Miracle-dz/UniFAR-FTUs huggingface dataset:
Knockdown of the premature ovarian insufficiency candidate gene NUP107 in ovarian granulosa cells affects cell functions, including receptor expression and estrogen synthesis

Objective: Mutations in NUP107 have been discovered in patients with premature ovarian insufficiency and may have tissue-specific effects in ovarian development. However, the role of NUP107 in human granulosa cell (GC) function and female fertility still remains unknown. In this study, we used RNA interference to investigate how NUP107 dysfunction influences GCs and ovarian development. Methods: Immunohistochemical staining was used to detect the expression of NUP107 in ovaries. Cell counting kit-8 assay, real-time cell analysis, and flow cytometry were used to explore cell proliferation and apoptosis, and an enzyme-linked immunosorbent assay was used to assess the estrogen concentrations. Quantitative real-time reverse transcription-quantitative polymerase chain reaction and Western blot analyses were used to determine the expression of NUP107 and functional receptors. Results: Knockdown of NUP107 expression had little effect on the growth and number of GCs. Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Conclusions: These data revealed that NUP107 may impede follicle growth and maturation by regulating hormone synthesis, sensitivity to follicle-stimulating hormone, and expression of functional receptors in GCs, and may, therefore, interfere with female fertility.
Psoriasis Patients Suffer From Worse Periodontal Status—A Meta-Analysis

Background and Objective: Patients with psoriasis have a significantly elevated risk of periodontitis compared with the nonpsoriasis controls. However, the data regarding the difference in the periodontal health status of the psoriasis patients and the nonpsoriasis controls are limited and inconsistent; hence, a specialized meta-analysis that quantitatively compared the periodontal status between the psoriasis and nonpsoriasis subjects by evaluating the related clinical periodontal indexes was needed. The aim of this meta-analysis was to quantitatively evaluate whether the periodontal status of psoriasis patients is worse than that of nonpsoriasis subjects. Methods: We searched PubMed and EMBASE for all eligible studies that compared the periodontal status between psoriasis patients and nonpsoriasis subjects. The studies were screened based on pre-established inclusion criteria. After extracting the available periodontal indexes from the included studies, the weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated by pooling the mean and standard deviations (SD) of each index. Results: In total, 8 studies, including 812 psoriasis patients and 772 nonpsoriasis subjects, were included in our meta-analysis, and the publication dates ranged from 2013 to 2019; eight periodontal indexes were analyzed. The WMD (95% CIs) for each index were: bleeding on probing (%), 9.188 (4.046–14.330, P < 0.001); probing depth (mm), 0.524 (0.183–0.865, P = 0.003); clinical attachment loss (mm), 0.408 (0.051–0.765, P = 0.025); plaque index, 0.186 (−0.170 to 0.543, P = 0.306); gingival index, 0.458 (−0.413 to 1.328, P = 0.303), remaining teeth, −1.709 (−2.106 to −1.312, P < 0.001); missing teeth, 1.130 (0.275–1.985, P = 0.010); the level of alveolar bone loss (mm), 0.400 (0.102–0.698, P = 0.008). Conclusion: In summary, our meta-analysis revealed that psoriasis patients suffer from worse periodontal health than do nonpsoriasis subjects, mainly characterized by worse gingival inflammation, more alveolar bone loss, fewer remaining teeth and more missing teeth. Considering the limitations of this meta-analysis, more high-quality and well-designed studies are needed to validate our conclusions in the future.
MARTINI-Based Protein-DNA Coarse-Grained HADDOCKing

Modeling biomolecular assemblies is an important field in computational structural biology. The inherent complexity of their energy landscape and the computational cost associated with modeling large and complex assemblies are major drawbacks for integrative modeling approaches. The so-called coarse-graining approaches, which reduce the degrees of freedom of the system by grouping several atoms into larger “pseudo-atoms,” have been shown to alleviate some of those limitations, facilitating the identification of the global energy minima assumed to correspond to the native state of the complex, while making the calculations more efficient. Here, we describe and assess the implementation of the MARTINI force field for DNA into HADDOCK, our integrative modeling platform. We combine it with our previous implementation for protein-protein coarse-grained docking, enabling coarse-grained modeling of protein-nucleic acid complexes. The system is modeled using MARTINI topologies and interaction parameters during the rigid body docking and semi-flexible refinement stages of HADDOCK, and the resulting models are then converted back to atomistic resolution by an atom-to-bead distance restraints-guided protocol. We first demonstrate the performance of this protocol using 44 complexes from the protein-DNA docking benchmark, which shows an overall ~6-fold speed increase and maintains similar accuracy as compared to standard atomistic calculations. As a proof of concept, we then model the interaction between the PRC1 and the nucleosome (a former CAPRI target in round 31), using the same information available at the time the target was offered, and compare all-atom and coarse-grained models.
Triggering Receptor Expressed on Myeloid Cells-1 Inhibitor Targeted to Endothelium Decreases Cell Activation

TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an immunoreceptor expressed on neutrophils, monocytes/macrophages, and endothelial cells. It amplifies the inflammatory response driven by Toll-Like Receptors (TLR) engagement. The pharmacological inhibition of TREM-1 confers protection in several pre-clinical models of acute inflammation. In this study, we aimed to investigate the role of TREM-1 in endothelial cells using a sneaking ligand construct (SLC) inhibiting TREM-1 in the endothelium. The SLC was made of 3 modules: an E-selectin targeting domain, a Pseudomonas aeruginosa exotoxin a translocation domain, and a 7 aa peptide (LSKSLVF) that contains the interaction site between TREM-1 and its adaptor protein DAP-12. SLC peptide was effectively picked up by endothelial cells following LPS stimulation. It decreased LPS induced TREM-1 up-regulation and cell activation, neutrophils extravasation, and improved median survival time during experimental peritonitis in mice. We reported that a targeted endothelial TREM-1 inhibition is able to dampen cell activation and to confer protection during septic shock in mice. The use of such cell-specific, ligand- independent TREM-1 inhibitors deserve further investigations during acute or chronic inflammatory disorders.
Treatment of Breast Cancer With Gonadotropin-Releasing Hormone Analogs

Although significant progress has been made in the implementation of new breast cancer treatments over the last three decades, this neoplasm annually continues to show high worldwide rates of morbidity and mortality. In consequence, the search for novel therapies with greater effectiveness and specificity has not come to a stop. Among the alternative therapeutic targets, the human gonadotropin-releasing hormone type I and type II (hGnRH-I and hGnRH–II, respectively) and its receptor, the human gonadotropin-releasing hormone receptor type I (hGnRHR-I), have shown to be powerful therapeutic targets to decrease the adverse effects of this disease. In the present review, we describe how the administration of GnRH analogs is able to reduce circulating concentrations of estrogen in premenopausal women through their action on the hypothalamus–pituitary–ovarian axis, consequently reducing the growth of breast tumors and disease recurrence. Also, it has been mentioned that, regardless of the suppression of synthesis and secretion of ovarian steroids, GnRH agonists exert direct anticancer action, such as the reduction of tumor growth and cell invasion. In addition, we discuss the effects on breast cancer of the hGnRH-I and hGnRH-II agonist and antagonist, non-peptide GnRH antagonists, and cytotoxic analogs of GnRH and their implication as novel adjuvant therapies as antitumor agents for reducing the adverse effects of breast cancer. In conclusion, we suggest that the hGnRH/hGnRHR system is a promising target for pharmaceutical development in the treatment of breast cancer, especially for the treatment of advanced states of this disease.
Machine Learning Assisted MRI Characterization for Diagnosis of Neonatal Acute Bilirubin Encephalopathy

Background: The use of magnetic resonance imaging (MRI) in diagnosis of neonatal acute bilirubin encephalopathy (ABE) in newborns has been limited by its difficulty in differentiating confounding image contrast changes associated with normal myelination. This study aims to demonstrate the feasibility of building a machine learning prediction model based on radiomics features derived from MRI to better characterize and distinguish ABE from normal myelination. Methods: In this retrospective study, we included 32 neonates with clinically confirmed ABE and 29 age-matched controls with normal myelination. Radiomics features were extracted from the manually segmented region of interest (ROI) on T1-weighted spin echo images, followed by the feature selection using two-sample independent t-test, least absolute shrinkage and selection operator (Lasso) regression, and Pearson's correlation matrix. Additional feature quantifying the relative mean intensity of ROI was defined and calculated. A prediction model based on the selected features was built to classify ABE and normal myelination using multiple machine learning classifiers and a leave-one-out cross-validation scheme. Receiver operating characteristics (ROC) analysis was used to evaluate the prediction performance with the area under the curve (AUC) and feature importance ranked based on the Fisher score. Results: Among 1319 radiomics features, one radiologist-defined intensity-based feature and 12 texture features were selected as the most discriminative features. Based on these features, decision trees had the best classification performance with the largest AUC of 0.946, followed by support vector machine (SVM), tree-bagger, logistic regression, Naïve Bayes, discriminant analysis, and k-nearest neighborhood (KNN), which have an AUC of 0.931, 0.925, 0.905, 0.891, 0.883, and 0.817, respectively. The relative mean intensity outperformed other 12 texture features in differentiating ABE from controls. Conclusions: The results from this study demonstrated a new strategy of characterizing ABE-induced intensity and morphological changes in MRI, which are difficult to be recognized, interpreted, or quantified by the routine experience and visual-based reading strategy. With more quantitative and objective measurements, the reported machine learning assisted radiomics features-based approach can improve the diagnosis and support clinical decision-making.
Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System

Since bifidobacteria are among the pioneering colonizers of the human infant gut, their interaction with their host is believed to start soon following birth. Several members of the Bifidobacterium genus are purported to exert various health-promoting effects at local and systemic levels, e.g., limiting pathogen colonization/invasion, influencing gut homeostasis, and influencing the immune system through changes in innate and/or adaptive immune responses. This has promoted extensive research efforts to shed light on the precise mechanisms by which bifidobacteria are able to stimulate and interact with the host immune system. These studies uncovered a variety of secreted or surface-associated molecules that act as essential mediators for the establishment of a bifidobacteria-host immune system dialogue, and that allow interactions with mucosa-associated immune cells. Additionally, the by-products generated from bifidobacterial carbohydrate metabolism act as vectors that directly and indirectly trigger the host immune response, the latter by stimulating growth of other commensal microorganisms such as propionate- or butyrate-producing bacteria. This review is aimed to provide a comprehensive overview on the wide variety of strategies employed by bifidobacteria to engage with the host immune system.
Three-Dimensional Graphene-Based Composite Hydrogel Materials for Flexible Supercapacitor Electrodes

Three-dimensional (3D) graphene-based hydrogels have attracted great interest for applying in supercapcacitors electrodes, owing to their intriguing properties that combine the structural interconnectivities and the outstanding properties of graphene. However, the pristine graphene hydrogel can not satisfy the high-performance demands, especial in high specific capacitance. Consequently, novel graphene-based composite hydrogels with increased electrochemical properties have been developed. In this mini review, a brief summary of recent progress in the research of the three-dimensional graphene-based composite hydrogel for flexible supercapacitors electrodes materials is presented. The latest progress in the graphene-based composite hydrogel consisting of graphene/metal, graphene/polymer, and atoms doped graphene is discussed. Furthermore, future perspectives and challenges in graphene-based composite hydrogel for supercapacitor electrodes are also expressed.
Social Memory and the Role of the Hippocampal CA2 Region

The CA2 region of the hippocampus is a somewhat obscure area lacking in an understanding of its form and function. Until recently, the CA2 has been thought of as merely an extension of the CA3, with some referring to it as the CA3a region. Recent investigations into this area have not only delineated the CA2, but also defined it as a region distinct from both CA1 and CA3, with a unique set of cortical inputs and outputs and contributions to cognitive processes. One such process that has been shown to depend on the CA2 is the ability to recognize a novel or familiar conspecific, known as social recognition memory. Here, we review these findings and discuss the parallels between CA2 dysfunction and social impairments.
Syncytiotrophoblast-Derived Extracellular Vesicles in Pathophysiology of Preeclampsia

Preeclampsia is a common obstetric complication associated with pregnancy and it endangers lives of the mother and the infant. The histopathological changes associated with preeclampsia include systemic endothelial dysfunction, persistent inflammatory state, and coagulation and fibrinolysis dysregulations. Preeclampsia is considered to be caused by the systemic vasoconstriction of small arteries and disruption of the endothelial integrity, resulting in hypertension, proteinuria, and multiple organ dysfunction. However, mediators that trigger or propagate the pathology of preeclampsia remain poorly defined. Syncytiotrophoblast-derived extracellular vesicles (SDEVs) are increasingly recognized as a key mediator for the development of preeclampsia, but the underlying mechanisms through which these SDEVs are released and induce systemic responses are not fully understood. This review focuses on multiple roles of SDEVs in the pathogenesis of preeclampsia.
Mayaro Virus Replication Restriction and Induction of Muscular Inflammation in Mice Are Dependent on Age, Type-I Interferon Response, and Adaptive Immunity

Mayaro virus (MAYV) is an emergent arbovirus first described in forest regions of the American continent, with recent and increasing notification of urban area circulation. Similar to Chikungunya (CHIKV) and other arthritogenic Alphavirus, MAYV-induced disease shows a high prevalence of persistent arthralgia, and myalgia. Despite this, knowledge regarding pathogenesis and characteristics of host immune response of MAYV infections are still limited. Here, using different ages of wild-type (WT), adult Type I Interferon receptor deficient (IFNAR–/–), and adult recombination activation gene-1 deficient (RAG–/–) mice, we have investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication, tissue damage, and inflammation in mice. We have found that MAYV induces clinical signal and replicates in young WT mice, which gain the ability to restrict MAYV replication with aging. In addition, we observed that mice age and type I interferon response are related to restriction of MAYV infection and muscular inflammation in mice. Moreover, MAYV continues to replicate persistently in RAG–/– mice, being detected at blood and tissues 40 days post infection, indicating that adaptive immunity is essential to MAYV clearance. Despite chronic replication, infected adult RAG–/– mice did not develop an apparent signal of muscle damage in early and late infection. On the other hand, MAYV infection in young WT and adult IFNAR-/- mice triggers an increase in the expression of pro-inflammatory mediators, such as TNF, IL-6, KC, IL-1β, MCP-1, and RANTES, in muscle tissue, and decreases TGF-β expression, that were not significantly modulated in adult WT and RAG–/– mice. Taken together, our data demonstrated that age, innate and adaptive immunity are important to restrict MAYV replication and that adaptive immunity is also involved in MAYV-induced tissue damage. These results contribute to the comprehension of MAYV pathogenesis, and describe translational mice models for further studies of MAYV infection, vaccine tests, and therapeutic strategies against this virus.
Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells

Zinc is an essential micronutrient which regulates diverse physiological functions and has been shown to play a crucial role in viral infections. Zinc has a necessary role in the replication of many viruses, however, antiviral action of zinc has also been demonstrated in in vitro infection models most likely through induction of host antiviral responses. Therefore, depending on the host machinery that the virus employs at different stages of infection, zinc may either facilitate, or inhibit virus infection. In this study, we show that zinc plays divergent roles in rotavirus and dengue virus infections in epithelial cells. Dengue virus infection did not perturb the epithelial barrier functions despite the release of virus from the basolateral surface whereas rotavirus infection led to disruption of epithelial junctions. In rotavirus infection, zinc supplementation post-infection did not block barrier disruption suggesting that zinc does not affect rotavirus life-cycle or protects epithelial barriers post-infection suggesting the involvement of cellular pathways in the beneficial effect of zinc supplementation in enteric infections. Zinc depletion by N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) inhibited dengue virus and Japanese encephalitis virus (JEV) infection but had no effect on rotavirus. Time-of-addition experiments suggested that zinc chelation affected both early and late stages of dengue virus infectious cycle and zinc chelation abrogated dengue virus RNA replication. We show that transient zinc chelation induces ER stress and antiviral response by activating NF-kappaB leading to induction of interferon signaling. These results suggest that modulation of zinc homeostasis during virus infection could be a component of host antiviral response and altering zinc homeostasis may act as a potent antiviral strategy against flaviviruses.
Microenvironmental Heterogeneity in Brain Malignancies

Brain tumors are among the deadliest malignancies. The brain tumor microenvironment (TME) hosts a unique collection of cells, soluble factors, and extracellular matrix components that regulate disease evolution of both primary and metastatic brain malignancies. It is established that macrophages and other myeloid cells are abundant in the brain TME and strongly correlate with aggressive phenotypes and distinct genetic signatures, while lymphoid cells are less frequent but are now known to have a pronounced effect on disease progression. Different types of brain tumors vary widely in their microenvironmental contexture, and the proportion of various stromal components impacts tumor biology. Indeed, emerging evidence suggests an intimate link between the molecular signature of tumor cells and the composition of the TME, shedding light on the mechanisms which underlie microenvironmental heterogeneity in brain cancer. In this review, we discuss the association between TME composition and the diverse molecular profiles of primary gliomas and brain metastases. We also discuss the implications of these associations on the efficacy of immunotherapy in brain malignancies. An appreciation for the causes and functional consequences of microenvironmental heterogeneity in brain cancer will be of crucial importance to the rational design of microenvironment-targeted therapies for these deadly diseases.
Submarine Groundwater Discharge: Updates on Its Measurement Techniques, Geophysical Drivers, Magnitudes, and Effects

The number of studies concerning Submarine Groundwater Discharge (SGD) grew quickly as we entered the twenty-first century. Many hydrological and oceanographic processes that drive and influence SGD were identified and characterized during this period. These processes included tidal effects on SGD, water and solute fluxes, biogeochemical transformations through the subterranean estuary, and material transport via SGD from land to sea. Here we compile and summarize the significant progress in SGD assessment methodologies, considering both the terrestrial and marine driving forces, and local as well as global evaluations of groundwater discharge with an emphasis on investigations published over the past decade. Our treatment presents the state-of-the-art progress of SGD studies from geophysical, geochemical, bio-ecological, economic, and cultural perspectives. We identify and summarize remaining research questions, make recommendations for future research directions, and discuss potential future challenges, including impacts of climate change on SGD and improved estimates of the global magnitude of SGD.