bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep-Seated Deformation Mechanisms of Excavated Slope and Control Methods: A Case Study
Authors: Wu Yongjin , Zhang Qing , Ding Xiuli , Wang Hui , Huang Shuling , Yin Xiansong
Published: March 2022

High slope stability control is a crucial technical issue in water conservancy and hydropower project construction. This issue is relevant throughout the entire engineering-related survey, design, construction, and operation process. This paper reports a recent case in which significant deep-seated deformation occurred during slope excavation. Several unfavorable structural surfaces were revealed throughout the slope’s undercutting process, particularly fault fz39, which ran diagonally through the entire slope from top to bottom. On the slope surface, damage such as cracking, bulging, and local slippage appeared. The measured value of multipoint displacement meters increased in a stepwise pattern with each blast, and the maximum measured value exceeded 100 mm. The studied slope’s whole excavation and reinforcement process is described in detail. We analyzed the deformation mechanism of the excavation slope by combining the geological conditions, real-time safety monitoring findings, and site deformation characteristics. The slope reinforcement scheme was optimized based on the preceding analyses. We used a three-dimensional numerical calculation program to simulate the slope excavation and unloading process to reproduce the current mechanical state of the slope, evaluate the reinforcement measures, and provide a useful reference for decision making. The analysis shows that the deformation behavior of the studied slope is closely related to fault fz39 and fracture L920, and presents a typical wedge failure mode. The deep-seated deformation of the excavation slope occurs at the junction of the wedge and bedrock, which is mainly affected by unfavorable geological structure surfaces, excavation unloading, and blasting vibration. The reinforcement scheme of unloading at the top of the slope and large-tonnage cables are established. The numerical analysis results showed that the design of the slope reinforcement measures was appropriate and ensured slope stability. The work described in this paper deepens our understanding of the occurrence of large deep-seated deformation on the structural-controlled slope under the action of excavation and improves the design philosophy.
Impact of Regional Climate Change on the Development of Lithium Resources in Zabuye Salt Lake, Tibet
Authors: Ding Tao , Zheng Mianping , Nie Zhen , Ma Lichun , Ye Chuanyong , Wu Qian , Zhao Yuanyi , Yang Donghui , Wang Kai
Published: March 2022

Climate change has important implication for the ecological environment and human social activities. The Qinghai-Tibet Plateau is a sensitive area for climate change, and the lakes on the Qinghai-Tibet Plateau are known as the “guardians” of climate change. However, there are few studies on the impact of climate variations on the exploitation of lithium resources in salt lakes. In this work, the collected data from Zabuye Salt Lake Observation Station and the experimental data of brine at different temperatures were employed as the research objects to investigate the relationship between regional climate change and lithium resources in salt lakes. The results indicated that Zabuye Salt Lake had abundant solar energy resources from 1991 to 2020 with the annual average sunshine duration of 3,122.4 h, the average annual evaporation of 2,579.07 mm/yr, and the annual average precipitation of 168.65 mm/yr. The average annual evaporation is around 15.3 times the average annual precipitation, owing to the short rainy season and the low rainfall. The phase diagram displayed that two lithium carbonate precipitation peaks clearly appeared at 25°C, and no obvious precipitation peak appeared at 15°C, indicating that a high-grade lithium carbonate mixed salt was prone to be formed at a higher temperature while lithium ions was more inclined to enrich in brine at a lower temperature. Therefore, Zabuye Salt Lake with the characteristics of low temperature, large temperature difference, less precipitation, strong radiation and large evaporation could be applied as unique lithium resources in the salt gradient solar pond, which would play a positive role in the development of salt lake resources.
An Exploratory Interview Study About Student Perceptions of Using Social Media to Facilitate Their Undergraduate Studies
Authors: Fuchs Kevin
Published: March 2022

The true power of social media lies in its ability to enable users to connect and share information with anyone around the globe. The use of social media in education helps students get more useful information and connect with learning groups and other educational systems that make education convenient. The purpose of this exploratory interview study is to identify how undergraduate students use social media to support their studies. Moreover, the study examines student perceptions concerning the benefits and limitations of using social media for educational purposes. The empirical data for this study was generated through a series of semi-structured interviews with undergraduate students (n = 27) and analyzed thematically. Three themes emerged through the thematic analysis: (1) perceived usage of social media, (2) invasion of privacy, and (3) the approachable teacher. The results of the study offer practical implications for educators and policymakers about incorporating social media in their curricula.
Increased Central and Peripheral Thyroid Resistance Indices During the First Half of Gestation Were Associated With Lowered Risk of Gestational Diabetes—Analyses Based on Huizhou Birth Cohort in South China
Authors: Liu Zhao-min , Li Guoyi , Wu Yi , Zhang Di , Zhang Sujuan , Hao Yuan-Tao , Chen Weiqing , Huang Qi , Li Shuyi , Xie Yaojie , Ye Mingtong , He Chun , Chen Ping , Pan Wenjing
Published: March 2022

Objectives

The study aimed to explore the relationship of thyroid function and resistance indices with subsequent risk of gestational diabetes (GDM).

Design

This was a longitudinal study embedded in the Huizhou Birth Cohort.

Methods

A total of 2,927 women of singleton pregnancy were recruited from January to October of 2019. Thyroid central resistance indices were evaluated by Thyroid Feedback Quartile-Based index (TFQI), Thyrotrophy T4 Resistance Index (TT4RI), and TSH Index (TSHI) based on plasma-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels during the first half of pregnancy. Thyroid peripheral sensitivity was assessed by free triiodothyronine (FT3) to FT4 ratio (FT3/FT4), a proxy of deiodinase activity. GDM was diagnosed between 24 and 28 weeks of gestation by a standardized 75 g oral glucose tolerance test. Multivariable linear and logistic regression was applied to examine the associations of thyroid markers with GDM risk.

Results

FT3 and FT3/FT4 were positively associated with both fasting and post-load glucose levels, while TSH, TSHI, TT4RI, and TFQI were negatively associated with 1 and 2 h post-load glucose levels. Compared with the lowest quartile, GDM risk in the highest quartile increased by 44% [odds ratio (OR) = 1.44; 95%CI, 1.08–1.92; ptrend = 0.027] for FT3 and 81% (OR = 1.81; 95%CI, 1.33–2.46; ptrend < 0.001) for FT3/FT4, while it lowered by 37% (OR = 0.63; 95%CI, 0.47–0.86; ptrend = 0.002] for TSHI, 28% for TT4RI (OR = 0.72; 95%CI, 0.54–0.97; ptrend = 0.06), and 37% for TFQI (OR = 0.63; 95%CI, 0.46–0.85; ptrend < 0.001).

Conclusions

This longitudinal study indicated that higher FT3 and FT3/FT4 and lower central thyroid resistance indices were associated with increased risk of GDM.
A Study on Nexus Between Renewable Energy and Fossil Fuel Consumption in Commercial Sectors of United States Using Wavelet Coherence and Quantile-on-Quantile Regression
Authors: Singh Sanjeet , Bansal Pooja , Bhardwaj Nav
Published: March 2022

The inertia of fossil fuels in the commercial sector of the United States has maintained its momentum throughout, and efforts to replace it with renewable energy has continuously been made. This dynamic relationship is impacted by multi-economic and political variables both in the domestic and international markets. In this paper, we have explored the dynamic impact of total renewable energy consumption (RE) on the decomposed wavelet frequencies of energy consumed by fossil fuels (FE) in the commercial sectors of the United States economy. In particular, we have applied wavelet coherence and quantile-on-quantile regression methodologies to evaluate this relationship. The monthly data from the US Energy Information Administration over a period of January 2001 to July 2021 was procured for the present study. Our empirical findings based on wavelet coherence showed significant co-movements between FE and RE with positive association in short-run while negative association in long-run monthly frequency bands. For our five models based on quantiles and decomposed wavelet frequencies of FE, four models show that renewable energy consumption has an antagonistic relation with the FE in the commercial sector of the United States.
Multi-Scale Video Flame Detection for Early Fire Warning Based on Deep Learning
Authors: Dai Peiwen , Zhang Qixing , Lin Gaohua , Shafique Muhammad Masoom , Huo Yinuo , Tu Ran , Zhang Yongming
Published: March 2022

The widespread use of renewable energy resources requires more immediate and effective fire alarms as a preventive measure. The fire is usually weak in the initial stages, which is not conducive to detection and identification. This paper validates a solution to resolve that problem by a flame detection algorithm that is more sensitive to small flames. Based on Yolov3, the parallel convolution structure of Inception is used to obtain multi-size image information. In addition, the receptive field of the convolution kernel is increased with the dilated convolution so that each convolution output contains a range of information to avoid information omission of tiny flames. The model accuracy has improved by introducing a Feature Pyramid Network in the feature extraction stage that has enhanced the feature fusion capability of the model. At the same time, a flame detection database for early fire has been established, which contains more than 30 fire scenarios and is suitable for flame detection under various challenging scenes. Experiments validate the proposed method not only improves the performance of the original algorithm but are also advantageous in comparison with other state-of-the-art object detection networks, and its false positives rate reaches 1.2% in the test set.
Continuous Variation in an Aposematic Pattern Affects Background Contrast, but Is Not Associated With Differences in Microhabitat Use
Authors: Yeager Justin , Barnett James B.
Published: March 2022

Variation in aposematic signals was once predicted to be rare, yet in recent years it has become increasingly well documented. Despite increases in the frequency with which polytypism and polymorphism have been suggested to occur, population-wide variance is rarely quantified. We comprehensively sampled a subpopulation of the poison frog Oophaga sylvatica, a species which is polytypic across its distribution and also shows considerable within-population polymorphism. On one hand, color pattern polymorphism could be the result of multifarious selection acting to balance different signaling functions and leading to the evolution of discrete sub-morphs which occupy different fitness peaks. Alternatively, variance could simply be due to relaxed selection, where variation would be predicted to be continuous. We used visual modeling of conspecific and heterospecific observers to quantify the extent of within population phenotypic variation and assess whether this variation produced distinct signals. We found that, despite considerable color pattern variation, variance could not be partitioned into distinct groups, but rather all viewers would be likely to perceive variation as continuous. Similarly, we found no evidence that frog color pattern contrast was either enhanced or diminished in the frogs’ chosen microhabitats compared to alternative patches in which conspecifics were observed. Within population phenotypic variance therefore does not seem to be indicative of strong selection toward multiple signaling strategies, but rather pattern divergence has likely arisen due to weak purifying selection, or neutral processes, on a signal that is highly salient to both conspecifics and predators.
A Joint Model of Random Forest and Artificial Neural Network for the Diagnosis of Endometriosis
Authors: She Jiajie , Su Danna , Diao Ruiying , Wang Liping
Published: March 2022

Endometriosis (EM), an estrogen-dependent inflammatory disease with unknown etiology, affects thousands of childbearing-age couples, and its early diagnosis is still very difficult. With the rapid development of sequencing technology in recent years, the accumulation of many sequencing data makes it possible to screen important diagnostic biomarkers from some EM-related genes. In this study, we utilized public datasets in the Gene Expression Omnibus (GEO) and Array-Express database and identified seven important differentially expressed genes (DEGs) (COMT, NAA16, CCDC22, EIF3E, AHI1, DMXL2, and CISD3) through the random forest classifier. Among these DEGs, AHI1, DMXL2, and CISD3 have never been reported to be associated with the pathogenesis of EMs. Our study indicated that these three genes might participate in the pathogenesis of EMs through oxidative stress, epithelial–mesenchymal transition (EMT) with the activation of the Notch signaling pathway, and mitochondrial homeostasis, respectively. Then, we put these seven DEGs into an artificial neural network to construct a novel diagnostic model for EMs and verified its diagnostic efficacy in two public datasets. Furthermore, these seven DEGs were included in 15 hub genes identified from the constructed protein–protein interaction (PPI) network, which confirmed the reliability of the diagnostic model. We hope the diagnostic model can provide novel sights into the understanding of the pathogenesis of EMs and contribute to the clinical diagnosis and treatment of EMs.
Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma
Authors: Li Yi-Ran , Zong Rui-Qing , Zhang Hong-Yan , Meng Xiao-Yan , Wu Fei-Xiang
Published: March 2022

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression.

Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC.

Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration.

Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.
RA Fibroblast-Like Synoviocytes Derived Extracellular Vesicles Promote Angiogenesis by miRNA-1972 Targeting p53/mTOR Signaling in Vascular Endotheliocyte
Authors: Chen Yixiong , Dang Junlong , Lin Xiaorong , Wang Manli , Liu Yan , Chen Jingrong , Chen Ye , Luo Xiqing , Hu Zuoyu , Weng Weizhen , Shi Xiaoyi , Bi Xuan , Lu Yan , Pan Yunfeng
Published: March 2022

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory in joints. Invasive pannus is a characteristic pathological feature of RA. RA fibroblast-like synoviocytes (FLSs) are showed tumor-like biological characters that facilitate pannus generation. Importantly, it has been documented that extracellular vesicle (EVs) derived microRNAs have a vital role of angiogenesis in various immune inflammatory diseases. However, whether RA FLSs derived EVs can facilitate angiogenesis and the underlying mechanism is undefined. Herein, we aim to investigate the key role of RA FLSs derived EVs on angiogenesis in endothelial cells (ECs). We indicate that RA FLSs derived EVs promote ECs angiogenesis by enhancing migration and tube formation of ECs in vitro. Also, we confirm that RA FLSs derived EVs can significantly facilitate ECs angiogenesis with a matrigel angiogenesis mice model. In terms of the mechanisms, both RNAs and proteins in EVs play roles in promoting ECs angiogenesis, but the RNA parts are more fundamental in this process. By combining microRNA sequencing and qPCR results, miR-1972 is identified to facilitate ECs angiogenesis. The blockage of miR-1972 significantly abrogated the angiogenesis stimulative ability of RA FLSs derived EVs in ECs, while the overexpression of miR-1972 reversed the effect in ECs. Specifically, the p53 level is decreased, and the phosphorylated mTOR is upregulated in miR-1972 overexpressed ECs, indicating that miR-1972 expedites angiogenesis through p53/mTOR pathway. Collectively, RA FLSs derived EVs can promote ECs angiogenesis via miR-1972 targeted p53/mTOR signaling, targeting on RA FLSs derived EVs or miR-1972 provides a promising strategy for the treatment of patients with RA.
The Direct Exposure of Cortisol Does Not Modulate the Expression of Immune-Related Genes on Tissue Explants of Mucosal Surfaces in Rainbow Trout (Oncorhynchus mykiss) Nor in Gilthead Sea Bream (Sparus aurata)
Authors: Vallejos-Vidal Eva , Khansari Ali Reza , Soliva-Dueso Lluc , Balasch Joan Carles , Tort Lluis , Reyes-López Felipe E.
Published: March 2022

The stress response in fish is characterized by the activation of the HPI axis resulting in the release of cortisol. Previous studies in rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata) have shown that an acute stressor modulates the expression of immune- and stress-related genes in mucosal-associated lymphoid tissues (MALTs), particularly in the skin (SALT), gills (GIALT), and gut (GALT). However, there are no antecedents on whether the modulation on the mucosal transcriptomic profile is coordinated through the local presence of cortisol in the mucosal tissue surface. Thus, the aim of this study was to evaluate the effect of cortisol upon the modulation of a set of immune- (il-1β, il-6, tnf-α, and cox-2) and stress-related (hsp70, gr1) genes. For this purpose, tissue explants cultures were incubated with cortisol (100 ng/100 mg tissue) for 2-, 4-, and 24 h and the gene expression profile was evaluated at each time-point by real-time PCR. No differences were found in the gene expression between cortisol-incubated tissue explants and mock-incubated tissues in any of the time-points tested for both species. These results suggest that the quick modulation of the gene expression during the first 24 h after the exposure to stressor challenge reported in previous studies, is probably coordinated and mediated through a systemic-dependent mechanism but not through a peripheral/local response on mucosal tissue surfaces.
Effect of Material Composition on Freeze-Thaw Resistance of Asphalt Fine Aggregate Matrix at Low-Temperatures From Mesoscopic Perspective
Authors: Gong Xiangbing , Zheng Heqi , Liu Wei , Li Xi
Published: March 2022

To explore the significant factors related to the cracking resistance at low temperatures of asphalt mixture from mesoscopic perspective, asphalt fine aggregate matrix (FAM) was selected as the researched material because of its important role in mesoscopic structure of asphalt mixture. Bending Beam Rheometer (BBR) was utilized to investigate low-temperature properties of FAM. Due to the frequent occurrence of freeze-thaw action in seasonally frozen regions, this paper introduces a freeze-thaw cycle test. The structural characteristics of internal air voids in FAM and hot-mix asphalt (HMA) were analyzed using the industrial Computerized Tomography (CT). Results indicate that frost heaving damage of FAM-2.36 is more obvious than that of FAM-1.18, and the damage level increases as the bath temperature rises. After 32 freeze-thaw cycles, FAM-1.18 exhibits the rise of creep stiffness than original beams, and the hardening degree become serious with the decease of temperature. It could be concluded that the BBR has been proved to be an effective tool in evaluating the low-temperature properties of FAM. The expanding limit of small air voids and the hardening of binder in rich asphalt FAM contribute to completely different mechanisms of freezing-thawing damage within FAM. Therefore, asphalt content, fine aggregate passing rate and air voids size could be optimized through BBR test of FAM subjected to freeze-thaw cycle.
Low and High-Density Lipoprotein Cholesterol and 10-Year Mortality in Community-Dwelling Older Adults: The Shanghai Aging Study
Authors: Wu Wanqing , Xiao Zhenxu , Liang Xiaoniu , Zhao Qianhua , Luo Jianfeng , Ding Ding
Published: March 2022

Background

The relationship between serum cholesterol and mortality remains disputed. This study aimed to examine the association of low and high-density lipoprotein cholesterol (LDL-C and HDL-C) with all-cause mortality among community-dwelling older adults in the Shanghai Aging Study.

Methods

We followed 3,239 participants free of lipid-lowering agents for a median of 10 years. Levels of LDL-C and HDL-C were measured at baseline using fasting blood samples. Survival status was confirmed by the local mortality surveillance system. The associations between the levels of LDL-C, HDL-C, and all-cause mortality were assessed by Cox proportional hazards models.

Results

The increment of LDL-C concentration was related to a lower risk of mortality (p for trend < 0.05). Using the highest quintile of LDL-C (≥4.10 mmol/L) as a reference, the lowest quintile of LDL-C (<2.61 mmol/L) was associated with the highest risk of mortality, after adjusting for confounders (HR 1.67; 95% CI 1.26–2.21), exclusion of death within the first 2 years of follow-up (HR 1.57; 95% CI 1.17–2.11), and exclusion of functionally impaired participants (HR 1.46; 95% CI 1.07–2.00). A U-shape relationship was found between HDL-C level and the mortality risk. Using the third quintile of HDL-C (1.21–1.39 mmol/L) as a reference, HR (95% CI) was 1.46 (1.09–1.95) for the lowest quintile (<1.09 mmol/L) and 1.45 (1.07–1.96) for the highest quintile (≥1.61 mmol/L) of HDL-C, after adjusting for confounders; and 1.57 (1.15–2.15) for the lowest quintile and 1.45 (1.04–2.01) for the highest quintile of HDL-C, after exclusion of death within the first 2 years of follow-up; and 1.55 (1.11–2.16) for the lowest quintile and 1.42 (1.00–2.02) for the highest quintile of HDL-C, after exclusion of functionally impaired participants.

Conclusions

We found an inverse association of LDL-C and a U-shape relationship of HDL-C with long-term all-cause mortality in a cohort with community-dwelling older Chinese adults. Levels of LDL-C and HDL-C are suggested to be managed properly in late life.
Pseudomonas stutzeri and Kushneria marisflavi Alleviate Salinity Stress-Associated Damages in Barley, Lettuce, and Sunflower
Authors: Szymańska Sonia , Lis Marta Izabela , Piernik Agnieszka , Hrynkiewicz Katarzyna
Published: March 2022

Soil salinity is one of the most important abiotic factors limiting plant productivity. The aim of this study was to determine the effect of selected halotolerant plant growth-promoting endophytes (PGPEs,Pseudomonas stutzeriISE12 andKushneria marisflaviCSE9) on the growth parameters of barley (Hordeum vulgare), lettuce (Lactuca sativa), and sunflower (Helianthus annuus) cultivated under salt stress conditions. A negative effect of two higher tested salinities (150 and 300 mM NaCl) was observed on the growth parameters of all investigated plants, including germination percentage and index (decreasing compared to the non-saline control variant in the ranges 5.3–91.7 and 13.6–90.9%, respectively), number of leaves (2.2–39.2%), fresh weight (24.2–81.6%); however, differences in salt stress tolerance among the investigated crops were observed (H. annuus>H. vulgare>L. sativa). Our data showed that the most crucial traits affected by endophyte inoculation under salt stress were chlorophyll concentration, leaf development, water storage, root development, and biomass accumulation. Thus, the influence of endophytes was species specific.K. marisflaviCSE9 promoted the growth of all tested plant species and could be considered a universal PGPEs for many plant genotypes cultivated under saline conditions (e.g., increasing of fresh weight compared to the non-inoculated control variant of barley, lettuce, and sunflower in the ranges 11.4–246.8, 118.9–201.2, and 16.4–77.7%, respectively).P. stutzeriISE12 stimulated growth and mitigated salinity stress only in the case of barley. Bioaugmentation of crops with halotolerant bacterial strains can alleviate salt stress and promote plant growth; however, the selection of compatible strains and the verification of universal plant stress indicators are the key factors.
Berberine Improves Vascular Dysfunction by Inhibiting Trimethylamine-N-oxide via Regulating the Gut Microbiota in Angiotensin II-Induced Hypertensive Mice
Authors: Wang Zhichao , Wu Fang , Zhou Qianbing , Qiu Yumin , Zhang Jianning , Tu Qiang , Zhou Zhe , Shao Yijia , Xu Shiyue , Wang Yan , Tao Jun
Published: March 2022

Berberine (BBR) has been demonstrated to exert cardiovascular protective effects by regulating gut microbiota. However, few studies examine the effect of BBR on the gut microbiota in hypertension. This study aims to investigate the role of BBR in regulating microbial alterations and vascular function in hypertension. C57BL/6 J mice were infused with Ang II (0.8 mg/kg/day) via osmotic minipumps and treated with BBR (150 mg/kg/day) or choline (1%) for 4 weeks. Blood pressure was detected by tail-cuff measurement once a week. Abdominal aorta pulse wave velocity (PWV) and endothelium dependent vasodilatation were measured to evaluate vascular function. Vascular remodeling was assessed by histological staining of aortic tissue. The fecal microbiota was profiled using 16S ribosomal DNA (rDNA) sequencing. Plasma trimethylamine (TMA)/trimethylamine-N-oxide (TMAO) and hepatic FMO3 expression were measured. We found that BBR treatment significantly alleviated the elevated blood pressure, vascular dysfunction, and pathological remodeling in Ang II-induced hypertensive mice, while choline treatment aggravated hypertension-related vascular dysfunction. 16S rDNA gene sequencing results showed that BBR treatment altered gut microbiota composition (reduced the Firmicutes/Bacteroidetes (F/B) ratio and increased the abundances of Lactobacillus). Moreover, BBR inhibited FMO3 expression and plasma TMA/TMAO production in hypertensive mice. TMAO treatment increased the apoptosis and oxidative stress of human aortic endothelial cells (HAECs) and aggravated Ang II-induced HAECs dysfunction in vitro. These results indicate that the protective effect of BBR in hypertension might be attributed (at least partially) to the inhibition of TMAO production via regulating the gut microbiota.
Sub-Lineage Specific Phenolic Glycolipid Patterns in the Mycobacterium tuberculosis Complex Lineage 1
Authors: Gisch Nicolas , Utpatel Christian , Gronbach Lisa M. , Kohl Thomas A. , Schombel Ursula , Malm Sven , Dobos Karen M. , Hesser Danny C. , Diel Roland , Götsch Udo , Gerdes Silke , Shuaib Yassir A. , Ntinginya Nyanda E. , Khosa Celso , Viegas Sofia , Kerubo Glennah , Ali Solomon , Al-Hajoj Sahal A. , Ndung’u Perpetual W. , Rachow Andrea , Hoelscher Michael , Maurer Florian P. , Schwudke Dominik , Niemann Stefan , Reiling Norbert , Homolka Susanne
Published: March 2022

“Ancestral” Mycobacterium tuberculosis complex (MTBC) strains of Lineage 1 (L1, East African Indian) are a prominent tuberculosis (TB) cause in countries around the Indian Ocean. However, the pathobiology of L1 strains is insufficiently characterized. Here, we used whole genome sequencing (WGS) of 312 L1 strains from 43 countries to perform a characterization of the global L1 population structure and correlate this to the analysis of the synthesis of phenolic glycolipids (PGL) – known MTBC polyketide-derived virulence factors. Our results reveal the presence of eight major L1 sub-lineages, whose members have specific mutation signatures in PGL biosynthesis genes, e.g., pks15/1 or glycosyltransferases Rv2962c and/or Rv2958c. Sub-lineage specific PGL production was studied by NMR-based lipid profiling and strains with a completely abolished phenolphthiocerol dimycoserosate biosynthesis showed in average a more prominent growth in human macrophages. In conclusion, our results show a diverse population structure of L1 strains that is associated with the presence of specific PGL types. This includes the occurrence of mycoside B in one sub-lineage, representing the first description of a PGL in an M. tuberculosis lineage other than L2. Such differences may be important for the evolution of L1 strains, e.g., allowing adaption to different human populations.
Novel Cesium Resistance Mechanism of Alkaliphilic Bacterium Isolated From Jumping Spider Ground Extract
Authors: Koretsune Takahiro , Ishida Yoshiki , Kaneda Yuri , Ishiuchi Eri , Teshima Miyu , Marubashi Nanami , Satoh Katsuya , Ito Masahiro
Published: March 2022

The radionuclide isotopes (134Cs and 137Cs) of Cesium (Cs), an alkali metal, are attracting attention as major causes of radioactive contamination. Although Cs+ is harmful to the growth of plants and bacteria, alkaliphilic bacterium Microbacterium sp. TS-1, isolated from a jumping spider, showed growth even in the presence of 1.2 M CsCl. The maximum concentration of Cs+ that microorganisms can withstand has been reported to be 700 mM till date, suggesting that the strain TS-1 is resistant to a high concentration of Cs ions. Multiple reports of cesium ion-resistant bacteria have been reported, but the detailed mechanism has not yet been elucidated. We obtained Cs ion-sensitive mutants and their revertant mutants from strain TS-1 and identified a Cs ion resistance-related gene, MTS1_00475, by performing SNP analysis of the whole-genome sequence data. When exposed to more than 200 mM Cs+ concentration, the intracellular Cs+ concentration was constantly lowered by MTS1_00475, which encodes the novel low-affinity Cs+/H+ antiporter. This study is the first to clarify the mechanism of cesium resistance in unexplained cesium-resistant microorganisms. By clarifying the new cesium resistance mechanism, it can be expected to be used as a bioremediation tool for treating radioactive Cs+ contaminated water.
Microbiota Survey of Sliced Cooked Ham During the Secondary Shelf Life
Authors: Spampinato Gloria , Candeliere Francesco , Amaretti Alberto , Licciardello Fabio , Rossi Maddalena , Raimondi Stefano
Published: March 2022

Sliced cooked ham packaged in a modified atmosphere is a popular ready-to-eat product, subjected to abundant microbial contamination throughout its shelf life that can lead to deterioration of both sensorial properties and safety. In this study, the microbial load and the chemical–physical features of cooked ham of five producers were monitored for a period of 12 days after the opening of the packages (i.e., the secondary shelf life), during which the products were stored in a domestic refrigerator at 5.2 ± 0.6°C. The sensorial properties presented a perceivable decay after 8 days and became unacceptable after 12 days. High-performance liquid chromatography analysis and solid-phase microextraction coupled with gas chromatography profiling of volatile metabolites indicated that lactic acid, ethanol, acetic acid, acetoin, 3-methyl-1-butanol, and 2-3 butanediol were the main metabolites that characterized the evolution of the analyzed cooked ham. The microbiota was monitored by 16S ribosomal RNA gene profiling and culture-dependent techniques. Already at the opening of packages, all the products presented high microbial load, generally dominated by lactic acid bacteria, with evident differences among the products. The increase of lactic acid bacteria somehow protected samples from abundant contamination by other bacteria, concurring with the evolution of more safe products. This role was exerted by numerous Latilactobacillus, Leuconostoc, and Carnobacterium species, among which the most frequently detected were Latilactobacillus sakei, Latilactobacillus sakei carnosum, Leuconostoc mesenteroides, and Carnobacterium divergens. Some products presented more complex communities that encompassed Proteobacteria such as Moellerella wisconsensis, Proteus hauseri, Brochothrix thermosphacta, and less frequently Pseudomonas, Erwinia, and Massilia. Opportunistic pathogenic bacteria such as Escherichia coli and Vibrio sp. were found in small quantities. The yeasts Kazachstania servazzii and Debaryomyces hansenii occurred already at 0 days, whereas various species of Candida (Candida zeylanoides, Candida sake, Candida norvegica, and Candida glaebosa) were abundant only after 12 days. These results indicated that the microbiological contaminants overgrowing during the secondary shelf life did not derive from environmental cross-contamination at the opening of the tray but were already present when the packages were opened, highlighting the phases of production up to the packaging as those crucial in managing the safety risk associated to this product.
Multifunctional pMGF505-7R Is a Key Virulence-Related Factor of African Swine Fever Virus
Authors: Huang Li , Li Jiangnan , Zheng Jun , Li Dan , Weng Changjiang
Published: March 2022

African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), and it is an enveloped, icosahedral, double-stranded DNA virus with a genome length ranging from 170 to 193 kb. The ASFV genome contains at least five multigene families (MGFs): MGF100, MGF110, MGF300, MGF360, and MGF505 at the right and left terminal variable regions. The members of the same MGF family are most similar and have conserved sequence motifs, whereas the genetic diversity of different MGF families varies widely. MGF genes play a crucial role in determining ASFV host range, virulence and reducing early cell death post-infection. pMGF505-7R is a multifunctional protein. Recent research advances of pMGF505-7R provide a few new clues to understand the functions of pMGF505-7R either in antagonizing the induction of type I IFN production and IFN downstream signaling or in suppressing inflammatory responses by inhibition of NF-κB signaling and NLRP3 inflammasome, which may be related to ASFV infection-induced pathogenesis.
Continuous Renal Replacement Therapy in Acute Brain Injury
Authors: Cruz-Llanos Luis , Molano Alejandra , Rizo-Topete Lilia
Published: March 2022

Acute brain injury is the sudden and reversible loss of brain self regulation capacity as a disruption of the blood-brain barrier that conditions metabolic and inflammatory disorders that can exacerbate acute kidney injury in a critical setting; specifically it has been described that the alterations of the internal environment that come from the severity of the acute kidney injury increases the risk of endocranial hypertension and cerebral edema; in this context, injuries should be identified and treated in a timely manner with a comprehensive approach. Continuous renal replacement therapy is an extracorporeal purification technique that has been gaining ground in the management of acute kidney injury in critically ill patients. Within its modalities, continuous venous venous hemofiltration is described as the therapy of choice in patients with acute brain injury due to its advantages in maintaining hemodynamic stability and reducing the risk of cerebral edema. Optimal control of variables such as timing to start renal replacement therapy, the prescribed dose, the composition of the replacement fluid and the anticoagulation of the extracorporeal circuit will have a significant impact on the evolution of the neurocritical patient with acute kidney injury. There are limited studies evaluating the role of hemofiltration in this context.
Effect of Impaired Stereoscopic Vision on Large-Scale Resting-State Functional Network Connectivity in Comitant Exotropia Patients
Authors: Jin Han , Chen Ri-Bo , Zhong Yu-Lin , Lai Ping-Hong , Huang Xin
Published: March 2022

Background

Comitant exotropia (CE) is a common eye movement disorder, characterized by impaired eye movements and stereoscopic vision. CE patients reportedly exhibit changes in the central nervous system. However, it remains unclear whether large-scale brain network changes occur in CE patients.

Purpose

This study investigated the effects of exotropia and stereoscopic vision dysfunction on large-scale brain networks in CE patients via independent component analysis (ICA).

Methods

Twenty-eight CE patients (mean age, 15.80 ± 2.46 years) and 27 healthy controls (HCs; mean age, 16.00 ± 2.68 years; closely matched for age, sex, and education) underwent resting-state magnetic resonance imaging. ICA was applied to extract resting-state networks (RSNs) in both groups. Two-sample’s t-tests were conducted to investigate intranetwork functional connectivity (FC) within RSNs and interactions among RSNs between the two groups.

Results

Compared with the HC group, the CE group showed increased intranetwork FC in the bilateral postcentral gyrus of the sensorimotor network (SMN). The CE group also showed decreased intranetwork FC in the right cerebellum_8 of the cerebellum network (CER), the right superior temporal gyrus of the auditory network (AN), and the right middle occipital gyrus of the visual network (VN). Moreover, functional network connectivity (FNC) analysis showed that CER-AN, SMN-VN, SN-DMN, and DMN-VN connections were significantly altered between the two groups.

Conclusion

Comitant exotropia patients had abnormal brain networks related to the CER, SMN, AN, and VN. Our results offer important insights into the neural mechanisms of eye movements and stereoscopic vision dysfunction in CE patients.
Biochemical Characterization of Some Varieties of Apricot Present in the Vesuvius Area, Southern Italy
Authors: Fratianni Florinda , Cozzolino Rosaria , d'Acierno Antonio , Ombra Maria Neve , Spigno Patrizia , Riccardi Riccardo , Malorni Livia , Stocchero Matteo , Nazzaro Filomena
Published: March 2022

The witnesses of the millenary history ofCampania felixin southern Italy highlighted that several fruit and vegetables cultivated in such territory could potentially be a treasure trove of important health elements. Our work evaluated the content of β-carotene, ascorbic acid, and total phenolics and the antioxidant activity of ten typical varieties of apricots cultivated in the Vesuvius area in the Campania region. The total polyphenols varied between 10.24 and 34.04 mg/100 g of a fresh sample. The amount of ascorbic acid also varied greatly, ranging from 2.65 to 10.65 mg/100 g of a fresh product. B-Carotene reached values up to 0.522 mg/100 g of the fresh sample. The correlation analysis performed, accounting for these parameters, showed that the antioxidant activity, calculated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay) and azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) tests, was influenced mainly by the content of total polyphenols, with ρ = −0.762 and ρ = 0.875 when we considered DPPH and ABTS tests, respectively, slightly less by the content of ascorbic acid, and not by β-carotene. The dendrogram clustered eight varieties into two main groups; on the other hand, two varieties (“Vitillo” and “Preveta bella”) seemed hierarchically distant. The gas chromatography–mass spectrometry (GC–MS) analysis of volatile organic compounds (VOCs), herein performed for the first time, demonstrated the influence of the varieties on the VOC profiles, both from a qualitative and semiquantitative perspective, discriminating the varieties in different clusters, each of which was characterized by specific notes. α-Terpinolene was the only terpene identified by GC–MS that appeared to affect the antioxidant activity.
A Risk Scoring System Utilizing Machine Learning Methods for Hepatotoxicity Prediction One Year After the Initiation of Tyrosine Kinase Inhibitors
Authors: Han Ji Min , Yee Jeong , Cho Soyeon , Kim Min Kyoung , Moon Jin Young , Jung Dasom , Kim Jung Sun , Gwak Hye Sun
Published: March 2022

Background

There is currently no method to predict tyrosine kinase inhibitor (TKI) -induced hepatotoxicity. The purpose of this study was to propose a risk scoring system for hepatotoxicity induced within one year of TKI administration using machine learning methods.

Methods

This retrospective, multi-center study analyzed individual data of patients administered different types of TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib) selected in five previous studies. The odds ratio and adjusted odds ratio from univariate and multivariate analyses were calculated using a chi-squared test and logistic regression model. Machine learning methods, including five-fold cross-validated multivariate logistic regression, elastic net, and random forest were utilized to predict risk factors for the occurrence of hepatotoxicity. A risk scoring system was developed from the multivariate and machine learning analyses.

Results

Data from 703 patients with grade II or higher hepatotoxicity within one year of TKI administration were evaluated. In a multivariable analysis, male and liver metastasis increased the risk of hepatotoxicity by 1.4-fold and 2.1-fold, respectively. The use of anticancer drugs increased the risk of hepatotoxicity by 6.0-fold. Patients administered H2 blockers or PPIs had a 1.5-fold increased risk of hepatotoxicity. The area under the receiver-operating curve (AUROC) values of machine learning methods ranged between 0.73-0.75. Based on multivariate and machine learning analyses, male (1 point), use of H2 blocker or PPI (1 point), presence of liver metastasis (2 points), and use of anticancer drugs (4 points) were integrated into the risk scoring system. From a training set, patients with 0, 1, 2-3, 4-7 point showed approximately 9.8%, 16.6%, 29.0% and 61.5% of risk of hepatotoxicity, respectively. The AUROC of the scoring system was 0.755 (95% CI, 0.706-0.804).

Conclusion

Our scoring system may be helpful for patient assessment and clinical decisions when administering TKIs included in this study.
Upregulation of MTA1 in Colon Cancer Drives A CD8+ T Cell-Rich But Classical Macrophage-Lacking Immunosuppressive Tumor Microenvironment
Authors: Zhou Yantong , Nan Peng , Li Chunxiao , Mo Hongnan , Zhang Ying , Wang Haijuan , Xu Dongkui , Ma Fei , Qian Haili
Published: March 2022

Background

The MTA1 protein encoded by metastasis-associated protein 1 (MTA1) is a key component of the ATP-dependent nucleosome remodeling and deacetylase (NuRD) complex, which is widely upregulated in cancers. MTA1 extensively affects downstream gene expression by participating in chromatin remodeling. Although it was defined as a metastasis-associated gene in first reports and metastasis is a process prominently affected by the tumor microenvironment, whether it affects the microenvironment has not been investigated. In our study, we elucidated the regulatory effect of MTA1 on tumor-associated macrophages (TAMs) and how this regulation affects the antitumor effect of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment of colorectal cancer.

Methods

We detected the cytokines affected by MTA1 expression via a cytokine antibody array in control HCT116 cells and HCT116 cells overexpressing MTA1. Multiplex IHC staining was conducted on a colorectal cancer tissue array from our cancer cohort. Flow cytometry (FCM) was performed to explore the polarization of macrophages in the coculture system and the antitumor killing effect of CTLs in the coculture system. Bioinformatics analysis was conducted to analyze the Cancer Genome Atlas (TCGA) colorectal cancer cohort and single-cell RNA-seq data to assess the immune infiltration status of the TCGA colorectal cancer cohort and the functions of myeloid cells.

Results

MTA1 upregulation in colorectal cancer was found to drive an immunosuppressive tumor microenvironment. In the tumor microenvironment of MTA1-upregulated colorectal cancer, although CD8+ T cells were significantly enriched, macrophages were significantly decreased, which impaired the CTL effect of the CD8+ T cells on tumor cells. Moreover, upregulated MTA1 in tumor cells significantly induced infiltrated macrophages into tumor-associated macrophage phenotypes and further weakened the cytotoxic effect of CD8+ T cells.

Conclusion

Upregulation of MTA1 in colorectal cancer drives an immunosuppressive tumor microenvironment by decreasing the microphages from the tumor and inducing the residual macrophages into tumor-associated microphage phenotypes to block the activation of the killing CTL, which contributes to cancer progression.