Miracle-dz/UniFAR-FTUs huggingface dataset:
High temperature promotes amyloid β-protein production and γ-secretase complex formation via Hsp90.

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of β-amyloid-protein (Aβ) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25-40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aβ production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aβ production. Here, we report temperature-dependent regulation of Aβ production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aβ production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aβ production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aβ production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.
Spectroscopy of cyanine dyes in fluid solution at atmospheric and high pressure: the effect of viscosity on nonradiative processes

The spectroscopy of cyanine dyes was examined at atmospheric pressure and at high pressure in a series of alcohols and other solvents. Variation of external pressure provides the means to control viscosity over a wide range in one solvent at constant temperature. The findings reveal that the nonradiative relaxation of cyanines in fluid solution can occur when the motion leading to the formation of the cis isomer is stopped completely. Analysis of the viscosity dependence of the nonradiative relaxation rate constant reveals consistent deviation from the Kramers-DSE relation. 33 refs., 5 figs., 2 tabs.
Physiological effects of inactivation and the roles of Elovl3/ELOVL3 in maintaining ocular homeostasis

Recently, elongase of very long chain fatty acids‐3 (ELOVL3) was demonstrated to play a pivotal role in physiology and biochemistry of the ocular surface by maintaining a proper balance in the lipid composition of meibum. The goal of this study was to further investigate the effects of ELOVL3 ablation in homozygous Elovl3‐knockout mice (E3hom) in comparison with age and sex matched wild‐type controls (E3wt). Slit lamp examination of the ocular surface of mice, and histological examination of their ocular tissues, highlighted a severe negative impact of Elovl3 inactivating mutation on the Meibomian glands (MG) and conjunctiva of mice. MG transcriptomes of the E3hom and E3wt mice were assessed and revealed a range of up‐ and downregulated genes related to lipid biosynthesis, inflammation, and stress response, compared with E3wt mice. Heat stage polarized light microscopy was used to assess melting characteristics of normal and abnormal meibum. The loss of Elovl3 led to a 8°C drop in the melting temperature of meibum in E3hom mice, and increased its fluidity. Also noted were the excessive accumulation of lipid material and tears around the eye and severe ocular inflammation, among other abnormalities.
The Influence of Non-Linear Frequency Compression on the Perception of Speech and Music in Patients with High Frequency Hearing Loss

Background and Objectives Non-linear frequency compression (NLFC) technology compresses and shifts higher frequencies into a lower frequency area that has better residual hearing. Because consonants are uttered in the high-frequency area, NLFC could provide better speech understanding. The aim of this study was to investigate the clinical effectiveness of NLFC technology on the perception of speech and music in patients with high-frequency hearing loss. Subjects and Methods Twelve participants with high-frequency hearing loss were tested in a counter-balanced order, and had two weeks of daily experience with NLFC set on/off prior to testing. Performance was repeatedly evaluated with consonant tests in quiet and noise environments, speech perception in noise, music perception and acceptableness of sound quality rating tasks. Additionally, two questionnaires (the Abbreviated Profile of Hearing Aid Benefit and the Korean version of the International Outcome Inventory-Hearing Aids) were administered. Results Consonant and speech perception improved with hearing aids (NLFC on/off conditions), but there was no significant difference between NLFC on and off states. Music perception performances revealed no notable difference among unaided and NLFC on and off states. The benefits and satisfaction ratings between NLFC on and off conditions were also not significantly different, based on questionnaires, however great individual variability preferences were noted. Conclusions Speech perception as well as music perception both in quiet and noise environments was similar between NLFC on and off states, indicating that real world benefits from NLFC technology may be limited in Korean adult hearing aid users.
Spectroscopic studies on the interaction of aspartame with human serum albumin

Abstract In this work the binding of artificial sweetener aspartame with human serum albumin (HSA) was studied at physiological pH. Binding studies of aspartame (APM) with HSA are useful to understand APM -HSA interaction, mechanism and providing guidance for the application and design of new and more efficient artificial sweeteners. The interaction was investigated by spectrophotometric, spectrofluorometric competition experiment and circular dichroism (CD) techniques. The results indicated that the binding of APM to HSA caused fluorescence quenching of HSA through static quenching mechanism with binding constant 1.42 × 10+4 M−1 at 298 K and the number of binding sites is approximately one. Thermodynamic parameters, enthalpy changes (ΔH) and entropy changes (ΔS) were calculated to be −41.20 kJ mol−1 and −58.19 J mol−1 K−1, respectively, according to van’t Hoff equation, which indicated that reaction is enthalpically driven. Quenching of the fluorescence of HSA was found to be a static quenching process. The binding constants and number of binding sites were obtained at three different temperatures (298, 308 and 318 K). Combining above results and those of spectrofluorometric competition experiment and circular dichroism (CD), indicated that APM binds to HSA via Sudlow’s site I. Furthermore, the study of molecular docking on HSA binding also indicated that APM can strongly bind to the site I (subdomain IIA) of HSA mainly by hydrophobic interaction and hydrogen bond interactions exist between APM and HSA.
Oxidation of NO to NO2 Using the Ozonization Method for the Improvement of Selective Catalytic Reduction

Removal of nitrogen oxides (NOx) using an ozonization and catalysis hybrid process was investigated. The role of the ozonization in the hybrid process is to increase NO2 content by oxidizing a part of NO, thereby leading to improving the performance of the catalytic reduction. It was found that the rate of the oxidation of NO to NO2 in the ozonization chamber was very fast in a temperature range of 443 to 473 K, almost completed in a few tens of milliseconds. The decomposition of ozone into molecular oxygen was not significant, and one mole of ozone approximately reacted with one mole of NO. In addition, a kinetic study revealed that the ozonization method produces a negligible amount of byproducts such as NO3 and N2O5. The effect of the content of NO2 in NOx on the catalytic reduction efficiency was examined by adjusting the degree of NO oxidation in the ozonization chamber. The selective reduction of NOx to N2 by a monolithic catalyst (V2O5-WO3/TiO2) was largely enhanced when the content of NO2 was equal to that of NO, indicating that the mixture of NO and NO2 reacts faster than NO.
Bacterial iron detoxification at the molecular level

Iron is an essential micronutrient, and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable “free” iron be tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exist, but overaccumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species. To avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage, and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review, we seek to highlight the similarities of iron homeostasis between different bacteria, while acknowledging important variations. In this way, we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron.
Voice and Emphasis in Arabic Coronal Stops: Evidence for Phonological Compensation

The current study investigates multiple acoustic cues–voice onset time (VOT), spectral center of gravity (SCG) of burst, pitch (F0), and frequencies of the first (F1) and second (F2) formants at vowel onset—associated with phonological contrasts of voicing and emphasis in production of Arabic coronal stops. The analysis of the acoustic data collected from eight native speakers of the Qatari dialect showed that the three stops form three distinct modes on the VOT scale: [d] is (pre)voiced, voiceless [t] is aspirated, and emphatic [ṭ] is voiceless unaspirated. The contrast is also maintained in spectral cues. Each cue influences production of coronal stops while their relevance to phonological contrasts varies. VOT was most relevant for voicing, but F2 was mostly associated with emphasis. The perception experiment revealed that listeners were able to categorize ambiguous tokens correctly and compensate for phonological contrasts. The listeners’ results were used to evaluate three categorization models to predict the intended category of a coronal stop: a model with unweighted and unadjusted cues, a model with weighted cues compensating for phonetic context, and a model with weighted cues compensating for the voicing and emphasis contrasts. The findings suggest that the model with phonological compensation performed most similar to human listeners both in terms of accuracy rate and error pattern.
Cancer-Associated Venous Thromboembolism Treatment With Anti-Xa Versus Weight-Based Enoxaparin: A Retrospective Evaluation of Safety and Efficacy

Background Venous thromboembolism (VTE) is a complication of cancer, for which low-molecular-weight heparin (LMWH) remains the preferred anticoagulant. Enoxaparin is traditionally dosed using weight. In certain populations, monitoring anti-Xa levels for therapeutic effect provides pharmacokinetic guidance for dose adjustments. There is a paucity of data regarding anti-Xa–directed enoxaparin dosing for treatment of VTE in patients with cancer. Objective This study aims to evaluate efficacy (recurrent VTE) and safety (major bleed) between enoxaparin anti-Xa–guided dose adjustments and weight-based dosing in patients with cancer-associated VTE. Methods This single-center, retrospective cohort study examined patients treated with enoxaparin for cancer-associated VTE using data from electronic health records. Results There were 674 patients who met the inclusion criteria, with 283 receiving anti-Xa–directed dose adjustments. Recurrent VTE, major bleed, or all-cause death occurred in 102 of 283 patients (36%) in the anti-Xa cohort and 166 of 391 patients (42.5%) in the weight-based cohort (hazard ratio [HR] = 0.73; 95% CI = 0.57-0.93; P = 0.01). When death was removed from the composite end point, there was no significant difference between the cohorts in recurrent VTE or major bleed (HR = 1.18; P = 0.38). In the anti-Xa cohort, a total of 1584 anti-Xa peak levels were collected, with 1324 (83.6%) drawn correctly in relation to enoxaparin administration. Of those, 714 (53.9%) were within therapeutic range. Conclusion and Relevance Patients with cancer receiving anti-Xa–guided enoxaparin dose adjustments for initial VTE, compared with weight-based dosing, had no significant difference in the rate of recurrent VTE or major bleed.
Lasererwärmung zur Verbesserung des Umformergebnisses beim Kragenziehen von Aluminium‐ und Magnesiumknetlegierungen

Die Halbwarmblechumformung hat sich bei der Herstellung von geometrisch komplexen Bauteilen aus Magnesium‐ und Aluminiumknetlegierungen als nützlich erwiesen. In vielen Fällen, z. B. beim Tiefziehen, ist eine großfläche Erwärmung sinnvoll. Sollen aber, wie beim Kragenziehen, nur kleine Bereiche eines größeren Bauteils ausgeformt werden, ist eine lokale Erwärmung mittels Laserstrahlung vorteilhafter. Auf diese Weise lässt sich die Wärmemenge zeitlich und örtlich gut dosiert einbringen. In Versuchen konnte das Aufweitverhältnis gegenüber dem kalten Zustand bei einer lokalen Bauteiltemperatur von rd. 200 °C je nach Werkstoff um mehr als das doppelte gesteigert werden. Es zeigte sich, dass hierbei ein relativ enges Prozessfenster einzuhalten ist, da Werkstoffversagen nicht nur bei zu geringer, sondern auch bei zu hoher Umformtemperatur auftritt.
CXCL5/CXCL8 is a promising potential prognostic and tumor microenvironment-related cluster in hepatocellular carcinoma.

Background Immune checkpoint blockers (ICBs) are increasingly applied to treat patients with advanced HCC. However, the overall survival (OS) of HCC patients is still unsatisfactory, and there is no confirmed immune-related and prognostic gene to identify patients who could clinically benefit from this treatment. The tumor microenvironment (TME) is known to be closely related to immunotherapy and plays a pivotal role in the recurrence and progression of HCC. Our aim is to explore TME-related genes and identify the prognostic value in HCC patients. Methods ESTIMATE, immune, and stromal scores were calculated for HCC patients based on RNA expression data from The Cancer Genome Atlas database. Differential expression analysis was performed to screen the differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed to identify the key DEGs. Univariate and multivariate Cox analyses were adopted to validate hub DEGs associated with clinical prognosis, and a single-sample gene set enrichment analysis (ssGSEA) algorithm was used to dissect the landscape of tumor-infiltrating cells (TIC) in HCC. Finally, the relationship between hub immune-related genes and TIC was explored through difference and correlation analyses. Results ESTIMATE, immune and stromal scores were all found to be associated with the OS of patients (P<0.05). A total of 1,112 DEGs were identified by comparing low and high score groups of immune and stromal scores. Most of DEGs were enriched in immune-related gene sets by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, the top 34 genes were included in the protein-protein interaction (PPI) network, and univariate Cox analysis focus on a novel prognosis-related gene cluster CXCL5/CXCL8 (P<0.001). Regarding the immune landscape of HCC, univariable Cox regression analysis showed six immune cells to be associated with OS. Finally, 21 immune cells were commonly determined between high and low expression of CXCL5/CXCL8, suggesting there is a close relationship between expression of CXCL5 and CXCL8 . Conclusions Our study has revealed that the immune-related gene cluster of CXCL5 /CXCL8 could be a promising prognostic indicator for HCC and a potential novel biomarker to guide the selection of HCC patients for ICB immunotherapy.
A Retrospective Study on the Benefits of Combined Citicoline, Memantine, and Acetylcholinesterase Inhibitor Treatments in Older Patients Affected with Alzheimer's Disease.

BACKGROUND Background: Citicoline has been proven to have beneficial effects in patients with cognitive impairment. In previous studies, combined treatment with memantine and acetylcholinesterase inhibitors (AChEIs) maintained cognitive function in patients with Alzheimer's disease (AD) better than memantine or AChEIs alone. OBJECTIVE To evaluate the effectiveness and safety of a combination therapy of oral citicoline, memantine, and an AChEI in AD when compared with memantine and an AChEI without citicoline. METHODS This was a retrospective multi-centric case-control study, conducted in Italian Centers for Cognitive Impairment and Dementia. Overall, 170 patients were recruited (34.11%of men, mean age 76,81±4.93 years): 48.8%treated with memantine and donepezil; 48.2%with memantine and rivastigmine; 2.9%with memantine and galantamine. 89 patients (control-group) were treated with memantine and an AChEI, whereas 81 patients (case-group) were treated with oral citicoline 1000 mg/day added to memantine and an AChEI given orally. Cognitive functions, activities of daily living, instrumental activities of daily living, comorbidities, mood and behavioral disturbances were assessed at baseline, month 6, and month 12. RESULTS In the case group, MMSE score had a statistically significant increasing trend between T0 and T2 (14.88±2.95 versus 15.09±3.00; p = 0.040), whereas in the control group, MMSE score showed a statistically significant decrease trend (14.37±2.63 versus 14.03±2.92 p = 0.024). CONCLUSION In older patients with AD, a triple therapy with citicoline, memantine, and AChEI was more effective than memantine and AChEI without citicoline in maintaining the MMSE total score after 12 months.
Effect of proteolytic enzymes in gastrointestinal fluids on drug release from polyelectrolyte complex microspheres based on partially phosphorylated chitosan

This study investigated the effect of proteolytic enzymes on in vitro release of ibuprofen from phosphorylated chitosan (PCS) microspheres in simulated gastric fluid (SGF) (pH 1.4) and simulated intestinal fluid (SIF) (pH 7.4). To reduce the enzymatic degradability and to enhance the sustained release property, polyelectrolyte complex microspheres based on PCS were developed and characterized. The ibuprofen release from PCS microspheres was found to be sustained more effectively than that from CS microspheres in the medium containing proteolytic enzymes. It was concluded that the PCS microspheres can be used more successfully as sustained oral drug-delivery vehicles than CS microspheres due to their lesser enzymatic degradability. Copyright © 2004 Society of Chemical Industry
Serum uric acid level as a biomarker for chronic obstructive pulmonary disease: a meta-analysis

Objective To determine if there is a relationship between the levels of serum uric acid and the different Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (1–4) classified by the severity of the airflow limitation in patients with stable chronic obstructive pulmonary disease (COPD). Methods Electronic databases, including PubMed®, Embase®, Web of Science™ and China National Knowledge Infrastructure (CNKI), were searched from inception to December 2018. Observational studies that reported serum uric acid levels in stable COPD patients were included. Two investigators independently extracted data and RevMan version 5.3 was used to carry out the statistical analyses. Results Seven studies with 932 stable COPD patients and 401 healthy control subjects were included in this meta-analysis. Serum uric acid levels were significantly higher in stable COPD patients compared with healthy control subjects (mean difference [MD] 1.91, 95% confidence interval [CI] 1.55, 2.28). Serum uric acid levels were significantly lower in the GOLD 1+2 subgroup compared with the GOLD 3+4 subgroup (MD −1.39, 95% CI −1.63, −1.15). Conclusion Serum uric acid might be a useful biomarker for identifying disease severity in stable COPD patients, but further studies are needed to confirm this finding.
Laser resonance frequency analysis of pedicle screw stability: A cadaveric model bone study

There is no evaluation method currently available to assess intraoperative pedicle screw fixation (PSF) strength. In this study, we established a laser‐based resonance frequency analysis (RFA) system with high‐speed, noncontact, quantitative measurements of PSF. Clinical investigations in the future can assess surgical failure risk of implants. We investigated the characteristics of the laser RFA and compared them with the conventional methods. We inserted a pedicle screw in the vertebral pedicle of human cadaver or model bone, followed by screw pull‐out, peak torque, implant stability quotient (ISQ) value obtained by the magnetic dental RFA system, and fixation force of laser RFA. We compared the outcomes using best‐fit linear or logarithmic approximations. For the model bone study, the resonance frequency (RF) versus peak torque/pull‐out force (POF) demonstrated strong correlations using logarithmic approximation (vs. peak torque: R = 0.931, p < .001, vs. POF: R = 0.931, p < .001). RF strongly correlated with the ISQ value using linear approximation (R = 0.981, p < .001). For the cadaveric vertebrae study, the correlation coefficients between RF and the peak torque/POF were significant regardless of approximation method (peak torque: logarithmic: R = 0.716 vs. linear: R = 0.811; p < .001) (POF: logarithmic: R = 0.644 vs. linear: R = 0.548; p < .05). Thus, the results of this study revealed a constant correlation between RFA and conventional methods as a measurement validation, predicting favorable support for intraoperative PSF. RFA has the potential to be a new index for evaluating the implant fixation force.