Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis

Background: Focal segmental glomerulosclerosis (FSGS) is a type of nephrotic syndrome leading to end-stage renal disease, and this study aimed to explore the hub genes and pathways associated with FSGS to identify potential diagnostic and therapeutic targets. Methods: We downloaded the microarray datasets GSE121233 and GSE129973 from the Gene Expression Omnibus (GEO) database. The datasets comprise 25 FSGS samples and 25 normal samples. The differential expression genes (DEGs) were identified using the R package “limma”. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID) to identify the pathways and functional annotation of the DEGs. The protein–protein interaction (PPI) was constructed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape software. The hub genes of the DEGs were then evaluated using the cytoHubba plugin of Cytoscape. The expression of the hub genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) using the FSGS rat model, and receiver operating characteristic (ROC) curve analysis was performed to validate the accuracy of these hub genes. Results: A total of 45 DEGs including 18 upregulated and 27 downregulated DEGs, were identified in the two GSE datasets (GSE121233 and GSE129973). Among them, five hub genes with a high degree of connectivity were selected. From the PPI network, of the top five hub genes, FN1 was upregulated, while ALB, EGF, TTR, and KNG1 were downregulated. The qRT-PCR analysis of FSGS rats confirmed that the expression of FN1 was upregulated and that of EGF and TTR was downregulated. The ROC analysis indicated that FN1, EGF, and TTR showed considerable diagnostic efficiency for FSGS. Conclusion: Three novel FSGS-specific genes were identified through bioinformatic analysis combined with experimental validation, which may promote our understanding of the molecular underpinning of FSGS and provide potential therapeutic targets for the clinical management.
The Perirhinal Cortex Engages in Area and Layer-Specific Encoding of Item Dimensions

The perirhinal cortex (PRC), subdivided into areas 35 and 36, belongs to the parahippocampal regions that provide polysensory input to the hippocampus. Efferent and afferent connections along its rostro-caudal axis, and of areas 35 and 36, are extremely diverse. Correspondingly functional tasks in which the PRC participates are manifold. The PRC engages, for example, in sensory information processing, object recognition, and attentional processes. It was previously reported that layer II of the caudal area 35 may be critically involved in the encoding of large-scale objects. In the present study we aimed to disambiguate the roles of the different PRC layers, along with areas 35 and 36, and the rostro-caudal compartments of the PRC, in processing information about objects of different dimensions. Here, we compared effects on information encoding triggered by learning about subtle and discretely visible (microscale) object information and overt, highly visible landmark (macroscale) information. To this end, nuclear expression of the immediate early gene Arc was evaluated using fluorescence in situ hybridization. Increased nuclear Arc expression occurred in layers III and V-VI of the middle and caudal parts of area 35 in response to both novel microscale and macroscale object exposure. By contrast, a significant increase in Arc expression occurred in area 36 only in response to microscale objects. These results indicate that area 36 is specifically involved in the encoding of small and less prominently visible items. In contrast, area 35 engages globally (layer III to VI) in the encoding of object information independent of item dimensions.
Multivariate GWAS of Structural Dental Anomalies and Dental Caries in a Multi-Ethnic Cohort

Odontogenesis is a complex process, where disruption can result in dental anomalies and/or increase the risk of developing dental caries. Based on previous studies, certain dental anomalies tend to co-occur in patients, suggesting that these traits may share common genetic and etiological components. The main goal of this study was to implement a multivariate genome wide association study approach to identify genetic variants shared between correlated structural dental anomalies and dental caries. Our cohort (N = 3,579) was derived from the Pittsburgh Orofacial Clefts Study, where multiple dental traits were assessed in both the unaffected relatives of orofacial cleft (OFC) cases (n = 2,187) and unaffected controls (n = 1,392). We identified four multivariate patterns of correlated traits in this data: tooth agenesis, impaction, and rotation (AIR); enamel hypoplasia, displacement, and rotation (HDR); displacement, rotation, and mamelon (DRM); and dental caries, tooth agenesis and enamel hypoplasia (CAH). We analyzed each of these four models using genome-wide multivariate tests of association. No genome-wide statistically significant results were found, but we identified multiple suggestive association signals (P ≤ 10−5) near genes with known biological roles during tooth development, including ADAMTS9 and PRICKLE2 associated with AIR; GLIS3, WDR72, and ROR2 associated with HDR and DRM; ROBO2 associated with DRM; BMP7 associated with HDR; and ROBO1, SMAD2, and MSX2 associated with CAH. This is the first study to investigative genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.
Transcriptomic Analysis Reveals Competitive Growth Advantage of Non-pigmented Serratia marcescens Mutants

Serratia marcescens is a common bacterium well-known for the red secondary metabolite prodigiosin. However, color mutants have long been described. Non-pigmented strains can be found to exist both naturally and under laboratory conditions. It is unclear why S. marcescens loses prodigiosin synthesis capacity in certain conditions. In the present study, we find that the spontaneous color mutants arise within a few generations (about five passages) and rapidly replace the wild-type parent cells (about 24 passages), which indicates a growth advantage of the former. Although, the loss of prodigiosin synthesis genes (pigA-N) is frequently reported as the major reason for pigment deficiency, it was unexpected that the whole gene cluster is completely preserved in the different color morphotypes. Comparative transcriptomic analysis indicates a dramatic variation at the transcriptional level. Most of the pig genes are significantly downregulated in the color morphotypes which directly lead to prodigiosin dyssynthesis. Besides, the transcriptional changes of several other genes have been noticed, of which transcriptional regulators, membrane proteins, and nearly all type VI secretion system (T6SS) components are generally downregulated, while both amino acid metabolite and transport systems are activated. In addition, we delete the transcription regulator slyA to generate a non-pigmented mutant. The ΔslyA strain loses prodigiosin synthesis capacity, but has a higher cell density, and surprisingly enhances the virulence as an entomopathogen. These data indicate that S. marcescens shuts down several high-cost systems and activates the amino acid degradation and transport pathways at the transcriptional level to obtain extra resources, which provides new insights into the competitive growth advantage of bacterial spontaneous color mutants.
Topsoil Texture Regionalization for Agricultural Soils in Germany—An Iterative Approach to Advance Model Interpretation

Site-specific spatially continuous soil texture data is required for many purposes such as the simulation of carbon dynamics, the estimation of drought impact on agriculture, or the modeling of water erosion rates. At large scales, there are often only conventional polygon-based soil texture maps, which are hardly reproducible, contain abrupt changes at polygon borders, and therefore are not suitable for most quantitative applications. Digital soil mapping methods can provide the required soil texture information in form of reproducible site-specific predictions with associated uncertainties. Machine learning models were trained in a nested cross-validation approach to predict the spatial distribution of the topsoil (0–30 cm) clay, silt, and sand contents in 100 m resolution. The differential evolution algorithm was applied to optimize the model parameters. High-quality nation-wide soil texture data of 2,991 soil profiles was obtained from the first German agricultural soil inventory. We tested an iterative approach by training models on predictor datasets of increasing size, which contained up to 50 variables. The best results were achieved when training the models on the complete predictor dataset. They explained about 59% of the variance in clay, 75% of the variance in silt, and 77% of the variance in sand content. The RMSE values ranged between approximately 8.2 wt. % (clay), 11.8 wt. % (silt), and 15.0 wt. % (sand). Due to their high performance, models were able to predict the spatial texture distribution. They captured the high importance of the soil forming factors parent material and relief. Our results demonstrate the high predictive power of machine learning in predicting soil texture at large scales. The iterative approach enhanced model interpretability. It revealed that the incorporated soil maps partly substituted the relief and parent material predictors. Overall, the spatially continuous soil texture predictions provide valuable input for many quantitative applications on agricultural topsoils in Germany.
theLiTE™: A Screening Platform to Identify Compounds that Reinforce Tight Junctions

Tight junctions (TJ) are formed by transmembrane and intracellular proteins that seal the intercellular space and control selective permeability of epithelia. Integrity of the epithelial barrier is central to tissue homeostasis and barrier dysfunction has been linked to many pathological conditions. TJ support the maintenance of cell polarity through interactions with the Par complex (Cdc42-Par-6-Par-3-aPKC) in which Par-6 is an adaptor and links the proteins of the complex together. Studies have shown that Par-6 overexpression delays the assembly of TJ proteins suggesting that Par-6 negatively regulates TJ assembly. Because restoring barrier integrity is of key therapeutic and prophylactic value, we focus on finding compounds that have epithelial barrier reinforcement properties; we developed a screening platform (theLiTE™) to identify compounds that modulate Par-6 expression in follicular epithelial cells from Par-6-GFP Drosophila melanogaster egg chambers. Hits identified were then tested whether they improve epithelial barrier function, using measurements of transepithelial electrical resistance (TEER) or dye efflux to evaluate paracellular permeability. We tested 2,400 compounds, found in total 10 hits. Here we present data on six of them: the first four hits allowed us to sequentially build confidence in theLiTE™ and two compounds that were shortlisted for further development (myricetin and quercetin). We selected quercetin due to its clinical and scientific validation as a compound that regulates TJ; food supplement formulated on the basis of this discovery is currently undergoing clinical evaluation in gastroesophageal reflux disease (GERD) sufferers.
Multimodal Imaging-Based Phenotyping of a Singaporean Hospital-Based Cohort of High Myopia Patients

Purpose: To assess the effect of axial length (AL) on the prevalence of pathologic myopia (PM) and associated myopic features in a Singaporean hospital-based cohort of patient with high myopia (HM). Methods: In total, 923 HM eyes from 495 individuals were recruited from the Myopic and Pathologic Eyes in Singapore (MyoPES) cohort and underwent ocular biometry, fundus photography, fundus autofluorescence, and swept-source optical coherence tomography (SS-OCT). Images were analyzed for the presence of myopic macular degeneration (MMD), myopic choroidal neovascularization (mCNV), myopic traction maculopathy (MTM), peripapillary atrophy (PPA), myopic tilted disc, posterior staphyloma (PS), dome-shaped macula (DSM), vitremacular adhesions (VMA), and the epiretinal membrane (ERM). Eyes were stratified into quartiles based on ALs to determine cut-off values to perform comparisons between shorter-length and longer-length groups. A χ2-test was done to determine the difference in the prevalence of pathologies between groups. Results: Overall, mean AL was 29.2 ± 2.2 mm (range 25.0–36.7 mm). Myopic macular degeneration, PPA, myopic tilted disc, and ERM have AL threshold of ≥27.5 mm, whereas MTM has an AL threshold of ≥29.0 mm. We found that there was a significantly higher prevalence of MMD (88.2 vs. 49.4%; p < 0.001), PPA (98.1 vs. 80.1%; p < 0.001), myopic tilted disc (72.7 vs. 50.2%; p < 0.001), and ERM (81.4 vs. 17.3%; p = 0.003) in eyes with AL ≥ 27.5 mm vs. eyes without AL <27.5 mm. Prevalence of MTM (34.7 vs. 32.1%; p < 0.001), mCNV (17.4 vs. 12.1%; p = 0.03), PS (43.4 vs. 34.7%; p = 0.012), DSM (21.3 vs. 13.2%; p = 0.002), and VMA (5.9 vs. 2.6%; p = 0.014) in eyes with AL ≥ 29.0 mm compared with AL < 29.0 mm. Conclusion: Our study describes the overall prevalence of PM and related pathologies among patients with HM in our hospital-based cohort. Longer eyes even among HM eyes had a significantly higher prevalence of PM-associated pathologies studied. This supports the premise that eyes with longer AL, even among HM eyes may be at greater risk of vision-threatening changes and therefore merit regular follow-up.
Synergy of Effectuation and Causation: An Emotional Complexity Perspective

This study enriches the literature on entrepreneurial decisions by investigating the antecedents of the synergetic use of causal and effectual logic. Based on entrepreneurial metacognition and emotional complexity theories, we argued that the emotional complexity of an entrepreneur, referred to as the granular experience of, or variety in, experienced emotions during the entrepreneurial task, would contribute to the synergetic use of decision logic. With survey data gathered from 218 Chinese entrepreneurs, we found that entrepreneurs with higher emotional complexity are more likely to adopt two types of entrepreneurial logic in tandem, and cognitive flexibility mediates this positive relationship. Thereby, this study helps to unravel some of the complexities behind the choice of decision logic of entrepreneurs.
Epichloë Fungal Endophytes Influence Seed-Associated Bacterial Communities

Seeds commonly harbour diverse bacterial communities that can enhance the fitness of future plants. The bacterial microbiota associated with mother plant’s foliar tissues is one of the main sources of bacteria for seeds. Therefore, any ecological factor influencing the mother plant’s microbiota may also affect the diversity of the seed’s bacterial community. Grasses form associations with beneficial vertically transmitted fungal endophytes of genus Epichloë. The interaction of plants with Epichloë endophytes and insect herbivores can influence the plant foliar microbiota. However, it is unknown whether these interactions (alone or in concert) can affect the assembly of bacterial communities in the produced seed. We subjected Lolium multiflorum plants with and without its common endophyte Epichloë occultans (E+, E-, respectively) to an herbivory treatment with Rhopalosiphum padi aphids and assessed the diversity and composition of the bacterial communities in the produced seed. The presence of Epichloë endophytes influenced the seed bacterial microbiota by increasing the diversity and affecting the composition of the communities. The relative abundances of the bacterial taxa were more similarly distributed in communities associated with E+ than E- seeds with the latter being dominated by just a few bacterial groups. Contrary to our expectations, seed bacterial communities were not affected by the aphid herbivory experienced by mother plants. We speculate that the enhanced seed/seedling performance documented for Epichloë-host associations may be explained, at least in part, by the Epichloë-mediated increment in the seed-bacterial diversity, and that this phenomenon may be applicable to other plant-endophyte associations.
Development and Psychometric Evaluation of the Gender Identity Scale for Transgender Women in China

Transgender women are an important subgroup of the transgender umbrella and have their own unique gender identity. This article aimed to understand and measure the latent concept of gender identity among Chinese transgender women from a multi-dimensional perspective. Through a two-phase, iterative scale development process, we developed the Gender Identity Scale for Transgender Women (GIS-TW) in Chinese. Literature reviews, expert consultations, and focus groups constitute phrase 1 of the study, which resulted in the first version of GIS-TW with 30 items. In phrase 2, exploratory factor analysis on a sample of 244 Chinese transgender women revealed a six-factor solution across the 22 items. The Bem Sex Role Inventory was included to test for convergent validity, and the Rosenberg Self-Esteem Scale was used to test discriminant validity. Then we conducted the confirmatory factor analysis with an independent sample of 420 Chinese transgender women, which produced the final version of GIS-TW with 21 items. The internal consistency (Cronbach’s alpha = 0.71–0.87) and test-retest stability (r = 0.73–0.87) of each factor was good. In conclusion, the GIS-TW is a reliable and valid psychometric tool for the assessment of Chinese transgender women’s gender identity. Future application of the scale will help transgender women obtain better gender confirmative interventions.
Multiplexed Genome Editing via an RNA Polymerase II Promoter-Driven sgRNA Array in the Diatom Phaeodactylum tricornutum: Insights Into the Role of StLDP

CRISPR/Cas9-mediated genome editing has been demonstrated in the model diatom P. tricornutum, yet the currently available genetic tools do not combine the various advantageous features into a single, easy-to-assemble, modular construct that would allow the multiplexed targeting and creation of marker-free genome-edited lines. In this report, we describe the construction of the first modular two-component transcriptional unit system expressing SpCas9 from a diatom episome, assembled using the Universal Loop plasmid kit for Golden Gate assembly. We compared the editing efficiency of two constructs with orthogonal promoter-terminator combinations targeting the StLDP gene, encoding the major lipid droplet protein of P. tricornutum. Multiplexed targeting of the StLDP gene was confirmed via PCR screening, and lines with homozygous deletions were isolated from primary exconjugants. An editing efficiency ranging from 6.7 to 13.8% was observed in the better performing construct. Selected gene-edited lines displayed growth impairment, altered morphology, and the formation of lipid droplets during nutrient-replete growth. Under nitrogen deprivation, oversized lipid droplets were observed; the recovery of cell proliferation and degradation of lipid droplets were impaired after nitrogen replenishment. The results are consistent with the key role played by StLDP in the regulation of lipid droplet size and lipid homeostasis.
Binding Pattern Reconstructions of FGF-FGFR Budding-Inducing Signaling in Reef-Building Corals

Reef-building corals play an important role in marine ecosystems. However, owing to climate change, ocean acidification, and predation by invasive crown-of-thorns starfish, these corals are declining. As marine animals comprise polyps, reproduction by asexual budding is pivotal in scleractinian coral growth. The fibroblast growth factor (FGF) signaling pathway is essential in coral budding morphogenesis. Here, we sequenced the full-length transcriptomes of four common and frequently dominant reef-building corals and screened out the budding-related FGF and FGFR genes. Thereafter, three-dimensional (3D) models of FGF and FGFR proteins as well as FGF-FGFR binding models were reconstructed. Based on our findings, the FGF8-FGFR3 binding models in Pocillopora damicornis, Montipora capricornis, and Acropora muricata are typical receptor tyrosine kinase-signaling pathways that are similar to the Kringelchen (FGFR) in hydra. However, in P. verrucosa, FGF8 is not the FGFR3 ligand, which is found in other hydrozoan animals, and its FGFR3 must be activated by other tyrosine kinase-type ligands. Overall, this study provides background on the potentially budding propagation signaling pathway activated by the applications of biological agents in reef-building coral culture that could aid in the future restoration of coral reefs.
Magnesium Isoglycyrrhizinate Ameliorates Concanavalin A-Induced Liver Injury by Inhibiting Autophagy

Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury. Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry. Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy. Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.