bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the quality of Napier grass silage with pyroligneous acid: Fermentation, aerobic stability, and microbial communities
Authors: Chen Dandan , Zheng Mingyang , Zhou Yuxin , Gao Lin , Zhou Wei , Wang Mingya , Zhu Yongwen , Xu Weijie
Published: November 2022

The presence of undesirable microorganisms in silage always leads to poor fermentation quality and low aerobic stability. Pyroligneous acid (PA), a by-product of biochar production, is known to have strong antimicrobial and antioxidant activities. To investigate the effects of PA on fermentation characteristics, aerobic stability, and microbial communities, Napier grass was ensiled with or without 1 and 2% PA for 30 days and then aerobically stored for 5 days. The results showed that PA application decreased (P < 0.01) the pH value, ammonia nitrogen content, and number of undesirable microorganisms (coliform bacteria, yeasts, and molds) after 30 days of ensiling and 5 days of exposure to air. The temperature of the PA-treated group was stable during the 5-day aerobic test, which did not exceed room temperature more than 2°C. The addition of PA also enhanced the relative abundance of Lactobacillus and reduced that of Klebsiella and Kosakonia. The relative abundance of Candida was higher in PA-treated silage than in untreated silage. The addition of PA decreased the relative abundance of Kodamaea and increased that of Monascus after 5 days of exposure to air. The abundances of Cladosporium and Neurospora were relatively high in 2% PA-treated NG, while these genera were note observed in the control group. These results suggested that the addition of PA could improve fermentation characteristics and aerobic stability, and alter microbial communities of silage.
In vitro and in vivo production and split-intein mediated ligation (SIML) of circular bacteriocins
Authors: Peña Nuria , Bland Michael J. , Sevillano Ester , Muñoz-Atienza Estefanía , Lafuente Irene , Bakkoury Mohamed El , Cintas Luis M. , Hernández Pablo E. , Gabant Philippe , Borrero Juan
Published: November 2022

Circular bacteriocins are antimicrobial peptides produced by bacteria that after synthesis undergo a head-to-tail circularization. Compared to their linear counterparts, circular bacteriocins are, in general, very stable to temperature and pH changes and more resistant to proteolytic enzymes, being considered as one of the most promising groups of antimicrobial peptides for their potential biotechnological applications. Up to now, only a reduced number of circular bacteriocins have been identified and fully characterized, although many operons potentially coding for new circular bacteriocins have been recently found in the genomes of different bacterial species. The production of these peptides is very complex and depends on the expression of different genes involved in their synthesis, circularization, and secretion. This complexity has greatly limited the identification and characterization of these bacteriocins, as well as their production in heterologous microbial hosts. In this work, we have evaluated a synthetic biology approach for the in vitro and in vivo production combined with a split-intein mediated ligation (SIML) of the circular bacteriocin garvicin ML (GarML). The expression of one single gene is enough to produce a protein that after intein splicing, circularizes in an active peptide with the exact molecular mass and amino acid sequence as native GarML. In vitro production coupled with SIML has been validated with other, well described and not yet characterized, circular bacteriocins. The results obtained suggest that this synthetic biology tool holds great potential for production, engineering, improving and testing the antimicrobial activity of circular bacteriocins.
Genome-guided purification and characterization of polymyxin A1 from Paenibacillus thiaminolyticus SY20: A rarely explored member of polymyxins
Authors: Wu Ya-ping , Liu Dong-mei , Liang Ming-hua , Huang Yan-yan , Lin Jin , Xiao Lan-fang
Published: November 2022

Polymyxin A1 was a rarely investigated member in the polymyxins family produced by Bacillus aerosporus. As a cyclic non-ribosomal lipopeptide, it was purified from Paenibacillus thiaminolyticus for the first time. The producing strain SY20 was screened from Chinese natural fermented bamboo shoots and identified as P. thiaminolyticus SY20 using 16S rRNA homology along with whole genome sequencing. The optimum incubation time was 32 h by the growth kinetics of antimicrobial agent production. The proteinaceous nature of antimicrobial agents was characterized according to the physicochemical properties of the cell-free supernatant. Subsequently, the active antimicrobial agent was purified from the supernatant using ammonium sulfate–graded precipitation, ion-exchange chromatography, and C18-H chromatography. The active agent was identified as polymyxin A1 with a molecular weight 1156.7 Da and antimicrobial activity mainly against Gram-negative bacteria. The molecular structure, a cyclic heptapeptide and a tripeptide side chain acylated by a fatty acid at the amino terminus, was elucidated using the combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), amino acid analysis, and whole genome mining tool. Meanwhile, the biosynthetic gene cluster of polymyxin A1 including five open reading frames (ORFs) was demonstrated in the genome. The compound should be further explored for its efficacy and toxicity in vivo to develop its application.
Molecular docking and proteomics reveals the synergistic antibacterial mechanism of theaflavin with β-lactam antibiotics against MRSA
Authors: Guan Shuhan , Zhong Ling , Yu Hangqian , Wang Li , Jin Yajing , Liu Jingyu , Xiang Hua , Yu Hao , Wang Lin , Wang Dacheng
Published: November 2022

Recurrent epidemics of methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) have illustrated that the effectiveness of antibiotics in clinical application is rapidly fading. A feasible approach is to combine natural products with existing antibiotics to achieve an antibacterial effect. In this molecular docking study, we found that theaflavin (TF) preferentially binds the allosteric site of penicillin-binding protein 2a (PBP2a), inducing the PBP2a active site to open, which is convenient for β-lactam antibiotics to treat MRSA infection, instead of directly exerting antibacterial activity at the active site. Subsequent TMT-labeled proteomics analysis showed that TF treatment did not significantly change the landscape of the S. aureus USA300 proteome. Checkerboard dilution tests and kill curve assays were performed to validate the synergistic effect of TF and ceftiofur, and the fractional inhibitory concentration index (FICI) was 0.1875. The antibacterial effect of TF combined with ceftiofur was better than that of single-drug treatment in vitro. In addition, TF effectively enhanced the activity of ceftiofur in a mouse model of MRSA-induced pneumonia. Our findings provide a potential therapeutic strategy to combine existing antibiotics with natural products to resolve the prevalent infections of multidrug-resistant pathogens.
Role of CXCR5+ CD8+ T cells in human immunodeficiency virus-1 infection
Authors: Gao Leiqiong , Zhou Jing , Ye Lilin
Published: November 2022

Human immunodeficiency virus (HIV) infection can be effectively suppressed by life-long administration of combination antiretroviral therapy (cART). However, the viral rebound can occur upon cART cessation due to the long-term presence of HIV reservoirs, posing a considerable barrier to drug-free viral remission. Memory CD4+ T cell subsets, especially T follicular helper (TFH) cells that reside in B-cell follicles within lymphoid tissues, are regarded as the predominant cellular compartment of the HIV reservoir. Substantial evidence indicates that HIV-specific CD8+ T cell-mediated cellular immunity can sustain long-term disease-free and transmission-free HIV control in elite controllers. However, most HIV cure strategies that rely on expanded HIV-specific CD8+ T cells for virus control are likely to fail due to cellular exhaustion and TFH reservoir-specialized anatomical structures that isolate HIV-specific CD8+ T cell entry into B-cell follicles. Loss of stem-like memory properties is a key feature of exhaustion. Recent studies have found that CXC chemokine receptor type 5 (CXCR5)-expressing HIV-specific CD8+ T cells are memory-like CD8+ T cells that can migrate into B-cell follicles to execute inhibition of viral replication. Furthermore, these unique CD8+ T cells can respond to immune checkpoint blockade (ICB) therapy. In this review, we discuss the functions of these CD8+ T cells as well as the translation of findings into viable HIV treatment and cure strategies.
Plasmalogens in bacteria, sixty years on
Authors: Goldfine Howard
Published: November 2022

The presence of plasmalogens in bacteria has been known for 60 years. The recent discovery of two genes encoding reductases that convert diacyl lipids to 1-alk-1′-enyl 2-acyl lipids has confirmed the derivation of plasmalogens from the corresponding diacyl lipids in bacteria. These genes are widely distributed in anaerobic and in some facultatively anaerobic bacteria. Plasmalogens evolved very early in the history of life on earth. Their persistence during eons of evolution suggests that they play a fundamental role in living organism. The phase behavior of plasmalogens and their conformation in membranes is discussed.
Magnetic resonance imaging findings in painful hemiplegic shoulder patients with or without subluxation: A retrospective cohort study
Authors: Xie Hui-Min , Zhang Xiao-Tan , Xu Lin , Wang Ning , Wang Rui , Jia Zi-Shan , Zhang Li-Ning
Published: November 2022

The relationship between hemiplegic shoulder pain (HSP) and subluxation is unclear. This study aimed to determine the differences of magnetic resonance imaging (MRI) findings in HSP patients with or without subluxation after stroke, and to analyze the etiology of shoulder pain. This retrospective study included 53 patients with HSP after stroke from September 2013 to February 2020. Patients underwent MRI of the shoulder because of shoulder pain. Clinical characteristics, including age, sex, stroke duration, body mass index, stroke type, visual analog scale score, Brunnstrom stage, and MRI arthrography findings of the affected shoulder, were recorded. Patients were classified into the glenohumeral subluxation (GHS) group (n = 27) or non-glenohumeral subluxation (nGHS) group (n = 26). We found that patients with HSP may be prone to bursa effusion, rotator cuff injury, ligament injury, and cartilage injury, even though there was no significant difference between the GHS and nGHS groups. MRI revealed 14 cases of long bicipital tendon-glenoid labrum injury (51.8%) in the GHS group and 6 cases (23.1%) in the nGHS group (p = 0.030). We also found 10 cases (37%) of glenoid labrum injury in the GHS group and 2 cases (7.7%) in the nGHS group (p = 0.026). Eight cases (29.6%) and 1 case (3.8%) of bone marrow edema were found in the GHS and nGHS groups, respectively (p = 0.033). Compared with painful hemiplegic shoulder patients without subluxation, patients with subluxation may be more susceptible to some injuries, such as long bicipital tendon-glenoid labrum injury, glenoid labrum injury, and bone marrow edema. During rehabilitation, physicians need to pay attention to these injuries.
Rebaseline no evidence of disease activity (NEDA-3) as a predictor of long-term disease course in a Norwegian multiple sclerosis population
Authors: Simonsen Cecilia Smith , Flemmen Heidi Øyen , Broch Line , Brekke Kamilla , Brunborg Cathrine , Berg-Hansen Pål , Celius Elisabeth Gulowsen
Published: November 2022

Introduction

No evidence of disease activity with three components (NEDA-3) is achieved if the person with MS (pwMS) has no new MRI lesions, no new relapses and no change in Expanded disability status scale (EDSS) over 1 year. Whether NEDA-3 is a good tool in measuring disease activity is up for discussion, but it is superior to the individual parameters separately and user-friendly. There is disagreement on whether NEDA-3 is a good predictor of long-term disability.

Methods

This is a retrospective cohort study using real-world data with limited selection bias from the complete MS population at two hospitals in the southeast of Norway. We included pwMS diagnosed between 2006 and 2017 who had enough information to determine time to failure of NEDA-3 after diagnosis.

Results

Of 536 pwMS, only 38% achieved NEDA 1 year after diagnosis. PwMS achieving NEDA were more likely to be started on a high efficacy drug as the initial drug, but there were no demographic differences. Mean time to NEDA failure was 3.3 (95% CI 2.9–3.7) years. Starting a high efficiacy therapy was associated with an increased risk of sustaining NEDA as compared to those receiving moderate efficacy therapy. PwMS who achieved NEDA at year one had a mean time to EDSS 6 of 33.8 (95% CI 30.9–36.8) years vs. 30.8 (95% CI 25.0–36.6) years in pwMS who did not achieve NEDA, p < 0.001. When rebaselining NEDA 1 year after diagnosis, 52.2% achieved NEDA in the 1st year after rebaseline, mean time to NEDA failure was 3.4 (95% CI 3.0–3.7) years and mean time to EDSS 6 was 44.5 (95% CI 40.4–48.5) years in pwMS achieving NEDA vs. 29.6 (95% CI 24.2–35.0) years in pwMS not achieving NEDA, p < 0.001. After rebaseline, pwMS with a high efficacy therapy as the initial drug had a mean time from diagnosis to NEDA fail of 4.8 years (95% CI 3.9–5.8) vs. 3.1 years (95% CI 2.7–3.5) in pwMS started on a moderate efficacy therapy, p < 0.001. In pwMS with NEDA failure at year one, 70% failed one, 28% failed two and 2% failed three components. New MRI lesions were the most common cause of NEDA failure (63%), followed by new relapses (50%) and EDSS change (25%).

Conclusion

NEDA-3 from rebaseline after 1 year, once treatment is stabilized, can predict the long-term disease course in MS. Starting a high efficacy DMT is associated with longer time to NEDA failure than moderate therapies. Finally, most pwMS only fail one component and new MRI lesions are the most likely cause of NEDA failure.
Generative adversarial networks with adaptive normalization for synthesizing T2-weighted magnetic resonance images from diffusion-weighted images
Authors: Mao Yanyan , Chen Chao , Wang Zhenjie , Cheng Dapeng , You Panlu , Huang Xingdan , Zhang Baosheng , Zhao Feng
Published: November 2022

Recently, attention has been drawn toward brain imaging technology in the medical field, among which MRI plays a vital role in clinical diagnosis and lesion analysis of brain diseases. Different sequences of MR images provide more comprehensive information and help doctors to make accurate clinical diagnoses. However, their costs are particularly high. For many image-to-image synthesis methods in the medical field, supervised learning-based methods require labeled datasets, which are often difficult to obtain. Therefore, we propose an unsupervised learning-based generative adversarial network with adaptive normalization (AN-GAN) for synthesizing T2-weighted MR images from rapidly scanned diffusion-weighted imaging (DWI) MR images. In contrast to the existing methods, deep semantic information is extracted from the high-frequency information of original sequence images, which are then added to the feature map in deconvolution layers as a modality mask vector. This image fusion operation results in better feature maps and guides the training of GANs. Furthermore, to better preserve semantic information against common normalization layers, we introduce AN, a conditional normalization layer that modulates the activations using the fused feature map. Experimental results show that our method of synthesizing T2 images has a better perceptual quality and better detail than the other state-of-the-art methods.
Interoceptive accuracy correlates with precision of time perception in the millisecond range
Authors: Uraguchi Maki , Maulina Venie Viktoria Rondang , Ohira Hideki
Published: November 2022

It has been proposed that accuracy in time perception is related to interoceptive accuracy and vagal activity. However, studies investigating time perception in the supra-second range have provided mixed results, and few studies have investigated the sub-second range. Moreover, there is a lack of studies investigating the relationship between precision in time perception and interoceptive accuracy. A recent meta-analytic review of neuroimaging studies proposed a dynamic interaction between two types of timing processing—an endogenous time keeping mechanism and the use of exogenous temporal cues. Interoceptive accuracy may affect both accuracy and precision of primary temporal representations, as they are generated based on the endogenous time keeping mechanism. Temporal accuracy may vary when adapted to the environmental context. In contrast, temporal precision contains some constant noise, which may maintain the relationship with interoceptive accuracy. Based on these assumptions, we hypothesized that interoceptive accuracy would be associated with temporal precision in the sub-second range, while vagal activity would be associated with temporal accuracy. We used the temporal generalization task, which allowed us to calculate the indices of temporal accuracy and temporal precision in line with the existing research, and also compute the index of participants’ sensitivity according to the signal detection theory. Specifically, we investigated whether (1) interoceptive accuracy would correlate with temporal accuracy, temporal precision, or sensitivity and (2) resting-state vagal activity would correlate with temporal accuracy, temporal precision, or sensitivity. The results indicated that interoceptive accuracy was positively correlated with temporal precision as well as sensitivity, but not with temporal accuracy, in the sub-second range time perception. Vagal activity was negatively correlated only with sensitivity. Furthermore, we found a moderation effect of sensitivity on the relationship between vagal activity and perceived duration, which affected the association between vagal activity and temporal accuracy. These findings suggest the importance of precision as an aspect of time perception, which future studies should further explore in relation to interoception and vagal activity, and of the moderation effects of factors such as participants’ sensitivity in this context.
Neural response to repeated auditory stimuli and its association with early language ability in male children with Fragile X syndrome
Authors: An Winko W. , Nelson Charles A. , Wilkinson Carol L.
Published: November 2022

Background

Fragile X syndrome (FXS) is the most prevalent form of inherited intellectual disability and is commonly associated with autism. Previous studies have linked the structural and functional alterations in FXS with impaired sensory processing and sensory hypersensitivity, which may hinder the early development of cognitive functions such as language comprehension. In this study, we compared the P1 response of the auditory evoked potential and its habituation to repeated auditory stimuli in male children (2–7 years old) with and without FXS, and examined their association with clinical measures in these two groups.

Methods

We collected high-density electroencephalography (EEG) data in an auditory oddball paradigm from 12 male children with FXS and 11 age- and sex-matched typically developing (TD) children. After standardized EEG pre-processing, we conducted a spatial principal component (PC) analysis and identified two major PCs—a frontal PC and a temporal PC. Within each PC, we compared the P1 amplitude and inter-trial phase coherence (ITPC) between the two groups, and performed a series of linear regression analysis to study the association between these EEG measures and several clinical measures, including assessment scores for language abilities, non-verbal skills, and sensory hypersensitivity.

Results

At the temporal PC, both early and late standard stimuli evoked a larger P1 response in FXS compared to TD participants. For temporal ITPC, the TD group showed greater habituation than the FXS group. However, neither group showed significant habituation of the frontal or temporal P1 response. Despite lack of habituation, exploratory analysis of brain-behavior associations observed that within the FXS group, reduced frontal P1 response to late standard stimuli, and increased frontal P1 habituation were both associated with better language scores.

Conclusion

We identified P1 amplitude and ITPC in the temporal region as a contrasting EEG phenotype between the FXS and the TD groups. However, only frontal P1 response and habituation were associated with language measures. Larger longitudinal studies are required to determine whether these EEG measures could be used as biomarkers for language development in patients with FXS.
PP2A phosphatase regulates cell-type specific cytoskeletal organization to drive dendrite diversity
Authors: Bhattacharjee Shatabdi , Lottes Erin N. , Nanda Sumit , Golshir Andre , Patel Atit A. , Ascoli Giorgio A. , Cox Daniel N.
Published: November 2022

Uncovering molecular mechanisms regulating dendritic diversification is essential to understanding the formation and modulation of functional neural circuitry. Transcription factors play critical roles in promoting dendritic diversity and here, we identify PP2A phosphatase function as a downstream effector of Cut-mediated transcriptional regulation of dendrite development. Mutant analyses of the PP2A catalytic subunit (mts) or the scaffolding subunit (PP2A-29B) reveal cell-type specific regulatory effects with the PP2A complex required to promote dendritic growth and branching in Drosophila Class IV (CIV) multidendritic (md) neurons, whereas in Class I (CI) md neurons, PP2A functions in restricting dendritic arborization. Cytoskeletal analyses reveal requirements for Mts in regulating microtubule stability/polarity and F-actin organization/dynamics. In CIV neurons, mts knockdown leads to reductions in dendritic localization of organelles including mitochondria and satellite Golgi outposts, while CI neurons show increased Golgi outpost trafficking along the dendritic arbor. Further, mts mutant neurons exhibit defects in neuronal polarity/compartmentalization. Finally, genetic interaction analyses suggest β-tubulin subunit 85D is a common PP2A target in CI and CIV neurons, while FoxO is a putative target in CI neurons.
Sleep patterns modify the association of 25(OH)D with poor cardiovascular health in pregnant women
Authors: Yin Wan-jun , Yu Li-jun , Wang Peng , Tao Rui-xue , Jiang Xiao-min , Zhang Ying , Zhu Dao-min , Zhu Peng
Published: November 2022

Background

The relationship between vitamin D status and gestational cardiovascular health (CVH) is inconsistent in previous studies. Emerging evidence shows that sleep behaviors are related to vitamin D metabolism. However, no studies evaluate the interaction of vitamin D and sleep behaviors on gestational CVH.

Objective

We aimed to estimate the relationship between 25-hydroxyvitamin D [25(OH)D] concentrations and gestational CVH, and whether the relationship was modified by sleep behaviors.

Methods

The data of this study was from a multicenter birth cohort study. A total of 9,209 pregnant women at 16–23 weeks of gestation were included. 25(OH)D concentrations were measured from collected blood. Sleep patterns consisted of major sleep behaviors including duration, chronotype, insomnia, snoring, and excessive daytime sleepiness. Data on poor CVH was based on four “clinical” CVH metrics, including body mass index, blood pressure, total cholesterol, and glucose levels.

Results

The proportion of women with poor CVH was 25.0%. The relative risk (RR) (95%CI) of poor CVH was 0.67 (0.58–0.76) in women with 25(OH)D ≥ 50 nmol/L after multivariate adjustments. Lower 25(OH)D concentrations were significantly associated with poor CVH. Such association was also evident in subgroups analysis. We found a significant interaction of 25(OH)D (P for interaction = 0.01) with sleep patterns on the risk of poor CVH. A negative dose-response relation was observed between 25(OH)D concentrations and poor CVH risk in healthy or intermediate sleep, not poor sleep. 25(OH)D concentrations were lower and the risk of poor CVH was higher in pregnant women with poor sleep patterns (P < 0.05).

Conclusion

Our study suggests that sleep patterns modify the association of 25(OH)D concentrations with the CVH among pregnant women.
Simultaneous extraction and preliminary purification of polyphenols from grape pomace using an aqueous two-phase system exposed to ultrasound irradiation: Process characterization and simulation
Authors: Xie Guangjie , Shen Juan , Luo Ji , Li Dandan , Tao Yang , Song Changnian , Han Yongbin
Published: November 2022

In this study, an ultrasound-assisted aqueous two-phase (ATP) extraction method was used for the extraction and purification of phenolic compounds from grape pomace. The effect of acoustic energy densities (AED, 41.1, 63.5, 96.1, 111.2 W/L) and temperatures (20, 30, 40°C) on the yield of phenolics was investigated. An artificial neural network (ANN) was successfully used to correlate the extraction parameters with phenolic yield. Then, a diffusion model based on Fick's second law was used to model the mass transfer process during ultrasound-assisted ATP extraction and evaluate the effective diffusion coefficient of phenolics. The results revealed the increase in AED, and the temperature increased the effective diffusivity of phenolics. The HPLC analysis of anthocyanins and flavonols showed that ultrasound significantly increased the extraction yield of anthocyanins compared with the traditional method. High amounts of rutin and myricetin were recovered using the ATPS systems. Sugars were mainly distributed in the bottom phase, whereas phenolics were located in the top phase. Conclusively, ultrasound-assisted aqueous two-phase (ATP) extraction can be used as an effective method to achieve the simultaneous separation and preliminary purification of phenolics from grape pomace.
The role of noncoding RNAs in cancer lipid metabolism
Authors: Wang Ye , Li Qian , Wang Song , Wang Bi-jun , Jin Yan , Hu Hao , Fu Qing-sheng , Wang Jia-wei , Wu Qing , Qian Long , Cao Ting-ting , Xia Ya-bin , Huang Xiao-xu , Xu Li
Published: November 2022

Research on noncoding ribonucleic acids (ncRNAs) is mostly and broadly focused on microRNAs (miRNAs), cyclic RNAs (circRNAs), and long ncRNAs (lncRNAs), which have been confirmed to play important roles in tumor cell proliferation, invasion, and migration. Specifically, recent studies have shown that ncRNAs contribute to tumorigenesis and tumor development by mediating changes in enzymes related to lipid metabolism. The purpose of this review is to discuss the characterized ncRNAs involved in the lipid metabolism of tumors to highlight ncRNA-mediated lipid metabolism-related enzyme expression in malignant tumors and its importance to tumor development. In this review, we describe the types of ncRNA and the mechanism of tumor lipid metabolism and analyze the important role of ncRNA in tumor lipid metabolism and its future prospects from the perspectives of ncRNA biological function and lipid metabolic enzyme classification. However, several critical issues still need to be resolved. Because ncRNAs can affect tumor processes by regulating lipid metabolism enzymes, in the future, we can study the unique role of ncRNAs from four aspects: disease prevention, detection, diagnosis, and treatment. Therefore, in the future, the development of ncRNA-targeted therapy will become a hot direction and shoulder a major task in the medical field.
Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions
Authors: Baldavira Camila Machado , Prieto Tabatha Gutierrez , Machado-Rugolo Juliana , de Miranda Jurandir Tomaz , da Silveira Lizandre Keren Ramos , Velosa Ana Paula Pereira , Teodoro Walcy Rosolia , Ab’Saber Alexandre , Takagaki Teresa , Capelozzi Vera Luiza
Published: November 2022

Lung cancer still represents a global health problem, being the main type of tumor responsible for cancer deaths. In this context, the tumor microenvironment, and the extracellular matrix (ECM) pose as extremely relevant. Thus, this study aimed to explore the prognostic value of epithelial-to-mesenchymal transition (EMT), Wnt signaling, and ECM proteins expression in patients with non–small-cell lung carcinoma (NSCLC) with clinical stages I-IIIA. For that, we used 120 tissue sections from patients and evaluated the immunohistochemical, immunofluorescence, and transmission electron microscopy (TEM) to each of these markers. We also used in silico analysis to validate our data. We found a strong expression of E-cadherin and β-catenin, which reflects the differential ECM invasion process. Therefore, we also noticed a strong expression of chondroitin sulfate (CS) and collagens III and V. This suggests that, after EMT, the basal membrane (BM) enhanced the motility of invasive cells. EMT proteins were directly associated with WNT5A, and collagens III and V, which suggests that the WNT pathway drives them. On the other hand, heparan sulfate (HS) was associated with WNT3A and SPARC, while WNT1 was associated with CS. Interestingly, the association between WNT1 and Col IV suggested negative feedback of WNT1 along the BM. In our cohort, WNT3A, WNT5A, heparan sulfate and SPARC played an important role in the Cox regression model, influencing the overall survival (OS) of patients, be it directly or indirectly, with the SPARC expression stratifying the OS into two groups: 97 months for high expression; and 65 for low expression. In conclusion, the present study identified a set of proteins that may play a significant role in predicting the prognosis of NSCLC patients with clinical stages I-IIIA.
Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma
Authors: Li Su-Ran , Man Qi-Wen , Liu Bing
Published: November 2022

Hypoxia plays a critical role in head and neck squamous cell carcinoma (HNSCC) prognosis. However, till now, robust and reliable hypoxia-related prognostic signatures have not been established for an accurate prognostic evaluation in HNSCC patients. This article focused on establishing a risk score model to evaluate the prognosis and guide treatment for HNSCC patients. RNA-seq data and clinical information of 502 HNSCC patients and 44 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database. 433 samples from three Gene Expression Omnibus (GEO) datasets were incorporated as an external validation cohort. In the training cohort, prognostic-related genes were screened and LASSO regression analyses were performed for signature establishment. A scoring system based on SRPX, PGK1, STG1, HS3ST1, CDKN1B, and HK1 showed an excellent prediction capacity for an overall prognosis for HNSCC patients. Patients were divided into high- and low-risk groups, and the survival status of the two groups exhibited a statistically significant difference. Subsequently, gene set enrichment analysis (GSEA) was carried out to explore the underlying mechanisms for the prognosis differences between the high- and low-risk groups. The tumor immune microenvironment was evaluated by CIBERSORT, ESTIMATE, TIDE, and xCell algorithm, etc. Then, we explored the relationships between this prognostic model and the levels of immune checkpoint-related genes. Cox regression analysis and nomogram plot indicated the scoring system was an independent predictor for HNSCC. Moreover, a comparison of predictive capability has been made between the present signature and existing prognostic signatures for HNSCC patients. Finally, we detected the expression levels of proteins encoded by six-HRGs via immunohistochemical analysis in tissue microarray. Collectively, a novel integrated signature considering both HRGs and clinicopathological parameters will serve as a prospective candidate for the prognostic evaluation of HNSCC patients.
Accurate preoperative staging and HER2 status prediction of gastric cancer by the deep learning system based on enhanced computed tomography
Authors: Guan Xiao , Lu Na , Zhang Jianping
Published: November 2022

Purpose

To construct the deep learning system (DLS) based on enhanced computed tomography (CT) images for preoperative prediction of staging and human epidermal growth factor receptor 2 (HER2) status in gastric cancer patients.

Methods

The raw enhanced CT image dataset consisted of CT images of 389 patients in the retrospective cohort, The Cancer Imaging Archive (TCIA) cohort, and the prospective cohort. DLS was developed by transfer learning for tumor detection, staging, and HER2 status prediction. The pre-trained Yolov5, EfficientNet, EfficientNetV2, Vision Transformer (VIT), and Swin Transformer (SWT) were studied. The tumor detection and staging dataset consisted of 4860 enhanced CT images and annotated tumor bounding boxes. The HER2 state prediction dataset consisted of 38900 enhanced CT images.

Results

The DetectionNet based on Yolov5 realized tumor detection and staging and achieved a mean Average Precision (IoU=0.5) (mAP_0.5) of 0.909 in the external validation cohort. The VIT-based PredictionNet performed optimally in HER2 status prediction with the area under the receiver operating characteristics curve (AUC) of 0.9721 and 0.9995 in the TCIA cohort and prospective cohort, respectively. DLS included DetectionNet and PredictionNet had shown excellent performance in CT image interpretation.

Conclusion

This study developed the enhanced CT-based DLS to preoperatively predict the stage and HER2 status of gastric cancer patients, which will help in choosing the appropriate treatment to improve the survival of gastric cancer patients.
Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients
Authors: Friedrich Michel , Farrher Ezequiel , Caspers Svenja , Lohmann Philipp , Lerche Christoph , Stoffels Gabriele , Filss Christian P. , Weiss Lucas Carolin , Ruge Maximilian I. , Langen Karl-Josef , Shah Nadim J. , Fink Gereon R. , Galldiks Norbert , Kocher Martin
Published: November 2022

Background

In glioma patients, multimodality therapy and recurrent tumor can lead to structural brain tissue damage characterized by pathologic findings in MR and PET imaging. However, little is known about the impact of different types of damage on the fiber architecture of the affected white matter.

Patients and methods

This study included 121 pretreated patients (median age, 52 years; ECOG performance score, 0 in 48%, 1-2 in 51%) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median follow-up time of 14 months (range, 1-214 months), anatomic MR and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET images were acquired on a 3T hybrid PET/MR scanner. Post-therapeutic findings comprised resection cavities, regions with contrast enhancement or increased FET uptake and T2/FLAIR hyperintensities. Local fiber density was determined from high angular-resolution diffusion-weighted imaging and advanced tractography methods. A cohort of 121 healthy subjects selected from the 1000BRAINS study matched for age, gender and education served as a control group.

Results

Lesion types differed in both affected tissue volumes and relative fiber densities compared to control values (resection cavities: median volume 20.9 mL, fiber density 16% of controls; contrast-enhanced lesions: 7.9 mL, 43%; FET uptake areas: 30.3 mL, 49%; T2/FLAIR hyperintensities: 53.4 mL, 57%, p<0.001). In T2/FLAIR-hyperintense lesions caused by peritumoral edema due to recurrent glioma (n=27), relative fiber density was as low as in lesions associated with radiation-induced gliosis (n=13, 48% vs. 53%, p=0.17). In regions with pathologically increased FET uptake, local fiber density was inversely related (p=0.005) to the extent of uptake. Total fiber loss associated with contrast-enhanced lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on overall ECOG score.

Conclusions

These results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients’ performance status due to the larger volume affected.
Pediatric tuina for allergic rhinitis in children: A systematic review and meta-analysis of randomized controlled trials
Authors: Fu Shifang , Li Yuetong , Li Rongrong , Ren Fengjiao , Piao Yinjing , Wang Yanguo , Luo Mingchi
Published: November 2022

Aim

To evaluate the clinical efficacy of pediatric tuina for allergic rhinitis treatment in children.

Methods

Three English, four Chinese, one Japanese, and two Korean databases were searched for relevant literature published till February 2021, and eligible randomized controlled trials (RCTs) were included for analysis. Data were screened and extracted independently using predesigned forms. The methodological quality evaluation was performed using the tool of Cochrane bias risk assessment, and meta-analysis was performed through Review Manager 5.3.

Results

A total of 12 RCTs, which included 716 children, were selected for meta-analysis. Compared with Chinese herbal medicine, acupuncture, Western medicine, and other therapies, pediatric tuina alone or in combination with other treatments had a higher clinical effectiveness (relative risk = 1.16, 95% confidence interval [CI] = 1.08–1.25) in treating children with allergic rhinitis. Pediatric tuina also effectively improved the following signs and symptoms of allergic rhinitis in children: nasal congestion (mean difference [MD] = −0.44, 95% CI = −0.70 to −0.19), runny nose (MD = −0.39, 95% CI = −0.55 to −0.23), sneezing (MD = −0.23, 95% CI = −0.38 to −0.08), and turbinate swelling (MD = −0.26, 95% CI = −0.48 to −0.04); all differences were statistically significant.

Conclusions

The present study provided favorable evidence for the treatment of allergic rhinitis in children with pediatric tuina. However, owing to the impact of research quality, this evidence needs to be validated via strictly designed clinical trials.
Global trends and Frontier topics about vascular smooth muscle cells phenotype switch: A bibliometric analysis from 1999 to 2021
Authors: Han Ying , Yan Langchao , Xia Lu , Li Shifu , Zhang Qian , jin Chen
Published: November 2022

Objective: Vascular smooth muscle cell phenotype switch (VSMCPS) plays a significant role in vascular remodeling. This study aimed to conduct a bibliometric analysis and visualize the knowledge map of research on VSMCPS.

Methods: We retrieved publications focusing on VSMCPS from the Web of Science Core Collection database (SCI-EXPANDED) from 1999 to 2021. Using bibliometric tools, VOSviewer and CiteSpace, we identified the most productive researchers, journals, institutions, and countries. At the same time, the trends, hot topics, and knowledge networks were analyzed and visualized.

Results: A total of 2213 publications were included in this analysis. The number of annual publications in the VSMCPS field exhibited an upward trend and could be roughly divided into three phases. Until 2006, the most prolific authors were from the United States. As of 2008, the number of articles published in China increased dramatically to reach 126 papers in 2020. As of 2014, China was the most productive country in this field. The United States ranked first in the number of highly-influential authors, institutions, and literature from 1999 to 2022. Owens GK, Hata, Akiko, and Wen, jin-kun were the most prolific authors. Arteriosclerosis Thrombosis and Vascular Biology, Circulation Research, and Cardiovascular Research were the top-ranked journals in this field. “Vascular remodeling,” “atherosclerosis,” “neointima,” “hypertension”, and “inflammation” were the main researched topics. New diseases, new mechanisms, and new phenotype (e.g., micro RNA, macrophage-like-cell, hypoxia, autophagy, long noncoding RNA, oxidative stress, endoplasmic reticulum stress, senescence, aging, abdominal aortic aneurysm, and aortic dissection) represent the trending topics in recent years.

Conclusion: This study systematically analyzed and visualized the knowledge map of VSMCPS over the past 2 decades. Our findings provide a comprehensive overview for scholars who want to understand current trends and new research frontiers in this area.
Quantifying structure and dynamics of bound and bulk polymer in tailor-made rubber-silica nanocomposites
Authors: Philippe A.-M. , Sill C. , Westermann S. , Allgaier J. , Staropoli M. , Monkenbusch M. , Gerstner D. , Fleming Y. , Wischnewski A. , Hoffmann I. , Zolnierczuk P. , Do C. , Pyckhout-Hintzen W.
Published: November 2022

The dynamics of long polymer chains in the presence of nanoparticles have been investigated. The nanocomposites of interest were inspired by tire industry-like rubber materials and consisted of entangled polyisoprene linear chains mixed with chemically pre-treated silica nanoparticles. Combining rheology, dielectric spectroscopy, and neutron spin echo measurements, we measured the modification of the polymer chain dynamics from bulk state to high filler concentration over a broad range of time and length scales. We show that the end-to-end relaxation does not seem to be impacted, whereas the polymer dynamics is significantly slowed down at a very local scale in the presence of nano-fillers. In addition to this length scale dependent different dynamics, additional Neutron Spin Echo spectroscopy experiments and Small Angle Scattering on labelled polymer chains, irreversibly bound to the filler surface and re-dispersed in a fully deuterated matrix, revealed a negligible dynamical behavior of this particular population of localized chains in the rubber layer. The conformational statistics of these chains is that of self-avoiding walk train within a shell that is thinner than the size of the chain. To the best of our knowledge, this work is the first of its kind which measures the single chain form factor in the bound layer of chemically multi-linked chains to the filler surface.
Effects of trichothecene production by Trichoderma arundinaceum isolates from bean-field soils on the defense response, growth and development of bean plants (Phaseolus vulgaris)
Authors: Cardoza Rosa E. , Mayo-Prieto Sara , Martínez-Reyes Natalia , McCormick Susan P. , Carro-Huerga Guzmán , Campelo M. Piedad , Rodríguez-González Álvaro , Lorenzana Alicia , Proctor Robert H. , Casquero Pedro A. , Gutiérrez Santiago
Published: November 2022

The trichothecene toxin-producing fungus Trichoderma arundinaceum has potential as a biological control agent. However, most biocontrol studies have focused only on one strain, IBT 40837. In the current study, three Trichoderma isolates recovered from bean-field soils produced the trichothecene harzianum A (HA) and trichodermol, the latter being an intermediate in the HA biosynthesis. Based on phylogenetic analysis, the three isolates were assigned to the species T. arundinaceum. Their genome sequences had a high degree of similarity to the reference IBT 40837 strain, in terms of total genome size, number of predicted genes, and diversity of putative secondary metabolite biosynthetic gene clusters. HA production by these bean-field isolates conferred significant in vitro antifungal activity against Rhizoctonia solani and Sclerotinia sclerotiorum, which are some of the most important bean pathogens. Furthermore, the bean-field isolates stimulated germination of bean seeds and subsequent growth of above ground parts of the bean plant. Transcriptomic analysis of bean plants inoculated with these T. arundinaceum bean-field soil isolates indicated that HA production significantly affected expression of plant defense-related genes; this effect was particularly significant in the expression of chitinase-encoding genes. Together, these results indicate that Trichoderma species producing non-phytotoxic trichothecenes can induce defenses in plants without negatively affecting germination and development
Genetic mapping of the Andean anthracnose resistance gene present in the common bean cultivar BRSMG Realce
Authors: Gomes-Messias Lucas Matias , Vianello Rosana Pereira , Marinho Gabriella Ribeiro , Rodrigues Luana Alves , Coelho Alexandre Siqueira Guedes , Pereira Helton Santos , Melo Leonardo Cunha , de Souza Thiago Lívio Pessoa Oliveira
Published: November 2022

The rajado seeded Andean bean (Phaseolus vulgaris L.) cultivar BRSMG Realce (striped seed coat) developed by Embrapa expressed a high level of anthracnose resistance, caused by Colletotrichum lindemuthianum, in field and greenhouse screenings. The main goal of this study was to evaluate the inheritance of anthracnose resistance in BRSMG Realce, map the resistance locus or major gene cluster previously named as Co-Realce, identify resistance-related positional genes, and analyze potential markers linked to the resistance allele. F2 plants derived from the cross BRSMG Realce × BRS FC104 (Mesoamerican) and from the cross BRSMG Realce × BRS Notável (Mesoamerican) were inoculated with the C. lindemuthianum races 475 and 81, respectively. The BRSMG Realce × BRS FC104 F2 population was also genotyped using the DArTseq technology. Crosses between BRSMG Realce and BAT 93 (Mesoamerican) were also conducted and resulting F2 plants were inoculated with the C. lindemuthianum races 65 and 1609, individually. The results shown that anthracnose resistance in BRSMG Realce is controlled by a single locus with complete dominance. A genetic map including 1,118 SNP markers was built and shown 78% of the markers mapped at a distances less than 5.0 cM, with a total genetic length of 4,473.4 cM. A major locus (Co-Realce) explaining 54.6% of the phenotypic variation of symptoms caused by the race 475 was identified in Pv04, flanked by the markers snp1327 and snp12782 and 4.48 cM apart each other. These SNPs are useful for marker-assisted selection, due to an estimated selection efficiency of 99.2%. The identified resistance allele segregates independently of the resistance allele Co-33 (Pv04) present in BAT 93. The mapped genomic region with 704,867 bp comprising 63 putative genes, 44 of which were related to the pathogen-host interaction. Based on all these results and evidence, anthracnose resistance in BRSMG Realce should be considered as monogenic, useful for breeding purpose. It is proposed that locus Co-Realce is unique and be provisionally designated as CoPv04R until be officially nominated in accordance with the rules established by the Bean Improvement Cooperative Genetics Committee.