bluuebunny/crossref_metadata_2025 huggingface dataset:
A Pan-Cancer Analysis of IRAK1 Expression and Their Association With Immunotherapy Response
Authors: Liu Mengmeng , Que Yi , Hong Ye , Zhang Lian , Zhang Xing , Zhang Yizhuo
Published: May 2022

IRAK1 is an active kinase which plays a critical role in IL-1/TLR signaling pathway involved in inflammation and innate immune response. Recently, increasing evidence supports a potential role of IRAK1 in cancer progression. However, no immunological pan-cancer analysis of IRAK1 is available. We aimed to explore the prognostic value and the immunological functions of IRAK1. A series of datasets including The Cancer Genome Atlas, GEPIA2, cBioPortal, HPA, TIMER2.0 were performed to explore the oncogenic and immunological roles of IRAK1, including the relationship between IRAK1 and prognosis, genetic mutation, GO and KEGG enrichment pathway analysis, immune state of different tumors, The results showed that IRAK1 levels were upregulated in more than 20 types of cancers compared to the normal tissues. IRAK1 expression was associated with poorer prognosis in different cancer types. For the most frequent DNA alteration of IRAK1 is amplification. And the result of the enrichment analysis suggested that IRAK1 related to immune checkpoint pathway in cancer. IRAK1 inhibitor pacritinib inhibit proliferation and upregulate PD-L1 expression in different cancer cell lines. Moreover, the patients who receiving anti-PD-L1 therapy with low IRAK1 expression had a better prognosis, and the objective response rate to anti-PD-L1 therapy was higher in the low IRAK1 group than in the high IRAK1 group in IMvigor210 cohort. Our study reveals that IRAK1 can function as a prognostic marker in various malignant tumors. And pacritinib upregulated PD-L1 expression in several cancer cell lines, which indicating that IRAK1 can be used as a reliable marker to predict the efficacy of immunotherapy.
SRI-EEG: State-Based Recurrent Imputation for EEG Artifact Correction
Authors: Liu Yimeng , Höllerer Tobias , Sra Misha
Published: May 2022

Electroencephalogram (EEG) signals are often used as an input modality for Brain Computer Interfaces (BCIs). While EEG signals can be beneficial for numerous types of interaction scenarios in the real world, high levels of noise limits their usage to strictly noise-controlled environments such as a research laboratory. Even in a controlled environment, EEG is susceptible to noise, particularly from user motion, making it highly challenging to use EEG, and consequently BCI, as a ubiquitous user interaction modality. In this work, we address the EEG noise/artifact correction problem. Our goal is to detect physiological artifacts in EEG signal and automatically replace the detected artifacts with imputed values to enable robust EEG sensing overall requiring significantly reduced manual effort than is usual. We present a novel EEG state-based imputation model built upon a recurrent neural network, which we call SRI-EEG, and evaluate the proposed method on three publicly available EEG datasets. From quantitative and qualitative comparisons with six conventional and neural network based approaches, we demonstrate that our method achieves comparable performance to the state-of-the-art methods on the EEG artifact correction task.
A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy
Authors: Tong Xiangzhen , Zhang Zizhu , Zhu Jianping , Li Shuji , Qu Shaogang , Qin Bing , Guo Yanwu , Chen Rongqing
Published: May 2022

Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors for epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics. In this study, we hypothesized that AEDs that are used to control acute SE might affect the feasibility for the chronic development of epileptogenesis after SE. Therefore, we sought to compare the epileptogenic effects of SE that are terminated by three AEDs, i.e., diazepam, midazolam, and pentobarbital, which are widely used as first-line anti-SE AEDs. For this purpose, we used a mouse model of SE induced by intraperitoneal (i.p.) injection of lithium chloride (LiCl)-pilocarpine. The pilocarpine-induced SE was terminated with diazepam, midazolam, or pentobarbital. Then we compared short-term and long-term effects of SE with different AED treatments by examining SE-associated mortality and behavioral spontaneous recurrent seizures (SRSs) and by using magnetic resonance imaging (MRI) and immunohistochemistry to evaluate pathological and cellular alterations of mice in the different treatment groups. We found that i.p. injections of diazepam (5 mg/kg), midazolam (10 mg/kg), and pentobarbital (37.5 mg/kg) were able to terminate acute pilocarpine-SE effectively, while pentobarbital treatment showed less neuroprotective action against lethality in the short phase following SE. Long-term evaluation following SE revealed that SE treated with midazolam had resulted in relatively less behavioral SRS, less hippocampal atrophy, and milder neuronal loss and gliosis. Our data revealed an obvious advantage of midazolam vs. diazepam or pentobarbital in protecting the brain from epileptogenesis. Therefore, if midazolam provides as strong action to quench SE as other AEDs in clinics, midazolam should be the first choice of anti-SE AEDs as it provides additional benefits against epileptogenesis.
Quercetin Can Improve Spinal Cord Injury by Regulating the mTOR Signaling Pathway
Authors: Wang Xichen , Fu Yuke , Botchway Benson O. A. , Zhang Yufeng , Zhang Yong , Jin Tian , Liu Xuehong
Published: May 2022

The pathogenesis of spinal cord injury (SCI) is complex. At present, there is no effective treatment for SCI, with most current interventions focused on improving the symptoms. Inflammation, apoptosis, autophagy, and oxidative stress caused by secondary SCI may instigate serious consequences in the event of SCI. The mammalian target of rapamycin (mTOR), as a key signaling molecule, participates in the regulation of inflammation, apoptosis, and autophagy in several processes associated with SCI. Quercetin can reduce the loss of myelin sheath, enhance the ability of antioxidant stress, and promote axonal regeneration. Moreover, quercetin is also a significant player in regulating the mTOR signaling pathway that improves pathological alterations following neuronal injury. Herein, we review the therapeutic effects of quercetin in SCI through its modulation of the mTOR signaling pathway and elaborate on how it can be a potential interventional agent for SCI.
EEG-Based Index for Timely Detecting User’s Drowsiness Occurrence in Automotive Applications
Authors: Di Flumeri Gianluca , Ronca Vincenzo , Giorgi Andrea , Vozzi Alessia , Aricò Pietro , Sciaraffa Nicolina , Zeng Hong , Dai Guojun , Kong Wanzeng , Babiloni Fabio , Borghini Gianluca
Published: May 2022

Human errors are widely considered among the major causes of road accidents. Furthermore, it is estimated that more than 90% of vehicle crashes causing fatal and permanent injuries are directly related to mental tiredness, fatigue, and drowsiness of the drivers. In particular, driving drowsiness is recognized as a crucial aspect in the context of road safety, since drowsy drivers can suddenly lose control of the car. Moreover, the driving drowsiness episodes mostly appear suddenly without any prior behavioral evidence. The present study aimed at characterizing the onset of drowsiness in car drivers by means of a multimodal neurophysiological approach to develop a synthetic electroencephalographic (EEG)-based index, able to detect drowsy events. The study involved 19 participants in a simulated scenario structured in a sequence of driving tasks under different situations and traffic conditions. The experimental conditions were designed to induce prominent mental drowsiness in the final part. The EEG-based index, so-called “MDrow index”, was developed and validated to detect the driving drowsiness of the participants. The MDrow index was derived from the Global Field Power calculated in the Alpha EEG frequency band over the parietal brain sites. The results demonstrated the reliability of the proposed MDrow index in detecting the driving drowsiness experienced by the participants, resulting also more sensitive and timely sensible with respect to more conventional autonomic parameters, such as the EyeBlinks Rate and the Heart Rate Variability, and to subjective measurements (self-reports).
Infra-Low Frequency Neurofeedback in Tension-Type Headache: A Cross-Over Sham-Controlled Study
Authors: Arina Galina A. , Dobrushina Olga R. , Shvetsova Elizaveta T. , Osina Ekaterina D. , Meshkov Georgy A. , Aziatskaya Guzel A. , Trofimova Alexandra K. , Efremova Inga N. , Martunov Sergey E. , Nikolaeva Valentina V.
Published: May 2022

Primary headaches are highly prevalent and represent a major cause of disability in young adults. Neurofeedback is increasingly used in the treatment of chronic pain; however, there are few studies investigating its efficacy in patients with headaches. We report the results of a cross-over sham-controlled study on the efficacy of neurofeedback in the prophylactic treatment of tension-type headache (TTH). Participants received ten sessions of infra-low frequency electroencephalographic neurofeedback and ten sessions of sham-neurofeedback, with the order of treatments being randomized. The study also included a basic psychotherapeutic intervention — a psychoeducational session performed before the main study phases and emotional support provided throughout the study period. The headache probability was modeled as a function of the neurofeedback and sham-neurofeedback sessions performed to date. As a result, we revealed a strong beneficial effect of neurofeedback and no influence of the sham sessions. The study supports the prophylactic use of infra-low frequency neurofeedback in patients with TTH. From a methodological point of view, we advocate for the explicit inclusion of psychotherapeutic components in neurofeedback study protocols.
The Development of Mechanical Allodynia in Diabetic Rats Revealed by Single-Cell RNA-Seq
Authors: Zhou Han , Yang Xiaosheng , Liao Chenlong , Chen Hongjin , Wu Yiwei , Xie Binran , Ma Fukai , Zhang WenChuan
Published: May 2022

Mechanical allodynia (MA) is the main reason that patients with diabetic peripheral neuropathy (DPN) seek medical advice. It severely debilitates the quality of life. Investigating hyperglycemia-induced changes in neural transcription could provide fundamental insights into the complex pathogenesis of painful DPN (PDPN). Gene expression profiles of physiological dorsal root ganglia (DRG) have been studied. However, the transcriptomic changes in DRG neurons in PDPN remain largely unexplored. In this study, by single-cell RNA sequencing on dissociated rat DRG, we identified five physiological neuron types and a novel neuron type MAAC (Fxyd7+/Atp1b1+) in PDPN. The novel neuron type originated from peptidergic neuron cluster and was characterized by highly expressing genes related to neurofilament and cytoskeleton. Based on the inferred gene regulatory networks, we found that activated transcription factors Hobx7 and Larp1 in MAAC could enhance Atp1b1 expression. Moreover, we constructed the cellular communication network of MAAC and revealed its receptor-ligand pairs for transmitting signals with other cells. Our molecular investigation at single-cell resolution advances the understanding of the dynamic peripheral neuron changes and underlying molecular mechanisms during the development of PDPN.
Application of Ultrasound as Clean Technology for Extraction of Specialized Metabolites From Stinging Nettle (Urtica dioica L.)
Authors: Šic Žlabur Jana , Radman Sanja , Opačić Nevena , Rašić Anamaria , Dujmović Mia , Brnčić Mladen , Barba Francisco J. , Castagnini Juan Manuel , Voća Sandra
Published: May 2022

Nettle is a highly valued medicinal plant that is still largely neglected, both in terms of nutrition and use for pharmacological purposes. Tinctures, i.e., alcoholic extracts, are becoming increasingly popular nettle products, mainly because they allow better availability of phytochemicals and their stability over a longer period of time. The production of alcoholic extracts is a chemically demanding process that is still usually carried out using conventional techniques, which have numerous drawbacks. The use of green technologies such as ultrasound-assisted extraction (UAE), which is characterized by high efficiency of phytochemical extraction, shorter treatment time, and a much lower environmental footprint, is a suitable and sustainable solution. Therefore, the aim of this study is to determine the influence of the extraction method, conventional and ultrasound (by varying two ultrasound equipment systems), time and ethanol concentration on the extraction of specialized metabolites from nettle powder. Ultrasonic extraction using a probe system significantly contributed to increase the ascorbic acid yield, polyphenolic compounds, and antioxidant capacity of nettle extracts compared to conventional extraction. In addition, when a probe system was used during UAE, significantly less time was required for isolation of individual specialized metabolites compared to ultrasonic extraction in the bath. Ethanol concentration (50 and 80% v/v) also proved to be an important factor in the efficiency of extraction of specialized metabolites, with 80% ethanol being more effective for the isolation of ascorbic acid and pigment compounds (chlorophyll and carotenoids), while 50% v/v for the extraction of polyphenolic compounds. It can be concluded that extraction with the ultrasonic probe system is much more efficient in obtaining higher yields of specialized metabolites from nettle powder in a shorter time (average process duration 5–10 min) both compared to UAE in the bath and classical extraction. However, optimization of the key factors of time, solvent type, and ultrasonic power is necessary to maintain the nutritional quality of the nettle extract in order to obtain a final product with a high specialized metabolites content, antioxidant capacity, and functional value. The future application of alcoholic nettle extracts is based on the fact that these products have significant potential as functional foods and pharmacological preparations for the treatment of a number of but also to strengthen the immune system, mainly due to the rich nutritional composition and high content of various specialized metabolites. The prepared extracts can be safely taken orally by diluting the tinctures with water immediately before ingestion.
Development of Nutrition Literacy Scale for Middle School Students in Chongqing, China: A Cross-Sectional Study
Authors: Wang Tiankun , Zeng Mao , Xie Changxiao , Zhu Yuzhao , Shi Zumin , Sharma Manoj , Zhao Yong
Published: May 2022

Background

Information on nutrition literacy of middle schoolers is limited and tools for measuring nutrition literacy of middle schoolers are inadequate. Nutrition literacy has a positive effect on health. Improving children's nutrition literacy can help them to master the necessary nutritional knowledge, develop a healthy lifestyle, and learn to supplement nutrition according to their own needs for healthy growth.

Objectives

To develop the Chongqing Middle school student Nutrition Literacy Scale (CM-NLS).

Methods

Three experiments were conducted. A theoretical framework and an initial item pool of CM-NLS were established based on the literature review. And the two-round Delphi method was used to explore the suitable acceptance indicators and items. Item evaluation and reduction were performed using the classical test theory. Then, the items in the final CM-NLS were tested for their validity and reliability amongst 462 middle school students. The construct validity was assessed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The internal consistency reliability and split-half reliability were evaluated using Cronbach's alpha coefficients.

Results

The final CM-NLS consisting of 52 items that were based on three primary items (functional, interactive and critical) and six sub-items (obtain, understand, apply, interact, medial literacy and critical skill) was developed and validated. EFA suggested six factors explaining 69.44% of the total variance (Kaiser–Meyer–Olkin test = 0.916, Bartlett's test χ2 = 5,854.037, P < 0.001). CFA showed that the model fit the data adequately, with χ2/df = 1.911, root mean square error of approximation = 0.063, goodness-of-fit index = 0.822 and adjusted goodness of fit index = 0.790. The total CM-NLS Cronbach's alpha values of internal consistency and split-half reliability were 0.849 and 0.521, respectively, with reasonable reliability.

Conclusions

CM-NLS is a valid and reliable instrument for assessing nutrition literacy among middle school students in Chongqing. Specifically, it could be used by practitioners for needs assessment before the implementation of a nutrition education program.
Lumiflavin Reduces Cisplatin Resistance in Cancer Stem-Like Cells of OVCAR-3 Cell Line by Inducing Differentiation
Authors: Yang Ruhui , Liu Bingjin , Yang Mingyue , Xu Feng , Wu Songquan , Zhao Shufang
Published: May 2022

Ovarian cancer stem-like cells (CSCs) play a vital role in drug resistance and recurrence of ovarian cancer. Inducing phenotypic differentiation is an important strategy to enhance the effects of chemotherapy and reduce the drug resistance of CSCs. This study found that lumiflavin, a riboflavin decomposition product, reduced the development of CSC resistance and enhanced the chemotherapy effect of cisplatin (DDP) on CSCs in DDP-resistant ovarian cancer OVCAR-3 cell line (CSCs/DDP) and was related to the induction of CSC phenotypic differentiation. Results showed that the development of DDP-resistant OVCAR-3 cells was related to the increase in the proportion of CSCs/DDP, and the treatment with lumiflavin reduced the DDP-resistance levels of OVCAR-3 cells and proportion of CSCs/DDP. Further investigation found that lumiflavin synergistic with DDP increased apoptosis, decreased mitochondrial membrane potential, and inhibited the clonal formation of CSCs/DDP. Meanwhile, in vivo experiments showed that lumiflavin dose-dependently enhanced the chemotherapy effect of DDP on tumor-bearing nude mice inoculated by CSCs/DDP. Lumiflavin treatment also reduced the ratio of CD133+/CD177+ to CD44+/CD24 cells, which is the identification of CSCs, in CSCs/DDP. In addition, transcriptome sequencing results suggested that the role of lumiflavin was related to the notch and stem cell pathway, and Western blot analysis showed that lumiflavin inhibited the protein expression of notch signaling pathway in CSCs/DDP. In conclusion, lumiflavin reduces the development of the drug resistance of OVCAR-3 cell and increases the sensitivity of CSCs/DDP to DDP by inducing phenotypic differentiation, which may have a potential role in the chemotherapy treatment of ovarian cancer.
Identification of the Putative Tumor Suppressor Characteristics of FAM107A via Pan-Cancer Analysis
Authors: Ou Dehua , Zhang Zhiqin , Wu Zesong , Shen Peilin , Huang Yichuan , She Sile , She Sifan , Lin Ming-en
Published: May 2022

Family with sequence similarity 107, member A(FAM107A) was supposed as a tumor suppressor for various types of tumors. However, no pan-cancer analysis of FAM107A is available. Therefore, we conducted a FAM107A-related pan-cancer analysis across thirty-three tumors based on TCGA database to explore the molecular characteristics of FAM107A. The FAM107A expression is reduced in most cancers, and its down-regulated expression was linked to poor overall survival and progression-free survival of tumor patients. Analysis of DNA methylation of the FAM107A gene showed a negative correlation between FAM107A expression and promoter methylation in numerous cancers. Furthermore, FAM107A expression was noted to be involved in myeloid-derived suppressor cell infiltration in multiple cancers. To explore the mechanism of FAM107A in cancers, KEGG, and GO enrichment analysis was performed and the result showed “cell adhesion” and “cAMP signaling pathway” terms as the potential impact of FAM107A on cancers. An experiment in vitro showed FAM107A knockdown promoted the proliferation, migration, and invasion of bladder cancer and renal cancer cells. Our study indicates that FAM107A may be a putative tumor suppressor in bladder cancer and other tumors.
Effect of CRISPR Knockout of AXIN1 or ARID1A on Proliferation and Migration of Porcine Hepatocellular Carcinoma
Authors: Elkhadragy Lobna , Dasteh Goli Kimia , Totura William M. , Carlino Maximillian J. , Regan Maureen R. , Guzman Grace , Schook Lawrence B. , Gaba Ron C. , Schachtschneider Kyle M.
Published: May 2022

Hepatocellular carcinoma (HCC) is an aggressive disease lacking effective treatment. Animal models of HCC are necessary for preclinical evaluation of the safety and efficacy of novel therapeutics. Large animal models of HCC allow testing image-guided locoregional therapies, which are widely used in the management of HCC. Models with precise tumor mutations mimicking human HCC provide valuable tools for testing precision medicine. AXIN1 and ARID1A are two of the most frequently mutated genes in human HCC. Here, we investigated the effects of knockout of AXIN1 and/or ARID1A on proliferation, migration, and chemotherapeutic susceptibility of porcine HCC cells and we developed subcutaneous tumors harboring these mutations in pigs. Gene knockout was achieved by CRISPR/Cas9 and was validated by Next Generation Sequencing. AXIN1 knockout increased the migration of porcine HCC cells but did not alter the cell proliferation. Knockout of ARID1A increased both the proliferation and migration of porcine HCC cells. Simultaneous knockout of AXIN1 and ARID1A increased the migration, but did not alter the proliferation of porcine HCC cells. The effect of gene knockout on the response of porcine HCC cells to two of the most commonly used systemic and locoregional HCC treatments was investigated; sorafenib and doxorubicin, respectively. Knockout of AXIN1 and/or ARID1A did not alter the susceptibility of porcine HCC cells to sorafenib or doxorubicin. Autologous injection of CRISPR edited HCC cells resulted in development of subcutaneous tumors in pigs, which harbored the anticipated edits in AXIN1 and/or ARID1A. This study elucidates the effects of CRISPR-mediated knockout of HCC-associated genes in porcine HCC cells, and lays the foundation for development and utilization of genetically-tailored porcine HCC models for in vivo testing of novel therapeutic approaches in a clinically-relevant large animal model.
The Metabolic and Non-Metabolic Roles of UCK2 in Tumor Progression
Authors: Fu Yi , Wei Xin-dong , Guo Luoting , Wu Kai , Le Jiamei , Ma Yujie , Kong Xiaoni , Tong Ying , Wu Hailong
Published: May 2022

Enhanced nucleoside metabolism is one of the hallmarks of cancer. Uridine-cytidine kinase 2 (UCK2) is a rate-limiting enzyme of the pyrimidine salvage synthesis pathway to phosphorylate uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP), respectively. Recent studies have shown that UCK2 is overexpressed in many types of solid and hematopoietic cancers, closely associates with poor prognosis, and promotes cell proliferation and migration in lung cancer and HCCs. Although UCK2 is thought to catalyze sufficient nucleotide building blocks to support the rapid proliferation of tumor cells, we and other groups have recently demonstrated that UCK2 may play a tumor-promoting role in a catalytic independent manner by activating oncogenic signaling pathways, such as STAT3 and EGFR-AKT. By harnessing the catalytic activity of UCK2, several cytotoxic ribonucleoside analogs, such as TAS-106 and RX-3117, have been developed for UCK2-mediated cancer chemotherapy. Moreover, we have demonstrated that the concurrent targeting of the catalytic dependent and independent features of UCK2 could synergistically inhibit tumor growth. These findings suggest that UCK2 may serve as a potential therapeutic target for cancer treatment. In this mini-review, we introduced the genomic localization and protein structure of UCK2, described the role of UCK2 in tumor development, discussed the application of UCK2 in anti-tumor treatment, and proposed concurrent targeting of the catalytic and non-catalytic roles of UCK2 as a potential therapeutic strategy for cancer treatment.
Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)
Authors: Pompella Alfonso , Corti Alessandro , Visvikis Athanase
Published: May 2022

Cisplatin (CDDP) is currently employed for the treatment of several solid tumors, but cellular heterogeneity and the onset of drug resistance dictate that suitable biomarkers of CDDP sensitivity are established. Studies on triple-negative breast cancer (TNBC) have recently confirmed the involvement of gamma-glutamyltransferase 1 (GGT1), whose enzyme activity expressed at the cell surface favors the cellular resupply of antioxidant glutathione (GSH) thus offering cancer cells protection against the prooxidant effects of CDDP. However, an additional well-established mechanism depends on GGT1-mediated matabolism of extracellular GSH. It was in fact shown that glycyl-cysteine – the dipeptide originated by GGT1-mediated GSH metabolism at the cell surface – can promptly form adducts with exogenous CDDP, thus hindering its access to the cell, interactions with DNA and overall cytotoxicity. Both mechanisms: mainainance of intracellular GSH levels plus extracellular CDDP detoxication are likely concurring to determine GGT1-dependent CDDP resistance.
Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease
Authors: Elngar Enas F. , Azzam Mona A. , Gobarah Ayman A. , Toraih Eman A. , Fawzy Manal S. , AbdAllah Nouran B.
Published: May 2022

Background

Neonatal lung disease has a multifaceted etiopathology, including an explosive inflammatory sequence in the immature lung. Complement component 1 Esterase INHibitor (C1INH) is implicated in controlling inflammation in response to infection/injury.

Aim

To explore for the first time the association of the C1INH rs4926 (Val480Met) variant and circulatory transcript expression levels in the neonates that had evidence of lung disease and the clinic-laboratory data.

Methods

A total of 139 unrelated neonates were enrolled in this case-control study. C1INH genotyping and expression analyses were done using TaqMan Genotyping and Real-Time qPCR, respectively.

Results

A/A genotype carriers were two times more likely to develop in newborns with lung disease under homozygote (A/A vs. G/G: OR = 2.66, 95%CI = 1.03-6.87, p = 0.039) and recessive (A/A vs. G/G-A/G: OR = 2.42, 95%CI = 1.07-6.06, p = 0.047) models. Also, a higher frequency of A/A genotype was observed in the patient's cohort complicated with sepsis (44.2 vs. 14.3%, p = 0.002). Neonates with lung disease with A variant had more risk for developing sepsis under homozygote (A/A vs. G/G: OR = 5.19, 95%CI = 1.73-15.6, p = 0.002), dominant (A/G-A/A vs. G/G: OR = 2.39, 95%CI = 1.02-5.58, p = 0.041), and recessive (A/A vs. G/G-A/G: OR = 5.38, 95%CI = 1.86-15.5, p < 0.001) models. Regression analysis revealed rs4926*A/A genotype as an independent predictor risk factor for sepsis development in cohorts with lung disease (adjusted OR = 4.26, 95%CI = 1.38-13.1, p = 0.012). The circulatory transcript was significantly downregulated in neonates with lung disease in whom rs4926*A/A carriers had the least expression levels (median: −2.86, IQR: −3.55 to −1.71; p < 0.001). ROC curve analysis revealed C1INH expression could differentiate between cohorts with/without subsequent development of sepsis, and the discrimination ability was enhanced when combined with circulatory IL-6 and CRP levels (AUC = 0.926, 95%CI = 0.87-0.97).

Conclusion

The C1INH rs4926 variant might play an essential role in the susceptibility to neonatal lung disease and could predict sepsis development in this cohort. Furthermore, the circulatory expression levels of this gene were downregulated in the neonatal lung disease cohort, supporting its potential role in the pathophysiology of this disorder, and highlighting its promising role in future targeted therapy.
The Sedative Effects of Inhaled Nebulized Dexmedetomidine on Children: A Systematic Review and Meta-Analysis
Authors: Lin Jun , Wu Chujun , Zhao Dizhou , Du Xuhang , Zhang Wangzhi , Fang Jieyu
Published: May 2022

Background

Children that need surgery and medical examinations are often uncooperative, and preoperative sedation is necessary. We aimed to assess the safety and efficacy of inhaled nebulized dexmedetomidine in children for sedation that underwent medical examinations or surgery.

Methods

We systematically searched PubMed, Web of science, Embase, and Cochrane library, for randomized controlled trials of Intranasal dexmedetomidine using a spray or a mucosal atomization device in children undergoing examination or elective surgery. We included all studies that analyzed the sedation efficiency of intranasal dexmedetomidine in children.

Results

Ten studies with 1,233pediatric patients were included. Compared to other sedation treatments, inhaled nebulized dexmedetomidine showed similar sedation satisfaction [risk ratio RR: 1.02; 95% confidence interval (CI): 0.87–1.18; P = 0.83; I2 = 72%]. there was also no statistical difference in the success rate of separation from parents (RR: 0.96; 95% CI: 0.82–1.12; P = 0.58; I2 = 67%), and mask acceptability (RR: 1; 95% CI: 0.83–1.20; P = 0.99; I2 = 35%). But it is worth mentioning that nebulized dexmedetomidine combined with ketamine provided better sedation satisfaction (RR: 0.69; 95% CI: 0.49–0.96; I2 = 49%) and more satisfactory separation from parents (RR: 0.85; 95% CI: 0.74–0.97; I2 = 0%). Moreover, nebulized dexmedetomidine reduced the occurrences of nausea and vomiting (RR: 0.28; 95% CI: 0.15–0.51; P < 0.01; I2 = 10%) and emergence agitation (RR: 0.30; 95% CI: 0.18–0.49; P < 0.01; I2 = 0%). There are no hypotension or arrhythmia reported that required intervention in all articles.

Conclusion

Compared to other premedication treatments, inhaled nebulized dexmedetomidine provided equivalent sedation satisfaction for the examination or preoperative sedation of children, but it reduced the occurrences of emergence agitation and postoperative nausea and vomiting.
A Systematic Review and Meta-Analysis of Phytoestrogen Protects Against Myocardial Ischemia/Reperfusion Injury: Pre-Clinical Evidence From Small Animal Studies
Authors: Wang Yumeng , Shou Xintian , Fan Zongjing , Cui Jie , Xue Donghua , Wu Yang
Published: May 2022

Background: Phytoestrogens are a class of natural compounds that have structural similarities to estrogens. They have been identified to confer potent cardioprotective effects in experimental myocardial ischemia-reperfusion injury (MIRI) animal models. We aimed to investigate the effect of PE on MIRI and its intrinsic mechanisms.

Methods: A systematic search was conducted to identify PEs that have been validated in animal studies or clinical studies as effective against MIRI. Then, we collected studies that met inclusion and exclusion criteria from January 2016 to September 2021. The SYRCLE’s RoB tool was used to evaluate the quality. Data were analyzed by STATA 16.0 software.

Results: The search yielded 18 phytoestrogens effective against heart disease. They are genistein, quercetin, biochanin A, formononetin, daidzein, kaempferol, icariin, puerarin, rutin, notoginsenoside R1, tanshinone IIA, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rg1, ginsenoside Re, resveratrol, polydatin, and bakuchiol. Then, a total of 20 studies from 17 articles with a total of 355 animals were included in this meta-analysis. The results show that PE significantly reduced the myocardial infarct size in MIRI animals compared with the control group (p < 0.001). PE treatment significantly reduced the creatine kinase level (p < 0.001) and cTnI level (p < 0.001), increased left ventricular ejection fraction (p < 0.001) and left ventricular fractional shortening (p < 0.001) in MIRI animals. In addition, PE also exerts a significant heart rate lowering effect (p < 0.001).

Conclusion: Preclinical evidence suggests that PE can be multi-targeted for cardioprotective effects in MIRI. More large animal studies and clinical research are still needed in the future to further confirm its role in MIRI.
Proteomic Study on the Reproductive Toxicity of Tripterygium Glycosides in Rats
Authors: Dai Yanlin , Sun Lihui , Han Shanshan , Xu Shanshan , Wang Long , Ding Ying
Published: May 2022

Tripterygium glycoside tablet (TGT) is a common clinically used and effective non-steroidal immunosuppressant. However, its reproductive toxicity limits its application in pediatric immune diseases, warranting the study of the molecular mechanism behind its reproductive toxicity. In the present study, 4-week-old male Sprague Dawley (SD) rats were provided TGT through continuous gavage with a clinically equivalent dose of 12 mg/kg for 12 weeks. The reproductive toxicity of TGT was recorded, and its toxicity mechanism was verified through experimental validation and proteomics analyses. Our results demonstrated that TGT could significantly reduce the testosterone level in the serum as well as the concentration and survival rate of sperms. Pathological sections of the testis revealed that TGT could reduce spermatocytes at different levels and make the convoluted meridians vacuolated. Based on tandem mass tag (TMT)-labeled quantitative rats testicular tissue proteomics, 34 differential proteins were screened, involving protein digestion and absorption, PPAR signaling pathway, PI3K-Akt, and other pathways, among which PI3K-Akt plays an important role in the study of reproductive injury. Western blotting results revealed that TGT could significantly downregulate the Col1A1, Col1A2, p-PI3K, and p-Akt expressions and inhibit the expression of proteins related to the PI3K-Akt signaling pathway. In summary, the clinically equivalent dose of TGT induced reproductive toxicity of 4-week-old male SD rats, possibly in relation to the inhibition of the PI3K-Akt pathway expression.
Concurrent Training Promotes Greater Gains on Body Composition and Components of Physical Fitness Than Single-Mode Training (Endurance or Resistance) in Youth With Obesity
Authors: Bouamra Marwa , Zouhal Hassane , Ratel Sébastien , Makhlouf Issam , Bezrati Ikram , Chtara Mokhtar , Behm David G. , Granacher Urs , Chaouachi Anis
Published: May 2022

The prevalence of obesity in the pediatric population has become a major public health issue. Indeed, the dramatic increase of this epidemic causes multiple and harmful consequences, Physical activity, particularly physical exercise, remains to be the cornerstone of interventions against childhood obesity. Given the conflicting findings with reference to the relevant literature addressing the effects of exercise on adiposity and physical fitness outcomes in obese children and adolescents, the effect of duration-matched concurrent training (CT) [50% resistance (RT) and 50% high-intensity-interval-training (HIIT)] on body composition and physical fitness in obese youth remains to be elucidated. Thus, the purpose of this study was to examine the effects of 9-weeks of CT compared to RT or HIIT alone, on body composition and selected physical fitness components in healthy sedentary obese youth. Out of 73 participants, only 37; [14 males and 23 females; age 13.4 ± 0.9 years; body-mass-index (BMI): 31.2 ± 4.8 kg·m-2] were eligible and randomized into three groups: HIIT (n = 12): 3-4 sets×12 runs at 80–110% peak velocity, with 10-s passive recovery between bouts; RT (n = 12): 6 exercises; 3–4 sets × 10 repetition maximum (RM) and CT (n = 13): 50% serial completion of RT and HIIT. CT promoted significant greater gains compared to HIIT and RT on body composition (p < 0.01, d = large), 6-min-walking test distance (6 MWT-distance) and on 6 MWT-VO2max (p < 0.03, d = large). In addition, CT showed substantially greater improvements than HIIT in the medicine ball throw test (20.2 vs. 13.6%, p < 0.04, d = large). On the other hand, RT exhibited significantly greater gains in relative hand grip strength (p < 0.03, d = large) and CMJ (p < 0.01, d = large) than HIIT and CT. CT promoted greater benefits for fat, body mass loss and cardiorespiratory fitness than HIIT or RT modalities. This study provides important information for practitioners and therapists on the application of effective exercise regimes with obese youth to induce significant and beneficial body composition changes. The applied CT program and the respective programming parameters in terms of exercise intensity and volume can be used by practitioners as an effective exercise treatment to fight the pandemic overweight and obesity in youth.
TWIK-Related Acid-Sensitive Potassium Channels (TASK-1) Emerge as Contributors to Tone Regulation in Renal Arteries at Alkaline pH
Authors: Shvetsova Anastasia A. , Lazarenko Varvara S. , Gaynullina Dina K. , Tarasova Olga S. , Schubert Rudolf
Published: May 2022

Aim: TASK-1 channels are established regulators of pulmonary artery tone but their contribution to the regulation of vascular tone in systemic arteries is poorly understood. We tested the hypothesis that TASK-1 channel functional impact differs among systemic vascular beds, that this is associated with differences in their expression and may increase with alkalization of the extracellular environment. Therefore, we evaluated the expression level of TASK-1 channels and their vasomotor role in mesenteric and renal arteries.

Methods: Pulmonary, mesenteric and renal arteries from male Wistar rats were used for TASK-1 channel mRNA (qPCR) and protein content (Western blotting) measurements. The functional role of TASK-1 channels was studied by wire myography using the TASK-1 channel blocker AVE1231. In some experiments, the endothelium was removed with a rat whisker.

Results: Expression levels of both mRNA and protein of the TASK-1 channel pore-forming subunit were highest in pulmonary arteries, lowest in mesenteric arteries and had an intermediate value in renal arteries. Blockade of TASK-1 channels by 1 µM AVE1231 increased U46619-induced contractile responses of pulmonary arteries but did not affect basal tone and contractile responses to methoxamine of mesenteric and renal arteries at physiological extracellular pH (pHo = 7.41). At alkaline extracellular pH = 7.75 (increase of NaHCO3 to 52 mM) AVE1231 evoked the development of basal tone and increased contractile responses to low concentrations of methoxamine in renal but not mesenteric arteries. This effect was independent of the endothelium.

Conclusion: In the rat systemic circulation, TASK-1 channels are abundant in renal arteries and have an anticontractile function under conditions of extracellular alkalosis.
A Perspective on Plant Phenomics: Coupling Deep Learning and Near-Infrared Spectroscopy
Authors: Vasseur François , Cornet Denis , Beurier Grégory , Messier Julie , Rouan Lauriane , Bresson Justine , Ecarnot Martin , Stahl Mark , Heumos Simon , Gérard Marianne , Reijnen Hans , Tillard Pascal , Lacombe Benoît , Emanuel Amélie , Floret Justine , Estarague Aurélien , Przybylska Stefania , Sartori Kevin , Gillespie Lauren M. , Baron Etienne , Kazakou Elena , Vile Denis , Violle Cyrille
Published: May 2022

The trait-based approach in plant ecology aims at understanding and classifying the diversity of ecological strategies by comparing plant morphology and physiology across organisms. The major drawback of the approach is that the time and financial cost of measuring the traits on many individuals and environments can be prohibitive. We show that combining near-infrared spectroscopy (NIRS) with deep learning resolves this limitation by quickly, non-destructively, and accurately measuring a suite of traits, including plant morphology, chemistry, and metabolism. Such an approach also allows to position plants within the well-known CSR triangle that depicts the diversity of plant ecological strategies. The processing of NIRS through deep learning identifies the effect of growth conditions on trait values, an issue that plagues traditional statistical approaches. Together, the coupling of NIRS and deep learning is a promising high-throughput approach to capture a range of ecological information on plant diversity and functioning and can accelerate the creation of extensive trait databases.
Invasion History of the Pinewood Nematode Bursaphelenchus xylophilus Influences the Abundance of Serratia sp. in Pupal Chambers and Tracheae of Insect-Vector Monochamus alternatus
Authors: Tian Haokai , Koski Tuuli-Marjaana , Zhao Lilin , Liu Ziying , Sun Jianghua
Published: May 2022

Pine wilt disease (PWD) has caused extensive mortality in pine forests worldwide. This disease is a result of a multi-species interaction among an invasive pinewood nematode (PWN) Bursaphelenchus xylophilus, its vector Monochamus sp. beetle, and the host pine tree (Pinus sp.). In other systems, microbes have been shown to attenuate negative impacts on invasive species after the invasion has reached a certain time point. Despite that the role of PWD associated microbes involved in the PWD system has been widely studied, it is not known whether similar antagonistic “hidden microbial players” exist in this system due to the lack of knowledge about the potential temporal changes in the composition of associated microbiota. In this study, we investigated the bacteria-to-fungi ratio and isolated culturable bacterial isolates from pupal chambers and vector beetle tracheae across five sampling sites in China differing in the duration of PWN invasion. We also tested the pathogenicity of two candidate bacteria strains against the PWN-vector beetle complex. A total of 118 bacterial species belonging to 4 phyla, 30 families, and 54 genera were classified based on 16S sequencing. The relative abundance of the genus Serratia was lower in pupal chambers and tracheae in newly PWN invaded sites (<10 years) compared to the sites that had been invaded for more than 20 years. Serratia marcescens strain AHPC29 was widely distributed across all sites and showed nematicidal activity against PWN. The insecticidal activity of this strain was dependent on the life stage of the vector beetle Monochamus alternatus: no insecticidal activity was observed against final-instar larvae, whereas S. marcescens was highly virulent against pupae. Our findings improved the understanding of the temporal variation in the microbial community associated with the PWN-vector beetle complex and the progress of PWD and can therefore facilitate the development of biological control agents against PWN and its vector beetle.
Combating Salinity Through Natural Plant Extracts Based Biostimulants: A Review
Authors: Ahmad Ali , Blasco Begoña , Martos Vanessa
Published: May 2022

Enhanced crop growth and yield are the recurring concerns in agricultural field, considering the soaring world population and climate change. Abiotic stresses are one of the major limiting factors for constraining crop production, for several economically important horticultural crops, and contribute to almost 70% of yield gap. Salt stress is one of these unsought abiotic stresses that has become a consistent problem in agriculture over the past few years. Salinity further induces ionic, osmotic, and oxidative stress that result in various metabolic perturbations (including the generation of reactive oxygen, carbonyl, and nitrogen species), reduction in water potential (ψw), distorted membrane potential, membrane injury, altered rates of photosynthesis, leaf senescence, and reduced nitrogen assimilation, among others); thereby provoking a drastic reduction in crop growth and yield. One of the strategies to mitigate salt stress is the use of natural plant extracts (PEs) instead of chemical fertilizers, thus limiting water, soil, and environmental pollution. PEs mainly consist of seeds, roots, shoots, fruits, flowers, and leaves concentrates employed either individually or in mixtures. Since PEs are usually rich in bioactive compounds (e.g., carotenoids, flavonoids, phenolics, etc.), therefore they are effective in regulating redox metabolism, thereby promoting plant growth and yield. However, various factors like plant growth stage, doses applied, application method, soil, and environmental conditions may greatly influence their impact on plants. PEs have been reported to enhance salt tolerance in plants primarily through modulation of signaling signatures and pathways (e.g., Na+, ANNA4, GIPC, SOS3, and SCaBP8 Ca2+ sensors, etc.), and regulation of redox machinery [e.g., superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), non-specific peroxidase (POX), glutathione peroxidase (GPX), peroxiredoxin (Prx), ascorbic acid (AsA), glutathione (GSH), α-tocopherol, etc.]. The current study highlights the role of PEs in terms of their sources, methods of preparation, and mode of action with subsequent physiological changes induced in plants against salinity. However, an explicit mode of action of PEs remains nebulous, which might be explicated utilizing transcriptomics, proteomics, metabolomics, and bioinformatics approaches. Being ecological and economical, PEs might pave the way for ensuring the food security in this challenging era of climate change.
Cotton miR319b-Targeted TCP4-Like Enhances Plant Defense Against Verticillium dahliae by Activating GhICS1 Transcription Expression
Authors: Jia Pei , Tang Ye , Hu Guang , Quan Yonggang , Chen Aimin , Zhong Naiqin , Peng Qingzhong , Wu Jiahe
Published: May 2022

Teosinte branched1/Cincinnata/proliferating cell factor (TCP) transcription factors play important roles in plant growth and defense. However, the molecular mechanisms of TCPs participating in plant defense remain unclear. Here, we characterized a cotton TCP4-like fine-tuned by miR319b, which could interact with NON-EXPRESSER OF PATHOGEN-RELATED GENES 1 (NPR1) to directly activate isochorismate synthase 1 (ICS1) expression, facilitating plant resistance against Verticillium dahliae. mRNA degradome data and GUS-fused assay showed that GhTCP4-like mRNA was directedly cleaved by ghr-miR319b. Knockdown of ghr-miR319b increased plant resistance to V. dahliae, whereas silencing GhTCP4-like increased plant susceptibility by the virus-induced gene silencing (VIGS) method, suggesting that GhTCP4-like is a positive regulator of plant defense. According to the electrophoretic mobility shift assay and GUS reporter analysis, GhTCP4-like could transcriptionally activate GhICS1 expression, resulting in increased salicylic acid (SA) accumulation. Yeast two-hybrid and luciferase complementation image analyses demonstrated that GhTCP4-like interacts with GhNPR1, which can promote GhTCP4-like transcriptional activation in GhICS1 expression according to the GUS reporter assay. Together, these results revealed that GhTCP4-like interacts with GhNPR1 to promote GhICS1 expression through fine-tuning of ghr-miR319b, leading to SA accumulation, which is percepted by NPR1 to increase plant defense against V. dahliae. Therefore, GhTCP4-like participates in a positive feedback regulation loop of SA biosynthesis via NPR1, increasing plant defenses against fungal infection.