Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Gut Microbiota in an Ischemic Stroke

The intestinal microbiome, the largest reservoir of microorganisms in the human body, plays an important role in neurological development and aging as well as in brain disorders such as an ischemic stroke. Increasing knowledge about mediators and triggered pathways has contributed to a better understanding of the interaction between the gut-brain axis and the brain-gut axis. Intestinal bacteria produce neuroactive compounds and can modulate neuronal function, which affects behavior after an ischemic stroke. In addition, intestinal microorganisms affect host metabolism and immune status, which in turn affects the neuronal network in the ischemic brain. Here we discuss the latest results of animal and human research on two-way communication along the gut-brain axis in an ischemic stroke. Moreover, several reports have revealed the impact of an ischemic stroke on gut dysfunction and intestinal dysbiosis, highlighting the delicate play between the brain, intestines and microbiome after this acute brain injury. Despite our growing knowledge of intestinal microflora in shaping brain health, host metabolism, the immune system and disease progression, its therapeutic options in an ischemic stroke have not yet been fully utilized. This review shows the role of the gut microflora-brain axis in an ischemic stroke and assesses the potential role of intestinal microflora in the onset, progression and recovery post-stroke.
Mechanical Properties and Bioactivity of Poly(Lactic Acid) Composites Containing Poly(Glycolic Acid) Fiber and Hydroxyapatite Particles

To enhance the mechanical strength and bioactivity of poly(lactic acid) (PLA) to the level that can be used as a material for spinal implants, poly(glycolic acid) (PGA) fibers and hydroxyapatite (HA) were introduced as fillers to PLA composites. To improve the poor interface between HA and PLA, HA was grafted by PLA to form HA-g-PLA through coupling reactions, and mixed with PLA. The size of the HA particles in the PLA matrix was observed to be reduced from several micrometers to sub-micrometer by grafting PLA onto HA. The tensile and flexural strength of PLA/HA-g-PLA composites were increased compared with those of PLA/HA, apparently due to the better dispersion of HA and stronger interfacial adhesion between the HA and PLA matrix. We also examined the effects of the length and frequency of grafted PLA chains on the tensile strength of the composites. By the addition of unidirectionally aligned PGA fibers, the flexural strength of the composites was greatly improved to a level comparable with human compact bone. In the bioactivity tests, the growth of apatite on the surface was fastest and most uniform in the PLA/PGA fiber/HA-g-PLA composite.
Influence of Drug Incorporation on the Physico-Chemical Properties of Poly(l-Lactide) Implant Coating Matrices—A Systematic Study

Local drug delivery has become indispensable in biomedical engineering with stents being ideal carrier platforms. While local drug release is superior to systemic administration in many fields, the incorporation of drugs into polymers may influence the physico-chemical properties of said matrix. This is of particular relevance as minimally invasive implantation is frequently accompanied by mechanical stresses on the implant and coating. Thus, drug incorporation into polymers may result in a susceptibility to potentially life-threatening implant failure. We investigated spray-coated poly-l-lactide (PLLA)/drug blends using thermal measurements (DSC) and tensile tests to determine the influence of selected drugs, namely sirolimus, paclitaxel, dexamethasone, and cyclosporine A, on the physico-chemical properties of the polymer. For all drugs and PLLA/drug ratios, an increase in tensile strength was observed. As for sirolimus and dexamethasone, PLLA/drug mixed phase systems were identified by shifted drug melting peaks at 200 °C and 240 °C, respectively, whereas paclitaxel and dexamethasone led to cold crystallization. Cyclosporine A did not affect matrix thermal properties. Altogether, our data provide a contribution towards an understanding of the complex interaction between PLLA and different drugs. Our results hold implications regarding the necessity of target-oriented thermal treatment to ensure the shelf life and performance of stent coatings.
Sigma‐2 receptor antagonists rescue neuronal dysfunction induced by Parkinson’s patient brain‐derived α‐synuclein

α‐Synuclein oligomers are thought to have a pivotal role in sporadic and familial Parkinson's disease (PD) and related α‐synucleinopathies, causing dysregulation of protein trafficking, autophagy/lysosomal function, and protein clearance, as well as synaptic function impairment underlying motor and cognitive symptoms of PD. Moreover, trans‐synaptic spread of α‐synuclein oligomers is hypothesized to mediate disease progression. Therapeutic approaches that effectively block α‐synuclein oligomer‐induced pathogenesis are urgently needed. Here, we show for the first time that α‐synuclein species isolated from human PD patient brain and recombinant α‐synuclein oligomers caused similar deficits in lipid vesicle trafficking rates in cultured rat neurons and glia, while α‐synuclein species isolated from non‐PD human control brain samples did not. Recombinant α‐synuclein oligomers also increased neuronal expression of lysosomal‐associated membrane protein‐2A (LAMP‐2A), the lysosomal receptor that has a critical role in chaperone‐mediated autophagy. Unbiased screening of several small molecule libraries (including the NIH Clinical Collection) identified sigma‐2 receptor antagonists as the most effective at blocking α‐synuclein oligomer‐induced trafficking deficits and LAMP‐2A upregulation in a dose‐dependent manner. These results indicate that antagonists of the sigma‐2 receptor complex may alleviate α‐synuclein oligomer‐induced neurotoxicity and are a novel therapeutic approach for disease modification in PD and related α‐synucleinopathies.
Single-Pulse Transcranial Magnetic Stimulation-Evoked Potential Amplitudes and Latencies in the Motor and Dorsolateral Prefrontal Cortex among Young, Older Healthy Participants, and Schizophrenia Patients

Background: The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for non-invasive investigation of cortical response and connectivity in human cortex. This study aimed to examine the amplitudes and latencies of each TMS-evoked potential (TEP) component induced by single-pulse TMS (spTMS) to the left motor (M1) and dorsolateral prefrontal cortex (DLPFC) among healthy young participants (YNG), older participants (OLD), and patients with schizophrenia (SCZ). Methods: We compared the spatiotemporal characteristics of TEPs induced by spTMS among the groups. Results: Compared to YNG, M1-spTMS induced lower amplitudes of N45 and P180 in OLD and a lower amplitude of P180 in SCZ, whereas the DLPFC-spTMS induced a lower N45 in OLD. Further, OLD demonstrated latency delays in P60 after M1-spTMS and in N45-P60 over the right central region after left DLPFC-spTMS, whereas SCZ demonstrated latency delays in N45-P60 over the midline and right central regions after DLPFC-spTMS. Conclusions: These findings suggest that inhibitory and excitatory mechanisms mediating TEPs may be altered in OLD and SCZ. The amplitude and latency changes of TEPs with spTMS may reflect underlying neurophysiological changes in OLD and SCZ, respectively. The spTMS administered to M1 and the DLPFC can probe cortical functions by examining TEPs. Thus, TMS-EEG can be used to study changes in cortical connectivity and signal propagation from healthy to pathological brains.
Recreated Ancestral Opsin Associated with Marine to Freshwater Croaker Invasion Reveals Kinetic and Spectral Adaptation

Abstract Rhodopsin, the light-sensitive visual pigment expressed in rod photoreceptors, is specialized for vision in dim-light environments. Aquatic environments are particularly challenging for vision due to the spectrally dependent attenuation of light, which can differ greatly in marine and freshwater systems. Among fish lineages that have successfully colonized freshwater habitats from ancestrally marine environments, croakers are known as highly visual benthic predators. In this study, we isolate rhodopsins from a diversity of freshwater and marine croakers and find that strong positive selection in rhodopsin is associated with a marine to freshwater transition in South American croakers. In order to determine if this is accompanied by significant shifts in visual abilities, we resurrected ancestral rhodopsin sequences and tested the experimental properties of ancestral pigments bracketing this transition using in vitro spectroscopic assays. We found the ancestral freshwater croaker rhodopsin is redshifted relative to its marine ancestor, with mutations that recapitulate ancestral amino acid changes along this transitional branch resulting in faster kinetics that are likely to be associated with more rapid dark adaptation. This could be advantageous in freshwater due to the redshifted spectrum and relatively narrow interface and frequent transitions between bright and dim-light environments. This study is the first to experimentally demonstrate that positively selected substitutions in ancestral visual pigments alter protein function to freshwater visual environments following a transition from an ancestrally marine state and provides insight into the molecular mechanisms underlying some of the physiological changes associated with this major habitat transition.
Asymptomatic Leishmania infection in HIV-positive outpatients on antiretroviral therapy in Pernambuco, Brazil

Background Visceral leishmaniasis (VL) in HIV-positive individuals is a global health problem. HIV-Leishmania coinfection worsens prognosis and mortality risk, and HIV-Leishmania coinfected individuals are more susceptible to VL relapses. Early initiation of antiretroviral therapy can protect against Leishmania infection in individuals living in VL-endemic areas, and regular use of antiretrovirals might prevent VL relapses in these individuals. We conducted a cross-sectional study in Petrolina, Brazil, an VL-endemic area, to estimate the prevalence of asymptomatic Leishmania cases among HIV-positive outpatients. Methods We invited any HIV-positive patients, aged ≥ 18-years-old, under antiretroviral therapy, and who were asymptomatic for VL. Patients were tested for Leishmania with enzyme-linked immunosorbent assays (ELISA)-rK39, immunochromatographic test (ICT)-rK39, direct agglutination test (DAT), latex agglutination test (KAtex), and conventional polymerase chain reaction (PCR). HIV-Leishmania coinfection was diagnosed when at least one VL test was positive. Results A total of 483 patients were included. The sample was predominantly composed of single, < 48-years-old, black/pardo, heterosexual males, with fewer than 8 years of schooling. The prevalence of asymptomatic HIV-Leishmania coinfection was 9.11% (44/483). HIV mono-infected and HIV-Leishmania coinfected groups differed statistically significantly in terms of race (p = 0.045), marital status (p = 0.030), and HIV viral load (p = 0.046). Black/pardo patients, married patients, and those with an HIV viral load up to 100,000 copies/ml presented higher odds for HIV-Leishmania coinfection. Conclusions A considerable number of asymptomatic Leishmania cases were observed among HIV-positive individuals in a VL-endemic area. Given the potential impact on transmission and health costs, as well as the impact on these coinfected individuals, studies of asymptomatic Leishmania carriers can be useful for guiding public health policies in VL-endemic areas aiming to control and eliminate the disease.
Metal Contents in Soils of Alabama

Abstract Metal contamination of soils and water resources continues to be a serious public concern. Accumulations in the ecosystems and subsequent uptake by humans via the food chain pose a major health risk. The total copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), zinc (Zn), cadmium (Cd), chromium (Cr), and lead (Pb) contents of eight benchmark soils of north Alabama were determined. The overall goal was to provide information for future pedological studies. The specific objectives were to determine baseline values of total Cu, Fe, Mn, Ni, and Zn, which are plant nutrients, and Cd, Cr, and Pb, which are relatively serious pollutants. Expressed in mg kg−1 soil, the ranges, median, geometric mean, and arithmetic mean values, respectively in parentheses, were Cu (3.2–81.9, 24, 18.2, 24.8); Cd (< 0.2–2.85, 0.15, < 0.1, 0.40); Cr (13.4–132, 51.7, 54.6, 61); Fe (1535–70,840, 34,035, 26,783, 31,720); Mn (30.2–4643, 540, 426, 1012); Ni (7.6–61, 27.5, 25.3, 27.7); Pb (< 2.0–22.8, < 2.0, < 0.1, 3.63); and Zn (22.6–339, 116, 108, 125). The order of abundance in the soils was Fe > Mn > Zn > Cr > Ni > Cu > Pb > Cd. Total Pb, Cd, Zn, Cu, and Ni contents determined were comparable to the reported average values for most United States soils. The presence of Cd, Cr, and Pb in measurable amounts in some of the samples is of environmental concern.
The Functions of the Demethylase JMJD3 in Cancer

Cancer is a major cause of death worldwide. Epigenetic changes in response to external (diet, sports activities, etc.) and internal events are increasingly implicated in tumor initiation and progression. In this review, we focused on post-translational changes in histones and, more particularly, the tri methylation of lysine from histone 3 (H3K27me3) mark, a repressive epigenetic mark often under- or overexpressed in a wide range of cancers. Two actors regulate H3K27 methylation: Jumonji Domain-Containing Protein 3 demethylase (JMJD3) and Enhancer of zeste homolog 2 (EZH2) methyltransferase. A number of studies have highlighted the deregulation of these actors, which is why this scientific review will focus on the role of JMJD3 and, consequently, H3K27me3 in cancer development. Data on JMJD3’s involvement in cancer are classified by cancer type: nervous system, prostate, blood, colorectal, breast, lung, liver, ovarian, and gastric cancers.
Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study

Secondary metabolites isolated from plant endophytic fungi have been getting more and more attention. Some secondary metabolites exhibit high biological activities, hence, they have potential to be used for promising lead compounds in drug discovery. In this review, a total of 134 journal articles (from 2017 to 2019) were reviewed and the chemical structures of 449 new metabolites, including polyketides, terpenoids, steroids and so on, were summarized. Besides, various biological activities and structure-activity relationship of some compounds were aslo described.
Impact of palliative care on end-of-life care and place of death in children, adolescents, and young adults with life-limiting conditions: A systematic review

Abstract Objective To determine the impact of palliative care (PC) on end-of-life (EoL) care and the place of death (PoD) in children, adolescents, and young adults with life-limiting conditions. Method Eight online databases (PubMed, Medline, EMBASE, Cochrane Library, CINAHL, Airiti, GARUDA Garba Rujukan Digital, and OpenGrey) from 2010 to February 5, 2020 were searched for studies investigating EoL care and the PoD for pediatric patients receiving and not receiving PC. Results Of the 6,468 citations identified, 14 cohort studies and one case series were included. An evidence base of mainly adequate- and strong-quality studies shows that inpatient hospital PC, either with or without the provision of home and community PC, was found to be associated with a decrease in intensive care use and high-intensity EoL care. Conflicting evidence was found for the association between PC and hospital admissions, length of stay in hospital, resuscitation at the time of death, and the proportion of hospital and home deaths. Significance of results Current evidence suggests that specialist, multidisciplinary involvement, and continuity of PC are required to reduce the intensity of EoL care. Careful attention should be paid to the need for a longer length of stay in a medical setting late in life, and earlier EoL care discussion should take place with patients/caregivers, especially in regard to attempting resuscitation in toddlers, adolescents, and the young adult population. A lack of robust evidence has identified a gap in rigorous multisite prospective studies utilizing data collection.
Electron microscopy characterization of hexagonal molybdenum trioxide (MoO3) nanorods

A simple low-temperature chemical method to produce metastable hexagonal phase molybdenum oxide (h-MoO3) nanorods and their excellent structural characteristics has been demonstrated. In this approach, h-MoO3 samples were prepared by precipitating molybdenum oxide from an ammonium paramolybdate solution by the adding nitric acid. The structure of h-MoO3 nanorods was examined in detail using high-resolution scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM). The SEM data reveal that the nanorod h-MoO3 crystals have the shape of straight hexagonal rods with an aspect ratio ∼60. The HR-TEM results confirm the hexagonal structure of the MoO3 nanocrystals. Computations of the observed TEM data along with x-ray diffraction pattern further confirm the stability of the nanostructure of h-MoO3 rods.
Adaptive Fault-Tolerant Boundary Control for a Flexible String With Unknown Dead Zone and Actuator Fault

This study focuses on an adaptive fault-tolerant boundary control (BC) for a flexible string (FS) in the presence of unknown external disturbances, dead zone, and actuator fault. To tackle these issues, by employing some transformations, a part of the unknown dead zone and external disturbance can be regarded as a composite disturbance. Subsequently, an adaptive fault-tolerant BC is developed by utilizing strict formula derivations to compensate for unknown composite disturbance, dead zone, and actuator fault in the FS system. Under the proposed control strategy, the closed-loop system proves to be uniformly ultimately bounded, and the vibration amplitude is guaranteed to converge ultimately to a small compact set by choosing suitable design parameters. Finally, a numerical simulation is performed to demonstrate the control performance of the proposed scheme.
The gut microbiota as a target to control hyperuricemia pathogenesis: Potential mechanisms and therapeutic strategies

Abstract Hyperuricemia (HUA) is a metabolic disorder caused by abnormal uric acid (UA) metabolism, which is a complex physiological process involving multiple organs (liver, kidney, and intestine). Although UA metabolism in the liver and kidneys has been elucidated, only a few studies have focused on the process in the intestine. With our growing knowledge of the effects of gut microorganisms on health, the gut microbiota has been identified as a new target for HUA treatment. In this review, the relationship between HUA and the gut microbiota is elucidated, and anti-hyperuricemia mechanisms targeting the intestine are discussed, such as the promotion of purine and UA catabolism by the gut microbiota, increases in UA excretion by the gut microbiota and its metabolites, regulation of UA absorption or secretion in the intestinal tract by certain transporters, and the intestinal inflammatory response to the gut microbiota. Additionally, probiotics (Bifidobacteria and Lactobacilli) and prebiotics (polyphenols, peptides, and phytochemicals) with UA-lowering effects targeting the intestinal tract are summarized, providing reference and guidance for further research.
The Retrobulbar Spot Sign and Prominent Middle Limiting Membrane as Prognostic Markers in Non-Arteritic Retinal Artery Occlusion

Central retinal artery occlusion (CRAO) is characterized by the sudden, painless loss of vision. Typical sonographic and optic coherence tomography (OCT) findings are a retrobulbar spot sign and prominent middle limiting membrane (p-MLM) sign. It remains uncertain whether the retrobulbar spot sign alone or coinciding with the appearance of p-MLM sign is a prognostic marker for visual acuity and the development of secondary retinal ischemia after CRAO. In our prospective cohort study, we included patients with a non-arteritic central artery occlusion < 4 weeks. We examined the following parameters at prespecified time points: ultrasound examination of orbital cavity, Spectral Domain-OCT examination, visual acuity test, and fundoscopy and ultra-widefield angiography to diagnose retinal vascularization. The presence of p-MLM sign in SD-OCT after CRAO was accompanied by significantly better vision during the first four weeks (2.3 (IQR 0.75) vs. 2.6 (IQR 0.33); p = 0.006). Moreover, the spot sign seems to be a prognostic factor for developing secondary retinal ischemia (8 (100%) vs. 0 (0%); p = 0.036). A retrobulbar spot sign seems to be a negative prognostic factor and is associated with secondary retinal ischemia, whereas a p-MLM sign is a somewhat positive prognostic factor for visual acuity.
Prebiotic Organic Chemistry of Formamide and the Origin of Life in Planetary Conditions: What We Know and What Is the Future

The goal of prebiotic chemistry is the depiction of molecular evolution events preceding the emergence of life on Earth or elsewhere in the cosmos. Plausible experimental models require geochemical scenarios and robust chemistry. Today we know that the chemical and physical conditions for life to flourish on Earth were at work much earlier than thought, i.e., earlier than 4.4 billion years ago. In recent years, a geochemical model for the first five hundred million years of the history of our planet has been devised that would work as a cradle for life. Serpentinization processes in the Hadean eon affording self-assembled structures and vesicles provides the link between the catalytic properties of the inorganic environment and the impressive chemical potential of formamide to produce complete panels of organic molecules relevant in pre-genetic and pre-metabolic processes. Based on an interdisciplinary approach, we propose basic transformations connecting geochemistry to the chemistry of formamide, and we hint at the possible extension of this perspective to other worlds.
Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Hyperhomocysteinemia has been suggested potentially to contribute to a variety of pathologies, such as Alzheimer’s disease (AD). While the impact of hyperhomocysteinemia on AD has been investigated extensively, there are scarce data on the effect of AD on hyperhomocysteinemia. The aim of this in vivo study was to investigate the kinetics of homocysteine (HCys) and homocysteic acid (HCA) and effects of AD-like pathology on the endogenous levels. The mice received a B-vitamin deficient diet for eight weeks, followed by the return to a balanced control diet for another eight weeks. Serum, urine, and brain tissues of AppNL-G-F knock-in and C57BL/6J wild type mice were analyzed for HCys and HCA using LC-MS/MS methods. Hyperhomocysteinemic levels were found in wild type and knock-in mice due to the consumption of the deficient diet for eight weeks, followed by a rapid normalization of the levels after the return to control chow. Hyperhomocysteinemic AppNL-G-F mice had significantly higher HCys in all matrices, but not HCA, compared to wild type control. Higher serum concentrations were associated with elevated levels in both the brain and in urine. Our findings confirm a significant impact of AD-like pathology on hyperhomocysteinemia in the AppNL-G-F mouse model. The immediate normalization of HCys and HCA after the supply of B-vitamins strengthens the idea of a B-vitamin intervention as a potentially preventive treatment option for HCys-related disorders such as AD.