Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics of soil properties and fungal community structure in continuous-cropped alfalfa fields in Northeast China

To compensate for the seasonal imbalance between livestock and forage yield in the cold region of Northeast China, alfalfa (Medicago sativa L.) continuous cropping has been widely employed in animal husbandry. However, the effects of continuous cropping of alfalfa on soil properties, including physical, chemical and biological properties, are poorly understood. In this study, we investigated the soil properties and fungal community composition of alfalfa fields under continuous cropping for different time periods (i.e., 1, 2, 6, 9, 12, 13 and 35 years). The results showed that soil moisture, total C, total N, NO3−-N and available K content decreased at less than 10 years of continuous cropping and then increased at more than 10 years of continuous cropping, but soil total P and available P content showed the opposite tendency. The soil fungal community composition determined using Illumina Miseq sequencing showed that continuous cropping increased the fungal alpha diversity and changed the fungal community structure. The relative abundances of Guehomyces and Chaetomium decreased, but the relative abundances of Phaeomycocentrospora and Paecilomyces increased with continuous cropping time. In addition, continuous cropping of alfalfa increased the relative abundances of some plant pathogens, such as Haematonectria haematococca and Cyphellophora sp. Soil total P and available P content were important soil factors affecting the soil fungal community diversity, fungal community structure and the relative abundances of specific fungi in this alfalfa continuous cropping system.
Heparinoid sevuparin inhibits Streptococcus‐induced vascular leak through neutralizing neutrophil‐derived proteins

Acute lung injury (ALI) and respiratory distress can develop as a consequence of sepsis with pathogens such as group A Streptococcus (GAS). In the pathogenesis of sepsis‐associated ALI, endothelial barrier disruption brought on by phagocyte activation is considered a causative factor. Here, we find that sevuparin, a heparinoid with low anticoagulant activity, prevents neutrophil‐induced lung plasma leakage in a murine model of systemic inflammation evoked by heat‐killed GAS (hkGAS). Furthermore, using human neutrophils and endothelial cell monolayers, we demonstrate that sevuparin inhibits hkGAS‐induced endothelial barrier disruption by neutralizing the activity of neutrophil‐derived proteins. By mass spectrometry of neutrophil secretion, we identify proteins, including serprocidins, S100 proteins, and histone H4, that interact with sevuparin and that are responsible for the disruptive effect on endothelial integrity. Collectively, our results demonstrate the critical role of neutrophil‐derived proteins in vascular hyperpermeability caused by GAS and suggest sevuparin as a potential therapeutic in acute neutrophilic inflammation. —Rasmuson, J., Kenne, E. , Wahlgren, M. , Soehnlein, O. , Lindbom, L. Heparinoid sevuparin inhibits Streptococcus‐induced vascular leak through neutralizing neutrophil‐derived proteins. FASEB J. 33, 10443–10452 (2019). www.fasebj. org
Pterostilbene reverses palmitic acid mediated insulin resistance in HepG2 cells by reducing oxidative stress and triglyceride accumulation

Abstract Insulin resistance (IR) is known to precede onset of type 2 diabetes and increased oxidative stress appears to be a deleterious factor leading to IR. In this study, we evaluated ability of pterostilbene (PTS), a methoxylated analogue of resveratrol and a known antioxidant, to reverse palmitic acid (PA)-mediated IR in HepG2 cells. PTS prevented reactive oxygen species (ROS) formation and subsequent oxidative lipid damage by reducing the expression of NADPH oxidase 3 (NOX3) in PA treated HepG2 cells. Hepatic glucose production was used as a measure of IR and PTS reversed PA-mediated increase in hepatic glucose production by reducing expression of genes coding for gluconeogenic enzymes namely glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate carboxylase (PC); and their transcription factors cAMP response element binding protein (CREB) and fork head class Box O (FOXO1) along with its coactivator peroxisome proliferator-activated receptor gamma co-activator-1 α (PGC1α). PTS reversed PA-mediated activation of c-Jun N-terminal kinase (JNK), which in turn altered insulin signalling pathway by phosphorylating IRS-1 at Ser 307, leading to inhibition of phosphorylation of Akt and GSK-3β. PTS also reduced PA-mediated lipid accumulation by reducing expression of transcription factors SREBP1c and PPARα. SREBP1c activates genes involved in fatty acid and triglyceride synthesis while PPARα activates CPT1, a rate limiting enzyme for controlling entry and oxidation of fatty acids into mitochondria. PTS, however, did not influence PA uptake confirmed by using BODIPY-labelled fluorescent C16 fatty acid analogue. Thus, our data provides a possible mechanistic explanation for reversal of PA-mediated IR in HepG2 cells.
Seed local adaptation and seedling plasticity account for Gleditsia triacanthos tree invasion across biomes.

BACKGROUND AND AIMS Phenotypic plasticity and local adaption can contribute to the success of invasive species. While the former is an environmentally induced trait, the latter involves a selection process to filter the best genotype for a location. We examined the evidence for phenotypic plasticity and local adaptation for seed and seedling traits of the invasive tree Gleditsia triacanthos, with three origins distributed along an approx. 10° latitude gradient across three biomes. METHODS In sub-tropical forests, dry woodlands and secondary temperate grasslands in Argentina, we harvested seeds from clusters of neighbouring trees (i.e. families) distributed within 15-20 km in each origin (biome). We manipulated the environmental conditions relevant to each biome, assuming that propagule availability did not represent an ecological barrier. In growth chambers, we evaluated seed imbibition and seed germination under different light, temperature and water potential. In a 2 year common garden, we evaluated the impact of resident vegetation removal on seedling survival and growth. KEY RESULTS Mean time to complete seed imbibition differed among origins; seeds from temperate grasslands reached full imbibition before seeds from dry woodlands and sub-tropical forests. Germination was always >70 %, but was differentially affected by water potential, and light quantity (dark-light) and quality (red-far red) among origins, suggesting local adaptation. In the common garden, vegetation removal rather than origin negatively affected seedling survival and enhanced seedling growth. Vegetation removal increased basal diameter, leaves per plant and spine number, and reduced the height:basal diameter ratio. CONCLUSIONS We conclude that local adaptation in seed germination traits and plastic changes in seedling allometry (e.g. height:diameter) may allow this tree to respond over the short and long term to changes in environmental conditions, and to contribute to shape G. triacanthos as a successful woody invader. Overall, our study revealed how local adaptation and plasticity can explain different aspects of tree invasion capacity across biomes.
Effects of Absence of Constitutive Androstane Receptor (CAR) on Bile Acid Homeostasis in Male and Female Mice.

Accumulation of BAs in hepatocytes has a role in liver disease and also in drug-induced liver injury. The Constitutive Androstane Receptor (CAR) has been shown to protect against BA-induced liver injury. The polymorphism of CAR has recently been shown to modify the pharmacokinetics and pharmacodynamics of various drugs. Thus it was hypothesized that polymorphism of CAR may also influence BA homeostasis. Using CAR-null and WT mice, this study modeled the potential consequences of CAR polymorphism on BA homeostasis. Our previous study showed that chemical activation of CAR decreases the total BA concentrations in livers of mice. Surprisingly the absence of CAR also decreased the BA concentrations in livers of mice, but to a lesser extent than in CAR-activated mice. Neither CAR activation nor elimination of CAR altered the biliary excretion of total BAs, but CAR activation increased the proportion of 6-OH BAs (TMCA), whereas the lack of CAR increased the excretion of TCA, TCDCA and TDCA. Serum BA concentrations did not parallel the decrease in BA concentrations in the liver in either the mice after CAR activation or mice lacking CAR. Gene expression of BA synthesis, transporter and regulator genes were mainly similar in livers of CAR-null and WT mice. In summary, CAR activation decreases primarily the 12-OH BA concentrations in liver, whereas lack of CAR decreases the concentrations of 6-OH BAs in liver. In bile, CAR activation increases the biliary excretion of 6-OH BAs, whereas absence of CAR increases the biliary excretion of 12-OH BAs and TCDCA.
Integrative Analysis of Genome-Wide Association Studies and DNA Methylation Profile Identified Genetic Control Genes of DNA Methylation for Kashin-Beck Disease

Objective Epigenetic modifications of DNA are regarded as a crucial factor for understanding the molecular basis of complex phenotypes. This study aims to uncover insight into the epigenetic modifications for Kashin-Beck disease (KBD) by integrating genome-wide association studies (GWAS), methylation quantitative trait loci (meQTLs), and DNA methylation profiles data. Design The knee articular cartilages of 5 KBD patients and 5 healthy controls were collected for DNA methylation profiling, using Illumina Infinium HumanMethylation450 BeadChip. Mass spectrograph validation of identified differently methylated genes was conducted using independent samples of 4 KBD patients and 3 healthy controls, together with a previous sample of 2743 Han Chinese individuals of GWAS study for KBD and a study of 697 normal subjects for meQTLs annotation datasets. KBD GWAS single nucleotide polymorphisms (SNPs) and normal meQTLs SNPs were integrated with DNA methylation profiles of KBD articular cartilage to identify genetic control (GC) genes of DNA methylation for KBD. Quantitative polymerase chain reaction (qPCR) was performed to validate the mRNA expression of several identified candidate genes. Results A total of 162 CpG sites, 253 SNPs, and 123 GC genes for KBD were identified. Enrichment analysis detected 642 marked GO terms and 19 KEGG pathways (P < 0.05). Six potential key GC genes were conducted for qPCR experiment (ERG, MN1, MITF, WISP1, TRIO, and NOSTRIN). Conclusions The results suggest that GC genes of DNA methylation may lead to the erosion of cartilage in KBD, which may help us in understanding the epigenetic alteration of KBD.
Body weight course in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1)—A 20-year observational study

Background Although weight gain increases risk of type 2 diabetes, real-life data on the weight course in patients with established type 2 diabetes are scarce. We assessed weight course in a real-life diabetes secondary care setting and analyzed its association with patient characteristics, lifestyle habits and initiation of insulin, glucagon like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i). Methods Data on weight, insulin, GLP-1 RA and SGLT-2i use were collected retrospectively (12 years) and prospectively (8 years) from patients included in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1, n = 450, age 63 ± 9 years, 58% men, diabetes duration [7–18] years). Lifestyle habits were assessed using validated questionnaires. The association of clinical parameters with body mass index (BMI) course was determined using linear mixed models. Patients who underwent bariatric surgery (n = 19) had a distinct BMI course and were excluded from the study. Results Baseline BMI was 31.3 (0.3) and was higher in women, patients aged <60 years and patients with unfavorable lifestyle habits. BMI increased to 32.5 (0.3) after 12 years (P<0.001), and thereafter decreased to 31.5 (0.3) after 20 years, resulting in a similar BMI as the baseline BMI (P = 0.96, compared to baseline). Clinical parameters or initiation of insulin or SGLT-2i were not associated with BMI course. Patients who initiated GLP-1 RA declined in BMI compared to non-users (Pinteraction = 0.003). Conclusions High BMI that real-life patients with type 2 diabetes gained earlier in life, remained stable in the following decades. Weight loss interventions should remain a priority, and GLP-1 RA might be considered to support weight loss.
Modeling Flaw Pulse-Echo Signals in Cylindrical Components Using an Ultrasonic Line-Focused Transducer with Consideration of Wave Mode Conversion

Investigations on flaw responses can benefit the nondestructive testing of cylinders using line-focused transducers. In this work, the system function, the wave beam model, and a flaw scattering model are combined to develop an ultrasonic measurement model for line-focused transducers to predict flaw responses in cylindrical components. The system function is characterized using reference signals by developing an acoustic transfer function for line-focused transducers, which works at different distances for both planar and curved surfaces. The wave beams in cylindrical components are modeled using a multi-Gaussian beam model, where the effects of wave mode conversion and curvatures of cylinders are considered. Simulation results of wave beams are provided to analyze their propagation behaviors. The proposed ultrasonic measurement model is certified from good agreement between the experimental and predicted signals of side-drilled holes. This work provides guidance for evaluating the detection ability of line-focused transducers in cylindrical component testing applications.
Intrinsic Resistance to Immune Checkpoint Blockade in a Mismatch Repair–Deficient Colorectal Cancer

This case of PD-1 blockade resistance, despite microsatellite instability-high (MSI-H) molecular features, suggests that other biomarkers should be considered. Loss of β2-microglobulin expression and infiltration of NK cells and M2 macrophages may be informative in therapy selection. Immunotherapy with checkpoint inhibitors, such as the programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab, are effective in a variety of tumors, yet not all patients respond. Tumor microsatellite instability-high (MSI-H) has emerged as a biomarker of response to checkpoint blockade, leading to the tissue agnostic approval of pembrolizumab in MSI-H cancers. Here we describe a patient with MSI-H colorectal cancer that was treated with this immune checkpoint inhibitor and exhibited progression of disease. We examined this intrinsic resistance through genomic, transcriptional, and pathologic characterization of the patient's tumor and the associated immune microenvironment. The tumor had typical MSI-H molecular features, including a high neoantigen load. We also identified biallelic loss of the gene for β2-microglobulin (B2M), whose product is critical for antigen presentation. Immune infiltration deconvolution analysis of bulk transcriptome data from this anti-PD-1–resistant tumor and hundreds of other colorectal cancer specimens revealed a high natural killer cell and M2 macrophage infiltration in the patient's cancer. This was confirmed by single-cell transcriptome analysis and multiplex immunofluorescence. Our study provides insight into resistance in MSI-H tumors and suggests immunotherapeutic strategies in additional genomic contexts of colorectal cancer.
Weighted Transfer Learning for Improving Motor Imagery-Based Brain–Computer Interface

One of the major limitations of motor imagery (MI)-based brain–computer interface (BCI) is its long calibration time. Due to between sessions/subjects variations in the properties of brain signals, typically, a large amount of training data needs to be collected at the beginning of each session to calibrate the parameters of the BCI system for the target user. In this paper, we propose a novel transfer learning approach on the classification domain to reduce the calibration time without sacrificing the classification accuracy of MI-BCI. Thus, when only few subject-specific trials are available for training, the estimation of the classification parameters is improved by incorporating previously recorded data from other users. For this purpose, a regularization parameter is added to the objective function of the classifier to make the classification parameters as close as possible to the classification parameters of the previous users who have feature spaces similar to that of the target subject. In this paper, a new similarity measure based on the Kullback–Leibler divergence (KL) is used to measure the similarity between two feature spaces obtained using subject-specific common spatial patterns (CSP). The proposed transfer learning approach is applied on the logistic regression classifier and evaluated using three datasets. The results showed that compared with the subject-specific classifier, the proposed weighted transfer learning classifier improved the classification results, particularly when few subject-specific trials were available for training (p < 0.05). Importantly, this improvement was more pronounced for users with medium and poor accuracy. Moreover, the statistical results showed that the proposed weighted transfer learning classifier performed significantly better than the considered comparable baseline algorithms.
Cooperation via wireless network coding

Recently, the network coding in cooperative communications has been categorized into two mainstreams, Digital Network Coding (DNC) and Analog Network Coding (ANC), which we both discuss in the article. First a brief survey of these two sub-branches is given. Then, to the very wireless characteristics fading and interference, DNC and ANC network coding way were proposed respectively, which aims at combating fading and embracing interference in wireless medium. Specifically, the idea of network-coded cooperative protocol in this paper is to combine different source nodes' information at the bit-level and signal-level corresponding to DNC and ANC in the relay node and then perform joint decoding in the destination node. The proposed DNC and ANC are demonstrated to obtain both capacity and reliability gains.
The venodilation effects of tapping versus massaging for venipuncture.

AIM To compare the effectiveness of tapping and massaging venodilation techniques by evaluating venous cross-sectional area, venous depth, venous palpation score, and questionnaire responses of study participants. METHODS This study had a quasi-experimental design. Between August 2016 and October 2016, healthy adult volunteers (n = 30, mean ± standard deviation of age: 22.3 ± 2.2 years) were enrolled in this study. Three venodilation techniques were evaluated: the application of a tourniquet (Control Group), the application of a tourniquet and tapping of the participant's forearm (Tapping Group), and the application of a tourniquet and massaging of the participant's forearm (Massage Group). RESULTS In all three groups, venous cross-sectional areas increased significantly after the application of the venodilation technique. The change ratio of venous cross-sectional area was significantly larger in the Massage Group than in the Control Group. Additionally, 83.3% of the participants selected massaging as their preferred venodilation technique, stating the technique was comfortable and provided a feeling of relief. CONCLUSIONS No significant differences were observed between the degrees of venodilation that were achieved using the three investigated venodilation techniques. Nonetheless, massaging was deemed the most effective technique after considering the participants' subjective comments.
Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

Interleukin (IL)‐6 signalling has been implicated in allergic asthma by animal, genetic association and clinical studies. In this study, we tested the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL‐6 signalling, can prevent the development of allergen‐induced bronchoconstriction in humans.
Mutations of the AtYAK1 Kinase Suppress TOR Deficiency in Arabidopsis.

The target of rapamycin (TOR) kinase is a conserved energy sensor that regulates growth in response to environmental cues. However, little is known about the TOR signaling pathway in plants. We used Arabidopsis lines affected in the lethal with SEC13 protein 8 (LST8-1) gene, a core element of the TOR complex, to search for suppressor mutations. Two suppressor lines with improved growth were isolated that carried mutations in the Yet Another Kinase 1 (AtYAK1) gene encoding a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. Atyak1 mutations partly rescued the developmental defects of lst8-1-1 mutants and conferred resistance to the TOR inhibitor AZD-8055. Moreover, atyak1 mutations suppressed the transcriptomic and metabolic perturbations as well as the abscisic acid (ABA) hypersensitivity of the lst8-1-1 mutants. AtYAK1 interacted with the regulatory-associated protein of TOR (RAPTOR), a component of the TOR complex, and was phosphorylated by TOR. Thus, our findings reveal that AtYAK1 is a TOR effector that probably needs to be switched off to activate plant growth.
Copy number variations in individuals with conotruncal heart defects reveal some shared developmental pathways irrespective of 22q11.2 deletion status

Over 50% of patients with 22q11.2 deletion syndrome (DS) have a conotruncal or related cardiac defect (CTRD). We hypothesized that similar genetic variants, developmental pathways and biological functions, contribute to disease risk for CTRD in patients without a 22q11.2 deletion (ND‐CTRD) and with a 22q11.2 deletion (DS‐CTRD). To test this hypothesis, we performed rare CNV (rCNV)‐based analyses on 630 ND‐CTRD cases and 602 DS‐CTRD cases with comparable cardiac lesions separately and jointly. First, we detected a collection of heart development related pathways from Gene Ontology and Mammalian Phenotype Ontology analysis. We then constructed gene regulation networks using unique genes collected from the rCNVs found in the ND‐CTRD and DS‐CTRD cohorts. These gene networks were clustered and their predicted functions were examined. We further investigated expression patterns of those unique genes using publicly available mouse embryo microarray expression data from single‐cell embryos to fully developed hearts. By these bioinformatics approaches, we identified a commonly shared gene expression pattern in both the ND‐CTRD and DS‐CTRD cohorts. Computational analysis of gene functions characterized with this expression pattern revealed a collection of significantly enriched terms related to cardiovascular development. By our combined analysis of rCNVs in the ND‐CTRD and DS‐CTRD cohorts, a group of statistically significant shared pathways, biological functions, and gene expression patterns were identified that can be tested in future studies for their biological relevance.