Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening of Herbal Medicines for Synergistic Effects of Metformin and Herbal Extracts Combination in RAW 264.7 Cells

Received: May 20, 2014 Revised: May 31, 2014 Accepted: June 2, 2014 Objectives: This study was performed to evaluate the effects of Metformin and Lonicerae Flos, Agrobacterium Rhizogenes, Coptidis Rhizoma, Atractylodis Rhizoma Alba, Houttuyniae Herba extracs combinations on hypoglycemia in RAW 264.7 cells. Methods: Expressions of Sirt1, p-adenosine monophosphate-activated kinase (p-AMPK), AMPKalpha, peroxisome proliferator activated receptor (PPAR)-alpha, PPAR-gamma, X-box binding protein 1 (XBP-1), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were analyzed by real time polymerase chain reaction and Western blotting analysis. Results: The level of gene expression of Sirt1, p-AMPK, AMPK-alpha, PPAR-alpha and XBP-1 in relation to that of beta-actin were increased or decreased significantly with the Metformin and Lonicerae Flos, Agrobacterium Rhizogenes extracts combination groups. The level of gene expression of TNF-alpha and IL-6 were increased significantly with the Metformin and Houttuyniae Herba, Coptidis Rhizoma extracts combination groups. Conclusions: Metformin and Lonicerae Flos, Agrobacterium Rhizogenes extracts combination groups showed synergistic hypoglycemic effects by increasing AMPK and PPAR gene expression in RAW 264.7 cells.
Molecular evidence for the adaptive evolution of Geobacter sulfurreducens to perform dissimilatory iron reduction in natural environments

The electrically conductive pili (e‐pili) of Geobacter species enable extracellular electron transfer to insoluble metallic minerals, electrodes and other microbial species, which confers biogeochemical significance and global prevalence on Geobacter in diverse anaerobic environments. E‐pili are constructed by truncated PilA which is considered to have evolved from full‐length pilin by gene fission under positive evolutionary selection. However, this hypothesis is based on phylogenetic analysis and has not yet been experimentally confirmed. Here, we reconstructed an ancestral strain of G. sulfurreducens (designated COMB) carrying full‐length PilA by combining genes GSU1496 and GSU1497. The results demonstrated that strain COMB expressed and assembled the full‐length fused PilA and exhibited an outer membrane c‐type cytochrome profile similar to the wild‐type strain. Surprisingly, the generated COMB‐pili were also conductive, indicating the evolution of truncated PilA did not occur for conductivity. Moreover, strain COMB minimally reduced Fe(III) oxides but maintained its ability to respire electrodes, demonstrating the truncation of pilin enables iron respiration. This study provides the first experimental evidence that the truncation of pilin in Geobacter species confers adaption to Fe(III)‐mineral‐mediated selective pressures, and suggests an evolutionary event during which the separation of the GSU1497 gene helped Geobacter survive and thrive in natural environments.
The Peroxisome Proliferator–Activated Receptor (PPAR)-γ Antagonist 2-Chloro-5-Nitro-N-Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPARδ and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor family, playing pivotal roles in regulating glucose and lipid metabolism as well as inflammation. While characterizing potential PPARγ ligand activity of natural compounds in macrophages, we investigated their influence on the expression of adipophilin [perilipin 2 (PLIN2)], a well-known PPARγ target. To confirm that a compound regulates PLIN2 expression via PPARγ, we performed experiments using the widely used PPARγ antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662). Surprisingly, instead of blocking upregulation of PLIN2 expression in THP-1 macrophages, expression was concentration-dependently induced by GW9662 at concentrations and under conditions commonly used. We found that this unexpected upregulation occurs in many human and murine macrophage cell models and also primary cells. Profiling expression of PPAR target genes showed upregulation of several genes involved in lipid uptake, transport, and storage as well as fatty acid synthesis by GW9662. In line with this and with upregulation of PLIN2 protein, GW9662 elevated lipogenesis and increased triglyceride levels. Finally, we identified PPARδ as a mediator of the substantial unexpected effects of GW9662. Our findings show that: 1) the PPARγ antagonist GW9662 unexpectedly activates PPARδ-mediated signaling in macrophages, 2) GW9662 significantly affects lipid metabolism in macrophages, 3) careful validation of experimental conditions and results is required for experiments involving GW9662, and 4) published studies in a context comparable to this work may have reported erroneous results if PPARγ independence was demonstrated using GW9662 only. In light of our findings, certain existing studies might require reinterpretation regarding the role of PPARγ. SIGNIFICANCE STATEMENT Peroxisome proliferator–activated receptors (PPARs) are targets for the treatment of various diseases, as they are key regulators of inflammation as well as lipid and glucose metabolism. Hence, reliable tools to characterize the molecular effects of PPARs are indispensable. We describe profound and unexpected off-target effects of the PPARγ antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662) involving PPARδ and in turn affecting macrophage lipid metabolism. Our results question certain existing studies using GW9662 and make better experimental design of future studies necessary.
Variation and evolution of C:N ratio among different organs enable plants to adapt to N‐limited environments

Carbon (C) and nitrogen (N) are the primary elements involved in the growth and development of plants. The C:N ratio is an indicator of nitrogen use efficiency (NUE) and an input parameter for some ecological and ecosystem models. However, knowledge remains limited about the convergent or divergent variation in the C:N ratios among different plant organs (e.g., leaf, branch, trunk, and root) and how evolution and environment affect the coefficient shifts. Using systematic measurements of the leaf–branch–trunk–root of 2,139 species from tropical to cold‐temperate forests, we comprehensively evaluated variation in C:N ratio in different organs in different taxa and forest types. The ratios showed convergence in the direction of change but divergence in the rate of change. Plants evolved toward lower C:N ratios in the leaf and branch, with N playing a more important role than C. The C:N ratio of plant organs (except for the leaf) was constrained by phylogeny, but not strongly. Both the change of C:N during evolution and its spatial variation (lower C:N ratio at midlatitudes) help develop the adaptive growth hypothesis. That is, plants with a higher C:N ratio promote NUE under strong N‐limited conditions to ensure survival priority, whereas plants with a lower C:N ratio under less N‐limited environments benefit growth priority. In nature, larger proportion of species with a high C:N ratio enabled communities to inhabit more N‐limited conditions. Our results provide new insights on the evolution and drivers of C:N ratio among different plant organs, as well as provide a quantitative basis to optimize land surface process models.
Cognitive dysfunction in mice lacking proper glucocorticoid receptor dimerization

Stress is a major risk factor for depression and anxiety. One of the effects of stress is the (over-) activation of the hypothalamic-pituitary-adrenal (HPA) axis and the release of stress hormones such as glucocorticoids (GCs). Chronically increased stress hormone levels have been shown to have detrimental effects on neuronal networks by inhibiting neurotrophic processes particularly in the hippocampus proper. Centrally, GCs modulate metabolic as well as behavioural processes by activating two classes of corticoid receptors, high-affinity mineralocorticoid receptors (MR) and low-affinity glucocorticoid receptors (GR). Upon activation, GR can modulate gene transcription either as a monomeric protein, or as a dimer interacting directly with DNA. GR can also modulate cellular processes via non-genomic mechanisms, for example via a GPCR-protein interaction. We evaluated the behavioral phenotype in mice with a targeted mutation in the GR in a FVB/NJ background. In GRdim/dim mice, GR proteins form poor homodimers, while the GR monomer remains intact. We evaluated the effect of poor GR dimerization on hippocampus-dependent cognition as well as on exploration and emotional behavior under baseline and chronically increased stress hormone levels. We found that GRdim/dim mice did not behave differently from GRwt/wt littermates under baseline conditions. However, after chronic elevation of stress hormone levels, GRdim/dim mice displayed a significant impairment in hippocampus-dependent memory compared to GRwt/wt mice, which correlated with differential expression of hippocampal Bdnf/TrkB and Fkbp5.
Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β‐cell mass and function

There are numerous lines of clinical evidence that inhibition of the renin–angiotensin system (RAS) can prevent and delay the development of diabetes. Also, the role of RAS in the pathogenesis of diabetes, including insulin resistance and β‐cell dysfunction, has been extensively investigated. Nevertheless, this role had not yet been fully shown. A variety of possible protective mechanisms for RAS blockers in the regulation of glucose homeostasis have been suggested. However, the direct effect on pancreatic islet fibrosis has only recently been spotlighted. Various degrees of islet fibrosis are often observed in the islets of patients with type 2 diabetes mellitus, which can be associated with a decrease in β‐cell mass and function in these patients. Pancreatic stellate cells are thought to be deeply involved in this islet fibrosis. In this process, the activation of RAS in islets is shown to transform quiescent pancreatic stellate cells into the activated form, stimulates their proliferation and consequently leads to islet fibrotic destruction. In this article, we introduce existing clinical and experimental evidence for diabetes prevention through inhibition of RAS, and review the responsible local RAS signaling pathways in pancreatic stellate cells. Finally, we propose possible targets for the prevention of islet fibrosis.
MRI-guided, transrectal, intraprostatic steam application as potential focal therapeutic modality for prostatic diseases in a large animal translational model: A feasibility follow-up study

Parallel to establishment of diagnostic surveillance protocols for detection of prostatic diseases, novel treatment strategies should be developed. The aim of the present study is to evaluate the feasibility and possible side effects of transrectal, MRI-targeted intraprostatic steam application in dogs as an established large animal translational model for prostatic diseases in humans. Twelve healthy experimental, intact, male beagle dogs without evidence of prostatic pathology were recruited. An initial MRI examination was performed, and MRI-targeted steam was applied intraprostatically immediately thereafter. Serum levels of C-reactive protein (CRP), clinical and ultrasonographic examinations were performed periodically following the procedure to assess treatment effect. Four weeks after treatment, all dogs underwent follow-up MRI examinations and three needle-core biopsies were obtained from each prostatic lobe. Descriptive statistics were performed. MRI-guided intraprostatic steam application was successfully performed in the study population. The first day after steam application, 7/12 dogs had minimal signs of discomfort (grade 1/24 evaluated with the short-form Glasgow Composite Measure Pain Scale) and no dogs showed any sign of discomfort by day 6. CRP elevations were detected in 9/12 dogs during the first week post steam application. Mild to moderate T2 hyperintense intraparenchymal lesions were identified during follow-up MRI in 11/12 dogs four weeks post procedure. Ten of these lesions enhanced mild to moderately after contrast administration. Coagulative necrosis or associated chronic inflammatory response was detected in 80.6% (58/72) of the samples obtained. MRI-targeted intraprostatic steam application is a feasible technique and displays minimal side effects in healthy dogs as translational model for human prostatic diseases. This opens the possibility of minimally invasive novel treatment strategies for intraprostatic lesions.
Divergent selection and drift shape the genomes of two avian sister species spanning a saline–freshwater ecotone

The role of species divergence due to ecologically-based divergent selection – or ecological speciation – in generating and maintaining biodiversity is a central question in evolutionary biology. Comparison of the genomes of phylogenetically related taxa spanning a selective habitat gradient enables discovery of divergent signatures of selection and thereby provides valuable insight into the role of divergent ecological selection in speciation. Tidal marsh ecosystems provide tractable opportunities for studying organisms’ adaptations to selective pressures that underlie ecological divergence. Sharp environmental gradients across the saline-freshwater ecotone within tidal marshes present extreme adaptive challenges to terrestrial vertebrates. Here we sequence 20 whole genomes of two avian sister species endemic to tidal marshes – the Saltmarsh Sparrow (Ammodramus caudacutus) and Nelson’s Sparrow (A. nelsoni) – to evaluate the influence of selective and demographic processes in shaping genome-wide patterns of divergence. Genome-wide divergence between these two recently diverged sister species was notably high (genome-wide FST = 0.32). Against a background of high genome-wide divergence, regions of elevated divergence were widespread throughout the genome, as opposed to focused within islands of differentiation. These patterns may be the result of genetic drift acting during past tidal march colonization events in addition to divergent selection to different environments. We identified several candidate genes that exhibited elevated divergence between Saltmarsh and Nelson’s sparrows, including genes linked to osmotic regulation, circadian rhythm, and plumage melanism – all putative candidates linked to adaptation to tidal marsh environments. These findings provide new insights into the roles of divergent selection and genetic drift in generating and maintaining biodiversity.
The acute myeloid leukemia associated AML1-ETO fusion protein alters the transcriptome and cellular progression in a single-oncogene expressing in vitro induced pluripotent stem cell based granulocyte differentiation model

Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect normal hematopoiesis. The analysis of human AMLs has mostly been performed using end-point materials, such as cell lines and patient derived AMLs that also carry additional contributing mutations. The molecular effects of a single oncogenic hit, such as expression of the AML associated oncoprotein AML1-ETO on hematopoietic development and transformation into a (pre-) leukemic state still needs further investigation. Here we describe the development and characterization of an induced pluripotent stem cell (iPSC) system that allows in vitro differentiation towards different mature myeloid cell types such as monocytes and granulocytes. During in vitro differentiation we expressed the AML1-ETO fusion protein and examined the effects of the oncoprotein on differentiation and the underlying alterations in the gene program at 8 different time points. Our analysis revealed that AML1-ETO as a single oncogenic hit in a non-mutated background blocks granulocytic differentiation, deregulates the gene program via altering the acetylome of the differentiating granulocytic cells, and induces t(8;21) AML associated leukemic characteristics. Together, these results reveal that inducible oncogene expression during in vitro differentiation of iPS cells provides a valuable platform for analysis of aberrant regulation in disease.
Understanding the development of amblyopia using macaque monkey models

Amblyopia is a sensory developmental disorder affecting as many as 4% of children around the world. While clinically identified as a reduction in visual acuity and disrupted binocular function, amblyopia affects many low- and high-level perceptual abilities. Research with nonhuman primate models has provided much needed insight into the natural history of amblyopia, its origins and sensitive periods, and the brain mechanisms that underly this disorder. Amblyopia results from abnormal binocular visual experience and impacts the structure and function of the visual pathways beginning at the level of the primary visual cortex (V1). However, there are multiple instances of abnormalities in areas beyond V1 that are not simply inherited from earlier stages of processing. The full constellation of deficits must be taken into consideration in order to understand the broad impact of amblyopia on visual and visual–motor function. The data generated from studies of animal models of the most common forms of amblyopia have provided indispensable insight into the disorder, which has significantly impacted clinical practice. It is expected that this translational impact will continue as ongoing research into the neural correlates of amblyopia provides guidance for novel therapeutic approaches.
Influence of Abstinence Time on Young Man Semen Quality

Purpose To compare semen quality with different abstinence times to provide suggestion to treat infertile couples. Methods Semen quality of all 562 men who aged 20 - 30 years old enrolled from 7 provinces were tested. Results Semen quantity, semen density and total semen count were all statistically increased with the longer abstinence time. The semen quantity indices(semen volume,semen density and total sperm number) was higher in the 5 - 6 days of abstinence, but semen quality indices have no statistical difference in the 3 - 6 days of abstinence. Conclusions Men with less sperm numbers maybe have a longer days of abstinence but not longer than 7 days. Those who have enough sperm numbers but poor sperm viability may have a abstinence time no more than 3 days which is very helpful to treat infertility couples to pregnant.
Predictive methods for efficacy of house dust mite subcutaneous immunotherapy in allergic rhinitis patients: a prospective study in a Chinese population

Allergen‐specific immunotherapy (AIT) is the only available treatment that can induce specific immune tolerance to allergens. However, the treatment course lasts >3 years, and there is no reliable method to predict treatment response. Therefore, in this study we aimed to establish a method that can predict treatment response to AIT in the second year.
LiveCoding.space: Towards P2P Collaborative Live Programming Environment for WebXR

WebVR and WebXR are the new standards of Virtual/Augment/Mixed Reality for the Web Browser. A wide variety of head mounted displays, motion controllers, mobile and standalone headsets bring that technology to the masses. But software engineering was not ready for these new challenges. Web applications become look like desktop apps with all advantages and disadvantages of application-centric approach. For example, using existed React VR or A-Frame libraries, someone could easily create a rich Web app, but it will lack of self-exploratory environment, multi-user collaboration and live programming at runtime mode. To address this problem, we propose to use the Virtual World’s concept for WebXR applications development. Virtual World as the new computational paradigm blurs the borders between application and hosted environment, runtime and development mode. The Virtual Worlds in conjunction with WebXR technologies offers to both programmers and domain experts nearly unlimited capabilities for creating novel computer-based simulated environments just in Web browser. Virtual time, user-defined meta language, live coding, avatar, selfexploratory environment become the new crucial concepts of the Web applications. This paper introduces the prototype of pure-decentralized P2P collaborative, live programming environment: LiveCoding.space. Having the tight integration of A-Frame, Virtual World Framework, Gun DB storage system and Ohm language, it provides all-in-one solution for development of creative applications in modern Web standards for virtual reality.
Unveiling Drivers of Deforestation: Evidence from the Brazilian Amazon

The drivers of deforestation are the subject of many spatially explicit studies with considerable policy impact, yet few studies account for spatial dependence, thus neglecting spillover effects. In this work, we use high-resolution remotely sensed land cover change maps, extended with socioeconomic panel data for 141 municipalities in the state of Mato Grosso, Brazil, to investigate the role of agriculture in deforestation from 2006 until 2016. Our econometric model specifically accounts for spatial indirect effects from the dependent and explanatory variables, thus avoiding biased and inconsistent estimates. We identify indirect spillover effects from croplands and direct effects from cattle as significant deforestation drivers. Neglecting to explicitly account for spatial dependence considerably underestimates deforestation pressure of soy production. We conclude that spatial dynamics play a crucial role in deforestation and need to be considered in econometric studies, in order to facilitate informed policy decisions.
A Comparative Study of The Effect of Demineralized Bone Matrix with and Without Low Level Laser Therapy on The Treatment of Periodontal Infra-Bony Defects (Randomized Clinical Trial)

Objective: This study aimed at comparing clinically and radiographically the therapeutic effect of low level laser therapy and demineralized bone matrix, used in management of periodontal intrabony defect. Subjects and methods: Thirty two non-smoking patients aged between 28-51 years with severe chronic periodontitis participated in this randomized clinical study. Patients were randomly assigned into one of 2 groups (16 patients each): demineralized bone grafting alone of the intrabony defect, control group (Group I), demineralized bone grafting and the application of low level laser therapy (LLLT) (Group II). Clinical and radiographic parameters including plaque index, bleeding index, probing depth, clinical attachment level (CAL) and intrabony defect depth were reassessed at 6 months after surgery. Results: Specifically, LLLT treated sites (Group II) showed statistically significant differences regarding pocket depth and CAL compared with Group I. Intrabony defect depth was significantly reduced for LLLT group compared to that of Group I control. Conclusion: The use of LLLT as an adjunct with demineralized bone matrix (DBM) in the treatment of intrabony defects was more significant in improving the probing depth, CAL and intrabony defect depth than using DBM alone.