Miracle-dz/UniFAR-FTUs huggingface dataset:
An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer’s Patients

Alzheimer’s disease (AD) is a common neurodegenerative disease, mainly manifested by cognitive dysfunction. It seriously reduces the quality of life, and there is no ideal treatment strategy in clinical practice. Clinical studies on the treatment of AD with Ginkgo biloba L. leaf extract (EGb) have been reported since 1980s, and many clinical studies have been carried out during the following 30 years. However, the benefits of EGb on the treatment of AD are still controversial. In this review, we collected the clinical trial reports of EGb on cognitive function from Pubmed, Elsevier, Europe PMC, and other database since the 1980s. Through analysis and comparison, we consider that EGb may be able to improve the cognitive function in patients who suffered from mild dementia during long-term administration (more than 24 weeks) and appropriate dosage (240 mg per day). The main evidences and existing problems of the negative and positive experimental results were summarized.
SIFamide Influences Feeding in the Chagas Disease Vector, Rhodnius prolixus

SIFamides are a family of highly conserved neuropeptides in arthropods, and in insects are mainly expressed in four medial neurons in the pars intercerebralis of the brain. Although SIFamide has been shown to influence sexual behavior, feeding, and sleep regulation in holometabolous insects such as Drosophila melanogaster, little is known about its role in hemimetabolous insects, including the blood-sucking bug, Rhodnius prolixus. In this study, we confirm the nucleotide sequence for R. prolixus SIFamide (Rhopr-SIFa) and find characteristic phenotypic expression of SIFamide in four cells of the pars intercerebralis in the brain. In addition to extensive SIFa projections throughout the entire central nervous system, SIFamidergic processes also enter into the corpus cardiacum, and project along the dorsal vessel, suggestive of Rhopr-SIFa acting as a neurohormone. Physiologically, Rhopr-SIFamide induces dose-dependent increases in heartbeat frequency in vitro suggesting the presence of peripheral receptors, and thereby indicating Rhopr-SIFa is released to act upon peripheral targets. We also explore the function of Rhopr-SIFa in R. prolixus, specifically in relation to feeding, since R. prolixus is a blood-gorging insect and a vector for Chagas disease. The intensity of SIFamide-like staining in the neurons in the brain is diminished 2 h following feeding, and restocking of those cells is finished 24 h later, indicating Rhopr-SIFa may be released at feeding. The results of temporal qPCR analysis were consistent with the immunohistochemical findings, showing an increase in Rhopr-SIFa transcript expression in the brain 2 h after feeding. We also observed enhanced feeding (size of meal) in insects injected with Rhopr-SIFa whereas insects with RNAi-mediated knockdown of the Rhopr-SIFa transcript consumed a significantly smaller blood meal relative to controls. These data suggest that the four SIFamidergic neurons and associated arborizations may play an important function in the neuronal circuitry controlling R. prolixus feeding, with Rhopr-SIFa acting as a central and peripheral neuromodulator/neurohormone.
Positive Schizotypy Increases the Acceptance of Unpresented Materials in False Memory Tasks in Non-clinical Individuals

Enhanced spreading of semantic activation has been hypothesized to underlie some of the most significant symptoms of schizotypal personality, like thought disorder, odd speech, delusion, or magical thinking. We applied the Deese/Roediger-McDermott false memory task to the study of semantic activation in a group of 123 non-clinical individuals varying in the three dimensions of schizotypal personality: positive, negative and disorganized schizotypy. In the study phase, we presented them with lists composed of words semantically associated to unpresented critical words. Then, they responded to a recognition questionnaire including previously presented words and critical unpresented lures, as well as weakly related and unrelated unpresented lures. Participants rated their confidence in recognizing each word. They also filled in a standardized schizotypal personality questionnaire. Confirming the false memory effect, recognition ratings provided in response to critical words were higher than those produced for both weakly related and unrelated items. Crucially, scores in the positive dimension increased recognition percentages and confidence ratings for weakly related and unrelated lures. This study indicates that high levels of positive schizotypy might influence the tendency to accept false memories of unrelated unpresented material.
Key Components of the Complement Lectin Pathway Are Not Only Required for the Development of Inflammatory Arthritis but Also Regulate the Transcription of Factor D

The complement system plays an important role in the pathogenesis of rheumatoid arthritis (RA). Besides driving lectin pathway (LP) activation, the mannan-binding lectin (MBL)-associated serine proteases (MASPs) also play a key role in regulating the alternative pathway (AP). We evaluated the effects of N-acetylgalactosamine (GalNAc)-conjugated MASP-1 and MASP-2 duplexes in vitro and in mice with and without arthritis to examine whether knockdown of MASP-1 and MASP-2 expression affects the development of arthritis. GalNAc-siRNAs for MASP-1 and MASP-2 demonstrated robust silencing of MASP-1 or MASP-2 at pM concentrations in vitro. To evaluate the impact of silencing in arthritic mice, we used the collagen antibody-induced arthritis (CAIA) mouse model of RA. Mice were injected a 10 mg/kg dose of GalNAc-siRNAs 3x s.q. prior to the induction of CAIA. Liver gene expression was examined using qRT-PCR, and protein levels were confirmed in the circulation by sandwich immunoassays and Western blot. At day 10, CAIA mice separately treated with MASP-1 and MASP-2 duplexes had a specific reduction in expression of liver MASP-1 (70–95%, p < 0.05) and MASP-2 (90%, p < 0.05) mRNA, respectively. MASP-1-siRNA treatment resulted in a 95% reduction in levels of MASP-1 protein in circulation with no effect on MASP-2 levels and clinical disease activity (CDA). In mice injected with MASP-2 duplex, there was a significant (p < 0.05) 90% decrease in ex vivo C4b deposition on mannan, with nearly complete elimination of MASP-2 in the circulation. MASP-2 silencing initially significantly decreased CDA by 60% but subsequently changed to a 40% decrease vs. control. Unexpectedly, GalNAc-siRNA-mediated knockdown of MASP-1 and MASP-2 revealed a marked effect of these proteins on the transcription of FD under normal physiological conditions, whereas LPS-induced inflammatory conditions reversed this effect on FD levels. LPS is recognized by Toll-like receptor 4 (TLR4), we found MBL not only binds to TLR4 an interaction with a Kd of 907 nM but also upregulated FD expression in differentiated adipocytes. We show that MASP-2 knockdown impairs the development of RA and that the interrelationship between proteins of the LP and the AP may extend to the transcriptional modulation of the FD gene.
Insights Into the Function of the NuA4 Complex in Plants

Chromatin remodeling plays a key role in the establishment and maintenance of gene expression patterns essential for plant development and responses to environmental factors. Post-translational modification of histones, including acetylation, is one of the most relevant chromatin remodeling mechanisms that operate in eukaryotic cells. Histone acetylation is an evolutionarily conserved chromatin signature commonly associated with transcriptional activation. Histone acetylation levels are tightly regulated through the antagonistic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In plants, different families of HATs are present, including the MYST family, which comprises homologs of the catalytic subunit of the Nucleosome Acetyltransferase of H4 (NuA4) complex in yeast. This complex mediates acetylation of histones H4, H2A, and H2A.Z, and is involved in transcriptional regulation, heterochromatin silencing, cell cycle progression, and DNA repair in yeast. In Arabidopsis and, other plant species, homologs for most of the yeast NuA4 subunits are present and although the existence of this complex has not been demonstrated yet, compelling evidence supports the notion that this type of HAT complex functions from mosses to angiosperms. Recent proteomic studies show that several Arabidopsis homologs of NuA4 components, including the assembly platform proteins and the catalytic subunit, are associated in vivo with additional members of this complex suggesting that a NuA4-like HAT complex is present in plants. Furthermore, the functional characterization of some Arabidopsis NuA4 subunits has uncovered the involvement of these proteins in the regulation of different plant biological processes. Interestingly, for most of the mutant plants deficient in subunits of this complex characterized so far, conspicuous defects in flowering time are observed, suggesting a role for NuA4 in the control of this plant developmental program. Moreover, the participation of Arabidopsis NuA4 homologs in other developmental processes, such as gametophyte development, as well as in cell proliferation and stress and hormone responses, has also been reported. In this review, we summarize the current state of knowledge on plant putative NuA4 subunits and discuss the latest progress concerning the function of this chromatin modifying complex.
Uterine Natural Killer Cell Heterogeneity: Lessons From Mouse Models

Natural killer (NK) cells are the most abundant lymphocytes at the maternal-fetal interface. Epidemiological data implicate NK cells in human pregnancy outcomes. Discoveries using mouse NK cells have guided subsequent advances in human NK cell biology. However, it remains challenging to identify mouse and human uterine NK (uNK) cell function(s) because of the dynamic changes in the systemic-endocrinological and local uterine structural microenvironments during pregnancy. This review discusses functional similarities and differences between mouse and human NK cells at the maternal-fetal interface.
Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

Metabolites of omega-6 and omega-3 polyunsaturated fatty acids are important signaling molecules implicated in the control of adipogenesis and energy balance regulation. Some of these metabolites belonging to the group of oxylipins have been associated with non-shivering thermogenesis in mice mediated by brown or brite adipose tissue. We aimed to identify novel molecules with thermogenic potential and to clarify the relevance of these findings in a translational context. Therefore, we characterized and compared the oxylipin profiles of murine and human adipose tissues with different abundance of brown or brite adipocytes. A broad panel of 36 fatty acid metabolites was quantified in brown and white adipose tissues of C57BL/6J mice acclimatized to different ambient temperatures and in biopsies of human supraclavicular brown and white adipose tissue. The oxylipin profile of murine brite adipose tissue was not distinguishable from white adipose tissue, suggesting that adipose tissue browning in vivo is not associated with major changes in the oxylipin metabolism. Human brown and white adipose tissue also exhibited similar metabolite profiles. This is in line with previous studies proposing human brown adipose tissue to resemble the nature of murine brite adipose tissue representing a heterogeneous mixture of brite and white adipocytes. Although the global oxylipin profile served as a marker for the abundance of thermogenic adipocytes in bona fide brown but not white adipose tissue, we identified 5-HETE and 5,6-EET as individual compounds consistently associated with the abundance of brown or brite adipocytes in human BAT and murine brite fat. Further studies need to establish whether these candidates are mere markers or functional effectors of thermogenic capacity.
Image-Derived Phenotyping Informed by Independent Component Analysis—An Atlas-Based Approach

Independent Component Analysis (ICA) is a widely used, unsupervised, exploratory machine learning method (Comon, 1994) and is often applied to resting-state fMRI (rsfMRI) data (Nickerson et al., 2017). Though its usefulness is apparent, the most common applications of ICA involve substantial subjectivity. For example, the spatial components extracted through individual or group-level ICA are never identical between studies and are often labeled by visual inspection and expert opinion. The goal of this study was to establish a spatial component approach based on well-documented atlases derived from large-scale investigations. These components can subsequently be used in place of components tailored to fit each individual study’s dataset. The utility of ICA to extract meaningful functional connectivity patterns without the need for prior knowledge has been established by its application to large-scale studies like Human Connectome Project (HCP) and United Kingdom (UK) BioBank cohort (Miller et al., 2016; Smitha et al., 2017). Although ICA has been successfully applied to a wide range of applications in rsfMRI, there have long been some concerns about reproducibility and the subjectivity of ICA results (Friston, 1998). Also, ICA is a computationally-demanding approach, which may provide a barrier to researchers with limited resources or exceptionally large datasets. We present an approach that has the potential to substantially decrease both the subjectivity of ICA and its computational burden.
Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections

Pf bacteriophage are temperate phages that infect the bacterium Pseudomonas aeruginosa, a major cause of chronic lung infections in cystic fibrosis (CF) and other settings. Pf and other temperate phages have evolved complex, mutualistic relationships with their bacterial hosts that impact both bacterial phenotypes and chronic infection. We and others have reported that Pf phages are a virulence factor that promote the pathogenesis of P. aeruginosa infections in animal models and are associated with worse skin and lung infections in humans. Here we review the biology of Pf phage and what is known about its contributions to pathogenesis and clinical disease. First, we review the structure, genetics, and epidemiology of Pf phage. Next, we address the diverse and surprising ways that Pf phages contribute to P. aeruginosa phenotypes including effects on biofilm formation, antibiotic resistance, and motility. Then, we cover data indicating that Pf phages suppress mammalian immunity at sites of bacterial infection. Finally, we discuss recent literature implicating Pf in chronic P. aeruginosa infections in CF and other settings. Together, these reports suggest that Pf bacteriophage have direct effects on P. aeruginosa infections and that temperate phages are an exciting frontier in microbiology, immunology, and human health.
Multi-Talker Speech Promotes Greater Knowledge-Based Spoken Mandarin Word Recognition in First and Second Language Listeners

Spoken word recognition involves a perceptual tradeoff between the reliance on the incoming acoustic signal and knowledge about likely sound categories and their co-occurrences as words. This study examined how adult second language (L2) learners navigate between acoustic-based and knowledge-based spoken word recognition when listening to highly variable, multi-talker truncated speech, and whether this perceptual tradeoff changes as L2 listeners gradually become more proficient in their L2 after multiple months of structured classroom learning. First language (L1) Mandarin Chinese listeners and L1 English-L2 Mandarin adult listeners took part in a gating experiment. The L2 listeners were tested twice – once at the start of their intermediate/advanced L2 language class and again 2 months later. L1 listeners were only tested once. Participants were asked to identify syllable-tone words that varied in syllable token frequency (high/low according to a spoken word corpus) and syllable-conditioned tonal probability (most probable/least probable in speech given the syllable). The stimuli were recorded by 16 different talkers and presented at eight gates ranging from onset-only (gate 1) through onset +40 ms increments (gates 2 through 7) to the full word (gate 8). Mixed-effects regression modeling was used to compare performance to our previous study which used single-talker stimuli (Wiener et al., 2019). The results indicated that multi-talker speech caused both L1 and L2 listeners to rely greater on knowledge-based processing of tone. L1 listeners were able to draw on distributional knowledge of syllable-tone probabilities in early gates and switch to predominantly acoustic-based processing when more of the signal was available. In contrast, L2 listeners, with their limited experience with talker range normalization, were less able to effectively transition from probability-based to acoustic-based processing. Moreover, for the L2 listeners, the reliance on such distributional information for spoken word recognition appeared to be conditioned by the nature of the acoustic signal. Single-talker speech did not result in the same pattern of probability-based tone processing, suggesting that knowledge-based processing of L2 speech may only occur under certain acoustic conditions, such as multi-talker speech.
Using Gas-Driven Shock Tubes to Produce Blast Wave Signatures

The increased incidence of improvised explosives in military conflicts has brought about an increase in the number of traumatic brain injuries (TBIs) observed. Although physical injuries are caused by shrapnel and the immediate blast, encountering the blast wave associated with improvised explosive devices (IEDs) may be the cause of traumatic brain injuries experienced by warfighters. Assessment of the effectiveness of personal protective equipment (PPE) to mitigate TBI requires understanding the interaction between blast waves and human bodies and the ability to replicate the pressure signatures caused by blast waves. Prior research has validated compression-driven shock tube designs as a laboratory method of generating representative pressure signatures, or Friedlander-shaped blast profiles; however, shock tubes can vary depending on their design parameters and not all shock tube designs generate acceptable pressure signatures. This paper presents a comprehensive numerical study of the effects of driver gas, driver (breech) length, and membrane burst pressure of a constant-area shock tube. Discrete locations in the shock tube were probed, and the blast wave evolution in time at these points was analyzed to determine the effect of location on the pressure signature. The results of these simulations are used as a basis for suggesting guidelines for obtaining desired blast profiles.
Sphingosine-1-Phosphate Receptors Modulators Decrease Signs of Neuroinflammation and Prevent Parkinson’s Disease Symptoms in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model

Sphingosine-1-phosphate (S1P) is a potent bioactive lipid mediator that acts as a natural ligand upon binding to five different receptors that are located in astrocytes, oligodendrocytes, microglial and neuronal cells. Recently, global activation of these receptors by FTY720 (fingolimod) has been suggested to provide neuroprotection in animal model of Parkinson’s disease (PD). Among S1P receptors, the subtype 1 (S1P1R) has been linked to features of neuroprotection and, using the selective agonist SEW2871, the present investigation assessed potential benefits (and mechanisms) of this receptor subtype in an established animal model of PD. We demonstrated that oral treatments with SEW2871 are able to provide protection to the same levels as FTY720 against loss of dopaminergic neurons and motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg, i.p., 5 days) mouse model of PD. At the molecular level, we observed that the beneficial effects of both S1PR agonists were not associated with alterations in ERK and Akt levels, two markers of molecular adaptations in the striatum neurons. However, these compounds have the capacity to prevent signs of neuroinflammation such as the activation of astrocytes and glial cells, as well as MPTP-induced reduction of BDNF levels in key regions of the brain implicated in motor functions. These findings suggest that selective S1P1R modulation has the ability to provide neuroprotection in response to MPTP neurotoxicity. Targeting S1P1R in PD therapy may represent a prominent candidate for treatment of this neurodegenerative conditions.
Exploring the Mechanism of the Palladium-Catalyzed 3-Butene-2-ol Amination Reaction: A DFT Study

Palladium-catalyzed asymmetric allylic substitution, due to its valuable reactive profile, has become a quite useful tool in organic synthesis fields. In the present study, density functional theory (DFT) calculations were applied to investigate the important factors for palladium-catalyzed 3-butene-2-ol and methylaniline amination reaction, with tetrahydrofuran (THF) as solvent. We find that this catalytic protocol results in high regio- and stereoselectivity, which is in line with the experimental result. According to our calculations, the high regio- and stereoselectivity is caused by the steric hindrance between the substrate and the catalyst ligand. To verify this point, we further explore the reactive process with different axial chirality on the catalyst ligand (altering the steric hindrance), and the results suggest that the preponderant R chiral configuration product has reversed. These results could lead to a better understanding of the mechanism for 3-butene-2-ol amination reaction and are helpful for the design of the corresponding catalyst ligand in the industry.
Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake

ABSTRACT Extracellular vesicles (EVs) from cancer are delivered both proximal and distal organs. EVs are highly glycosylated at the surface where EVs interact with cells and therefore has an impact on their properties and biological functions. Aberrant glycosylation in cancer is associated with cancer progression and metastasis. However, the biological function of glycosylation on the surface of EV is uncovered. We first demonstrated differential glycosylation profiles of EVs and their originated cells, and distinct glycosylation profiles in a brain-metastatic subline BMD2a from its parental human breast cancer cell line, MDA-MB-231-luc-D3H2LN by lectin blot. We then investigated the roles of surface glycoconjugates on EV uptake. N- and/or O-glycosylation removal of fluorescent-labelled BMD2a EVs enhanced cellular uptake to endothelial cells, suggesting that surface glycosylation has inhibitory effects on cellular uptake. Biodistribution of glycosylation-deprived BMD2a EVs administrated intravenously into mice was further analysed ex vivo using near-infrared lipophilic dye. EVs treated with O-deglycosylation enzymes enhanced the accumulation of EVs to the lungs after 24 h from the injection, while N-deglycosylation did not markedly alter biodistribution. As the lungs are first organs in which intravenous blood flows, we suggest that surface glycosylation of cancer-derived EVs avoid promiscuous adhesion to proximal tissues to be delivered to distant organs.