bluuebunny/crossref_metadata_2025 huggingface dataset:
Hippocampal ceRNA networks from chronic intermittent ethanol vapor-exposed male mice and functional analysis of top-ranked lncRNA genes for ethanol drinking phenotypes
Authors: Plasil Sonja L. , Collins Valerie J. , Baratta Annalisa M. , Farris Sean P. , Homanics Gregg E.
Published: December 2022

The molecular mechanisms regulating the development and progression of alcohol use disorder (AUD) are largely unknown. While noncoding RNAs have previously been implicated as playing key roles in AUD, long-noncoding RNA (lncRNA) remains understudied in relation to AUD. In this study, we first identified ethanol-responsive lncRNAs in the mouse hippocampus that are transcriptional network hub genes. Microarray analysis of lncRNA, miRNA, circular RNA, and protein coding gene expression in the hippocampus from chronic intermittent ethanol vapor- or air- (control) exposed mice was used to identify ethanol-responsive competing endogenous RNA (ceRNA) networks. Highly interconnected lncRNAs (genes that had the strongest overall correlation to all other dysregulated genes identified) were ranked. The top four lncRNAs were novel, previously uncharacterized genes named Gm42575, 4930413E15Rik, Gm15767, and Gm33447, hereafter referred to as Pitt1, Pitt2, Pitt3, and Pitt4, respectively. We subsequently tested the hypothesis that CRISPR/Cas9 mutagenesis of the putative promoter and first exon of these lncRNAs in C57BL/6J mice would alter ethanol drinking behavior. The Drinking in the Dark (DID) assay was used to examine binge-like drinking behavior, and the Every-Other-Day Two-Bottle Choice (EOD-2BC) assay was used to examine intermittent ethanol consumption and preference. No significant differences between control and mutant mice were observed in the DID assay. Female-specific reductions in ethanol consumption were observed in the EOD-2BC assay for Pitt1, Pitt3, and Pitt4 mutant mice compared to controls. Male-specific alterations in ethanol preference were observed for Pitt1 and Pitt2. Female-specific increases in ethanol preference were observed for Pitt3 and Pitt4. Total fluid consumption was reduced in Pitt1 and Pitt2 mutants at 15% v/v ethanol and in Pitt3 and Pitt4 at 20% v/v ethanol in females only. We conclude that all lncRNAs targeted altered ethanol drinking behavior, and that lncRNAs Pitt1, Pitt3, and Pitt4 influenced ethanol consumption in a sex-specific manner. Further research is necessary to elucidate the biological mechanisms for these effects. These findings add to the literature implicating noncoding RNAs in AUD and suggest lncRNAs also play an important regulatory role in the disease.
Multiobjective optimization algorithm for accurate MADYMO reconstruction of vehicle-pedestrian accidents
Authors: Zou Donghua , Fan Ying , Liu Ningguo , Zhang Jianhua , Liu Dikun , Liu Qingfeng , Li Zhengdong , Wang Jinming , Huang Jiang
Published: December 2022

In vehicle–pedestrian accidents, the preimpact conditions of pedestrians and vehicles are frequently uncertain. The incident data for a crash, such as vehicle deformation, injury of the victim, distance of initial position and rest position of accident participants, are useful for verification in MAthematical DYnamic MOdels (MADYMO) simulations. The purpose of this study is to explore the use of an improved optimization algorithm combined with MADYMO multibody simulations and crash data to conduct accurate reconstructions of vehicle–pedestrian accidents. The objective function of the optimization problem was defined as the Euclidean distance between the known vehicle, human and ground contact points, and multiobjective optimization algorithms were employed to obtain the local minima of the objective function. Three common multiobjective optimization algorithms—nondominated sorting genetic algorithm-II (NSGA-II), neighbourhood cultivation genetic algorithm (NCGA), and multiobjective particle swarm optimization (MOPSO)—were compared. The effect of the number of objective functions, the choice of different objective functions and the optimal number of iterations were also considered. The final reconstructed results were compared with the process of a real accident. Based on the results of the reconstruction of a real-world accident, the present study indicated that NSGA-II had better convergence and generated more noninferior solutions and better final solutions than NCGA and MOPSO. In addition, when all vehicle-pedestrian-ground contacts were considered, the results showed a better match in terms of kinematic response. NSGA-II converged within 100 generations. This study indicated that multibody simulations coupled with optimization algorithms can be used to accurately reconstruct vehicle-pedestrian collisions.
Multi-level multi-domain statistical shape model of the subtalar, talonavicular, and calcaneocuboid joints
Authors: Peterson Andrew C. , Lisonbee Rich J. , Krähenbühl Nicola , Saltzman Charles L. , Barg Alexej , Khan Nawazish , Elhabian Shireen Y. , Lenz Amy L.
Published: December 2022

Traditionally, two-dimensional conventional radiographs have been the primary tool to measure the complex morphology of the foot and ankle. However, the subtalar, talonavicular, and calcaneocuboid joints are challenging to assess due to their bone morphology and locations within the ankle. Weightbearing computed tomography is a novel high-resolution volumetric imaging mechanism that allows detailed generation of 3D bone reconstructions. This study aimed to develop a multi-domain statistical shape model to assess morphologic and alignment variation of the subtalar, talonavicular, and calcaneocuboid joints across an asymptomatic population and calculate 3D joint measurements in a consistent weightbearing position. Specific joint measurements included joint space distance, congruence, and coverage. Noteworthy anatomical variation predominantly included the talus and calcaneus, specifically an inverse relationship regarding talar dome heightening and calcaneal shortening. While there was minimal navicular and cuboid shape variation, there were alignment variations within these joints; the most notable is the rotational aspect about the anterior-posterior axis. This study also found that multi-domain modeling may be able to predict joint space distance measurements within a population. Additionally, variation across a population of these four bones may be driven far more by morphology than by alignment variation based on all three joint measurements. These data are beneficial in furthering our understanding of joint-level morphology and alignment variants to guide advancements in ankle joint pathological care and operative treatments.
Reduction of the in vitro toxicity of elevated concentrations of SPIONLA by its administration through PHBV/curcumin composite microspheres
Authors: Aguilar-Rabiela Arturo E. , Unterweger Harald , Alexiou Christoph , Boccaccini Aldo R.
Published: December 2022

Superparamagnetic iron oxide nanoparticles have been developed for various biomedical applications for decades. In this work, lauric acid-coated SPION (SPIONLA) were incorporated into poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) at different ratios to produce composite microspheres, which were evaluated for their properties, including potential cytotoxicity. Additionally, a phytotherapeutic extract, curcumin, was loaded into the resulting microspheres to develop magnetic drug delivery capsules. The results show a significant improvement in the cytocompatibility after 7 days of SPIONLA administrated in cells through the composite microspheres compared to pristine SPIONLA. The composite also exhibited prolonged cumulative release of curcumin in a simulated body fluid environment. The results confirmed the efficacy of the mixture of PHBV and curcumin in attenuating potential side effects due to direct administration of high initial amounts of SPIONLA while maintaining magnetic properties in the resulting composite. The results add evidence to the potential of these composite devices for targeted drug delivery applications.
Mechanochemical subcellular-element model of crawling cells
Authors: Tarama Mitsusuke , Mori Kenji , Yamamoto Ryoichi
Published: December 2022

Constructing physical models of living cells and tissues is an extremely challenging task because of the high complexities of both intra- and intercellular processes. In addition, the force that a single cell generates vanishes in total due to the law of action and reaction. The typical mechanics of cell crawling involve periodic changes in the cell shape and in the adhesion characteristics of the cell to the substrate. However, the basic physical mechanisms by which a single cell coordinates these processes cooperatively to achieve autonomous migration are not yet well understood. To obtain a clearer grasp of how the intracellular force is converted to directional motion, we develop a basic mechanochemical model of a crawling cell based on subcellular elements with the focus on the dependence of the protrusion and contraction as well as the adhesion and de-adhesion processes on intracellular biochemical signals. By introducing reaction-diffusion equations that reproduce traveling waves of local chemical concentrations, we clarify that the chemical dependence of the cell-substrate adhesion dynamics determines the crawling direction and distance with one chemical wave. Finally, we also perform multipole analysis of the traction force to compare it with the experimental results. Our present work sheds light on how intracellular chemical reactions are converted to a directional cell migration under the force-free condition. Although the detailed mechanisms of actual cells are far more complicated than our simple model, we believe that this mechanochemical model is a good prototype for more realistic models.
Last resort beta-lactam antibiotics for treatment of New-Delhi Metallo-Beta-Lactamase producing Enterobacterales and other Difficult-to-Treat Resistance in Gram-negative bacteria: A real-life study
Authors: Larcher Romaric , Laffont-Lozes Paul , Roger Claire , Doncesco Regine , Groul-Viaud Celine , Martin Aurelie , Loubet Paul , Lavigne Jean-Philippe , Pantel Alix , Sotto Albert
Published: December 2022

Introduction

Novel last resort beta-lactam antibiotics are now available for management of infections due to New-Delhi Metallo-Beta-Lactamase (NDM) producing Enterobacterales and non-fermenters with Difficult-to-Treat Resistance. However, data regarding the use of imipenem-cilastatin-relebactam (IMI-REL), cefiderocol (CFD) and ceftazidime-avibactam plus aztreonam (CAZ-AVI-ATM) are scarce in real-life settings. This study aimed to describe the use of last resort beta-lactam antibiotics, the microbiology and the outcome, in patients hospitalized in a tertiary hospital.

Methods

We conducted a monocentric observational cohort study from 2020/01/01, to 2022/08/31. We screened all patients admitted to Nimes University Hospital who have received ≥ 1 dose of last resort beta-lactam antibiotics during the study period, using the Pharmacy database. We included patients treated with IMI-REL, CFD and CAZ-AVI-ATM. The primary endpoint was the infection-free survival rate. We also calculated rates of microbiological and clinical cure, recurrent infection, death and adverse events.

Results

Twenty-seven patients were included in the study and 30 treatment courses were analyzed: CFD (N=24; 80%), CAZ-AVI-ATM (N=3; 10%) and IMI-REL (N=3; 10%). Antibiotics were used in 21 males (70%) and 9 females (30%) with a median age at 65-year-old [50-73.5] and a median Charlson index at 1 [0-2]. Almost all the patients had ≥ 1 risk factor for carbapenem resistant bacteria, a half of them was hospitalized for severe COVID-19, and most of antibiotic courses (N=26; 87%) were associated with ICU admission. In the study population, the probability of infection-free survival at day-90 after last resort beta-lactam therapy initiation was 48.4% CI95% [33.2-70.5]. Clinical failure rate was at 30%, microbiological failure rate at 33% and mortality rate at 23%. Adverse events were documented in 5 antibiotic courses (17%). In details, P. aeruginosa were mainly treated with CFD and IMI-REL, S. maltophilia with CFD and CAZ-AVI-ATM, A. baumannii with CFD, and NDM producing-K. pneumoniae with CAZ-AVI-ATM and CFD. After a treatment course with CFD, CAZ-AVI-ATM and IMI-REL, the probability of infection-free survival was 48% CI95% [10.4-73.5], 33.3% CI95% [6.7-100], 66.7% CI95% [30-100], respectively.

Discussion/conclusion

Use of last resort beta-lactam antimicrobials in real-life settings was a safe and efficient therapeutic option for severe infections related to Gram-negative bacteria with Difficult-to-Treat Resistance.
Collective behavior and virulence arsenal of the fish pathogen Piscirickettsia salmonis in the biofilm realm
Authors: Levipan Héctor A. , Irgang Rute , Opazo L. Felipe , Araya-León Henry , Avendaño-Herrera Ruben
Published: December 2022

Piscirickettsiosis is a fish disease caused by the Gram-negative bacteriumPiscirickettsia salmonis.This disease has a high socio-economic impact on the Chilean salmonid aquaculture industry. The bacterium has a cryptic character in the environment and their main reservoirs are yet unknown. Bacterial biofilms represent a ubiquitous mechanism of cell persistence in diverse natural environments and a risk factor for the pathogenesis of several infectious diseases, but their microbiological significance for waterborne veterinary diseases, including piscirickettsiosis, have seldom been evaluated. This study analyzed thein vitrobiofilm behavior ofP.salmonisLF-89T(genogroup LF-89) and CA5 (genogroup EM-90) using a multi-method approach and elucidated the potential arsenal of virulence of theP.salmonisLF-89Ttype strain in its biofilm state.P.salmonisexhibited a quick kinetics of biofilm formation that followed a multi-step and highly strain-dependent process. There were no major differences in enzymatic profiles or significant differences in cytotoxicity (as tested on the Chinook salmon embryo cell line) between biofilm-derived bacteria and planktonic equivalents. The potential arsenal of virulence ofP.salmonisLF-89Tin biofilms, as determined by whole-transcriptome sequencing and differential gene expression analysis, consisted of genes involved in cell adhesion, polysaccharide biosynthesis, transcriptional regulation, and gene mobility, among others. Importantly, the global gene expression profiles ofP.salmonisLF-89Twere not enriched with virulence-related genes upregulated in biofilm development stages at 24 and 48 h. An enrichment in virulence-related genes exclusively expressed in biofilms was also undetected. These results indicate that early and mature biofilm development stages ofP.salmonisLF-89Twere transcriptionally no more virulent than their planktonic counterparts, which was supported by cytotoxic trials, which, in turn, revealed that both modes of growth induced important and very similar levels of cytotoxicity on the salmon cell line. Our results suggest that the aforementioned biofilm development stages do not represent hot spots of virulence compared with planktonic counterparts. This study provides the first transcriptomic catalogue to select specific genes that could be useful to prevent or control the (in vitroand/orin vivo) adherence and/or biofilm formation byP.salmonisand gain further insights into piscirickettsiosis pathogenesis.
Metastatic patterns and prognosis of patients with primary malignant cardiac tumor
Authors: Guan Tianwang , Wei Qingqian , Tang Yongshi , Zhao Hongjun , Lu Zhenxing , Feng Weijing , Teng Yintong , Luo Zehao , Chi Kaiyi , Ou Caiwen , Chen Minsheng
Published: December 2022

Background

Distant metastases are independent negative prognostic factors for patients with primary malignant cardiac tumors (PMCT). This study aims to further investigate metastatic patterns and their prognostic effects in patients with PMCT.

Materials and methods

This multicenter retrospective study included 218 patients with PMCT diagnosed between 2010 and 2017 from Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was utilized to identify metastatic risk factors. A Chi-square test was performed to assess the metastatic rate. Kaplan–Meier methods and Cox regression analysis were used to analyze the prognostic effects of metastatic patterns.

Results

Sarcoma (p = 0.002) and tumor size¿4 cm (p = 0.006) were independent risk factors of distant metastases in patients with PMCT. Single lung metastasis (about 34%) was the most common of all metastatic patterns, and lung metastases occurred more frequently (17.9%) than bone, liver, and brain. Brain metastases had worst overall survival (OS) and cancer-specific survival (CSS) among other metastases, like lung, bone, liver, and brain (OS: HR = 3.20, 95% CI: 1.02–10.00, p = 0.046; CSS: HR = 3.53, 95% CI: 1.09–11.47, p = 0.036).

Conclusion

Patients with PMCT who had sarcoma or a tumor larger than 4 cm had a higher risk of distant metastases. Lung was the most common metastatic site, and brain metastases had worst survival among others, such as lung, bone, liver, and brain. The results of this study provide insight for early detection, diagnosis, and treatment of distant metastases associated with PMCT.
The optimal pulse pressures for healthy adults with different ages and sexes correlate with cardiovascular health metrics
Authors: Chou Chung-Hsing , Yin Jiu-Haw , Lin Yu-Kai , Yang Fu-Chi , Chu Ta-Wei , Chuang Yuan Chieh , Lin Chia Wen , Peng Giia-Sheun , Sung Yueh-Feng
Published: December 2022

Background

Pulse pressure (PP) may play a role in the development of cardiovascular disease, and the optimal PP for different ages and sexes is unknown. In a prospective cohort, we studied subjects with favorable cardiovascular health (CVH), proposed the mean PP as the optimal PP values, and demonstrated its relationship with healthy lifestyles.

Methods and results

Between 1996 and 2016, a total of 162,636 participants (aged 20 years or above; mean age 34.9 years; 26.4% male subjects; meeting criteria for favorable health) were recruited for a medical examination program. PP in male subjects was 45.6 ± 9.4 mmHg and increased after the age of 50 years. PP in female subjects was 41.8 ± 9.5 mmHg and increased after the age of 40 years, exceeding that of male subjects after the age of 50 years. Except for female subjects with a PP of 40–70 mmHg, PP increase correlates with both systolic blood pressure (BP) increase and diastolic BP decrease. Individuals with mean PP values are more likely to meet health metrics, including body mass index (BMI) <25 kg/m2 (chi-squared = 9.35, p<0.01 in male subjects; chi-squared = 208.79, p < 0.001 in female subjects) and BP <120/80 mmHg (chi-squared =1,300, p < 0.001 in male subjects; chi-squared =11,000, p < 0.001 in female subjects). We propose a health score (Hscore) based on the sum of five metrics (BP, BMI, being physically active, non-smoking, and healthy diet), which significantly correlates with the optimal PP.

Conclusion

The mean PP (within ±1 standard deviation) could be proposed as the optimal PP in the adult population with favorable CVH. The relationship between health metrics and the optimal PP based on age and sex was further demonstrated to validate the Hscore.
Risk of stroke and retinopathy during GLP-1 receptor agonist cardiovascular outcome trials: An eight RCTs meta-analysis
Authors: Wei Jinjing , Yang Bing , Wang Ruxin , Ye Haowen , Wang Ying , Wang Lihong , Zhang Xiaofang
Published: December 2022

Purpose

To explore the risk of stroke (including ischemic and hemorrhagic stroke) in type 2 diabetes mellitus treated with glucagon-like peptide 1 receptor agonist (GLP-1RA) medication according to data from the Cardiovascular Outcome Trials(CVOT).

Methods

Randomized controlled trials (RCT) on GLP-1RA therapy and cardiovascular outcomes in type 2 diabetics published in full-text journal databases such as Medline (via PubMed), Embase, Clinical Trials.gov, and the Cochrane Library from establishment to May 1, 2022 were searched. We assess the quality of individual studies by using the Cochrane risk of bias algorithm. RevMan 5.4.1 software was use for calculating meta- analysis.

Results

A total of 60,081 randomized participants were included in the data of these 8 GLP-1RA cardiovascular outcomes trials. Pooled analysis reported statistically significant effect on total stroke risk[RR=0.83, 95%CI(0.73, 0.95), p=0.005], and its subtypes such as ischemic Stroke [RR=0.83, 95%CI(0.73, 0.95), p=0.008] from treatment with GLP-1RA versus placebo, and have no significant effect on the risk of hemorrhagic stroke[RR=0.83, 95%CI(0.57, 1.20), p=0.31] and retinopathy [RR=1.54, 95%CI(0.74, 3.23), p=0.25]

Conclusion

GLP-1RA significantly reduces the risk of ischemic stroke in type 2 diabetics with cardiovascular risk factors.
Sclerostin as a biomarker of physical exercise in osteoporosis: A narrative review
Authors: Oniszczuk Anna , Kaczmarek Agnieszka , Kaczmarek Mateusz , Ciałowicz Maria , Arslan Ersan , Silva Ana Filipa , Clemente Filipe Manuel , Murawska-Ciałowicz Eugenia
Published: December 2022

Osteoporosis, a disease of low bone mass, is characterized by reduced bone mineral density (BMD) through abnormalities in the microarchitecture of bone tissue. It affects both the social and economic areas, therefore it has been considered a lifestyle disease for many years. Bone tissue is a dynamic structure exhibiting sensitivity to various stimuli, including mechanical ones, which are a regulator of tissue sclerostin levels. Sclerostin is a protein involved in bone remodeling, showing an anti-anabolic effect on bone density. Moderate to vigorous physical activity inhibits secretion of this protein and promotes increased bone mineral density. Appropriate exercise has been shown to have an osteogenic effect. The effectiveness of osteogenic training depends on the type, intensity, regularity and frequency of exercise and the number of body parts involved. The greatest osteogenic activity is demonstrated by exercises affecting bone with high ground reaction forces (GRF) and high forces exerted by contracting muscles (JFR). The purpose of this study was to review the literature for the effects of various forms of exercise on sclerostin secretion.
Decay processes in Salix psammophila sand barriers increase soil microbial element stoichiomery ratios
Authors: Liang Yumei , Ri Ana , Wang Ning
Published: December 2022

Salix psammophilasand barriers are a widely used engineering measure to control quicksand in northwest China. Thus, it is important to elucidate the influence of the sand barrier decay process on soil microbial ecological stoichiometric characteristics in desert environments. In the present study, fieldin situsampling and laboratory index measurements were used to evaluate and compare the performance degradation, variation in soil physical and chemical properties, and soil microbial ecological stoichiometry of sand barriers during decay. The results showed that with the worsening of the decay degree, all indexes of the decay characteristics decreased significantly, among which the flexural strength of mechanical properties decreased the most, which directly led to collapse and damage. The cellulose and lignin contents of the chemical components also exhibited varying degrees of decomposition, and the soil physical and chemical properties showed a significant increase. The changes in the microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) contents were consistent with the trend of the soil properties, and both reached their peak at 7 years. With the aggravation of decay, the stoichiometric ratios of soil microbial elements C, N, and P increased continuously. However, there was no significant increase in MBC/MBP and MBN/MBP in the early period (≤3 years) of the sand barrier establishment, but there was a significant increase in the later period (≥5 years). These results indicated thatS. psammophilasand barriers mainly played the role of windbreak and sand fixation in the early period, and made soil microorganisms susceptible to phosphorus limitation in the later period. Stepwise linear regression analysis showed that MBC/MBN, MBC/MBP, and MBN/MBP were mainly affected by basic density (BD). Therefore, the sand barrier changes soil properties by degrading its own chemical components during the decay process and the loss of basic density is the main driving factor for increasing the C:N:P stoichiometry of soil microbial biomass. It can still be further promoted and used in the resource utilization process of mechanical sand barriers in the future.
Upsurge in biomedical waste due to COVID-19 in India: A statistical correlation, challenges and recommendations
Authors: Khosla Ritu , Jha Ashima , Dua Shweta , Varmani Shivani G. , Rajput Namita , Pani Balaram
Published: December 2022

Proper management of Biomedical Waste (BMW) is an essential component of any sustainable healthcare sector. With the burst of COVID-19 pandemic when every hospital and treatment facility was overburdened patients, efficient handling of the huge amount of generated BMW became a task for the entire world. This review compares the BMW generated before and during the second wave of COVID-19, highlights the challenges in managing the exuberated amount of COVID-19 waste and sites recommendations to promote sustainable design thinking, in order to address this grave concern in the current setting of the Indian system. The study indicated that inappropriate management of waste and the lacunae in the entire chain from segregation to collection until its disposal has posed a serious threat to the wellbeing of healthcare workers, sanitation staff as well as the operators and housekeeping staff at the hospitals, isolation centers and Municipal Corporation. Many states had inadequate number of common BMW treatment facilities (CBMWTFs) leading to inefficient treatment of the excess waste. The behavioural and attitudinal barriers of neglect and ignorance of different stakeholders further aggravated the problem of BMW management to manifolds. To achieve better management we recommend spreading awareness regarding the kind and infectious nature of waste generated by COVID-19 patients and their caregivers, segregation and decontamination of such waste at source and increasing the capacity as well as number of CBMWTFs. Creative ways to recycle the waste must be devised so as to reduce the burden on disposal sites.
GC-MS/FID/EAD: A method for combining mass spectrometry with gas chromatography-electroantennographic detection
Authors: Shuttleworth Adam , Johnson Steven D.
Published: December 2022

Gas chromatography-electroantennographic detection (GC-EAD), typically combined with a flame ionization detector (FID), is a widely used technique for studying insect semiochemicals. Combining mass spectrometry (MS) with GC-EAD is extremely beneficial, but has seldom been adopted, possibly due to the practical challenges associated with incorporating an MS (under vacuum) into a GC-EAD system. We describe a novel method of incorporating MS into a GC-EAD system, where the FID is maintained in the system rather than being replaced by an MS. With this method, effluent is still split between EAD and FID, with the FID being used to assign components that elicit antennal responses, as in a normal GC-FID/EAD system. The MS is introduced via a second effluent splitter inserted before the split between the EAD and the FID. This method allows for EAD, FID, and MS data to be obtained from a single injection, which is especially useful for analysis of thermally desorbed and solid-phase microextraction (SPME) samples. This configuration is also relatively simple to implement and resolves some of the practical challenges associated with dividing effluent between a detector at atmospheric pressure (a live antenna) and a detector under vacuum (the MS). We present test runs with hawkmoth antennae and floral volatiles to demonstrate the effectiveness of this system, and discuss the challenges and practical solutions to incorporating MS into a GC-EAD system that retains an FID detector.
Integrative analyses of a mitophagy-related gene signature for predicting prognosis in patients with uveal melanoma
Authors: Cheng Yanhua , Liu Jingying , Fan Huimin , Liu Kangcheng , Zou Hua , You Zhipeng
Published: December 2022

We aimed to create a mitophagy-related risk model via data mining of gene expression profiles to predict prognosis in uveal melanoma (UM) and develop a novel method for improving the prediction of clinical outcomes. Together with clinical information, RNA-seq and microarray data were gathered from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ConsensusClusterPlus was used to detect mitophagy-related subgroups. The genes involved with mitophagy, and the UM prognosis were discovered using univariate Cox regression analysis. In an outside population, a mitophagy risk sign was constructed and verified using least absolute shrinkage and selection operator (LASSO) regression. Data from both survival studies and receiver operating characteristic (ROC) curve analyses were used to evaluate model performance, a bootstrap method was used test the model. Functional enrichment and immune infiltration were examined. A risk model was developed using six mitophagy-related genes (ATG12, CSNK2B, MTERF3, TOMM5, TOMM40, and TOMM70), and patients with UM were divided into low- and high-risk subgroups. Patients in the high-risk group had a lower chance of living longer than those in the low-risk group (p < 0.001). The ROC test indicated the accuracy of the signature. Moreover, prognostic nomograms and calibration plots, which included mitophagy signals, were produced with high predictive performance, and the risk model was strongly associated with the control of immune infiltration. Furthermore, functional enrichment analysis demonstrated that several mitophagy subtypes may be implicated in cancer, mitochondrial metabolism, and immunological control signaling pathways. The mitophagy-related risk model we developed may be used to anticipate the clinical outcomes of UM and highlight the involvement of mitophagy-related genes as prospective therapeutic options in UM. Furthermore, our study emphasizes the essential role of mitophagy in UM.
EMILIN2 is associated with prognosis and immunotherapy in clear cell renal cell carcinoma
Authors: Zhao Guangjian , Zheng Jianpei , Tang Kai , Chen Qi
Published: December 2022

Background: EMILIN2 is a platelet-associated elastin that regulates angiogenesis. It has recently been found to play an essential role in various tumors. Nevertheless, the mechanism of action of EMILIN2 in clear cell renal cell carcinoma (ccRCC) remains unclear.

Methods: Samples from 33 cancers were obtained from UCSC Xena and The Cancer Genome Atlas (TCGA) database. The relationship between EMILIN2 expression and the clinicopathological characteristics and immune infiltration of ccRCC was investigated. Nonnegative matrix factorization (NMF) was used to classify ccRCC patients. A multigene risk prediction model of ccRCC was constructed using LASSO regression and multivariate regression analysis. A nomogram survival probability prediction map and calibration curve were constructed based on clinical information.

Results: EMILIN2 is significantly overexpressed in ccRCC, a phenomenon that is associated with poor prognosis. Meanwhile, EMILIN2 expression is closely related to tumor immune infiltration in ccRCC. Patients with clear cell renal cell carcinoma were divided into two subtypes using NMF, with subtype 2 showed poor prognosis. Next, we established a risk score model for ccRCC based on the common differentially expressed genes (DEGs) between subtypes and groups based on EMILIN2 expression. The results indicated poor prognosis in the high-risk group in the training set and were confirmed in the validation set.

Conclusion: Our findings suggest that EMILIN2 expression is closely associated with immune infiltration in ccRCC. EMILIN2 expression is negatively correlated with the prognosis of ccRCC patients. Here, we developed a tool that could predict the prognosis of ccRCC patients.
Inflammation-related pathways involved in damaged articular cartilage of rats exposed to T-2 toxin based on RNA-sequencing analysis
Authors: Shi Longyan , Liu Qiuliang , Yang Heying , Wang Qi , Wang Jiaxiang , Fan Yingzhong
Published: December 2022

Many studies have shown that ingestion of the T-2 toxin is harmful to articular cartilage. However, the mechanisms underlying damaged articular cartilage induced by T-2 toxin have not been elucidated. Twenty-four SD rats were randomly divided into T-2 toxin and control groups. In the control group, the 12 rats were administered 4% absolute ethanol by gavage, and in the T-2 toxin group, the 12 rats were administered T-2 toxin (100 ng/g, BW/day) by gavage. After the rats were sacrificed, the knee joints were collected, and RNA was extracted using TRIzol reagent for RNA sequencing (RNA-seq). Differentially expressed mRNA was identified based on p < 0.05 and | log2 (fold change) | > 1. The T-2 toxin-related genes were obtained from the GeneCards database. An online tool (https://www.bioinformatics.com.cn) was used for enrichment analysis. Hematoxylin and eosin (H&E) staining was used to observe damaged articular cartilage, and immunohistochemical (IHC) staining was used to validate differentially expressed proteins. The H&E staining shows the number of cells decreased significantly, and the arrangement of chondrocytes became disordered in the T-2 toxin group. RNA-seq analysis identified 195 upregulated and 89 downregulated mRNAs in the T-2 toxin group. The top immune-related biological processes (Gene Ontology) were regulation of hormone secretion, regulation of peptide hormone secretion, and regulation of transcription involved in cell fate commitment. KEGG pathway enrichment analysis revealed that the IL-17 and tumor necrosis factor signaling pathways were significantly expressed, and the IL-17 signaling pathway was also identified in the enrichment analysis of T-2 toxin-related genes. Also, Mmp3, Tnf, Mapk10, Ccl11, Creb5, Cxcl2, and Cebpb were significantly enriched in the two pathways. The immunohistochemical staining showed that the levels of Mmp3 and Tnf proteins were significantly increased in the T-2 toxin group, which was consistent with the RNA-seq results. This study revealed the critical roles of IL-17 and TNF signaling pathways in damaged cartilage induced by T-2 toxin.
Genome-wide characterization of the NLR gene family in tomato (Solanum lycopersicum) and their relatedness to disease resistance
Authors: Bashir Sehrish , Rehman Nazia , Fakhar Zaman Fabia , Naeem Muhammad Kashif , Jamal Atif , Tellier Aurélien , Ilyas Muhammad , Silva Arias Gustavo Adolfo , Khan Muhammad Ramzan
Published: December 2022

Nucleotide-binding leucine-rich-repeat receptors (NLR), the largest group of genes associated with plant disease resistance (R), have attracted attention due to their crucial role in protecting plants from pathogens. Genome-wide studies of NLRs have revealed conserved domains in the annotated tomato genome. The 321 NLR genes identified in the tomato genome have been randomly mapped to 12 chromosomes. Phylogenetic analysis and classification of NLRs have revealed that 211 genes share full-length domains categorized into three major clades (CNL, TNL, and RNL); the remaining 110 NLRs share partial domains and are classified in CN, TN, and N according to their motifs and gene structures. The cis-regulatory elements of NLRs exhibit the maximum number of these elements and are involved in response to biotic and abiotic stresses, pathogen recognition, and resistance. Analysis of the phylogenetic relationship between tomato NLRs and orthologs in other species has shown conservation among Solanaceae members and variation with A. thaliana. Synteny and Ka/Ks analyses of Solanum lycopersicum and Solanum tuberosum orthologs have underscored the importance of NLR conservation and diversification from ancestral species millions of years ago. RNA-seq data and qPCR analysis of early and late blight diseases in tomatoes revealed consistent NLR expression patterns, including upregulation in infected compared to control plants (with some exceptions), suggesting the role of NLRs as key regulators in early blight resistance. Moreover, the expression levels of NLRs associated with late blight resistance (Solyc04g007060 [NRC4] and Solyc10g008240 [RIB12]) suggested that they regulate S. lycopersicum resistance to P. infestans. These findings provide important fundamental knowledge for understanding NLR evolution and diversity and will empower the broader characterization of disease resistance genes for pyramiding through speed cloning to develop disease-tolerant varieties.
Intracerebral opportunistic infections caused by immunosuppressants after orthotopic liver transplantation: Report of two cases and literature review
Authors: Guo Yafei , Zhu Zebin , Cai Wei , Tao Shengwei , Yin Dalong
Published: December 2022

Central nervous system (CNS) infections in adults are rare because of normal immunity and the existence of the blood brain barrier, which prevents the invasion of pathogenic microorganisms. Liver transplant recipients are at an increased risk of opportunistic infections (OI) due to immunosuppressive therapy compared to those with normal immunity. Early diagnosis and timely implementation of treatment are critical for the successful treatment of these infections. We present two cases of intracerebral OI after orthotopic liver transplantation (OLT), with different clinical presentations. Patient 1 presented with epileptic seizures, mainly manifested as unresponsiveness, unconsciousness, and coma complicated with involuntary limb twitching. Patient 2 presented with a consciousness disorder, mainly manifested as unclear consciousness content, poor orientation, calculation power, and logical ability. Next-generation sequencing (NGS) examination of the cerebrospinal fluid confirmed human herpesvirus 6 B (HHV-6B) infection in patient 1 and intracranial Aspergillus infection in patient 2. Intracranial OI has insidious onset and atypical clinical manifestations. NGS can allow for the proper diagnosis and monitoring of the effects of treatment.
Boolean modeling reveals that cyclic attractors in macrophage polarization serve as reservoirs of states to balance external perturbations from the tumor microenvironment
Authors: de León Ugo Avila-Ponce , Vázquez-Jiménez Aarón , Matadamas-Guzmán Meztli , Resendis-Antonio Osbaldo
Published: December 2022

Cyclic attractors generated from Boolean models may explain the adaptability of a cell in response to a dynamical complex tumor microenvironment. In contrast to this idea, we postulate that cyclic attractors in certain cases could be a systemic mechanism to face the perturbations coming from the environment. To justify our conjecture, we present a dynamic analysis of a highly curated transcriptional regulatory network of macrophages constrained into a cancer microenvironment. We observed that when M1-associated transcription factors (STAT1 or NF-κB) are perturbed and the microenvironment balances to a hyper-inflammation condition, cycle attractors activate genes whose signals counteract this effect implicated in tissue damage. The same behavior happens when the M2-associated transcription factors are disturbed (STAT3 or STAT6); cycle attractors will prevent a hyper-regulation scenario implicated in providing a suitable environment for tumor growth. Therefore, here we propose that cyclic macrophage phenotypes can serve as a reservoir for balancing the phenotypes when a specific phenotype-based transcription factor is perturbed in the regulatory network of macrophages. We consider that cyclic attractors should not be simply ignored, but it is necessary to carefully evaluate their biological importance. In this work, we suggest one conjecture: the cyclic attractors can serve as a reservoir to balance the inflammatory/regulatory response of the network under external perturbations.
High titre neutralizing antibodies in response to SARS–CoV–2 infection require RBD–specific CD4 T cells that include proliferative memory cells
Authors: Phetsouphanh Chansavath , Khoo Weng Hua , Jackson Katherine , Klemm Vera , Howe Annett , Aggarwal Anupriya , Akerman Anouschka , Milogiannakis Vanessa , Stella Alberto Ospina , Rouet Romain , Schofield Peter , Faulks Megan L. , Law Hannah , Danwilai Thidarat , Starr Mitchell , Munier C. Mee Ling , Christ Daniel , Singh Mandeep , Croucher Peter I. , Brilot-Turville Fabienne , Turville Stuart , Phan Tri Giang , Dore Gregory J. , Darley David , Cunningham Philip , Matthews Gail V. , Kelleher Anthony D. , Zaunders John J.
Published: December 2022

Background

Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden.

Methods

We have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects.

Findings

Higher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorouslyin vitro. Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres.

Interpretation

Our results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines.
Downregulation of T-cell cytotoxic marker IL18R1 promotes cancer proliferation and migration and is associated with dismal prognosis and immunity in lung squamous cell carcinoma
Authors: Guo Qiang , Wu Chuang-Yan , Jiang Ni , Tong Song , Wan Jun-Hao , Xiao Xiao-Yue , Mei Pei-Yuan , Liu Hua-Song , Wang Si-Hua
Published: December 2022

Immunotherapy can improve the survival of patients with advanced lung squamous cell carcinoma (LUSC). T cytotoxic cells are one of the main members of the immune microenvironment. Herein, we aimed to identify the roles of T-cell cytotoxic markers interleukin 18 (IL18) receptor 1 (IL18R1) in the LUSC progression using bioinformatics, clinical tissue specimen, and cell experiment. We assessed the association between the IL18R1 expression and immune infiltration and IL18R1-related competing RNA network. The IL18R1 expression was downregulated in the LUSC tissues. The IL18R1 expression downregulation was associated with diagnosis and short overall survival and disease-specific survival, and it was also an independent risk factor for dismal survival time in LUSC. IL18R1-related nomograms predicted the survival time of patients with LUSC. IL18R1 overexpression inhibited the proliferation, migration, and invasion of LUSC cells. The IL18R1 expression was significantly associated with the microenvironment (stromal, immune, and estimate scores), immune cells (such as the T cells, cytotoxic cells, CD8 T cells), and immune cell markers (such as the CD8A, PD-1, and CTLA4) in LUSC. AC091563.1 and RBPMS-AS1 downregulation was positively associated with the IL18R1 expression, negatively associated with the miR-128-3p expression, and associated with short disease-specific survival and progression in LUSC. In conclusion, IL18R1 was significantly downregulated and associated with the prognosis and immune microenvironment. IL18R1 overexpression inhibits the growth and migration of cancer cells in LUSC. Furthermore, AC091563.1 and RBPMS-AS1 might compete with IL18R1 to bind miR-128-3p for participating in LUSC progression. These results showed that IL18R1 is a biomarker for evaluating the prognosis of patients with LUSC.
Temporally integrated transcriptome analysis reveals ASFV pathology and host response dynamics
Authors: Lv Lin , Zhang Tianyun , Jia Hanying , Zhang Yanyan , Ahsan Asif , Zhao Xiaoyang , Chen Teng , Shen Zhiqiang , Shen Ning
Published: December 2022

African swine fever virus (ASFV) causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pig industry. The pathogenesis of ASFV infection and its interaction with host responses remain poorly understood. In this study, we profiled the temporal viral and host transcriptomes in porcine alveolar macrophages (PAMs) with virulent and attenuated ASFV strains. We identified profound differences in the virus expression programs between SY18 and HuB20, which shed light on the pathogenic functions of several ASFV genes. Through integrated computational analysis and experimental validation, we demonstrated that compared to the virulent SY18 strain, the attenuated HuB20 quickly activates expression of receptors, sensors, regulators, as well as downstream effectors, including cGAS, STAT1/2, IRF9, MX1/2, suggesting rapid induction of a strong antiviral immune response in HuB20. Surprisingly, in addition to the pivotal DNA sensing mechanism mediated by cGAS-STING pathway, infection of the DNA virus ASFV activates genes associated with RNA virus response, with stronger induction by HuB20 infection. Taken together, this study reveals novel insights into the host-virus interaction dynamics, and provides reference for future mechanistic studies of ASFV pathogenicity.
Experimental assessment and numerical simulation of the large deformation of a flexible composite tank
Authors: Liu Yuxi , Chen Yu , Shan Zhiyong , Li Qian , Lin Guochang
Published: December 2022

A flexible composite tank is developed for the storage of oil and gas. The tank is made of coated fabric, which is a thermoplastic polyurethane reinforced aramid fiber, to satisfy strength, sealing, and fluid compatibility requirements. The top and bottom areas of the tank are connected with a rod to fix the tank height during inflation. The tank deformation is studied. Experimental tests are conducted on two prototypes of 0.4 m height and a prototype of 1.7 m height in a water basin. The test for the small prototypes focuses on obtaining deformed shapes. The test for the 1.7-m height prototype focuses on obtaining strain sensor readings. The tank collapses initially from the bottom part, propagates upward, and then finally only the top part retains the initial shape when the tank is empty. The deformation process is also simulated using a finite element analysis (FEA) model. Results show that the deformation shape of the tank was simulated effectively compared with that in the experimental results. The FEA results are conservative compared with the test results, given that the tank deformation is irregular and the maximum strain was difficult to record during the test. This research provides insight into the deformation behavior of a flexible tank, and the validated FEA model can be used for future design optimization.