Miracle-dz/UniFAR-FTUs huggingface dataset:
Liang-Ge-San, a Classic Traditional Chinese Medicine Formula, Attenuates Lipopolysaccharide-Induced Acute Lung Injury Through Up-Regulating miR-21

Background: Acute lung injury (ALI) is a life-threatening disease without effective chemotherapy at present. Liang-Ge-San (LGS) is a famous traditional Chinese medicine formula, which is used to treat ALI in China. However, only a few studies have addressed the mechanisms of LGS in ALI. Purpose: To evaluate the anti-inflammatory effects of LGS on lipopolysaccharide (LPS)-induced ALI, and to explore its underlying molecular mechanism. Methods: Murine RAW264.7 cells were treated with LGS and LPS (1 μg/ml). The generation of IL-6, TNF-α, IL-1β was detected by ELISA. The protein expressions of STAT3 and P-STAT3 (Tyr705) were determined by Western blotting and fluorescence confocal microscopy. STAT3 transcriptional activity was investigated by luciferase reporter gene assay. qPCR was used to detect the expressions of microRNA-21 (miR-21), STAT3, and IL-6. DSS cross-linking assay was used to assess the change of STAT3 dimer. In vivo anti-inflammatory effects of LGS were evaluated in an ALI mouse model induced by tracheal instillation of LPS (3 mg/kg). The anti-ALI effects were evaluated by ELISA, qPCR, Western blotting, BCA, and H&E assays. Results: LGS suppressed LPS-stimulated IL-6, TNF-α, and IL-1β generation in murine macrophages RAW264.7. Moreover, LGS down-regulated protein levels of P-STAT3 (Tyr705) and STAT3, inhibited STAT3 transcriptional activity, and up-regulated miR-21. Furthermore, blockage of miR-21 antagonized the inhibitory effects of LGS on the production of IL-6 and the expressions of P-STAT3 (Tyr705) and STAT3 as well as the formation of STAT3 dimer. Critically, LGS up-regulated the expression of miR-21 and inhibited the protein expressions of STAT3 and P-STAT3 (Tyr705) to reduce the release of IL-6 and inflammatory cell infiltration as well as the degree of edema in LPS-induced ALI mice. Conclusion: LGS inhibited LPS-induced ALI through up-regulating miR-21 and subsequently inhibiting the STAT3 signaling pathway, thereby decreasing the release of IL-6.
Isovitexin-Mediated Regulation of Microglial Polarization in Lipopolysaccharide-Induced Neuroinflammation via Activation of the CaMKKβ/AMPK-PGC-1α Signaling Axis

Microglia are the brain's immune cells and play an important role in regulating the microenvironment in the central nervous system. Activated microglia are capable of acquiring the pro-inflammatory (M1) phenotype and anti-inflammatory (M2) phenotype. Overactivation of microglia is neurotoxic and may lead to neuroinflammatory brain disorders. Neuroinflammation in the brain plays a crucial role part in the pathophysiology of many psychiatric and neurological diseases. The inhibition of M1 microglia and promotion of M2 microglia was demonstrated to treat and prevent these diseases through reduced neuroinflammation. Isovitexin (IVX) has anti-inflammatory properties and passes through the blood-brain barrier; however, the molecular mechanism that modulates IVX-mediated microglial polarization remains unclear. In BV-2 cells and mouse primary microglia, IVX suppressed the expression of M1 microglial markers, enhanced the expression of M2 microglial markers, and enhanced the release of interleukin 10 (IL-10). IVX promoted the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) in LPS-induced microglial activation. The inhibition of PPARγ and PGC-1α attenuated the regulatory effect of IVX in LPS-induced microglial polarization. IVX increased the expression of p-CaMKKβ, p-AMPK, and PGC-1α in BV-2 cells. Inhibition of CaMKKβ with STO-609 or knockdown of CaMKKβ with CaMKKβ siRNA attenuated IVX-mediated M2 microglial polarization in LPS-treated cells. In LPS-treated mice, the inhibition of CaMKKβ and PGC-1α attenuated the IVX-mediated prevention of sickness behavior and enhanction of IVX-mediated M2 microglial polarization. IVX promoted M2 microglial polarization which exerted anti-inflammatory effects on LPS-induced neuroinflammation via the activation of the CaMKKβ/AMPK-PGC-1α signaling axis.
Preclinical Research of Dihydromyricetin for Brain Aging and Neurodegenerative Diseases

Brain aging and neurodegenerative diseases share the hallmarks of slow and progressive loss of neuronal cells. Flavonoids, a subgroup of polyphenols, are broadly present in food and beverage and numerous studies have suggested that it could be useful for preventing or treating neurodegenerative diseases in humans. Dihydromyricetin (DHM) is one of the main flavonoids of some Asian medicinal plants that are used to treat diverse illness. The effects of DHM have been studied in different in vitro systems of oxidative damage and neuroinflammation, as well as in animal models of several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Here we analyzed the most important effects of DHM, including its antioxidant, anti-inflammatory, and neuroprotective effects, as well as its ability to restore GABA neurotransmission and improve motor and cognitive behavior. We propose new areas of research that might contribute to a better understanding of the mechanism of action of this flavonoid, which could help develop a new therapy for aging and age-related brain diseases.
Analysis of a Biathlon Sprint Competition and Associated Laboratory Determinants of Performance

Biathlon is an Olympic winter-sport where cross-country (XC) skiing in the skating technique is combined with rifle shooting. In the biathlon sprint competition for men, three laps of 3.3-km are interspersed with a 5-shot shooting sequence in the prone and standing position. Our purpose was to investigate the contribution from overall XC skiing performance, the performance in different terrain sections and shooting performance to the overall biathlon sprint race performance, as well as the relationship to laboratory-measured capacities obtained during treadmill roller ski skating. Eleven elite male biathletes were tracked by a Global Positioning System (GPS) device and a heart rate (HR) monitor during an international 10-km biathlon sprint competition. Within a period of 6 weeks prior to the competition, physiological responses, and performance during submaximal and maximal treadmill roller skiing were measured. Stepwise multiple regression analysis revealed that XC skiing time, shooting performance, shooting time and range time explained 84, 14, 1.8, and 0.2% of the overall sprint race performance (all p < 0.01). Time in uphill, varied, and downhill terrains were all significantly correlated to the total XC skiing time (r = 0.95, 0.82, 0.72, respectively, all p < 0.05). Percent of maximal HR (HRmax) and rating of perceived exertion (RPE) during submaximal roller skiing, and time-to-exhaustion during incremental roller skiing correlated significantly with overall biathlon sprint race performance and overall XC skiing time (r = 0.64–0.95, all p < 0.05). In conclusion, XC skiing performance provided greatest impact on biathlon sprint performance, with most of the variance determined by XC skiing performance in the uphill terrain sections. Furthermore, the ability to roller ski with a low RPE and %HRmax during submaximal speeds, as well as time-to-exhaustion during incremental roller skiing significantly predicted biathlon performance. Such laboratory-derived measures may therefore be validly used to distinguish biathletes of different performance levels and to track progress of their XC skiing capacity.
Occurrence of Aflatoxin M1 in Raw Milk Marketed in Italy: Exposure Assessment and Risk Characterization

The current study is based on the AFM1 contamination of milk determined from April 2013 to December 2018 in the framework of a self-control plan of six milk processing plants in Italy. These data – together with the consumption data of milk consumers – were evaluated and used for the calculation of the Estimated Daily Intake (EDI), the Hazard Index (HI), and the fraction of hepatocarcinoma cases (HCC) due to AFM1 exposure in different population groups. Altogether a total of 31,702 milk samples were analyzed, representing 556,413 tons of milk, which is an outstanding amount compared to published studies. The results indicate the monthly fluctuation of AFM1 levels through a period of nearly 6 years. The EDI of AFM1 in different population groups was in the range of 0.025–0.328 ng kg−1 body weight (bw) per day, based on the average consumption levels and weighted mean contamination of the milk in the study period. Considering average consumptions, in the groups of infants and toddlers, the HI calculation resulted in 1.64 and 1.4, respectively, while for older age groups, it was <1. The estimated fractions of HCC incidences attributable to the AFM1 intakes were 0.005 and 0.004 cases per 100,000 individuals in the 0–0.9 and 1–2.9-year age groups, respectively, and below 0.004 cases in the other age categories. The monthly average AFM1 contamination of tested milk consignments ranged between 7.19 and 22.53 ng kg−1. Although the results of this extensive investigation showed a low risk of HCC, the variability of climatic conditions throughout years that influence AFB1 contamination of feed and consequently AFM1 contamination of milk justifies their continuous monitoring and update of the risk assessment.
Inappropriate Antidiuretic Hormone Secretion and Cerebral Salt-Wasting Syndromes in Neurological Patients

The differential diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt-wasting syndrome (CSWS) in patients with neurological disorders has been a perplexing clinical controversy. The purpose of this review is to summarize the characteristics and risk factors of patients with different types of neurological disorders complicated by hyponatremia (HN) and review various methods to distinguish SIADH from CSWS. Common neurological disorders with high rates of HN include subarachnoid hemorrhage (SAH), traumatic brain injuries, stroke, cerebral tumors, central nervous system (CNS) infections, and Guillain-Barré syndrome (GBS), which have their own characteristics. Extracellular volume (ECV) status of patients is a key point to differentiate SIADH and CSWS, and a comprehensive assessment of relevant ECV indicators may be useful in differentiating these two syndromes. Besides, instead of monitoring the urinary sodium excretion, more attention should be paid to the total mass balance, including Na+, K+, Cl−, and extracellular fluid. Furthermore, the dynamic detection of fractional excretions (FE) of urate before and after correction of HN and a short-term infusion of isotonic saline solution may be useful in identifying the etiology of HN. As for brain natriuretic peptide (BNP) or N-terminal prohormone of BNP (NT-proBNP), more prospective studies and strong evidence are needed to determine whether there is a pertinent and clear difference between SIADH and CSWS.
Automatic Processing Advantage of Cartoon Face in Internet Gaming Disorder: Evidence From P100, N170, P200, and MMN

Individuals with Internet gaming disorder (IGD) show deficits in face processing due to long-term Internet-game social activities based on cartoon faces in the popular online game "Strike of Kings. " However, the abnormal neurocognitive mechanism of face recognition and processing in individuals with IGD has not been systematically explored. This study used event-related potential (ERP) methods and the reversed deviant-standard oddball paradigm to comprehensively compare four ERP components, namely, P100, N170, P200, and mismatch negativity (MMN), induced in the unconscious and automatic processing of realistic and cartoon faces in individuals with IGD. Results showed that, with respect to cartoon faces, individuals with IGD exhibited not only P100, P200 and MMN enhancements but also the absence of the N170 dominance effect in the left hemisphere. Our results also demonstrated that individuals with IGD had the advantages of early automatic perception of cartoon faces and automatic detection of changes in "cartoon" features. This study enhances our understanding of the mechanism of IGD from the neurocognitive perspective and provides candidate electrophysiological indicators for the clinical diagnosis of IGD.
Multilingual Validation of the First French Version of Munich Dysphagia Test—Parkinson's Disease (MDT-PD) in the Luxembourg Parkinson's Study

Introduction: The Munich Dysphagia Test for Parkinson's disease (MDT-PD) was initially developed and validated in the German population as a highly sensitive and specific self-reported screening questionnaire to detect early oropharyngeal symptoms and aspiration risk in patients with idiopathic Parkinson's disease (iPD). In order to make this tool accessible for prevention in the French speaking populations worldwide, we performed the first French translation and provide a linguistic and psychometric validation in the unique multilingual environment of the Luxembourg Parkinson's Study. Methods: We performed the translation of the MDT-PD into French according to WHO guidelines and subsequently performed the linguistic validation including native speakers. For psychometric validation, 46 patients with parkinsonism from Luxembourg and the Greater Region without severe cognitive impairment were recruited in the frame of the Luxembourg Parkinson's Study. All patients were fluent in French and German completed the MDT-PD in both languages (three times in total). Results: Linguistic and psychometric validation of the French MDT-PD was reflected by a high test-retest (10/26 questions with K > 0.6 and 10/26 with 0.4 < K ≤ 0.6) and language reliability (12/26 K > 0.6 and 8/26 0.4 < K ≤ 0.6), with an internal consistency for the French (Cronbach's alpha 0.84) and German version (0.87); strong item collinerarity strengthens the internal consistency. No significant differences between MDT-PD score distribution and clinical parameters assessing, for example, disease progression, motor state, or cognition has been observed. Conclusion: Based on a multilingual approach in the Luxembourg Parkinson Study, we validated the translation of the first French MDT-PD as a non-invasive tool for early detection of dysphagia in patients with parkinsonism. The unexpectedly high number of positively screened patients at earlier disease stages indicate options for new prevention strategies in large French speaking populations worldwide. Diagnostic validation using clinical and endoscopic swallowing evaluation will be continued soon.
The Clock Counts – Length Effects in English Dyslexic Readers

In reading, length effects (LEs) are defined as an increment in the time taken to read as a function of word length and may indicate whether reading is proceeding in an efficient whole word fashion or by serial letter processing. LEs are generally considered to be a pathognomonic symptom of developmental dyslexia (DD) and predominantly have been investigated in transparent orthographies where reading impairment is characterized as slow and effortful. In the present study a sample of 18 adult participants with DD were compared to a matched sample of typical developing readers to investigate whether the LE is a critical aspect of DD in an opaque orthography, English. We expected that the DD group would present with marked LEs, in both words and non-words, compared to typical developing readers. The presence of LEs in the DD group confirmed our prediction. These effects were particularly strong in low frequency words and in non-words, as observed in reading speed. These preliminary findings may have important theoretical implications for current understanding of DD.
In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber

Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers in vitro and in vivo. CuC inhibited proliferation and clonogenic potential of multiple cancer cells in a dose-dependent manner. Low-dose CuC treatment induced cell cycle arrest at G1 or G2/M stage in different cancer lines, whereas high-dose treatment of CuC caused apoptosis in cancer cells. PI3K-Akt signaling pathway was found to be one of the major pathways involved in CuC-induced cell growth arrest and apoptosis by RNA-Seq and Western blotting. Mechanistic dissection further confirmed that CuC effectively inhibited the Akt signaling by inhibition of Akt phosphorylation at Ser473. In vivo CuC treatment (0.1 mg/kg body weight) effectively inhibited growth of cancer cell-derived xenograft tumors in athymic nude mice and caused significant apoptosis. Our findings for the first time demonstrated the potential therapeutic significance of CuC against human cancers.
Lipocalin 2 Protects Against Escherichia coli Infection by Modulating Neutrophil and Macrophage Function

Lipocalin 2 (Lcn2) is an essential component of the antimicrobial innate immune system. It attenuates bacterial growth by binding and sequestering the iron-scavenging siderophores to prevent bacterial iron acquisition. Whereas, the ability of Lcn2 to sequester iron is well-described, the role of Lcn2 in regulating immune cells during bacterial infection remains unclear. In this study, we showed that upon infection with Escherichia coli (O157:H7), Lcn2-deficient (Lcn2−/−) mice carried more bacteria in blood and liver, and the acute-phase sera lost their antibacterial activity in vitro. Neutrophils from Lcn2−/− mice were defective in homeostasis and morphological development. E. coli O157:H7 infection of Lcn2−/− mice resulted in a reduced neutrophil migration capacity, with 30% reduction of extravasated neutrophils, and impaired chemotaxis, as shown by a reduction in the secretion of chemoattractants, such as tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-2, which are instrumental in eliciting a neutrophil response. We also found that some secreted cytokines [interleukin (IL)-6, IL-1β, and TNF-α] were decreased. Transcripts of inflammatory cytokines (IL-6, IL-1β, TNF-α, and IL-10), chemokines (MIP-2 and MCP-1), and iNOS production were all strongly repressed in Lcn2−/− macrophages. Furthermore, Lcn2 could induce the production of chemokines and promote the migration and phagocytosis of macrophages. Thus, Lcn2 deficiency could impair the migration and chemotaxis ability of neutrophils and disturb the normal secretion of inflammatory cytokines of macrophages. Therefore, the heightened sensitivity of Lcn2−/− mice to E. coli O157:H7 is not only due to the antibacterial function of Lcn2 but also a consequence of impaired functions of immune cells, including neutrophils and macrophages.
Highly Efficient Adsorption of Phenylethanoid Glycosides on Mesoporous Carbon

PhGs are the major active compounds of Cistanche tubulosa, and it is extremely desirable for obtaining high purification of PhGs by adsorption from their extracts. To explore highly efficient adsorption of PhGs, a novel adsorption material for the efficient separation and purification of phenylethanoid glycosides (PhGs) from Cistanche tubulosa was explored. The three mesoporous carbons of ordered mesoporous carbon (CMK-3), disordered mesoporous carbon (DMC), and three-dimensional cubic mesoporous carbon (CMK-8) were compared for adsorption of PhGs. Meanwhile, adsorption isotherms, adsorption kinetics, and the optimization of adsorption conditions were investigated. The results indicated that CMK-3 showed the highest adsorption capacity of 358.09 ± 4.13 mg/g due to its high specific surface area, large pore volume and oxygen-containing functional groups. The experimental data can be accurately described using the Langmuir model and pseudo-second-order model. The intra-particle diffusion model suggested that the rate-limiting steps of adsorption were intra-particle diffusion.
Metabolic Cost of Dendritic Ca2+ Action Potentials in Layer 5 Pyramidal Neurons

Pyramidal neurons consume most signaling-related energy to generate action potentials (APs) and perform synaptic integration. Dendritic Ca2+ spike is an important integration mechanism for coupling inputs from different cortical layers. Our objective was to quantify the metabolic energy associated with the generation of Ca2+ APs in the dendrites. We used morphology-based computational models to simulate the dendritic Ca2+ spikes in layer 5 pyramidal neurons. We calculated the energy cost by converting Ca2+ influx into the number of ATP required to restore and maintain the homeostasis of intracellular Ca2+ concentrations. We quantified the effects of synaptic inputs, dendritic voltage, back-propagating Na+ spikes, and Ca2+ inactivation on Ca2+ spike cost. We showed that much more ATP molecules were required for reversing Ca2+ influx in the dendrites than for Na+ ion pumping in the soma during a Ca2+ AP. Increasing synaptic input increased the rate of dendritic depolarization and underlying Ca2+ influx, resulting in higher ATP consumption. Depolarizing dendritic voltage resulted in the inactivation of Ca2+ channels and reduced the ATP cost, while dendritic hyperpolarization increased the spike cost by de-inactivating Ca2+ channels. A back-propagating Na+ AP initiated in the soma increased Ca2+ spike cost in the apical dendrite when it coincided with a synaptic input within a time window of several milliseconds. Increasing Ca2+ inactivation rate reduced Ca2+ spike cost, while slowing Ca2+ inactivation increased the spike cost. The results revealed that the energy demand of a Ca2+ AP was dynamically dependent on the state of dendritic activity. These findings were important for predicting the energy budget for signaling in pyramidal cells, interpreting functional imaging data, and designing energy-efficient neuromorphic devices.
Eosinophil Polymorphonuclear Leukocytes in TB: What We Know so Far

Knowledge on the cellular immune responses to infection with Mycobacterium tuberculosis has improved drastically in recent years. Though eosinophils and hypereosinophilia are linked with the disease process of tuberculosis, there is paucity of information to prove the actual role played by these polymorphonuclear leukocytes. The aim of this review is to provide an overview of the existing literature on what is known so far about eosinophils and tuberculosis.
Development of a Post-stroke Upper Limb Rehabilitation Wearable Sensor for Use in Sub-Saharan Africa: A Pilot Validation Study

The development of context-appropriate sensor technologies could alleviate the significant burden of stroke in Sub-Saharan African rehabilitation clinicians and health care facilities. However, many commercially available wearable sensors are beyond the financial capabilities of the majority of African persons. In this study, we evaluated the concurrent validity of a low-cost wearable sensor (i.e., the outREACH sensor) to measure upper limb movement kinematics of 31 healthy persons, using an 8-camera Vicon motion capture system as the reference standard. The outREACH sensor showed high correlation (r range: 0.808–0.990) and agreement (mean difference range: −1.60 to 1.10) with the reference system regardless of task or kinematic parameter. Moreover, Bland-Altman analyses indicated that there were no significant systematic errors present. This study indicates that upper limb movement kinematics can be accurately measured using the outREACH sensor, and have the potential to enhance stroke evaluation and rehabilitation in sub-Saharan Africa.