Miracle-dz/UniFAR-FTUs huggingface dataset:
Porphyromonas somerae Invasion of Endometrial Cancer Cells

Recent evidence suggests an association between endometrial cancer and the understudied bacterial species Porphyromonas somerae. This association was demonstrated in previous work that indicated a significantly enriched abundance of P. somerae in the uterine microbiome of endometrial cancer patients. Given the known associations of the Porphyromonas genus and oral cancer, we hypothesized that P. somerae may play a similar pathogenic role in endometrial cancer via intracellular activity. Before testing our hypothesis, we first characterized P. somerae biology, as current background data is limited. These novel characterizations include growth curves in liquid medium and susceptibility tests to antibiotics. We tested our hypothesis by examining growth changes in response to 17β-estradiol, a known risk factor for endometrial cancer, followed by metabolomic profiling in the presence and absence of 17β-estradiol. We found that P. somerae exhibits increased growth in the presence of 17β-estradiol of various concentrations. However, we did not find significant changes in metabolite levels in response to 17β-estradiol. To study direct host-microbe interactions, we used in vitro invasion assays under hypoxic conditions and found evidence for intracellular invasion of P. somerae in endometrial adenocarcinoma cells. We also examined these interactions in the presence of 17β-estradiol but did not observe changes in invasion frequency. Invasion was shown using three lines of evidence including visualization via differential staining and brightfield microscopy, increased frequency of bacterial recovery after co-culturing, and in silico methods to detail relevant genomic and transcriptomic components. These results underscore potential intracellular phenotypes of P. somerae within the uterine microbiome. Furthermore, these results raise new questions pertaining to the role of P. somerae in the progression of endometrial cancer.
Mechanistic Modeling of a Novel Oncolytic Virus, V937, to Describe Viral Kinetic and Dynamic Processes Following Intratumoral and Intravenous Administration

V937 is an investigational novel oncolytic non-genetically modified Kuykendall strain of Coxsackievirus A21 which is in clinical development for the treatment of advanced solid tumor malignancies. V937 infects and lyses tumor cells expressing the intercellular adhesion molecule I (ICAM-I) receptor. We integrated in vitro and in vivo data from six different preclinical studies to build a mechanistic model that allowed a quantitative analysis of the biological processes of V937 viral kinetics and dynamics, viral distribution to tumor, and anti-tumor response elicited by V937 in human xenograft models in immunodeficient mice following intratumoral and intravenous administration. Estimates of viral infection and replication which were calculated from in vitro experiments were successfully used to describe the tumor response in vivo under various experimental conditions. Despite the predicted high clearance rate of V937 in systemic circulation (t1/2 = 4.3 min), high viral replication was observed in immunodeficient mice which resulted in tumor shrinkage with both intratumoral and intravenous administration. The described framework represents a step towards the quantitative characterization of viral distribution, replication, and oncolytic effect of a novel oncolytic virus following intratumoral and intravenous administrations in the absence of an immune response. This model may further be expanded to integrate the role of the immune system on viral and tumor dynamics to support the clinical development of oncolytic viruses.
Feeding Protocol Modulates the Digestive Process in Senegalese Sole (Solea senegalensis) Juveniles

Understanding the daily digestive function could lead to more efficient feeding practices in the farmed fish species. In this work, the effect of several daily feeding protocols was assessed on the daily expression of the genes related to the circadian system (arntl1, clock, per1, and cry1), appetite (cck), nutrients hydrolysis (try1, ctrb1, pga, atp4a, cel, and amy2a), peptides transport (slc15a1), pH, and activity of key digestive (trypsin, chymotrypsin, amylase, 4C- and 7C-like lipases) and absorptive (alkaline phosphatase) enzymes in the gastrointestinal tract (GIT) of Senegalese sole (Solea senegalensis) juveniles. Some of the tested feeding protocols demonstrated a significant influence on the entrainment of the peripheral oscillator. The synchrony of slc15a1 and some digestive proenzymes with per1 in some of the experimental treatments could underline the role of clock genes in the regulation of these biological functions. Unlike gene expression of the digestive proenzymes wherein feeding protocol occasionally affected the temporal organization, the influence of this factor was determinant on the daily average production and/or circadian pattern of their activities. Daily pH was maintained at approximately neutral levels in all the GIT segments, and no pepsin activity was detected. Fish fed a single diurnal meal showed the lowest activity for all the studied enzymes, except for amylase, suggesting an insufficient utilization of the ingested nutrients. Higher amylase activity in this group, on the other hand, implies the possible activation of alternative compensatory metabolic pathways. Overall, our results pointed to the suitability of higher feeding frequencies, especially during dark hours, for the aquaculture production of this species.
The Effects of Erchen Decoction on Gut Microbiota and Lipid Metabolism Disorders in Zucker Diabetic Fatty Rats

Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially Prevotella, Blautia, and Holdemania, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.
Integrated Analysis of Hepatic miRNA and mRNA Expression Profiles in the Spontaneous Reversal Process of Liver Fibrosis

Liver fibrosis results from the imbalance between extracellular matrix (ECM) production and degradation, which is a common pathological consequence of various chronic liver diseases. Although many miRNAs have been reported in liver fibrosis progression, miRNA-mRNA interactions in its reversal process remain to be elucidated. In the current study, we performed an integrated analysis of miRNA and mRNA expression profiles in the mouse model with the spontaneous reversal potency of liver fibrosis. A total of 102 miRNA and 2,845 mRNAs showed significant differential expression in reversal mice compared to fibrotic mice. Moreover, 3,769 putative negatively correlated miRNA-mRNA pairs were revealed to be potentially implicated in the biological function regulation of small molecule metabolism and ECM organization. By integrating miRNA-mRNA regulatory networks, mmu-miR-1843a-5p, mmu-miR-193a-5p, mmu-miR-194-2-3p, and mmu-miR-30c-2-3p were identified as lysyl oxidases-specific miRNAs that were correlated with fibrosis reversal. Our results provided potential candidate targets for the treatment of liver fibrosis.
How Do Spelling, Handwriting Speed, and Handwriting Quality Develop During Primary School? Cross-Classified Growth Curve Analysis of Children's Writing Development

Aim: Longitudinal studies are rare in the field of writing research, and little is known about the concurrent development of the two transcription skills: spelling and handwriting. This study was designed to provide a comprehensive picture of the development and the longitudinal relations between spelling, handwriting speed, and handwriting quality at the word level. Method: Over a period of 3 years (coh1: Grades 2–4; coh2: Grades 3–5), 117 French-speaking children were assessed on a single-word dictation task. At each testing time, measures of spelling accuracy, handwriting speed, and handwriting quality were collected on 40 words. Words varied in both orthographic and graphic complexity, making it possible to investigate the influence of these levels of complexity on transcription abilities. Results: Linear growth analyses using cross-classified Bayesian structural equation modeling (CC-BSEM) revealed that spelling and speed continued to improve until Grade 5, while handwriting quality reached an early plateau in Grade 2. In the younger cohort, graphic complexity had a significant influence on the pace of development of handwriting speed and on spelling and handwriting quality performance in Grade 2. In the older cohort, a positive relation between spelling and speed and a negative relation between handwriting speed and handwriting quality were found, indicating that fast handwriting is associated with high spelling ability and that fast handwriting is detrimental to handwriting quality. By providing a better understanding of writing development, this study yields innovative findings not only regarding the development of transcription skills but also regarding how spelling, handwriting speed, and handwriting quality can influence each other's performance throughout primary school.
Convex Approximation Algorithm for AC/DC Distribution Network With Energy Router

The optimal operation model of AC/DC distribution network with energy router (ER) is essentially a nonconvex nonlinear programming (NLP) problem. In order to improve the feasibility of solving the model, a convex approximation algorithm is proposed in this work. The steady-state model of ER is developed with considering the loss characteristics and multiport coordinated control strategy. It is embedded in the optimization formulations of AC/DC network as basic operating equations. Then, using second-order cone relaxation technology, the power flow equations of AC and DC distribution networks are convexly relaxed. On this basis, the highly nonlinear operating model of ER is linearized by introducing a successive approximation approach. Therefore, the original NLP problem is transformed into the convex programming problem and the solution efficiency is improved. Meanwhile, an iterative solution algorithm is developed to ensure the accuracy of the convex approximation approach. Simulation results verify the feasibility and efficiency of the proposed algorithm.
Synthetic Integrin-Targeting Dextran-Fc Hybrids Efficiently Inhibit Tumor Proliferation In Vitro

Herein, we present the design, synthesis, and biological evaluation of novel integrin-targeting molecular hybrids combining RGD peptides and a potent cytotoxin presented on dextran polysaccharides. Based on an aglycosylated Fc as a centerpiece, endosomal-cleavable cytotoxic agent monomethyl auristatin E (MMAE) and dextran as multimerization site were covalently connected by two bioorthogonal enzyme-mediated reactions site-specifically. Decoration of dextran with cyclic RGD peptides, introduced by copper “click” reaction, resulted in the final constructs with the potential to kill integrin-overexpressing tumor cells. We found that these modifications had little impact on the stability of the Fc scaffold and the RGD-bearing construct showed good binding properties of αvβ3-expressing U87MG cells. Furthermore, the construct showed a remarkable antiproliferative activity. These results demonstrate the general capability of our design to provoke receptor-mediated endocytosis upon binding to the cellular surface, followed by endosomal cleavage of the linkage between Fc-dextran and MMAE and its subsequent release. Our approach opens new avenues to transcribe small molecule binders into tailor-made multimeric molecular hybrids with antitumor potential.
ExoS/ChvI Two-Component Signal-Transduction System Activated in the Absence of Bacterial Phosphatidylcholine

Sinorhizobium meliloti contains the negatively charged phosphatidylglycerol and cardiolipin as well as the zwitterionic phosphatidylethanolamine (PE) and phosphatidylcholine (PC) as major membrane phospholipids. In previous studies we had isolated S. meliloti mutants that lack PE or PC. Although mutants deficient in PE are able to form nitrogen-fixing nodules on alfalfa host plants, mutants lacking PC cannot sustain development of any nodules on host roots. Transcript profiles of mutants unable to form PE or PC are distinct; they differ from each other and they are different from the wild type profile. For example, a PC-deficient mutant of S. meliloti shows an increase of transcripts that encode enzymes required for succinoglycan biosynthesis and a decrease of transcripts required for flagellum formation. Indeed, a PC-deficient mutant is unable to swim and overproduces succinoglycan. Some suppressor mutants, that regain swimming and form normal levels of succinoglycan, are altered in the ExoS sensor. Our findings suggest that the lack of PC in the sinorhizobial membrane activates the ExoS/ChvI two-component regulatory system. ExoS/ChvI constitute a molecular switch in S. meliloti for changing from a free-living to a symbiotic life style. The periplasmic repressor protein ExoR controls ExoS/ChvI function and it is thought that proteolytic ExoR degradation would relieve repression of ExoS/ChvI thereby switching on this system. However, as ExoR levels are similar in wild type, PC-deficient mutant and suppressor mutants, we propose that lack of PC in the bacterial membrane provokes directly a conformational change of the ExoS sensor and thereby activation of the ExoS/ChvI two-component system.
Comparing Greenland Ice Sheet Melt Variability From Different Satellite Passive Microwave Remote Sensing Products Over a Common 5-year Record

Satellite microwave brightness temperature (Tb) observations over the Greenland Ice Sheet permit determination of melted/frozen snow conditions at spatial and temporal scales that are uniquely suited for climate model validation and metrics of ice sheet change. Strong microwave sensitivity to the presence of liquid water in the snowpack is clear. Yet, a host of unique microwave-derived melt products covering the ice sheet are available, each based on different methodology, and with unknown inter-product agreement. Here, we compared five different published microwave melt products over a common 5-year (2003–2007) record to establish compatibility between products and agreement with in situ observations from a network of on-ice weather stations (AWS) spanning the ice sheet. A sixth product, leveraging both Tb seasonal trends and diurnal variability, was also introduced and included in the comparison. We found variable agreement between products and observations, with melt estimates based on microwave emissions modeling and the newly presented Adaptive Threshold (ADT) algorithm showing the best performance for AWS sites with more than 1-day average annual melt period (e.g., 68.9% of ADT melt days consistent with AWS observations; 31.1% of ADT frozen days contrasting with AWS observed melt). Spatial patterns of melting also varied between products. The different products showed substantial spread in melt occurrence even for products with the best AWS agreement. Product differences were generally larger under higher melt conditions; whereby, the fraction of the ice sheet experiencing ≥25 days of melting each year ranged from 4 to 25% for different products. While long-term satellite records have consistently shown increasing decadal trends in melt extent, our results imply that the melt frequency at any given location, particularly in the ice sheet interior where melting is less prevalent, is still subject to significant uncertainty.
Recommencement of Sport Leagues With Spectators at the Adelaide Oval During the COVID-19 Pandemic: Planning, Experience, and Impact of a Globally Unprecedented Approach

Non-pharmaceutical interventions including physical distancing and restriction on public gatherings were the cornerstone in controlling the COVID-19 pandemic, in the absence of effective vaccines and available treatment options. Many sport mega-events and sport leagues were canceled or indefinitely postponed, leaving stadiums globally empty or converted to be used as part of the COVID-19 response. There were calls for exit strategies to be developed. With the early containment of COVID-19 in South Australia, various restrictions were lifted in a staged and controlled manner, including the reopening of the Adelaide Oval for recommencement of sport leagues with spectator attendance. This involved the collaboration between public health authorities, other governmental agencies, Adelaide Oval Stadium Management Authority, various sporting leagues etc. Recommencement of sport leagues with staged increase in number of attending spectators allowed various measures to be introduced, revisited, and implemented accordingly, demonstrating that a case-by-case risk assessment can be conducted for mega-events during COVID-19, accounting for the epidemiological context at the time. Economic impacts and non-economic benefits of this recommencement were documented. This globally unprecedented, staged and controlled approach in returning spectators to sporting events during the COVID-19 pandemic could inform the reopening strategy of stadiums, recommencement of sport leagues and mega-events all over the world before herd immunity is achieved or in the event of future outbreaks.
Plastid-Localized EMB2726 Is Involved in Chloroplast Biogenesis and Early Embryo Development in Arabidopsis

Embryogenesis is a critical developmental process that establishes the body organization of higher plants. During this process, the biogenesis of chloroplasts from proplastids is essential. A failure in chloroplast development during embryogenesis can cause morphologically abnormal embryos or embryonic lethality. In this study, we isolated a T-DNA insertion mutant of the Arabidopsis gene EMBRYO DEFECTIVE 2726 (EMB2726). Heterozygous emb2726 seedlings produced about 25% albino seeds with embryos that displayed defects at the 32-cell stage and that arrested development at the late globular stage. EMB2726 protein was localized in chloroplasts and was expressed at all stages of development, such as embryogenesis. Moreover, the two translation elongation factor Ts domains within the protein were critical for its function. Transmission electron microscopy revealed that the cells in emb2726 embryos contained undifferentiated proplastids and that the expression of plastid genome-encoded photosynthesis-related genes was dramatically reduced. Expression studies of DR5:GFP, pDRN:DRN-GFP, and pPIN1:PIN1-GFP reporter lines indicated normal auxin biosynthesis but altered polar auxin transport. The expression of pSHR:SHR-GFP and pSCR:SCR-GFP confirmed that procambium and ground tissue precursors were lacking in emb2726 embryos. The results suggest that EMB2726 plays a critical role during Arabidopsis embryogenesis by affecting chloroplast development, possibly by affecting the translation process in plastids.
Trichoderma: A Treasure House of Structurally Diverse Secondary Metabolites With Medicinal Importance

Fungi play an irreplaceable role in drug discovery in the course of human history, as they possess unique abilities to synthesize diverse specialized metabolites with significant medicinal potential. Trichoderma are well-studied filamentous fungi generally observed in nature, which are widely marketed as biocontrol agents. The secondary metabolites produced by Trichoderma have gained extensive attention since they possess attractive chemical structures with remarkable biological activities. A large number of metabolites have been isolated from Trichoderma species in recent years. A previous review by Reino et al. summarized 186 compounds isolated from Trichoderma as well as their biological activities up to 2008. To update the relevant list of reviews of secondary metabolites produced from Trichoderma sp. , we provide a comprehensive overview in regard to the newly described metabolites of Trichoderma from the beginning of 2009 to the end of 2020, with emphasis on their chemistry and various bioactivities. A total of 203 compounds with considerable bioactivities are included in this review, which is worth expecting for the discovery of new drug leads and agrochemicals in the foreseeable future. Moreover, new strategies for discovering secondary metabolites of Trichoderma in recent years are also discussed herein.
A Tissue-Specific Landscape of Alternative Polyadenylation, lncRNAs, TFs, and Gene Co-expression Networks in Liriodendron chinense

Liriodendron chinense is an economically and ecologically important deciduous tree species. Although the reference genome has been revealed, alternative polyadenylation (APA), transcription factors (TFs), long non-coding RNAs (lncRNAs), and co-expression networks of tissue-specific genes remain incompletely annotated. In this study, we used the bracts, petals, sepals, stamens, pistils, leaves, and shoot apex of L. chinense as materials for hybrid sequencing. On the one hand, we improved the annotation of the genome. We detected 13,139 novel genes, 7,527 lncRNAs, 1,791 TFs, and 6,721 genes with APA sites. On the other hand, we found that tissue-specific genes play a significant role in maintaining tissue characteristics. In total, 2,040 tissue-specific genes were identified, among which 9.2% of tissue-specific genes were affected by APA, and 1,809 tissue-specific genes were represented in seven specific co-expression modules. We also found that bract-specific hub genes were associated plant defense, leaf-specific hub genes were involved in energy metabolism. Moreover, we also found that a stamen-specific hub TF Lchi25777 may be involved in the determination of stamen identity, and a shoot-apex-specific hub TF Lchi05072 may participate in maintaining meristem characteristic. Our study provides a landscape of APA, lncRNAs, TFs, and tissue-specific gene co-expression networks in L. chinense that will improve genome annotation, strengthen our understanding of transcriptome complexity, and drive further research into the regulatory mechanisms of tissue-specific genes.