Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator on BDNF, NKCC1 and KCC2 Expression in the Hippocampus following Lipopolysaccharide-induced Allodynia and Hyperalgesia in a Mouse Model of Inflammatory Pain.

BACKGROUND & OBJECTIVE Hyperalgesia and allodynia are frequent symptoms of inflammatory pain. Neuronal excitability induced by brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) cascade has a role in the modulation of inflammatory pain. The effects of 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline8-sulfonamide (TQS), an α7 nicotinic acetylcholine receptor positive allosteric modulator (nAChR PAM), on hippocampal BDNF, cation-chloride cotransporters, NKCC1 and KCC2, expression in inflammatory pain are not known. The objective of the study was to determine the effects of TQS on BDNF, NKCC1, and KCC2 expression in the hippocampus following lipopolysaccharide (LPS)-induced allodynia and hyperalgesia in a mouse model of inflammatory pain. METHODS Mice were treated with TQS followed by LPS (1 mg/kg, ip) administration. The effects of TQS on mRNA and BDNF in the hippocampus were examined using qRT-PCR and Western blot, respectively. Immunoreactivity of BDNF, NKCC1, and KCC2 in the hippocampus was measured after LPS administration using immunofluorescence assay. Allodynia and hyperalgesia were determined using von Frey filaments and hot plate, respectively. RESULTS The LPS (1 mg/kg) upregulates mRNA of BDNF and downregulates mRNA of KCC2 in the hippocampus and pretreatment of TQS (4 mg/kg) reversed the effects induced by LPS. In addition, the TQS decreased LPS-induced upregulation of BDNF and p-NKCC1 immunoreactivity in dentate gyrus and CA1 region of the hippocampus. BDNF receptor (TrkB) antagonist, ANA12 (0.50 mg/kg), and NKCC1 inhibitor bumetanide (30 mg/kg) reduced LPS-induced allodynia and hyperalgesia. Blockade of TrkB with ANA12 (0.25 mg/kg) enhanced the effects of TQS (1 mg/kg) against LPS-induced allodynia and hyperalgesia. Similarly, bumetanide (10 mg/kg) enhanced the effects of TQS (1 mg/kg) against allodynia and hyperalgesia. CONCLUSION These results suggest that antinociceptive effects of α7 nAChR PAM are associated with downregulation of hippocampal BDNF and p-NKCC1 and upregulation of KCC2 in a mouse model of inflammatory pain.
Electrochemical Power Generation Directly from Combustion Flame of Gases, Liquids, and Solids

The performance of a solid oxide fuel cell fueled with flames of combustible gases, liquids, and solids was studied. A cell structure in which cells were serially integrated within a disk was also examined. Open-circuit voltages indicated with a single cell and the integrated cell were ∼0.8 and ∼3.5 V, respectively. Maximum power density obtained with the flames of n-butane, kerosine, paraffin wax (candle), and wood were respectively 75, 65, 62, and 5 mW/cm 2 . The integrated cell gave a maximum power density of 318 mW/cm 2 with n-butane flame. Fuel to air ratio distinctly influenced the output.
Synthesis and delivery of Streptococcus pneumoniae capsular polysaccharides by recombinant attenuated Salmonella vaccines

Significance Pneumococcal infection-caused diseases are responsible for substantial morbidity and mortality worldwide. Traditional pneumococcal vaccines are developed based on purified capsular polysaccharides (CPS) or CPS conjugated to a protein carrier. Production processes of the traditional vaccines are laborious, and thereby increase the vaccine cost and limit their use in developing nations. A cost-effective pneumococcal vaccine using the recombinant attenuated Salmonella vaccine (RASV) was developed in this study. We cloned and expressed genes for seven serotypes of CPSs in the RASV strain. The RASV-delivered CPSs induced robust humoral and cell-mediated responses and mediated efficient protection of mice against pneumococcal infection. Our work provides an innovative strategy for mass producing low-cost bioconjugated polysaccharide vaccines for needle-free mucosal delivery against pneumococcal infections. Streptococcus pneumoniae capsular polysaccharides (CPSs) are major determinants of bacterial pathogenicity. CPSs of different serotypes form the main components of the pneumococcal vaccines Pneumovax, Prevnar7, and Prevnar13, which substantially reduced the S. pneumoniae disease burden in developed countries. However, the laborious production processes of traditional polysaccharide-based vaccines have raised the cost of the vaccines and limited their impact in developing countries. The aim of this study is to develop a kind of low-cost live vaccine based on using the recombinant attenuated Salmonella vaccine (RASV) system to protect against pneumococcal infections. We cloned genes for seven different serotypes of CPSs to be expressed by the RASV strain. Oral immunization of mice with the RASV-CPS strains elicited robust Th1 biased adaptive immune responses. All the CPS-specific antisera mediated opsonophagocytic killing of the corresponding serotype of S. pneumoniae in vitro. The RASV-CPS2 and RASV-CPS3 strains provided efficient protection of mice against challenge infections with either S. pneumoniae strain D39 or WU2. Synthesis and delivery of S. pneumoniae CPSs using the RASV strains provide an innovative strategy for low-cost pneumococcal vaccine development, production, and use.
Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations

For more than ten years, new synthetic cathinones (SCs) mimicking the effects of controlled cocaine-like stimulants have flooded the illegal drug market, causing numerous intoxications and fatalities. There are often no data on the pharmacokinetics of these substances when they first emerge onto the market. However, the detection of SC metabolites is often critical in order to prove consumption in clinical and forensic settings. In this research, the metabolite profile of two pyrrolidinyl SCs, α-pyrrolidinohexaphenone (α-PHP) and 4′′-fluoro-α-pyrrolidinovalerophenone (4F-α-PVP), were characterized to identify optimal intake markers. Experiments were conducted using pooled human hepatocyte incubations followed by liquid chromatography–high-resolution tandem mass spectrometry and data-mining software. We suggest α-PHP dihydroxy-pyrrolidinyl, α-PHP hexanol, α-PHP 2′-keto-pyrrolidinyl-hexanol, and α-PHP 2′-keto-pyrrolidinyl as markers of α-PHP use, and 4F-α-PVP dihydroxy-pyrrolidinyl, 4F-α-PVP hexanol, 4F-α-PVP 2′-keto-pyrrolidinyl-hexanol, and 4F-α-PVP 2′-keto-pyrrolidinyl as markers of 4F-α-PVP use. These results represent the first data available on 4F-α-PVP metabolism. The metabolic fate of α-PHP was previously studied using human liver microsomes and urine samples from α-PHP users. We identified an additional major metabolite (α-PHP dihydroxy-pyrrolidinyl) that might be crucial for documenting exposure to α-PHP. Further experiments with suitable analytical standards, which are yet to be synthesized, and authentic specimens should be conducted to confirm these results.
Replicating remembering “remembering”

ABSTRACT When examining spontaneously recovered memories of childhood sexual abuse, victims report that there had been periods in which they had forgotten the abuse. However, there are sometimes people with whom the victim had spoken about the abuse during the period in which the victim had supposedly forgotten the abuse, suggesting the victim had not forgotten the abuse but the prior recall of the abuse. The underestimation of previous knowledge is termed the forgot-it-all-along effect. The goal of the present study was replicating the results of a laboratory study that had provided a theoretical understanding for the forgot-it-all-along effect by showing that people have difficulties remembering “remembering” when the memory had previously been recalled in a different context. The effect was replicated by using the same neutral context sentences, suggesting the finding was robust. We also extended the experimental design by using positive and negative context sentences, but it did not become smaller when the positive sentences provided the different context or larger when the negative sentences provided the different context. Although the sample sizes were sufficiently large to provide statistical power for the forgot-it-all-along effect, they may not have been sufficiently large to observe the moderation effects of emotional context.
Subjective Oral Health-Related Quality of Life and Objective Oral Health in People with Ectodermal Dysplasia

Ectodermal dysplasia (ED) refers to a heterogeneous group of genetic diseases of the skin, skin appendages, and teeth. People with ED experience a poorer oral health-related quality of life (OHRQoL) compared to the general population. The aim of this study was to examine the OHRQoL of people with ED and to measure their objective physical oral health to confirm or disprove evidence of poorer oral health in this population. To determine OHRQoL, the German version of the 14-item Oral Health Impact Profile (OHIP-14G) was used. All the participants in the study were clinically examined, and the measured parameters were recorded using the Physical Oral Health Index (PhOX). In total, 10 male and 11 female participants, with an average age of 22.0 ± 9.0 years, were included in this study. The OHIP-14G summary score was 23.9 (±15.2) points (range: 0–56 points). The PhOX summary score was 61.2 (±5.1) points (range: 22–80 points). The findings indicated that both the OHRQoL and physical oral health of the participants were highly impaired and that their objective and subjective oral health were worse than those of the general population in Germany.
Comparison of Subjective Responses of Low Back Pain Patients and Asymptomatic Controls to Use of Spinal Exoskeleton during Simple Load Lifting Tasks: A Pilot Study

Spinal exoskeletons have been suggested as an approach for the prevention and rehabilitation of occupational low back pain (LBP). While the state-of-the-art exoskeletons were shown to substantially unload the back, user acceptance is still limited. Perceived discomfort and restriction of freedom of movement are commonly reported. In this pilot study, we explored the differences in subjective responses and user impressions to using passive spinal exoskeleton during a set of simple lifting tasks between LBP patients (n = 12) and asymptomatic individuals (n = 10). Visual analog scales (0–10) were used for all assessments. Overall, the results showed mostly similar responses or slightly more positive responses to the exoskeleton from LBP patients. Most notably, the LBP patients reported a statistically significant (p = 0.048) higher willingness to use the device daily (5.36 ± 4.05) compared to the control group (2.00 ± 1.85) and also gave the device a higher overall grade (6.58 ± 1.98 vs. 4.30 ± 2.26; p = 0.021). This study has demonstrated that individuals with current LBP responded more favorably to the use of the spinal exoskeleton for simple lifting tasks. This implies that current exoskeletons could be appropriate for LBP rehabilitation, but not preventions, as pain-free individuals are less willing to use such devices. Future studies should explore whether different exoskeleton designs could be more appropriate for people with no LBP issues.
Evaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control

Abstract Objective There is evidence that reactive oxygen species, especially free radicals, produced during the immune and inflammatory response may play important roles in the development of asthma.We aimed to evaluate the levels of certain oxidative stress biomarkers and antioxidant capacity in asthma patients with different asthma control levels in comparison to healthy subjects. Methods A total of 120 adult allergic asthma patients and 120 healthy individuals were included in this study. Using spectrophotometric methods, we analyzed two oxidative stress markers, levels of malondialdehyde (MDA) and protein carbonyls (PC), as well as reduced glutathione (GSH), total antioxidant capacity (FRAP) and catalase activity as critical antioxidant defense parameters in the blood samples of allergic asthma patients and healthy controls. The patients were divided into 3 subgroups according to asthma control test (ACT) results: totally controlled (TCG), partially controlled (PCG) and uncontrolled (UCG) subgroups. All biomarkers were compared between the three patient subgroups, as well as between total asthma patients and control subjects. Results There were remarkable differences between the control group and the combined patient group for all parameters. A significant increase in MDA and PC, especially in the UCG (p < 0.01 and p < 0.05, respectively) was detected in comparison to other subgroups. Additionally, increased MDA and PC levels, as well as decreased GSH levels were observed in all subgroups individually in comparison to the control (p < 0.001). Conclusions This research demonstrates the presence of severe oxidative stress, considering the increase in lipid peroxidation and protein oxidation, in patients with allergic asthma, even under controlled conditions.
Absorption of NO2/N2O4 in nitric acid

Laboratory-scale measurements were performed on the absorption of NO2 gas into diluted nitric acid. The concentration of NO2 gas, which represents an NO2/N2O4 equilibrium, varied from 1000 to 20000 ppm, the carrier gas being nitrogen. The concentration of nitric acid ranged from 15 to 60 mass-%. The absorption experiments were carried out in a double stirred cell, with a defined gas/liquid interface as the mass transfer area. The liquid phase was conducted periodically and the gas phase continuously. Mass flow rates were determined. The well-known film model of absorption was used for analyzing the experimental results. Only the N2O4 species was considered to pass the gas/liquid interface. The measured data yielded values of H(k D1)1/2 as well as their variation with temperature and nitric acid concentration.
Short-Term Exposure to Fine Particulate Matter and Hospitalizations for Acute Lower Respiratory Infection in Korean Children: A Time-Series Study in Seven Metropolitan Cities

Although several studies have evaluated the association between fine particulate matter (PM2.5) and acute lower respiratory infection (ALRI) in children, their results were inconsistent Therefore, we aimed to evaluate the association between short-term exposure to PM2.5 and ALRI hospitalizations in children (0–5 years) living in seven metropolitan cities of Korea. The ALRI hospitalization data of children living in seven metropolitan cities of Korea from 2008 to 2016 was acquired from a customized database constructed based on National Health Insurance data. The time-series data in a generalized additive model were used to evaluate the relationship between ALRI hospitalization and 7-day moving average PM2.5 exposure after adjusting for apparent temperature, day of the week, and time trends. We performed a meta-analysis using a two-stage design method. The estimates for each city were pooled to generate an average estimate of the associations. The average PM2.5 concentration in 7 metropolitan cities was 29.0 μg/m3 and a total of 713,588 ALRI hospitalizations were observed during the 9-year study period. A strong linear association was observed between PM2.5 and ALRI hospitalization. A 10 μg/m3 increase in the 7-day moving average of PM2.5 was associated with a 1.20% (95% CI: 0.71, 1.71) increase in ALRI hospitalization. While we found similar estimates in a stratified analysis by sex, we observed stronger estimates of the association in the warm season (1.71%, 95% CI: 0.94, 2.48) compared to the cold season (0.31%, 95% CI: −0.51, 1.13). In the two-pollutant models, the PM2.5 effect adjusted by SO2 was attenuated more than in the single pollutant model. Our results suggest a positive association between PM2.5 exposure and ALRI hospitalizations in Korean children, particularly in the warm season. The children need to refrain from going out on days when PM2.5 is high.
Daily Coffee Drinking Is Associated with Lower Risks of Cardiovascular and Total Mortality in a General Italian Population: Results from the Moli-sani Study.

BACKGROUND An inverse relationship between coffee intake and mortality has been observed in several population cohorts, but rarely within Mediterranean countries. Moreover, the biological pathways mediating such an association remain unclear. OBJECTIVES We assessed the associations between coffee consumption and total and cause-specific mortality and examined the mediating roles of N-terminal pro B-type natriuretic peptide (NTproBNP), high-sensitivity Troponin I, blood glucose, lipid metabolism, and selected biomarkers of inflammation and renal function. METHODS We longitudinally analyzed data on 20,487 men and women (35-94 years old at baseline) in the Moli-sani Study, a prospective cohort established in 2005-2010. Individuals were free from cardiovascular disease (CVD) and cancer and were followed-up for a median of 8.3 years. Dietary data were collected by a 188-item semi-quantitative FFQ. Coffee intake was standardized to a 30-mL Italian espresso cup size. HRs with 95% CIs were calculated by multivariable Cox regression. RESULTS In comparison with no/rare coffee consumption (up to 1 cup/d), HRs for all-cause mortality across categories of coffee consumption (>1 to ≤2, >2 to ≤3, >3 to ≤4 and >4 cups/d) were 0.79 (95% CI, 0.65-0.95), 0.84 (95% CI, 0.69-1.03), 0.72 (95% CI, 0.57-0.92), and 0.85 (95% CI, 0.62-1.12), respectively. For CVD mortality, a nonlinear (P for non-linearity = 0.021) J-shaped association was found (magnitude of the relative reduction = 37%; nadir at 3-4 cups/d). Circulating levels of NTproBNP explained up to 26.4% of the association between coffee and all-cause mortality, while systolic blood pressure was likely to be on the pathway between coffee and CVD mortality, although to a lesser extent. CONCLUSIONS In this large cohort of Italian adults, moderate consumption (3-4 cups/d) of Italian-style coffee was associated with lower risks of all-cause and, specifically, of CVD mortality. Among the known biomarkers investigated here, NTproBNP likely mediates the relationship between coffee intake and all-cause mortality.
Appraisal of sedimentary alkenones for the quantitative reconstruction of phytoplankton biomass

Significance Biomarker proxies, namely alkenones, are commonly used to reconstruct past primary productivity. However, their value has been questioned as they are posited to be controlled by diagenetic processes and often limited to draw qualitative inferences on the carbon cycle. In fact, most proxies have not been globally appraised with ocean biogeochemical data. Here, we use a combination of remote sensing and geochemical data to provide a spatial-based global scale calibration that shows the use of alkenones to quantify past sea surface chlorophyll-a concentration, which ultimately can be used to infer quantitatively past primary productivity in paleorecords. This calibration paves the way to clarify the relative role of the marine carbon cycle in climate variability using field data, and tests biogeochemical models. Marine primary productivity (PP) is the driving factor in the global marine carbon cycle. Its reconstruction in past climates relies on biogeochemical proxies that are not considered to provide an unequivocal signal. These are often based on the water column flux of biogenic components to sediments (organic carbon, biogenic opal, biomarkers), although other factors than productivity are posited to control the sedimentary contents of the components, and their flux is related to the fraction of export production buried in sediments. Moreover, most flux proxies have not been globally appraised. Here, we assess a proxy to quantify past phytoplankton biomass by correlating the concentration of C37 alkenones in a global suite of core-top sediments with sea surface chlorophyll-a (SSchla) estimates over the last 20 y. SSchla is the central metric to calculate phytoplankton biomass and is directly related to PP. We show that the global spatial distribution of sedimentary alkenones is primarily correlated to SSchla rather than diagenetic factors such as the oxygen concentration in bottom waters, which challenges previous assumptions on the role of preservation on driving concentrations of sedimentary organic compounds. Moreover, our results suggest that the rate of global carbon export to sediments is not regionally constrained, and that alkenones producers play a dominant role in the global export of carbon buried in the seafloor. This study shows the potential of using sedimentary alkenones to estimate past phytoplankton biomass, which in turn can be used to infer past PP in the global ocean.
Cholinergic Basal Forebrain Volumes Predict Gait Decline in Parkinson's Disease

Gait disturbance is an early, disabling feature of Parkinson's disease (PD) that is typically refractory to dopaminergic medication. The cortical cholinergic system, originating in the nucleus basalis of Meynert of the basal forebrain, has been implicated. However, it is not known if degeneration in this region relates to a worsening of disease‐specific gait impairment.
An asymmetry in past and future mental time travel following vmPFC damage

Abstract The role of ventromedial prefrontal cortex (vmPFC) in mental time travel toward the past and the future is debated. Here, patients with focal lesions to the vmPFC and brain-damaged and healthy controls mentally projected themselves to a past, present or future moment of subjective time (self-projection) and classified a series of events as past or future relative to the adopted temporal self-location (self-reference). We found that vmPFC patients were selectively impaired in projecting themselves to the future and in recognizing relative-future events. These findings indicate that vmPFC damage hinders the mental processing of and movement toward future events, pointing to a prominent, multifaceted role of vmPFC in future-oriented mental time travel.
6,8‐Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53

6,8‐Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8‐diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8‐diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8‐Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose‐ and time‐dependent manner. A 40 μM of 6,8‐diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8‐diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8‐diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen‐activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8‐diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N‐acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8‐diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8‐diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8‐diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS.