Miracle-dz/UniFAR-FTUs huggingface dataset:
The tomato yellow leaf curl virus C4 protein alters the expression of plant developmental genes correlating to leaf upward cupping phenotype in tomato

Tomato yellow leaf curl virus (TYLCV), a monopartite begomovirus in the family Geminiviridae, is efficiently transmitted by the whitefly, Bemisia tabaci, and causes serious economic losses to tomato crops around the world. TYLCV-infected tomato plants develop distinctive symptoms of yellowing and leaf upper cupping. In recent years, excellent progress has been made in the characterization of TYLCV C4 protein function as a pathogenetic determinant in experimental plants, including Nicotiana benthamiana and Arabidopsis thaliana. However, molecular mechanism leading to disease symptom development in natural host plant tomato has yet to be characterized. The aim of the current study was to generate transgenic tomato plants expressing the TYLCV C4 gene and evaluate differential gene expression through comparative transcriptome analysis between the transgenic C4 plants and the transgenic green fluorescent protein (Gfp) gene control plants. Transgenic tomato plants expressing the TYLCV C4 developed phenotypes, including leaf upward cupping and yellowing that are similar the disease symptom expressed on tomato plants infected with TYLCV. In a total of 241 differentially expressed genes identified in the transcriptome analysis, a series of plant development-related genes, including transcription factors, glutaredoxins, protein kinases, R-genes and microRNA target genes, were significantly altered. These results provide further evidence to support the important function of the C4 protein in begomovirus pathogenicity. These transgenic tomato plants could serve as basic genetic materials for further characterization of plant receptors that are interacting with the TYLCV C4.
Network visualisation of synthetic biology designs

1 ABSTRACT Visualising the complex information captured by synthetic biology designs is still a major challenge. The popular glyph approach where each genetic part is displayed on a linear sequence allows researchers to generate diagrams and visualise abstract designs [2], but only represents a single, static representation that results in visualisation that is not specific to the requirements of a user resulting in a one-size-fits-all visualisation. We developed a network visualisation technique that automatically turns all design information into a graph, displaying otherwise hidden data. The structure of the resulting graphs can be dynamically adjusted according to specific visualisation requirements, such as highlighting proteins, interactions or hierarchy. Since biological systems have an inherent affinity with network visualization [6], we advocate for adopting this approach to standardise and automate the representation of complex information.
Isolation, identification and molecular characterization of Aeromonas spp. from farmed loach (Misgurnus anguillicaudatus)

Gram-negative Aeromonas bacteria is known to contaminate aquaculture products and retains the ability to infect wide range of host including fishes, shrimps and humans. This study is designed to evaluate the presence of Aeromonas in healthy loaches (Misgurnus anguillicaudatus) collected from the markets in Hainan and Guangdong provinces of China. Based on the molecular sequencing and phylogenetic analysis with single 16S rRNA and concatenated genes (gyrA and ropD), 104 isolates were identified as Aeromonas species followed by further classification to A. veronii (83.65%), A. jandaei (9.62%), A. hydrophila (3.85%) and A. allosaccharophila (2.88%). More than half of the isolates displayed hemolytic activity of 87.5% and were able to form moderate biofilm (78.26%). Fourteen antibiotics from ten representative classes were screened that demonstrated complete resistance to ampicillin, 89.4% and 68.3% to lincomycin and nalidixic acid. Moreover, a notable detection and prevalence was found in screening of ten virulence-related and nine resistance genes. To our knowledge, it is the first report of its kind demonstrating potential threat of the commercial loaches carrying Aeromonas to human health. These findings will assist professionals working in clinical settings to optimize their prescription accordingly and researchers to access the impacts of Aeromonas resistance on human health. Importance This study demonstrates high infection rate of loaches by Aeromonas spp. in Hainan and Guangdong provinces of China. The most prevalent species was Aeromonas veronii. Most of the isolates displayed hemolytic activity and formed moderate biofilm. Multiple virulence genes, resistance genes and multi-antibiotic resistance were detected. Aeromonads risks should be considered in loach industry.
Allosteric modulation of the adenosine A2A receptor by cholesterol

Cholesterol is a major component of the cell membrane and commonly regulates membrane protein function. Here, we investigate how cholesterol modulates the conformational equilibria and signaling of the adenosine A2A receptor (A2AR) in reconstituted phospholipid bilayers. GTP hydrolysis assays show that cholesterol is a weak positive allosteric modulator of A2AR, as seen through enhanced basal signaling and a small decrease in agonist EC50. Fluorine nuclear magnetic resonance (19F NMR) spectroscopy suggests that this enhancement arises from an increase in the receptor’s active state populations and stronger G protein coupling. 19F NMR of fluorinated cholesterol analogs reveals transient and non-specific interactions with A2AR, indicating a lack of high-affinity binding sites or direct allosteric modulation. This is confirmed by computational analysis which suggests that cholesterol contacts confer a weak and possibly negative allosteric effect. The combined results suggest that the observed cholesterol allostery in A2AR is likely a result of indirect membrane effects through cholesterol-mediated changes in membrane properties, as shown by membrane fluidity measurements and high-pressure NMR.
Common micro- and macroscale principles of connectivity in the human brain

The brain requires efficient information transfer between neurons and between large-scale brain regions. Brain connectivity follows predictable organizational principles: at the cellular level, larger supragranular pyramidal neurons have larger dendritic trees, more synapses, more complex branching and perform more complex neuronal computations; at the macro-scale, region-to-region connections are suggested to display a diverse architecture with highly connected hub-areas facilitating complex information integration and computation. Here, we explore the hypothesis that the branching structure of large-scale region-to-region connectivity follows similar organizational principles as known for the neuronal scale. We examine microscale connectivity of basal dendritic trees of supragranular pyramidal neurons (300+) across ten cortical areas in five human donor brains (1M/4F). Dendritic complexity was quantified as the number of branch points, tree length, spine count, spine density and overall branching complexity. High-resolution diffusion-weighted MRI was used to construct ‘white matter trees’ of cortico-cortical wiring. Examining the complexity of the resulting white matter trees using the same measures as for dendritic trees shows multimodal association areas to have larger, more complexly branched white matter trees than primary areas (all p<0.0001) and regional macroscale complexity to run in parallel with microscale measures, in terms of number of inputs (r=0.677, p=0.032), branch points (r=0.790, p=0.006), total tree length (r=0.664, p=0.036) and branching complexity (r=0.724, p=0.018). Our findings support the integrative theory that brain connectivity is structured following similar ‘principles of connectivity’ at the neuronal and macroscale level, and provide a framework to study connectivity changes in brain conditions at multiple levels of brain organization.
The Functional Roles of RNAs Cargoes Released by Neutrophil-Derived Exosomes in Dermatomyositis

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by cutaneous manifestations. We first identified the profiles of noncoding RNAs (lncRNAs and miRNAs) in peripheral neutrophil exosomes (EXOs) of DM patients and explored their potential functional roles. Bioinformatics analyses were performed with R packages. Real-time quantitative PCR was used to validate the altered RNAs in DM neutrophil EXO-stimulated human dermal microvascular endothelial cells (HDMECs) and human skeletal muscle myoblasts (HSkMCs). In DM neutrophil EXOs, 124 upregulated lncRNAs (with 1,392 target genes), 255 downregulated lncRNAs (with 1867 target genes), 17 upregulated miRNAs (with 2,908 target genes), and 15 downregulated miRNAs (with 2,176 target genes) were identified. GO analysis showed that the differentially expressed (DE) lncRNAs and DE miRNAs participated in interleukin-6 and interferon-beta production, skeletal muscle cell proliferation and development, and endothelial cell development and differentiation. KEGG analysis suggested that DE lncRNAs and DE miRNAs were enriched in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways. Many novel and valuable DE lncRNAs and DE miRNAs interacted and cotargeted in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways. Our study suggests that neutrophil EXOs participate in DM pathogenesis through lncRNAs and miRNAs in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways.
Malaria Transmission, Vector Diversity, and Insecticide Resistance at a Peri-Urban Site in the Forest Zone of Ghana

Introduction Recent surge of Anopheles resistance to major classes of World Health Organization (WHO)-approved insecticides globally necessitates the need for information about local malaria vector populations. It is believed that insecticide efficacy loss may lead to operational failure of control interventions and an increase in malaria infection transmission. We investigated the susceptibility levels of malaria vectors to all classes of WHO-approved vector control insecticides and described the dynamics of malaria transmission in a peri-urban setting. Methods Fit 3–5-day-old adults that emerged from Anopheles larvae collected from several different sites in the study area were subjected to the WHO bioassay for detecting insecticide resistance. The knockdown resistance gene (kdr) mutations within the vector populations were detected using PCR. Entomological inoculation rates were determined using the human landing catch technique and Plasmodium falciparum circumsporozoite ELISA. Results The malaria vectors from the study area were resistant to all classes of insecticides tested. Out of the 284 Anopheles complex specimen assayed for the resistance study, 265 (93.30%) were identified as Anopheles gambiae s.s. The kdr gene was detected in 90% of the Anopheles gambiae s.s. assayed. In an area where Anopheles coluzzii resistance to insecticides had never been reported, the kdr gene was detected in 78% of the Anopheles coluzzii sampled. The entomological inoculation rate (EIR) for the dry season was 1.44 ib/m/n, whereas the EIR for the rainy season was 2.69 ib/m/n. Conclusions This study provides information on the high parasite inoculation rate and insecticide resistance of malaria vectors in a peri-urban community, which is critical in the development of an insecticide resistance management program for the community.
Regional Non-point Source Pollution Control Method: A Design of Ecological Compensation Standards

Reasonable ecological compensation standard is the key to solve farmland non-point source pollution. In the design of compensation standards, the current investigation included ecological benefits in selecting the experimental method. The Multinomial Logit model is used to analyze the willingness of farmers to receive compensation for non-point source pollution control of cultivated land. The results are as follows: 1) Financial compensation can effectively stimulate farmers’ willingness to control non-point source pollution. 2) The willingness of farmers to participate in the ecological compensation is greater when there prevails a higher level of risk preferences and higher understanding of farmland non-point source pollution control policy. Also, willingness is higher in younger, highly educated, and highly involved in a part-time family business with higher recognition degree in the ecological function of farmland non-point source pollution control. 3) The difference in treatment measures and compensation methods should be included in the standard compensation design. Therefore, the design of the ecological compensation standard should take into account the economic loss and ecological benefits of farmers at the same time, and environmental protection publicity and education for farmers can also be carried out with the help of modern media.
The Dynamic Changes of Transcription Factors During the Development Processes of Human Biparental and Uniparental Embryos

Previous studies have revealed that transcription factors (TFs) play important roles in biparental (BI) early human embryogenesis. However, the contribution of TFs during early uniparental embryo development is still largely unknown. Here we systematically studied the expression profiles of transcription factors in early embryonic development and revealed the dynamic changes of TFs in human biparental and uniparental embryogenesis by single-cell RNA sequencing (scRNA-seq). In general, the TF expression model of uniparental embryos showed a high degree of conformity with biparental embryos. The detailed network analysis of three different types of embryos identified that 10 out of 17 hub TFs were shared or specifically owned, such as ZNF480, ZNF581, PHB, and POU5F1, were four shared TFs, ZFN534, GTF3A, ZNF771, TEAD4, and LIN28A, were androgenic (AG) specific TFs, and ZFP42 was the only one parthenogenetic (PG) specific TF. All the four shared TFs were validated using human embryonic stem cell (hESC) differentiation experiments; most of their target genes are responsible for stem cell maintenance and differentiation. We also found that Zf-C2H2, HMG, and MYB were three dominant transcription factor families that appeared in early embryogenesis. Altogether, our work provides a comprehensive regulatory framework and better understanding of TF function in human biparental and uniparental embryogenesis.
Disease Burden and Attributable Risk Factors of Ovarian Cancer From 1990 to 2017: Findings From the Global Burden of Disease Study 2017

Aim: We aimed to estimate the disease burden and risk factors attributable to ovarian cancer, and epidemiological trends at global, regional, and national levels. Methods: We described ovarian cancer data on incidence, mortality, and disability-adjusted life-years as well as age-standardized rates from 1990 to 2017 from the Global Health Data Exchange database. We also estimated the risk factors attributable to ovarian cancer deaths and disability-adjusted life-years. Measures were stratified by region, country, age, and socio-demographic index. The estimated annual percentage changes and age-standardized rates were calculated to evaluate temporal trends. Results: Globally, ovarian cancer incident, death cases, and disability-adjusted life-years increased by 88.01, 84.20, and 78.00%, respectively. However, all the corresponding age-standardized rates showed downward trends with an estimated annual percentage change of −0.10 (−0.03 to 0.16), −0.33 (−0.38 to −0.27), and −0.38 (−0.32 to 0.25), respectively. South and East Asia and Western Europe carried the heaviest disease burden. The highest incidence, deaths, and disability-adjusted life-years were mainly in people aged 50–69 years from 1990 to 2017. High fasting plasma glucose level was the greatest contributor in age-standardized disability-adjusted life-years rate globally as well as in all socio-demographic index quintiles and most Global Disease Burden regions. Other important factors were high body mass index and occupational exposure to asbestos. Conclusion: Our study provides valuable information on patterns and trends of disease burden and risk factors attributable to ovarian cancer across age, socio-demographic index, region, and country, which may help improve the rational allocation of health resources as well as inform health policies.
A Novel Diagnostic Predictive Model for Idiopathic Short Stature in Children

Objective Idiopathic short stature (ISS), an endocrine-related disease, is difficult to diagnose. Previous studies have shown that many children with some inflammation-related diseases often have short stature, but whether inflammation is the underlying mechanism of ISS has not been studied. Here, we attempt to explore the role of inflammation in the occurrence and development of ISS and to demonstrate an available clinical diagnostic model of ISS. Methods Frozen serum samples were collected from ISS patients (n = 4) and control individuals (n = 4). Isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS analysis were applied to quantitative proteomics analysis. To assess clusters of potentially interacting proteins, functional enrichment (GO and KEGG) and protein-protein interaction network analyses were performed, and the crucial proteins were detected by Molecular Complex Detection (MCODE). Furthermore, serum levels of two selected proteins were measured by ELISA between ISS patients (n = 80) and controls (n = 80). In addition, experiments in vitro were used to further explore the effects of crucial proteins on endochondral ossification. Results A total of 437 proteins were quantified, and 84 DEPs (60 upregulated and 24 downregulated) were identified between patients with ISS and controls. Functional enrichment analysis showed that the DEPs were primarily enriched in blood microparticle, acute inflammatory response, protein activation cascade, collagen-containing extracellular matrix, platelet degranulation, etc. According to the results of top 10 fold change DEPs and MCODE analysis, C1QA and C1QB were selected to further experiment. The expression levels of C1QA and C1QB were validated in serum samples. Based on the logistic regression analysis and ROC curve analysis, we constructed a novel diagnostic model by serum levels of C1QA and C1QB with a specificity of 91.2% and a sensitivity of 75% (AUC = 0.900, p <0.001). Finally, the western blotting analysis confirmed the expression levels of OCN, OPN, RUNX2, and Collagen X were downregulated in chondrocytes, and the outcome of Collagen II was upregulated. Conclusion Our study is the first to demonstrate the significant role of inflammation in the development of ISS. In addition, we identify C1QA and C1QB as novel serum biomarkers for the diagnosis of ISS.
Berberine Alleviates Non-alcoholic Steatohepatitis Through Modulating Gut Microbiota Mediated Intestinal FXR Activation

Berberine is a natural plant alkaloid isolated from a diverse range of genera, it obtains anti-inflammatory, anti-obesity, and hepatoprotective properties, and is a promising agent for non-alcoholic steatohepatitis (NASH). Farnesoid X receptor (FXR) is a bile acid receptor and a drug target for NASH, however, the underlying mechanisms of berberine on regulating FXR are still unknown. In the present study, we feed mice with a 12-week high-fat diet with interval dextran sulfate sodium (0.5% in drinking water) diet to induce NASH, and treat the mice with berberine (100 mg/kg per day) via oral gavage for additional 4 weeks. We demonstrate that administration of berberine alleviates steatosis and infiltration of inflammatory cells in the liver of NASH mice. We apply 16S ribosomal DNA sequencing to screen the structure of gut microbiota, and ultra-performance liquid chromatography-tandem mass spectrometry analysis to determine the bile acid profiles. The results show that berberine modulates gut dysbiosis, and specifically increases the relative abundance of Clostridiales, Lactobacillaceae, and Bacteroidale. Berberine modulated microbiomes are associated with bile acid de-conjugation and transformation, which are consistent with the altered bile acid species (e.g., deoxycholic acid, ursodeoxycholic acid) upon berberine treatment. BA species that respond to berberine treatment are known FXR agonists, thus we performed quantitative Real Time-PCR and western blot to examine the FXR pathway, and find that berberine up-regulates intestinal FXR and fibroblast growth factor 15 (FGF15) expression, and the secretion of FGF15 further inhibits lipogenesis and nuclear factor-κB activation in the liver. Whereas the beneficial effects of berberine are blunted in FXR knockout mice. Our results reveal that berberine alleviates NASH by modulating the interplay of gut microbiota and bile acid metabolism, as well as the subsequent intestinal FXR activation.
Truncal Instability and Titubation in Patients With Acute Encephalopathy With Reduced Subcortical Diffusion

The present retrospective study aimed to investigate the presence of truncal instability or titubation after the first seizure and second phase in patients with acute encephalopathy with reduced subcortical diffusion (AED). Of the 15 patients with AED who were admitted to our hospital for 3 years and 2 months and had reached developmental milestones for sitting before disease onset, six experienced moderate-to-severe truncal instability while sitting after the first seizure. These patients had a significantly longer first seizure duration and significantly lower GCS scores 12–24 h after the first seizure, as well as significantly higher Tada score and Creatinine and blood glucose levels than those with mild or no truncal instability while in a seated position after the first seizure. Three 1-year-old children with bilateral frontal lobe lesions, particularly in the bilateral prefrontal lobe regions, demonstrated truncal titubation, which has not previously been reported as a clinical feature of AED. Tada score reported to be a predictor of AED prognosis and truncal instability in the sitting position after the first seizure may represent disease severity, but not the specific lesions. Conversely, truncal titubation might be suggestive of bilateral frontal lobe lesions, particularly in patients without severe instability. Further studies on the role of bilateral prefrontal lobe lesions to truncal titubation in patients with AED using more objective evaluation methods, such as stabilometry, are necessary.