Miracle-dz/UniFAR-FTUs huggingface dataset:
Leukemia Inhibitory Factor Induces Proopiomelanocortin via CRH/CRHR Pathway in Mouse Trophoblast

We previously showed that maternal leukemia inhibitory factor (LIF) induces placental production of adrenocorticotropic hormone (ACTH), which stimulates fetal nucleated red blood cells to further secrete LIF and promote neurogenesis in rodent brains. However, the underlying mechanism of LIF-dependent ACTH induction remains unclear. Recently, we found that LIF induces corticotropin-releasing hormone (CRH) in mouse trophoblast stem cells. This finding supports the results of a previous study that CRH, which is produced by the placenta, induces placental ACTH production. In this study, we examined whether the effects of LIF are mediated by the induction of Pomc via CRH upregulation in mouse trophoblast. In vivo, protein levels of LIF and CRH peak in mouse placenta at 13.5 days post coitum. In mouse placenta, Crh mRNA and protein levels significantly increased 3 h after intraperitoneal injection of LIF (5 μg/kg body weight) into dams at 13.5 days post coitum. We also examined the effect of LIF-induced CRH on the expression of Pomc induced by LIF in mouse trophoblast stem cells in vitro. After LIF supplementation for 3 days, we found that the increased expression of Crh-induced by new supplementation of LIF was earlier than that of Pomc. Furthermore, LIF-induced upregulation of Pomc in mouse trophoblast stem cells was attenuated by inhibition of the CRH/CRHR1 pathway, whereas LIF-induced secretion of ACTH was attenuated by inhibition of the JAK/STAT3 pathway. Therefore, LIF indirectly increases placental Pomc expression through the CRH/CRHR1 pathway, and placental ACTH secretion is induced directly by LIF via the JAK/STAT3 pathway.
The Cost of the Epistemic Step: Investigating Scalar Implicatures in Full and Partial Information Contexts

We present the first ERP experiments that test the online processing of the scalar implicature some ⇝ not all in contexts where the speaker competence assumption is violated. Participants observe game scenarios with four open cards on the table and two closed cards outside of the table, while listening to statements made by a virtual player. In the full access context, the player makes a fully informed statement by referring only to the open cards, as cards on the table; in the partial access context, she makes a partially informed statement by referring to the whole set of cards, as cards in the game. If all of the open cards contain a given object X (Fullset condition), then some cards on the table contain Xs is inconsistent with the not all reading, whereas it is unknown whether some cards in the game contain X is consistent with this reading. If only a subset of the open cards contains X (Subset condition), then both utterances are known to be consistent with the not all implicature. Differential effects are observed depending on the quantifier reading adopted by the participant: For those participants who adopt the not all reading in the full access context, but not in the partial access context (weak pragmatic reading), a late posterior negativity effect is observed in the partial access context for the Fullset relative to the Subset condition. This effect is argued to reflect inference-driven context retrieval and monitoring processes related to epistemic reasoning involved in evaluating the competence assumption. By contrast, for participants who adopt the logical interpretation of some (some and possibly all), an N400 effect is observed in the partial access context, when comparing the Subset against the Fullset condition, which is argued to result from the competition between the two quantifying expressions some cards on the table and some cards in the game functioning in the experiment as scalar alternatives.
Production of Sm-153 With Very High Specific Activity for Targeted Radionuclide Therapy

Samarium-153 (153Sm) is a highly interesting radionuclide within the field of targeted radionuclide therapy because of its favorable decay characteristics. 153Sm has a half-life of 1.93 d and decays into a stable daughter nuclide (153Eu) whereupon β− particles [E = 705 keV (30%), 635 keV (50%)] are emitted which are suitable for therapy. 153Sm also emits γ photons [103 keV (28%)] allowing for SPECT imaging, which is of value in theranostics. However, the full potential of 153Sm in nuclear medicine is currently not being exploited because of the radionuclide's limited specific activity due to its carrier added production route. In this work a new production method was developed to produce 153Sm with higher specific activity, allowing for its potential use in targeted radionuclide therapy. 153Sm was efficiently produced via neutron irradiation of a highly enriched 152Sm target (98.7% enriched, σth = 206 b) in the BR2 reactor at SCK CEN. Irradiated target materials were shipped to CERN-MEDICIS, where 153Sm was isolated from the 152Sm target via mass separation (MS) in combination with laser resonance enhanced ionization to drastically increase the specific activity. The specific activity obtained was 1.87 TBq/mg (≈ 265 times higher after the end of irradiation in BR2 + cooling). An overall mass separation efficiency of 4.5% was reached on average for all mass separations. Further radiochemical purification steps were developed at SCK CEN to recover the 153Sm from the MS target to yield a solution ready for radiolabeling. Each step of the radiochemical process was fully analyzed and characterized for further optimization resulting in a high efficiency (overall recovery: 84%). The obtained high specific activity (HSA) 153Sm was then used in radiolabeling experiments with different concentrations of 4-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA). Even at low concentrations of p-SCN-Bn-DOTA, radiolabeling of 0.5 MBq of HSA 153Sm was found to be efficient. In this proof-of-concept study, we demonstrated the potential to combine neutron irradiation with mass separation to supply high specific activity 153Sm. Using this process, 153SmCl3 suitable for radiolabeling, was produced with a very high specific activity allowing application of 153Sm in targeted radionuclide therapy. Further studies to incorporate 153Sm in radiopharmaceuticals for targeted radionuclide therapy are ongoing.
Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder

Background Alcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein. Methods We studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples. Results Patients with AUD had significantly increased abundance of the genera Candida, Debaryomyces, Pichia, Kluyveromyces, and Issatchenkia, and of the species Candida albicans and Candida zeylanoides compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera Candida, Malassezia, Pichia, Kluyveromyces, Issatchenkia, and the species C. albicans and C. zeylanoides. This was mirrored by significantly higher specific anti-C. albicans immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti-C. albicans IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus Malassezia was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease. Conclusion In conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of Candida and Malassezia, and lower serum anti-C. albicans IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.
Biological Effect of Streptococcus pyogenes-Released Extracellular Vesicles on Human Monocytic Cells, Induction of Cytotoxicity, and Inflammatory Response

Most bacteria naturally release spherical lipid-bilayered extracellular vesicles (EVs) containing proteins, nucleic acids, and virulence-related molecules, thus contributing to diverse biological functions including transport of virulence factors. The group A streptococcus, Streptococcus pyogenes (GAS), a major human pathogen, also releases EVs; however, it remains unclear how GAS EVs interact physiologically and pathologically with host cells, and what the differences are between invasive and non-invasive strains. The proteome profile in this study revealed that GAS EVs enclosed many virulence-related proteins such as streptolysin O and NAD-glycohydrolase, facilitating their pathogenicity, and invasive GAS EVs were more abundant than non-invasive counterparts. In terms of biological effects, invasive GAS EVs showed slo-dependent cytotoxic activity and the induction of cytokine expression, contributing to GAS pathogenicity directly. Although non-invasive GAS EVs did not show cytotoxic activity, they may be utilized as a means to prevent antibacterial mechanisms such as autophagy, leading to enhancement of their own survival in the intracellular environment after the infection. These results suggest that invasive and non-invasive GAS EVs play different roles in GAS infection strategy and pathogenicity. Our findings also indicate that EVs could be a key factor for GAS pathogenicity in GAS-host interactions.
Chlamydia trachomatis Polymorphic Membrane Proteins (Pmps) Form Functional Homomeric and Heteromeric Oligomers

Chlamydiae are Gram-negative, obligate intracellular bacteria, which infect animals and humans. Adhesion to host cells, the first step in the infection process, is mediated by polymorphic membrane proteins (Pmps). Pmps constitute the largest chlamydial protein family, with 9 members (subdivided into six subtypes) in C. trachomatis and 21 in C. pneumoniae, and are characterized by the presence of multiple copies of GGA(I,L,V) and FxxN motifs. Motif-rich fragments of all nine C. trachomatis Pmps act as adhesins and are essential for infection. As autotransporters, most Pmp proteins are secreted through their β-barrel domain and localize on the surface of the chlamydial cell, where most of them are proteolytically processed. Classical autotransporters are monomeric proteins, which can function as toxins, proteases, lipases and monoadhesive adhesins. Here we show that selected recombinant C. trachomatis Pmp fragments form functional adhesion-competent multimers. They assemble into homomeric and heteromeric filaments, as revealed by non-denaturing gel electrophoresis, size-exclusion chromatography and electron microscopy. Heteromeric filaments reach 2 μm in length, significantly longer than homomeric structures. Filament formation was independent of the number of motifs present in the fragment(s) concerned and their relative affinity for host cells. Our functional studies demonstrated that only adhesion-competent oligomers were able to block a subsequent infection. Pre-loading of infectious chlamydial cells with adhesion-competent Pmp oligomers maintained the subsequent infection, while adhesion-incompetent structures reduced infectivity, presumably by blocking the function of endogenous Pmps. The very large number of possible heteromeric and homomeric Pmp complexes represents a novel mechanism to ensure stable adhesion and possibly host cell immune escape.
Albiflorin Promotes Osteoblast Differentiation and Healing of Rat Femoral Fractures Through Enhancing BMP-2/Smad and Wnt/β-Catenin Signaling

Fracture healing is related to osteogenic differentiation and mineralization. Recently, due to the unwanted side effects and clinical limitations of existing treatments, various natural product-based chemical studies have been actively conducted. Albiflorin is a major ingredient in Paeonia lactiflora, and this study investigated its ability to promote osteogenic differentiation and fracture healing. To demonstrate the effects of albiflorin on osteoblast differentiation and calcified nodules, alizarin red S staining and von Kossa staining were used in MC3T3-E1 cells. In addition, BMP-2/Smad and Wnt/β-catenin mechanisms known as osteoblast differentiation mechanisms were analyzed through RT-PCR and western blot. To investigate the effects of albiflorin on fracture healing, fractures were induced using a chainsaw in the femur of Sprague Dawley rats, and then albiflorin was intraperitoneally administered. After 1, 2, and 3 weeks, bone microstructure was analyzed using micro-CT. In addition, histological analysis was performed by staining the fractured tissue, and the expression of osteogenic markers in serum was measured. The results demonstrated that albiflorin promoted osteoblastogenesis and the expression of RUNX2 by activating BMP-2/Smad and Wnt/β-catenin signaling in MC3T3-E1 cells. In addition, albiflorin upregulated the expression of various osteogenic genes, such as alkaline phosphatase, OCN, bone sialoprotein, OPN, and OSN. In the femur fracture model, micro-CT analysis showed that albiflorin played a positive role in the formation of callus in the early stage of fracture recovery, and histological examination proved to induce the expression of osteogenic genes in femur tissue. In addition, the expression of bone-related genes in serum was also increased. This suggests that albiflorin promotes osteogenesis, bone calcification and bone formation, thereby promoting the healing of fractures in rats.
Dynamics of Free-Living and Attached Bacterial Assemblages in Skeletonema sp. Diatom Cultures at Elevated Temperatures

In the context of global warming, changes in phytoplankton-associated bacterial communities have the potential to change biogeochemical cycling and food webs in marine ecosystems. Skeletonema is a cosmopolitan diatom genus in coastal waters worldwide. Here, we grew a Skeletonema strain with its native bacterial assemblage at different temperatures and examined cell concentrations of Skeletonema sp. and free-living bacteria, dissolved organic carbon (DOC) concentrations of cultures, and the community structure of both free-living and attached bacteria at different culture stages. The results showed that elevated temperature increased the specific growth rates of both Skeletonema and free-living bacteria. Different growth stages had a more pronounced effect on community structure compared with temperatures and different physical states of bacteria. The effects of temperature on the structure of the free-living bacterial community were more pronounced compared with diatom-attached bacteria. Carbon metabolism genes and those for some specific amino acid pathways were found to be positively correlated with elevated temperature, which may have profound implications on the oceanic carbon cycle and the marine microbial loop. Network analysis revealed evidence of enhanced cooperation with an increase in positive interactions among different bacteria at elevated temperature. This may help the whole community to overcome the stress of elevated temperature. We speculate that different bacterial species may build more integrated networks with a modified functional profile of the whole community to cope with elevated temperature. This study contributes to an improved understanding of the response of diatom-associated bacterial communities to elevated temperature.
Influence of Synthetic Flavorings on the Migration Activity of Tribolium confusum and Sitophilus granarius

Abstract Flavorings and volatile biologically active substances, used by humans for various purposes, may potentially have fumigating, repellent, or attractive effects on various species of anthropod storage pests. Tribolium confusum Jacquelin du Val, 1863 (Tenebrionidae) and Sitophilus granarius (Linnaeus, 1758) (Curculionidae) are the two most abundant pests of grain and grain products; the damage they cause to stored products of horticulture is 5–20% of the total yield of grain crops. In the experiment, we video-recorded migratory activity of beetles and evaluated it according to standard time periods (10, 20, 30, 60, and 120 seconds after the start of the experiment). No reliable influence of the 15 tested flavoring substances (benzyl alcohol, benzoic acid, toluene, hydroquinone, phenethyl alcohol, pinene, methylparaben, kojic acid, formic acid, isoamyl alcohol, tartaric acid, glycine, succinic acid, stearic acid, and ethylenediaminetetraacetic acid) on moving activity of Tribolium confusum was found. Exposure to benzyl alcohol brought a reliable decrease in locomotor activity of Sitophilus granarius (it exerted an attractant effect on imagoes as compared with the variant of the experiment without aromatic substances): 6.09 times more imagoes of S. granarius remained at a minimal distance from the aroma source than in the control, 6.07 more while exposed to hydroquinone, 5.50 to phenethyl alcohol, 4.50 to glycine, 3.44 to EDTA, 3.30 to toluene, 3.18 to methylparaben, 2.84 to succinic acid, 2.65 to benzoic acid, and 2.15 more when exposed to formic acid compared with the control variant of the experiment. Other surveyed flavoring substances (benzyl alcohol, pinene, kojic acid, isoamyl alcohol, tartaric acid, and stearic acid) had no significant effect on migratory activity of imagoes of S. granarius. The results allow us to recommend benzyl alcohol, hydroquinone, phenethyl alcohol, and glycine as potential luring substances or components of multicomponent flavoring mixtures during the assessment of the number of S. granarius in grain storage and processing facilities.
The Influence of Face Loss on Impulse Buying: An Experimental Study

In this research, the effect of face loss on impulsive buying is examined under the background of Chinese culture. Using experimental studies, we examined the mediating effect of emotion and the moderating effect of self-control. The results indicate that individuals who lost their face are more likely to purchase impulsively. For individuals high in self-control, face loss has no significant impact on their impulsive consumption. While for those with low self-control, face loss will significantly enhance their impulsive buying tendency. Finally, implications, limitations, and directions for future research are discussed.
Ductal Flow Ratio as Measure of Transition in Preterm Infants After Birth: A Pilot Study

Background: Cardiovascular changes during the transition from intra- to extrauterine life, alters the pressure gradient across the ductus arteriosus (DA). DA flow ratio (R-L/L-R) has been suggested to reflect the infant's transitional status and could potentially predict neonatal outcomes after preterm birth. Aim: Determine whether DA flow ratio correlates with oxygenation parameters in preterm infants at 1 h after birth. Methods: Echocardiography was performed in preterm infants born <32 weeks gestational age (GA), as part of an ancillary study. DA flow was measured at 1 h after birth. DA flow ratio was correlated with FiO2, SpO2, and SpO2/FiO2 (SF) ratio. The DA flow ratio of infants receiving physiological-based cord clamping (PBCC) or time-based cord clamping (TBCC) were compared. Results: Measurements from 16 infants were analysed (median [IQR] GA 29 [27–30] weeks; birthweight 1,176 [951–1,409] grams). R-L DA shunting was 16 [17–27] ml/kg/min and L-R was 110 [81–124] ml/kg/min. The DA flow ratio was 0.18 [0.11–0.28], SpO2 94 [93–96]%, FiO2 was 23 [21–28]% and SF ratio 4.1 [3.3–4.5]. There was a moderate correlation between DA flow ratio and SpO2 [correlation coefficient (CC) −0.415; p = 0.110], FiO2 (CC 0.384; p = 0.142) and SF ratio (CC −0.356; p = 0.175). There were no differences in DA flow measurements between infants where PBBC or TBCC was performed. Conclusion: In this pilot study we observed a non-significant positive correlation between DA flow ratio at 1 h after birth and oxygenation parameters in preterm infants.
RNA Is a Double-Edged Sword in ALS Pathogenesis

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that affects upper and lower motor neurons. Familial ALS accounts for a small subset of cases (<10–15%) and is caused by dominant mutations in one of more than 10 known genes. Multiple genes have been causally or pathologically linked to both ALS and frontotemporal dementia (FTD). Many of these genes encode RNA-binding proteins, so the role of dysregulated RNA metabolism in neurodegeneration is being actively investigated. In addition to defects in RNA metabolism, recent studies provide emerging evidence into how RNA itself can contribute to the degeneration of both motor and cortical neurons. In this review, we discuss the roles of altered RNA metabolism and RNA-mediated toxicity in the context of TARDBP, FUS, and C9ORF72 mutations. Specifically, we focus on recent studies that describe toxic RNA as the potential initiator of disease, disease-associated defects in specific RNA metabolism pathways, as well as how RNA-based approaches can be used as potential therapies. Altogether, we highlight the importance of RNA-based investigations into the molecular progression of ALS, as well as the need for RNA-dependent structural studies of disease-linked RNA-binding proteins to identify clear therapeutic targets.
Dysbiosis of Fecal Microbiota From Complement 3 Knockout Mice With Constipation Phenotypes Contributes to Development of Defecation Delay

Significant phenotypes for constipation were detected in complement 3 (C3) knockout (KO) mice, although no research has been conducted on an association with alteration of gut microbiota. To investigate the effects of dysbiosis on fecal microbiota from C3 KO mice with constipation, the composition of fecal microbiota was characterized in mid-colons of 16-week-old C3 KO mice, and their function for defecation delay development was examined after fecal microbiota transplantation (FMT) of C3 KO mice. Some significant alterations in constipation phenotypes, including stool parameters and histopathological structure, were detected in 16-week-old C3 KO mice compared to those of wild-type (WT) mice. Fecal microbiota of C3 KO mice exhibited decreases in Anaerocolumna, Caecibacterium, Christensenella, Kineothrix, and Oscillibacter populations and increases in Prevotellamassilia, Reuthenibacterium, Prevotella, Eubacterium, Culturomica, Bacteroides, and Muribaculum populations. In FMT study, key stool parameters, including weight and water content, were remarkably declined in a transplanted KO (KFMT) group of antibiotics-induced depletion of microbiota (AiDM)-WT and AiDM-KO mice, and a similar change was observed in fecal morphology. However, intestine length decreased in only the KFMT group of AiDM-WT mice compared with that of AiDM-KO mice. The mucosal layer and muscle thickness were commonly decreased in the KFMT group of AiDM-WT and AiDM-KO mice, and significant alterations in the crypt structure of Lieberkuhn and molecular regulators, including AQP8, C-kit, and 5-HT, were observed in the same group. Taken together, results of the present study indicate that dysbiosis of fecal microbiota from C3 KO mice with constipation phenotypes has a key role in the induction and regulation of defecation delay.