and 72 h and then compare those changes with those of the control. Treatment with exogenous melatonin and infection with B. elliptica caused differential expression of a large number of genes in Lilium leaves. KEGG pathway analysis showed that, after melatonin treatment, the defense-related DEGs were mainly enriched in plant–pathogen interactions, plant hormone signal transduction, MAPK signaling pathways, phenylpropanoid biosynthesis, and phenylalanine metabolism. RT–qPCR was used to verify the expression changes of 12 DEGs, the results of which were consistent with the RNA-seq analysis results. The expression of DEGs related to the MAPK pathway were significantly different between the MB group and the HB group, suggesting that, via the MAPK signaling cascade, melatonin may play a role in the disease resistance of Lilium to B. elliptica. This study provides a new perspective and information for molecular-based breeding of Lilium disease resistance.
Identification of Immune-Related Hub Genes in Thymoma: Defects in CD247 and Characteristics of Paraneoplastic Syndrome
Authors: Deng Lin-Fang
Published: June 2022

Background: Thymomas (Ts) and thymic carcinomas (TCs) are rare primary tumors of the mediastinum. Paraneoplastic syndrome (PNS) is an important feature of thymoma, which presents great challenges to clinicians.

Methods: The present study uses the weighted gene co-expression network analysis (WGCNA) to identify possible immunologic mechanisms of thymoma. RNA sequencing data from thymoma samples were downloaded from the TCGA. Core genes were taken from the module that is closely related to the WHO’s stage of classification. Enhanced analysis using the online database “Metascape” and an overall survival (OS) analysis were carried out via the Kaplan–Meier method. The hub genes were obtained from the protein–protein interaction (PPI) network. In addition, we jointly analyzed multiple sets of PNS data related to thymomas from other sources to verify the correlation between thymomas and PNS. The impact of hub genes on the prognosis of PNS was evaluated via the ROC curve, with simultaneous analysis of immune infiltration by CIBERSORT.

Findings: The 14 immune hub genes closely related to thymomas were found to be jointly involved in the T-cell receptor signaling pathway. Compared to the normal thymus and type B1/B2 thymoma, there is a lower number of T-cells in type A/B3 thymoma and thymic carcinoma. The expression of genes related to the T-cell receptor signaling pathway appeared defective. The low expression of CD247 and the decrease in the number of mature T-cells are common features among thymomas, specific pulmonary fibrosis, rheumatoid arthritis, and systemic lupus erythematosus.
Ontology Specific Alternative Splicing Changes in Alzheimer’s Disease
Authors: Lu Yanjun , Yue Daoyuan , Xie Jiazhao , Cheng Liming , Wang Xiong
Published: June 2022

Alternative splicing (AS) is a common phenomenon and correlates with aging and aging-related disorders including Alzheimer’s disease (AD). We aimed to systematically characterize AS changes in the cerebral cortex of 9-month-old APP/PS1 mice. The GSE132177 dataset was downloaded from GEO and ENA databases, aligned to the GRCm39 reference genome from ENSEMBL via STAR. Alternative 3′SS (A3SS), alternative 5′SS (A5SS), skipped exon (SE), retained intron (RI), and mutually exclusive exons (MXE) AS events were evaluated using rMATS, rmats2sashimiplot, and maser. Differential genes or transcripts were analyzed using the limma R package. Gene ontology analysis was performed with the clusterProfiler R package. A total of 60,705 raw counts of AS were identified, and 113 significant AS events were finally selected in accordance with the selection criteria: 1) average coverage >10 and 2) delta percent spliced in (ΔPSI) >0.1. SE was the most abundant AS event (61.95%), and RI was the second most abundant AS type (13.27%), followed by A3SS (12.39%), thereafter A5SS and MXE comprised of 12.39%. Interestingly, genes that experienced SE were enriched in histone acetyltransferase (HAT) complex, while genes spliced by RI were enriched in autophagy and those which experienced A3SS were enriched in methyltransferase activity revealed by GO analysis. In conclusion, we revealed ontology specific AS changes in AD. Our analysis provides novel pathological mechanisms of AD.
Emerging Concepts in Innate Lymphoid Cells, Memory, and Reproduction
Authors: Favaro Rodolfo R. , Phillips Katherine , Delaunay-Danguy Romane , Ujčič Kaja , Markert Udo R.
Published: June 2022

Members of the innate immune system, innate lymphoid cells (ILCs), encompass five major populations (Natural Killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells) whose functions include defense against pathogens, surveillance of tumorigenesis, and regulation of tissue homeostasis and remodeling. ILCs are present in the uterine environment of humans and mice and are dynamically regulated during the reproductive cycle and pregnancy. These cells have been repurposed to support pregnancy promoting maternal immune tolerance and placental development. To accomplish their tasks, immune cells employ several cellular and molecular mechanisms. They have the capacity to remember a previously encountered antigen and mount a more effective response to succeeding events. Memory responses are not an exclusive feature of the adaptive immune system, but also occur in innate immune cells. Innate immune memory has already been demonstrated in monocytes/macrophages, neutrophils, dendritic cells, and ILCs. A population of decidual NK cells characterized by elevated expression of NKG2C and LILRB1 as well as a distinctive transcriptional and epigenetic profile was found to expand during subsequent pregnancies in humans. These cells secrete high amounts of interferon-γ and vascular endothelial growth factor likely favoring placentation. Similarly, uterine ILC1s in mice upregulate CXCR6 and expand in second pregnancies. These data provide evidence on the development of immunological memory of pregnancy. In this article, the characteristics, functions, and localization of ILCs are reviewed, emphasizing available data on the uterine environment. Following, the concept of innate immune memory and its mechanisms, which include epigenetic changes and metabolic rewiring, are presented. Finally, the emerging role of innate immune memory on reproduction is discussed. Advances in the comprehension of ILC functions and innate immune memory may contribute to uncovering the immunological mechanisms underlying female fertility/infertility, placental development, and distinct outcomes in second pregnancies related to higher birth weight and lower incidence of complications.
A Recombinant MVA-Based RSV Vaccine Induces T-Cell and Antibody Responses That Cooperate in the Protection Against RSV Infection
Authors: Endt Kathrin , Wollmann Yvonne , Haug Jana , Bernig Constanze , Feigl Markus , Heiseke Alexander , Kalla Markus , Hochrein Hubertus , Suter Mark , Chaplin Paul , Volkmann Ariane
Published: June 2022

Respiratory syncytial virus (RSV) causes a respiratory disease with a potentially fatal outcome especially in infants and elderly individuals. Several vaccines failed in pivotal clinical trials, and to date, no vaccine against RSV has been licensed. We have developed an RSV vaccine based on the recombinant Modified Vaccinia Virus Ankara-BN®(MVA-RSV), containing five RSV-specific antigens that induced antibody and T-cell responses, which is currently tested in clinical trials. Here, the immunological mechanisms of protection were evaluated to determine viral loads in lungs upon vaccination of mice with MVA-RSV followed by intranasal RSV challenge. Depletion of CD4 or CD8 T cells, serum transfer, and the use of genetically engineered mice lacking the ability to generate either RSV-specific antibodies (T11µMT), the IgA isotype (IgA knockout), or CD8 T cells (β2M knockout) revealed that complete protection from RSV challenge is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. Thus, MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system.
The Regulation and Modification of GSDMD Signaling in Diseases
Authors: Li Zihao , Ji Senlin , Jiang Mei-Ling , Xu Yun , Zhang Cun-Jin
Published: June 2022

Gasdermin D (GSDMD) serves as a key executor to trigger pyroptosis and is emerging as an attractive checkpoint in host defense, inflammatory, autoimmune diseases, and many other systemic diseases. Although canonical and non-canonical inflammasome-mediated classic GSDMD cleavage, GSDMD-NT migration to cell membrane, GSDMD-NT oligomerization, and pore forming have been well recognized, a few unique features of GSDMD in specific condition beyond its classic function, including non-lytic function of GSDMD, the modification and regulating mechanism of GSDMD signaling have also come to great attention and played a crucial role in biological processes and diseases. In the current review, we emphasized the GSDMD protein expression, stabilization, modification, activation, pore formation, and repair during pyroptosis, especially the regulation and modification of GSDMD signaling, such as GSDMD complex in polyubiquitination and non-pyroptosis release of IL-1β, ADP-riboxanation, NINJ1 in pore forming, GSDMD binding protein TRIM21, GSDMD succination, and Regulator-Rag-mTOR-ROS regulation of GSDMD. We also discussed the novel therapeutic strategies of targeting GSDMD and summarized recently identified inhibitors with great prospect.
CASP-Model Sepsis Triggers Systemic Innate Immune Responses Revealed by the Systems-Level Signaling Pathways
Authors: Ai Hannan , Li Bizhou , Meng Fanmei , Ai Yuncan
Published: June 2022

Colon ascendens stent peritonitis (CASP) surgery induces a leakage of intestinal contents which may cause polymicrobial sepsis related to post-operative failure of remote multi-organs (including kidney, liver, lung and heart) and possible death from systemic syndromes. Mechanisms underlying such phenomena remain unclear. This article aims to elucidate the mechanisms underlying the CASP-model sepsis by analyzing real-world GEO data (GSE24327_A, B and C) generated from mice spleen 12 hours after a CASP-surgery in septic MyD88-deficient and wildtype mice, compared with untreated wildtype mice. Firstly, we identify and characterize 21 KO MyD88-associated signaling pathways, on which true key regulators (including ligands, receptors, adaptors, transducers, transcriptional factors and cytokines) are marked, which were coordinately, significantly, and differentially expressed at the systems-level, thus providing massive potential biomarkers that warrant experimental validations in the future. Secondly, we observe the full range of polymicrobial (viral, bacterial, and parasitic) sepsis triggered by the CASP-surgery by comparing the coordinated up- or down-regulations of true regulators among the experimental treatments born by the three data under study. Finally, we discuss the observed phenomena of “systemic syndrome”, “cytokine storm” and “KO MyD88 attenuation”, as well as the proposed hypothesis of “spleen-mediated immune-cell infiltration”. Together, our results provide novel insights into a better understanding of innate immune responses triggered by the CASP-model sepsis in both wildtype and MyD88-deficient mice at the systems-level in a broader vision. This may serve as a model for humans and ultimately guide formulating the research paradigms and composite strategies for the early diagnosis and prevention of sepsis.
Development and Validation of a Novel Ferroptosis-Related LncRNA Signature for Predicting Prognosis and the Immune Landscape Features in Uveal Melanoma
Authors: Ma Xiaochen , Yu Sejie , Zhao Bin , Bai Wei , Cui Yubo , Ni Jinglan , Lyu Qinghua , Zhao Jun
Published: June 2022

Background

Ferroptosis is a newly iron-dependent mode of programmed cell death that is involved in a variety of malignancies. But no research has shown a link between ferroptosis-related long non-coding RNAs (FRLs) and uveal melanoma (UM). We aimed to develop a predictive model for UM and explore its potential function in relation to immune cell infiltration.

Methods

Identification of FRLs was performed using the Cancer Genome Atlas (TCGA) and FerrDb databases. To develop a prognostic FRLs signature, univariate Cox regression and least absolute shrinkage and selection operator (LASSO) were used in training cohort. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses were used to assess the reliability of the risk model. The immunological functions of FRLs signature were determined using gene set enrichment analysis (GSEA). Immunological cell infiltration and immune treatment were studied using the ESTIMATE, CIBERSORT, and ssGSEA algorithms. Finally, in vitro assays were carried out to confirm the biological roles of FRLs with known primer sequences (LINC00963, PPP1R14B.AS1, and ZNF667.AS1).

Results

A five-genes novel FRLs signature was identified. The mean risk score generated by this signature was used to create two risk groups. The high-risk score UM patients had a lower overall survival rate. The area under the curve (AUC) of ROC and K-M analysis further validated the strong prediction capacity of the prognostic signature. Immune cells such as memory CD8 T cells, M1 macrophages, monocytes, and B cells showed a substantial difference between the two groups. GSEA enrichment results showed that the FRLs signature was linked to certain immune pathways. Moreover, UM patients with high-risk scores were highly susceptible to several chemotherapy drugs, such as cisplatin, imatinib, bortezomib, and pazopanib. Finally, the experimental validation confirmed that knockdown of three identified lncRNA (LINC00963, PPP1R14B.AS1, and ZNF667.AS1) suppressed the invasive ability of tumor cells in vitro.

Conclusion

The five-FRLs (AC104129.1, AC136475.3, LINC00963, PPP1R14B.AS1, and ZNF667.AS1) signature has effects on clinical survival prediction and selection of immunotherapies for UM patients.