bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforming IoT Events to Meaningful Business Events on the Edge: Implementation for Smart Farming Application
Authors: Gkoulis Dimitris , Bardaki Cleopatra , Kousiouris George , Nikolaidou Mara
Published: March 2023

This paper focuses on Internet of Things (IoT) architectures and knowledge generation out of streams of events as the primary elements concerning the creation of user-centric IoT services. We provide a general, symmetrical IoT architecture, which enables two-way bidirectional communication between things and users within an application domain. We focus on two main components of the architecture (i.e., Event Engine and Process Engine) that handle event transformation by implementing parametric Complex Event Processing (CEP). More specifically, we describe and implement the transformation cycle of events starting from raw IoT data to their processing and transformation of events for calculating information that we need in an IoT-enabled application context. The implementation includes a library of composite transformations grouping the gradual and sequential steps for transforming basic IoT events into business events, which include ingestion, event splitting, and calculation of measurements’ average value. The appropriateness and possibility of inclusion and integration of the implementation in an IoT environment are demonstrated by providing our implementation for a smart farming application domain with four scenarios that each reflect a user’s requirements. Further, we discuss the quality properties of each scenario. Ultimately, we propose an IoT architecture and, specifically, a parametric CEP model and implementation for future researchers and practitioners who aspire to build IoT applications.
Regional Variation in Feeding Patterns of Sheepshead (Archosargus probatocephalus) in the Northwest Gulf of Mexico
Authors: Gutierrez Elsa , Plumlee Jeffrey , Bolser Derek , Erisman Brad , Wells R.
Published: March 2023

Feeding patterns of sheepshead, Archosargus probatocephalus, in the northwest Gulf of Mexico were examined from samples collected at two locations in Texas, USA; Galveston and Port Aransas. A total of 53 sheepshead stomachs (Galveston, n = 35; Port Aransas, n = 18) had their contents analyzed along with tissue samples from the muscle and liver for a stable isotope analysis (δ13C, δ15N, and δ34S) because they provide a contrast between short-term (liver) and long-term (muscle) measurements. Multiple species of amphipods made up the majority of the prey items in sheepshead from Galveston (%IRI = 61.79), whereas barnacles were the primary diet item for sheepshead collected in Port Aransas (%IRI = 39.53). We observed diet shifts prior to and during the spawning season. MANOVA revealed significant differences in δ13C, δ15N, and δ34S stable isotope values from the muscle and liver tissue of sheepshead based on the location. In both muscle and liver samples, δ13C values were lower in Galveston than Port Aransas, but δ15N and δ34S values were higher in Galveston than Port Aransas. Niche size and overlap also differed between sheepshead from both locations and tissue types. Sheepshead collected in Galveston had a larger niche size in the muscle and liver samples ((mean ± SD) 479.3 ± 131.2, muscle; 433.3 ± 120.3, liver) than Port Aransas (178.8 ± 54.3, muscle; 270.0 ± 80.9, liver). The trophic niche of sheepshead from Galveston overlapped Port Aransas in muscle samples by 16.47% and 18.56% in liver samples. The trophic niche overlap of sheepshead from Port Aransas measured in muscle samples overlapped with sheepshead from Galveston by 18.49% and by 39.17% in liver samples. This study shows that there are subtle but significant differences between the diets of sheepshead along the Texas coast, with the majority of the differences potentially attributable to differences in the prey field along the natural salinity gradient of the Texas coast. This work provides an insight into the widely generalist grazing behavior of sheepshead, which potentially changes during the springtime spawning season.
Numerical Investigation of Flow-Induced Vibration for Cylinder-Plate Assembly at low Reynolds Number
Authors: Wu Ying , Lien Fue-Sang , Yee Eugene , Chen Guang
Published: March 2023

The transverse flow-induced vibration (FIV) of an elastically-supported cylinder-plate assembly (viz., a rigid splitter-plate attached to the downstream side of a circular cylinder) with a low mass ratio of 10 and zero structural damping is investigated using numerical simulations at a Reynolds number of 100. The structural oscillations and characteristics of the flow around the structure are analyzed in terms of the vibration characteristics and the fluid forces as a function of the plate length LSP and the reduced velocity Ur. These investigations involve a wide range of plate lengths LSP/D = 0–4 (where D is the cylinder diameter) over an extensive span of reduced velocities Ur = 2–30. For LSP/D ≤ 0.5, self-limiting oscillations are induced in the assembly—these oscillations correspond to either a vortex-induced vibration (VIV) or an integrated VIV-galloping response. For LSP/D ≥ 0.75, the amplitude response is no longer self-limiting in the sense that the oscillation amplitude increases linearly with increasing Ur—these oscillations correspond to either a strongly correlated VIV-galloping regime (for LSP/D = 0.75), or two clearly separated regimes: namely, a VIV regime with small-amplitude oscillation and a non-limiting galloping regime (for LSP/D > 0.75).
Measuring the Difficulties in Forming a Coalition Government
Authors: Hiller Tobias
Published: March 2023

Electoral thresholds in the context of parliamentary elections are an instrument for preventing the fragmentation of parliaments and facilitate the formation of a coalition government. However, the clauses also introduce distortions and modify the equality of electoral votes in an election. In order to decide to what extent these negative effects can be accepted, it is necessary to measure the difficulties in forming a coalition government and to quantify the effects of electoral thresholds on these difficulties. For this issue, we introduce a concept based on cooperative game theory which takes into account the distribution of seats in parliament and coalition statements of parties.
Genetic Improvement of Wheat with Pre-Harvest Sprouting Resistance in China
Authors: Chang Cheng , Zhang Haiping , Lu Jie , Si Hongqi , Ma Chuanxi
Published: March 2023

Wheat pre-harvest sprouting (PHS) refers to the germination of seeds directly on the spike due to rainy weather before harvest, which often results in yield reduction, quality deterioration, and seed value loss. In this study, we reviewed the research progress in the quantitative trait loci (QTL) detection and gene excavation related to PHS resistance in wheat. Simultaneously, the identification and creation of germplasm resources and the breeding of wheat with PHS resistance were expounded in this study. Furthermore, we also discussed the prospect of molecular breeding during genetic improvement of PHS-resistant wheat.
RNA Sequencing in Hypoxia-Adapted T98G Glioblastoma Cells Provides Supportive Evidence for IRE1 as a Potential Therapeutic Target
Authors: White Brian E. , Liu Yichuan , Hakonarson Hakon , Buono Russell J.
Published: March 2023

Glioblastoma (GBM) is an aggressive brain cancer with a median survival time of 14.6 months after diagnosis. GBM cells have altered metabolism and exhibit the Warburg effect, preferentially producing lactate under aerobic conditions. After standard-of-care treatment for GBM, there is an almost 100% recurrence rate. Hypoxia-adapted, treatment-resistant GBM stem-like cells are thought to drive this high recurrence rate. We used human T98G GBM cells as a model to identify differential gene expression induced by hypoxia and to search for potential therapeutic targets of hypoxia adapted GBM cells. RNA sequencing (RNAseq) and bioinformatics were used to identify differentially expressed genes (DEGs) and cellular pathways affected by hypoxia. We also examined expression of lactate dehydrogenase (LDH) genes using qRT-PCR and zymography as LDH dysregulation is a feature of many cancers. We found 2630 DEGs significantly altered by hypoxia (p < 0.05), 1241 upregulated in hypoxia and 1389 upregulated in normoxia. Hypoxia DEGs were highest in pathways related to glycolysis, hypoxia response, cell adhesion and notably the endoplasmic reticulum, including the inositol-requiring enzyme 1 (IRE1)-mediated unfolded protein response (UPR). These results, paired with numerous published preclinical data, provide additional evidence that inhibition of the IRE1-mediated UPR may have therapeutic potential in treating GBM. We propose a possible drug repurposing strategy to simultaneously target IRE1 and the spleen tyrosine kinase (SYK) in patients with GBM.
An in Silico Approach to Identifying TF Binding Sites: Analysis of the Regulatory Regions of BUSCO Genes from Fungal Species in the Ceratocystidaceae Family
Authors: Maseko Nomaswazi N. , Steenkamp Emma T. , Wingfield Brenda D. , Wilken P. Markus
Published: March 2023

Transcriptional regulation controls gene expression through regulatory promoter regions that contain conserved sequence motifs. These motifs, also known as regulatory elements, are critically important to expression, which is driving research efforts to identify and characterize them. Yeasts have been the focus of such studies in fungi, including in several in silico approaches. This study aimed to determine whether in silico approaches could be used to identify motifs in the Ceratocystidaceae family, and if present, to evaluate whether these correspond to known transcription factors. This study targeted the 1000 base-pair region upstream of the start codon of 20 single-copy genes from the BUSCO dataset for motif discovery. Using the MEME and Tomtom analysis tools, conserved motifs at the family level were identified. The results show that such in silico approaches could identify known regulatory motifs in the Ceratocystidaceae and other unrelated species. This study provides support to ongoing efforts to use in silico analyses for motif discovery.
The CRISPR/Cas System: A Customizable Toolbox for Molecular Detection
Authors: He Yuxuan , Yan Wei , Long Likun , Dong Liming , Ma Yue , Li Congcong , Xie Yanbo , Liu Na , Xing Zhenjuan , Xia Wei , Li Feiwu
Published: March 2023

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) are promising molecular diagnostic tools for rapidly and precisely elucidating the structure and function of genomes due to their high specificity, programmability, and multi-system compatibility in nucleic acid recognition. Multiple parameters limit the ability of a CRISPR/Cas system to detect DNA or RNA. Consequently, it must be used in conjunction with other nucleic acid amplification techniques or signal detection techniques, and the reaction components and reaction conditions should be modified and optimized to maximize the detection performance of the CRISPR/Cas system against various targets. As the field continues to develop, CRISPR/Cas systems have the potential to become an ultra-sensitive, convenient, and accurate biosensing platform for the detection of specific target sequences. The design of a molecular detection platform employing the CRISPR/Cas system is asserted on three primary strategies: (1) Performance optimization of the CRISPR/Cas system; (2) enhancement of the detection signal and its interpretation; and (3) compatibility with multiple reaction systems. This article focuses on the molecular characteristics and application value of the CRISPR/Cas system and reviews recent research progress and development direction from the perspectives of principle, performance, and method development challenges to provide a theoretical foundation for the development and application of the CRISPR/CAS system in molecular detection technology.
Evaluation of Structured, Semi-Structured, and Free-Text Electronic Health Record Data to Classify Hepatitis C Virus (HCV) Infection
Authors: Fong Allan , Hughes Justin , Gundapenini Sravya , Hack Benjamin , Barkhordar Mahdi , Huang Sean Shenghsiu , Visconti Adam , Fernandez Stephen , Fishbein Dawn
Published: March 2023

Evaluation of the United States Centers for Disease Control and Prevention (CDC)-defined HCV-related risk factors are not consistently performed as part of routine care, rendering risk-based testing susceptible to clinician bias and missed diagnoses. This work uses natural language processing (NLP) and machine learning to identify patients who are at high risk for HCV infection. Models were developed and validated to predict patients with newly identified HCV infection (detectable RNA or reported HCV diagnosis). We evaluated models with three types of variables: structured (structured-based model), semi-structured and free-text notes (text-based model), and all variables (full-set model). We applied each model to three stratifications of data: patients with no history of HCV prior to 2020, patients with a history of HCV prior to 2020, and all patients. We used XGBoost and ten-fold C-statistic cross-validation to evaluate the generalizability of the models. There were 3564 unique patients, 487 with HCV infection. The average C-statistics on the structured-based, text-based, and full-set models for all the patients were 0.777 (95% CI: 0.744–0.810), 0.677 (95% CI: 0.631–0.723), and 0.774 (95% CI: 0.735–0.813), respectively. The full-set model performed slightly better than the structured-based model and similar to text-based models for patients with no history of HCV prior to 2020; average C-statistics of 0.780, 0.774, and 0.759, respectively. NLP was able to identify six more risk factors inconsistently coded in structured elements: incarceration, needlestick, substance use or abuse, sexually transmitted infections, piercings, and tattoos. The availability of model options (structured-based or text-based models) with a similar performance can provide deployment flexibility in situations where data is limited.
Communicable Diseases Prevalence among Refugees and Asylum Seekers: Systematic Review and Meta-Analysis
Authors: Taha Haitham , Durham Jo , Reid Simon
Published: March 2023

Background: Communicable diseases remain a significant global health issue. The increase in refugees and asylum seekers associated with conflicts may alter the burden of communicable diseases in host countries. We conducted a systematic review of the prevalence of TB, HBC, HCV, and HIV among refugees and asylum seekers by regions of asylum and origin. Methods: Four electronic databases were searched from initiation to the 25 December 2022. Prevalence estimates were pooled into a random-effect model and were stratified by the region of origin and asylum. Meta-analysis was conducted to explore the heterogeneity of the included studies. Results: The most-reported asylum region was The Americas, represented by the United States of America. Asia and the Eastern Mediterranean was the region of the most-reported origin. The highest reported prevalence of active TB and HIV was among African refugees and asylum seekers. The highest reported prevalence of latent TB, HBV and HCV was among Asian and Eastern Mediterranean refugees and asylum seekers. High heterogeneity was found regardless of the communicable disease type or stratification. Conclusion: This review provided insights about refugees’ and asylum seekers’ status around the world and attempted to connect refugees’ and asylum seekers’ distribution and the burden of communicable diseases.
What Is a School Farm? Results of a Scoping Review
Authors: Blair Sammy A. , Edwards Gabrielle , Yu Katharine , Jovel Eduardo , Powell Lisa Jordan , Renwick Kerry , Conklin Annalijn I.
Published: March 2023

As school farms become more prominent programs to teach food education, research is needed to support school farms’ implementation and sustainability. This scoping review included 94 articles on school farms from three bibliometric databases covering broad international literature. Vocational agricultural training, animal husbandry, and crop production were common characteristics of school farms across 103 years of publications. Themes of sustainability, healthy eating, and food systems were more prominent in recent literature. Peer-reviewed studies (1985–2019) provided some empirical research showing school farms’ impact on students. This review discusses school farms’ structures and objectives as promising food education and production programming.
Combination of Risks of BMI and Health-Related Lifestyles on Kidney Function in the Prediabetic Japanese Population: A Prospective Cohort Study
Authors: Chen Jou-Yin , Deng Shiqi , Wagatsuma Yukiko
Published: March 2023

Diabetic overweight patients are more likely to show the progression of kidney damage than the general population. The majority of people in the early stages of kidney damage do not recognize the importance of risk modification, mainly due to the asymptomatic nature of the disease. This study aimed to examine specific risk combinations of lifestyle and BMI regarding the deterioration of kidney function and to explore whether there are gender-based differences among the prediabetic population. Prediabetic participants with normal kidney function were identified via annual health examination from April 2016 to March 2019. The information on health status and lifestyle was collected at enrollment. The study subjects were followed until March 2021 to observe the progression of kidney damage. There were 2241 participants enrolled in this study. Smoking (HR = 3.5, p < 0.001), eating snacks (HR = 3.2, p < 0.001), not engaging in regular exercise (HR = 2.9, p < 0.001), and not having adequate sleep (HR = 3.0, p < 0.001) showed accelerated risks for kidney damage progression among the prediabetic population in males. These lifestyle effects were not observed in females. In conclusion, risk-based modification of lifestyle behavior is important to prevent kidney function damage among the overweight prediabetic population in males.
Hugs and Cortisol Awakening Response the Next Day: An Ecological Momentary Assessment Study
Authors: Romney Chelsea E. , Arroyo Amber Carmen , Robles Theodore F. , Zawadzki Matthew J.
Published: March 2023

Previous research suggests that affectionate touch such as hugs might downregulate stress systems such as the hypothalamic pituitary adrenal (HPA) axis. However, the current literature lacks in generalizability beyond the laboratory setting and outside the context of romantic relationships. The cortisol awakening response (CAR) is a measure of the HPA axis and is responsive to daily fluctuations in stress and social information. However, associations between affectionate touch and the CAR have never been assessed. This study used ecological momentary assessment (EMA) to measure daily hugging behaviors in 104 first-year college students and salivary cortisol to assess the CAR. Participants who reported more daily hugs in their social interactions had significantly smaller CARs the next morning compared to days they reported fewer hugs. This study contributes to the literature on social interactions and stress responsive systems and emphasizes the importance of assessing affectionate touch behaviors such as hugs that can be exchanged outside the context of romantic relationships.
Parental Perception of Children’s Online Behaviour: A Study on Ethnic Communities in Australia
Authors: Imran Ahmed , Khanom Nilufa , Rahman Azizur
Published: March 2023

The overwhelming growth of the Internet in all spheres of life poses new challenges for young children growing up in the digital age, with potential short- and long-term ramifications. Parents have an essential role in the development of the attitudes and behaviour of their children. However, studies indicate that adults are not adequately mitigating the range of cyber risks that children face and that parent-oriented solutions are simply inadequate. This study attempts to fill research gaps in the status and nature of parents’ perceptions of the online use of their children in Australia based on their ethnic background. This study adopted a mixed-method approach, surveying 204 parents from different ethnic communities in Australia followed by 16 in-depth interviews and three focus-group discussions. The results indicate that parents’ perceptions of online risk for children differ based on their ethnicity, cultural adaptation, gender, and age. Parents from multicultural societies are less equipped to deal with cyber threats that their children face and are ill-equipped to monitor and mitigate the risks posed. The results of this study have important policy implications, from deepening our understanding of the nature of the problems to facilitating the development of short- and long-term strategies, appropriate information systems, policy guidelines, and interventions.
Visual Diagnostics of Dental Caries through Deep Learning of Non-Standardised Photographs Using a Hybrid YOLO Ensemble and Transfer Learning Model
Authors: Tareq Abu , Faisal Mohammad Imtiaz , Islam Md. Shahidul , Rafa Nafisa Shamim , Chowdhury Tashin , Ahmed Saif , Farook Taseef Hasan , Mohammed Nabeel , Dudley James
Published: March 2023

Background: Access to oral healthcare is not uniform globally, particularly in rural areas with limited resources, which limits the potential of automated diagnostics and advanced tele-dentistry applications. The use of digital caries detection and progression monitoring through photographic communication, is influenced by multiple variables that are difficult to standardize in such settings. The objective of this study was to develop a novel and cost-effective virtual computer vision AI system to predict dental cavitations from non-standardised photographs with reasonable clinical accuracy. Methods: A set of 1703 augmented images was obtained from 233 de-identified teeth specimens. Images were acquired using a consumer smartphone, without any standardised apparatus applied. The study utilised state-of-the-art ensemble modeling, test-time augmentation, and transfer learning processes. The “you only look once” algorithm (YOLO) derivatives, v5s, v5m, v5l, and v5x, were independently evaluated, and an ensemble of the best results was augmented, and transfer learned with ResNet50, ResNet101, VGG16, AlexNet, and DenseNet. The outcomes were evaluated using precision, recall, and mean average precision (mAP). Results: The YOLO model ensemble achieved a mean average precision (mAP) of 0.732, an accuracy of 0.789, and a recall of 0.701. When transferred to VGG16, the final model demonstrated a diagnostic accuracy of 86.96%, precision of 0.89, and recall of 0.88. This surpassed all other base methods of object detection from free-hand non-standardised smartphone photographs. Conclusion: A virtual computer vision AI system, blending a model ensemble, test-time augmentation, and transferred deep learning processes, was developed to predict dental cavitations from non-standardised photographs with reasonable clinical accuracy. This model can improve access to oral healthcare in rural areas with limited resources, and has the potential to aid in automated diagnostics and advanced tele-dentistry applications.
Analysis of Risky Riding Behavior Characteristics of the Related Road Traffic Injuries of Electric Bicycle Riders
Authors: Huang Jiayu , Song Ziyi , Xie Linlin , Lin Zeting , Li Liping
Published: March 2023

Electric bicycle (EB) riders, being vulnerable road users (VRUs), are increasingly becoming victims of road traffic injuries (RTIs). This study aimed to determine the current status and epidemiological characteristics of RTIs among EB riders through a questionnaire survey and roadside observations in Shantou to provide a scientific basis for the prevention and control of electric bicycle road traffic injuries (ERTIs). A total of 2412 EB riders were surveyed, and 34,554 cyclists were observed in the study. To analyze the relationship between riding habits and injuries among EB riders, chi-square tests and multi-factor logistic regression models were employed. The findings reveal that the prevalence of ERTIs in Shantou was 4.81%, and the most affected group was children under 16 years old, accounting for 9.84%. Risky behavior was widespread among EB riders, such as the infrequent wearing of safety helmets, carrying people on EBs, riding on sidewalks, and listening to music with headphones while bicycling. Notably, over 90% of those who wore headphones while bicycling engaged in this risky behavior. The logistic regression analysis showed that honking the horn (odds ratio (OR): 2.009, 95% CI: 1.245–3.240), riding in reverse (OR: 4.210, 95% CI: 2.631–6.737), and continuing to ride after a fault was detected (OR: 2.010, 95% CI: 1.188–3.402) all significantly increased the risk of ERTIs (all p < 0.05). Risky riding behavior was significantly less observed at traffic intersections with traffic officers than at those without (all p < 0.001).
Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment
Authors: Ailia Muhammad Joan , Heo Jeong , Yoo So Young
Published: March 2023

This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular carcinoma (HCC). Medline, EMBASE, and Cochrane Library database searches were conducted, revealing nine relevant cohort studies (seven PDL-1 and three PD-1). Our meta-analysis showed that PD-1/PDL-1 was a marker of poor survival, regardless of the assessment method (PD-1 overall survival (OS): hazard ratio (HR) 2.40; 95% confidence interval (CI), 1.30–4.42; disease-free survival (DFS): HR 2.12; 95% CI, 1.45–3.10; PDL-1: OS: HR 3.61; 95% CI, 2.75–4.75; and DFS: HR 2.74; 95% CI, 2.09–3.59). Additionally, high level of PD-1/PDL-1 expression was associated with aging, multiple tumors, high alpha-fetoprotein levels, and advanced Barcelona Clinic Liver Cancer stage. This high level significantly predicted a poor prognosis for HCC, suggesting that anti-PD-1 therapy is plausible for patients with HCC. Furthermore, HIF-1 induces PD-1 expression, and PD1lowSOCS3high is associated with a better prognosis. Taken together, combination therapy may be the key to effective immunotherapy. Thus, exploring other markers, such as HIF-1 and SOCS3, along with PD-1/PDL-1 immunotherapy, may lead to improved outcomes.
Galectin-1: A Traditionally Immunosuppressive Protein Displays Context-Dependent Capacities
Authors: Yu Xizhi , Qian Junjie , Ding Limin , Yin Shengyong , Zhou Lin , Zheng Shusen
Published: March 2023

Galectin–Carbohydrate interactions are indispensable to pathogen recognition and immune response. Galectin-1, a ubiquitously expressed 14-kDa protein with an evolutionarily conserved β-galactoside binding site, translates glycoconjugate recognition into function. That galectin-1 is demonstrated to induce T cell apoptosis has led to substantial attention to the immunosuppressive properties of this protein, such as inducing naive immune cells to suppressive phenotypes, promoting recruitment of immunosuppressing cells as well as impairing functions of cytotoxic leukocytes. However, only in recent years have studies shown that galectin-1 appears to perform a pro-inflammatory role in certain diseases. In this review, we describe the anti-inflammatory function of galectin-1 and its possible mechanisms and summarize the existing therapies and preclinical efficacy relating to these agents. In the meantime, we also discuss the potential causal factors by which galectin-1 promotes the progression of inflammation.
Combined lncRNA and mRNA Expression Profiles Identified the lncRNA–miRNA–mRNA Modules Regulating the Cold Stress Response in Ammopiptanthus nanus
Authors: Zhu Ming , Dong Qianshi , Bing Jie , Songbuerbatu  , Zheng Lamei , Dorjee Tashi , Liu Qi , Zhou Yijun , Gao Fei
Published: March 2023

Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in plants. Ammopiptanthus nanus can survive under severe low-temperature stress, and lncRNAs may play crucial roles in the gene regulation network underlying the cold stress response in A. nanus. To investigate the roles of lncRNAs in the cold stress response of A. nanus, a combined lncRNA and mRNA expression profiling under cold stress was conducted. Up to 4890 novel lncRNAs were identified in A. nanus and 1322 of them were differentially expressed under cold stress, including 543 up-regulated and 779 down-regulated lncRNAs. A total of 421 lncRNAs were found to participate in the cold stress response by forming lncRNA–mRNA modules and regulating the genes encoding the stress-related transcription factors and enzymes in a cis-acting manner. We found that 31 lncRNAs acting as miRNA precursors and 8 lncRNAs acting as endogenous competitive targets of miRNAs participated in the cold stress response by forming lncRNA–miRNA–mRNA regulatory modules. In particular, a cold stress-responsive lncRNA, TCONS00065739, which was experimentally proven to be an endogenous competitive target of miR530, contributed to the cold stress adaptation by regulating TZP in A. nanus. These results provide new data for understanding the biological roles of lncRNAs in response to cold stress in plants.
Biofilm-Based Biocatalysis for Galactooligosaccharides Production by the Surface Display of β-Galactosidase in Pichia pastoris
Authors: Chen Tianpeng , Wang Shimeng , Niu Huanqing , Yang Guanjia , Wang Sinan , Wang Yuqi , Zhou Chaowei , Yu Bin , Yang Pengpeng , Sun Wenjun , Liu Dong , Ying Hanjie , Chen Yong
Published: March 2023

Galactooligosaccharides (GOS) are one of the most important functional oligosaccharide prebiotics. The surface display of enzymes was considered one of the most excellent strategies to obtain these products. However, a rough industrial environment would affect the biocatalytic process. The catalytic process could be efficiently improved using biofilm-based fermentation with high resistance and activity. Therefore, the combination of the surface display of β-galactosidase and biofilm formation in Pichia pastoris was constructed. The results showed that the catalytic conversion rate of GOS was up to 50.3% with the maximum enzyme activity of 5125 U/g by screening the anchorin, and the number of the continuous catalysis batches was up to 23 times. Thus, surface display based on biofilm-immobilized fermentation integrated catalysis and growth was a co-culture system, such that a dynamic equilibrium in the consolidated integrative process was achieved. This study provides the basis for developing biofilm-based surface display methods in P. pastoris during biochemical production processes.
Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology
Authors: Luo Simin , Zhang Xuan , Xiao Xiang , Luo Wenting , Yang Zixuan , Tang Songqi , Huang Wei
Published: March 2023

Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein–protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein–protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.
Development of Highly Efficient Resistance to Beet Curly Top Iran Virus (Becurtovirus) in Sugar Beet (B. vulgaris) via CRISPR/Cas9 System
Authors: Yıldırım Kubilay , Kavas Musa , Küçük İlkay Sevgen , Seçgin Zafer , Saraç Çiğdem Gökcek
Published: March 2023

Beet Curly Top Iran Virus (BCTIV, Becurtovirus) is a dominant and widespread pathogen responsible for great damage and yield reduction in sugar beet production in the Mediterranean and Middle East. CRISPR-based gene editing is a versatile tool that has been successfully used in plants to improve resistance against many viral pathogens. In this study, the efficiency of gRNA/Cas9 constructs targeting the expressed genes of BCTIV was assessed in sugar beet leaves by their transient expression. Almost all positive control sugar beets revealed systemic infection and severe disease symptoms (90%), with a great biomass reduction (68%) after BCTIV agroinoculation. On the other hand, sugar beets co-agronioculated with BCTIV and gRNA/Cas9 indicated much lower systemic infection (10–55%), disease symptoms and biomass reduction (13–45%). Viral inactivation was also verified by RCA and qPCR assays for gRNA/Cas9 treated sugar beets. PCR-RE digestion and sequencing assays confirmed the gRNA/Cas9-mediated INDEL mutations at the target sites of the BCTIV genome and represented high efficiencies (53–88%), especially for those targeting BCTIV’s movement gene and its overlapping region between capsid and ssDNA regulator genes. A multiplex CRISPR approach was also tested. The most effective four gRNAs targeting all the genes of BCTIV were cloned into a Cas9-containing vector and agroinoculated into virus-infected sugar beet leaves. The results of this multiplex CRISPR system revealed almost complete viral resistance with inhibition of systemic infection and mutant escape. This is the first report of CRSIPR-mediated broad-spectrum resistance against Becurtovirus in sugar beet.
Prognostic Value and Genome Signature of m6A/m5C Regulated Genes in Early-Stage Lung Adenocarcinoma
Authors: Tian Long , Wang Yan , Tian Jie , Song Wenpeng , Li Lu , Che Guowei
Published: March 2023

RNA modifications implicate pathological and prognosis significance in cancer development and progression, of which, m6A and m5C are representative regulators. These RNA modifications could produce effects on the function of other RNA by regulating gene expression. Thus, in this study, we aimed to explore the correlation between m6A/m5C regulators and early-stage lung adenocarcinoma (LUAD). Only the early-stage LUAD samples were included in this investigation, and the RNA-seq dataset of The Cancer Genome Atlas (TCGA) cohort was utilized to evaluate the expression of 37 m6A/m5C regulated genes. Based on the expression level of these 37 genes, early-stage LUAD patients were divided into 2 clusters, which were performed by consensus clustering, and the m6A/m5C subtypes had significantly different prognostic outcomes (p < 0.001). Cluster1, which has a better prognosis, was characterized by the C3 (inflammatory) immune subtype, low immune infiltration, chemokine expression, major histocompatibility complex (MHC) expression, and immune checkpoint molecule expression. Furthermore, compared with cluster1, cluster2 showed a T cell exhaustion state, characterized by a high expression of immune checkpoint genes, and immune cells, such as T cells, CD8+ T cells, cytotoxic lymphocytes, NK cells, and so on. In addition, patients in cluster2 were with high tumor mutational burden (TMB) and numerous significant mutated oncogene and tumor suppressor genes, such as WNT10B, ERBB4, SMARCA4, TP53, and CDKN2A (p < 0.001). A total of 19 genes were mostly related to the prognosis of LUAD and were upregulated in cluster2 (p < 0.05), showing a positive correlation with the mRNA expression of 37 m6A/m5C regulated genes. The predictive risk model was constructed using Cox and LASSO (least absolute shrinkage and selection operator) regression analysis. Finally, a seven-gene m6A/m5C risk model, comprising of METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7, was constructed to stratify the prognosis of early-stage LUAD (p = 0.0049, AUC = 0.791). The high-risk score was associated with a poorer prognosis. This model was also validated using two additional GEO datasets: GSE72094 (p = 0.011, AUC = 0.736) and GSE50081 (p = 0.012, AUC = 0.628). In summary, it was established that the m6A/m5C-regulated genes performed a crosstalk function in the mRNA expression of early-stage LUAD. By interacting with other mRNA genes, m6A/m5C modification disturbs DNA replication and the tumor immune microenvironment (TIME). The seven-gene risk model may be a critical tool for the prognostic assessment of early-stage LUAD.
Tumor Microenvironment in Sporadic Vestibular Schwannoma: A Systematic, Narrative Review
Authors: Cazzador Diego , Astolfi Laura , Daloiso Antonio , Tealdo Giulia , Simoni Edi , Mazzoni Antonio , Zanoletti Elisabetta , Marioni Gino
Published: March 2023

Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.
Targeted Blood Plasma Proteomics and Hemostasis Assessment of Post COVID-19 Patients with Acute Myocardial Infarction
Authors: Kalinskaya Anna , Vorobyeva Daria , Rusakovich George , Maryukhnich Elena , Anisimova Alexandra , Dukhin Oleg , Elizarova Antonina , Ivanova Oxana , Bugrova Anna , Brzhozovskiy Alexander , Kononikhin Alexey , Nikolaev Evgeny , Vasilieva Elena
Published: March 2023

The molecular mechanisms underlying cardiovascular complications after the SARS-CoV-2 infection remain unknown. The goal of our study was to analyze the features of blood coagulation, platelet aggregation, and plasma proteomics in COVID-19 convalescents with AMI. The study included 66 AMI patients and 58 healthy volunteers. The groups were divided according to the anti-N IgG levels (AMI post-COVID (n = 44), AMI control (n = 22), control post-COVID (n = 31), and control (n = 27)). All participants underwent rotational thromboelastometry, thrombodynamics, impedance aggregometry, and blood plasma proteomics analysis. Both AMI groups of patients demonstrated higher values of clot growth rates, thrombus size and density, as well as the elevated levels of components of the complement system, proteins modifying the state of endothelium, acute-phase and procoagulant proteins. In comparison with AMI control, AMI post-COVID patients demonstrated decreased levels of proteins connected to inflammation and hemostasis (lipopolysaccharide-binding protein, C4b-binding protein alpha-chain, plasma protease C1 inhibitor, fibrinogen beta-chain, vitamin K-dependent protein S), and altered correlations between inflammation and fibrinolysis. A new finding is that AMI post-COVID patients opposite the AMI control group, are characterized by a less noticeable growth of acute-phase proteins and hemostatic markers that could be explained by prolonged immune system alteration after COVID-19.
α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain
Authors: Shelukhina Irina , Siniavin Andrei , Kasheverov Igor , Ojomoko Lucy , Tsetlin Victor , Utkin Yuri
Published: March 2023

Nicotinic acetylcholine receptors (nAChRs) present as many different subtypes in the nervous and immune systems, muscles and on the cells of other organs. In the immune system, inflammation is regulated via the vagus nerve through the activation of the non-neuronal α7 nAChR subtype, affecting the production of cytokines. The analgesic properties of α7 nAChR-selective compounds are mostly based on the activation of the cholinergic anti-inflammatory pathway. The molecular mechanism of neuropathic pain relief mediated by the inhibition of α9-containing nAChRs is not fully understood yet, but the role of immune factors in this process is becoming evident. To obtain appropriate drugs, a search of selective agonists, antagonists and modulators of α7- and α9-containing nAChRs is underway. The naturally occurring three-finger snake α-neurotoxins and mammalian Ly6/uPAR proteins, as well as neurotoxic peptides α-conotoxins, are not only sophisticated tools in research on nAChRs but are also considered as potential medicines. In particular, the inhibition of the α9-containing nAChRs by α-conotoxins may be a pathway to alleviate neuropathic pain. nAChRs are involved in the inflammation processes during AIDS and other viral infections; thus they can also be means used in drug design. In this review, we discuss the role of α7- and α9-containing nAChRs in the immune processes and in pain.
Antifungal Activity of 2-Allylphenol Derivatives on the Botrytis cinerea Strain: Assessment of Possible Action Mechanism
Authors: Olea Andres F. , Rubio Julia , Sedan Claudia , Carvajal Denisse , Nuñez Maria , Espinoza Luis , Llovera Ligia , Nuñez Gerard , Taborga Lautaro , Carrasco Héctor
Published: March 2023

Botrytis cinerea is a phytopathogenic fungus that causes serious damage to the agricultural industry by infecting various important crops. 2-allylphenol has been used in China as a fungicide for more than a decade, and it has been shown that is a respiration inhibitor. A series of derivatives of 2-allylphenol were synthesized and their activity against B. cinerea was evaluated by measuring mycelial growth inhibition. Results indicate that small changes in the chemical structure or the addition of substituent groups in the aromatic ring induce important variations in activity. For example, changing the hydroxyl group by methoxy or acetyl groups produces dramatic increases in mycelial growth inhibition, i.e., the IC50 value of 2-allylphenol decreases from 68 to 2 and 1 μg mL−1. In addition, it was found that the most active derivatives induce the inhibition of Bcaox expression in the early stages of B. cinerea conidia germination. This gene is associated with the activation of the alternative oxidase enzyme (AOX), which allows fungus respiration to continue in the presence of respiratory inhibitors. Thus, it seems that 2-allylphenol derivatives can inhibit the normal and alternative respiratory pathway of B. cinerea. Therefore, we believe that these compounds are a very attractive platform for the development of antifungal agents against B. cinerea.
Biofouling and Antifouling: Interactions between Microbes and Larvae of Invertebrates
Authors: Dobretsov Sergey , Rittschof Daniel
Published: March 2023

The biofouling process refers to the undesirable accumulation of micro- and macro-organisms on manufactured surfaces [...]
Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway
Authors: AL-Qabbaa Sarah M. , Qaboli Samaher I. , Alshammari Tahani K. , Alamin Maha A. , Alrajeh Haya M. , Almuthnabi Lama A. , Alotaibi Rana R. , Alonazi Asma S. , Bin Dayel Anfal F. , Alrasheed Nawal M. , Alrasheed Nouf M.
Published: March 2023

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. This study examined the therapeutic effects of sitagliptin, a dipeptidyl peptidase inhibitor, on DN and explored the underlying mechanism. Male Wistar albino rats (n = 12) were intraperitoneally administered a single dose of streptozotocin (30 mg/kg) to induce diabetes. Streptozotocin-treated and untreated rats (n = 12) were further divided into normal control, normal sitagliptin-treated control, diabetic control, and sitagliptin-treated diabetic groups (n = 6 in each). The normal and diabetic control groups received normal saline, whereas the sitagliptin-treated control and diabetic groups received sitagliptin (100 mg/kg, p.o.). We assessed the serum levels of DN and inflammatory biomarkers. Protein tyrosine phosphatase 1 B (PTP1B), phosphorylated Janus kinase 2 (P-JAK2), and phosphorylated signal transducer activator of transcription (P-STAT3) levels in kidney tissues were assessed using Western blotting, and kidney sections were examined histologically. Sitagliptin reduced DN and inflammatory biomarkers and the expression of PTP1B, p-JAK2, and p-STAT3 (p < 0.001) and improved streptozotocin-induced histological changes in the kidney. These results demonstrate that sitagliptin ameliorates inflammation by inhibiting DPP-4 and consequently modulating the PTP1B-related JAK/STAT axis, leading to the alleviation of DN.
Comparative Transcriptomic and Physiological Analyses Reveal Key Factors for Interstocks to Improve Grafted Seedling Growth in Tangor
Authors: Rong Yi , Liao Ling , Li Sichen , Wei Wen , Bi Xiaoyi , Sun Guochao , He Siya , Wang Zhihui
Published: March 2023

Interstock is an important agronomic technique for regulating plant growth and fruit quality, and overcoming the incompatibility between rootstocks and scions; however, the underlying mechanisms remain largely unknown. In this study, the effects and regulatory mechanisms of tangor grafting, with and without interstocks, on the growth and development of scions were analyzed by combining morphology, physiology, anatomy and transcriptomics. Morphological and physiological analyses showed that interstocks (‘Aiyuan 38’ and ‘Daya’) significantly improved the growth of seedlings, effectively enhanced the foliar accumulation of chlorophyll and carotenoids, and increased the thickness of leaf tissues. Using ‘Aiyuan 38’ as the interstock, photosynthetic efficiency and starch content of citrus seedlings improved. Transcriptomics showed that genes related to photosynthesis and photosynthetic antenna proteins were upregulated in interstock-treated seedlings, with significant upregulation of photosystem PSI- and PSII-related genes. In addition, multiple key genes may be involved in plant hormone signaling, starch and sucrose metabolism, and transcriptional regulation. Taken together, these findings provide novel insights into the role of interstocks in regulating and contributing to the growth and development of grafted seedlings, and will further define and deploy candidate genes to explore the mechanisms of rootstock-interstock-scion interactions.