Miracle-dz/UniFAR-FTUs huggingface dataset:
Biocompatibility of Biomaterials for Nanoencapsulation: Current Approaches

Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed.
High confidence spatial long-term memories produce greater cortical activity in males than females

ABSTRACT Many functional resonance imaging (fMRI) studies have reported sex differences during long-term memory. The present fMRI investigation aimed to identify whether sex differences exist during high- versus low-confidence accurate spatial memories. During the study phase, abstract shapes were presented to the left or right of fixation. During the test phase, each shape was presented at fixation and participants made an old-“left” or old-“right” judgment followed by an “unsure” or “sure” response. The conjunction of female high- versus low-confidence spatial memory and male high- versus low-confidence spatial memory identified common activity in visual processing regions and parietal cortex, which suggests amplification of activity in some of the regions commonly associated with long-term memory yields high confidence. The contrast of female high- versus low-confidence spatial memory and male high- versus low-confidence spatial memory did not produce any significant activity. However, the reverse contrast produced greater male than female activity in the lateral prefrontal cortex, parietal cortex, sensorimotor cortex, and visual processing regions. An independent region-of-interest (ROI) analysis (ROIs were identified by contrasting hits versus misses) produced complementary results in the lateral prefrontal cortex. Greater lateral prefrontal cortex activity suggests a higher degree of subjective confidence in males than females, greater parietal cortex and visual processing activity suggests more vivid visualization in males than females, and greater activity in sensorimotor cortex indicates that males have a more reactive processing style than females. More broadly, the present and previous functional sex differences argue against the practice of collapsing across sex in cognitive neuroscience studies.
Circulating MicroRNAs as Prognostic and Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

Breast cancer (BC) is a common and heterogeneous disease, of which six molecular subtypes, characterized by different biological features and clinical outcomes, were described. The identification of additional biomarkers able to further connote and distinguish the different BC subtypes is essential to improve the diagnostic, prognostic and therapeutic strategies in BC patients. MicroRNAs (miRNAs) are short non-coding RNA involved in several physiological and pathological processes, including cancer development and progression. In particular, circulating miRNAs, which can be found in an adequately stable structure in serum/plasma of cancer patients, are emerging as very promising non-invasive biomarkers. Several studies have analyzed the potential role of circulating miRNAs as prognostic and therapeutic markers in BC. In the present review we describe circulating miRNAs, identified as putative biomarker in BC, with special reference to different BC molecular subtypes.
Trajectories of the Psychological Status of Mothers of Infants With Nonsyndromic Orofacial Clefts: A Prospective Cohort Study From the Japan Environment and Children’s Study

Objective: This study examined psychological status trajectories of mothers of infants with nonsyndromic orofacial clefts in Japan. Design: Prospective cohort study. Setting: Data from the Japan Environment and Children’s Study. Participants: Infants with a nonsyndromic cleft (N = 148) including cleft lip and palate (CLP; n = 72), cleft lip (CL; n = 46), and cleft palate (CP; n = 30). The control group included unaffected infants (N = 84 454). Main Outcome Measures: At 15 weeks and 27 weeks of pregnancy and 12 months after birth, the Kessler Psychological Distress Scale (clinical cutoff ≥5) was used. At 1 month and 6 months after birth, the Edinburgh Postnatal Depression Scale (clinical cutoff ≥9) was used. Results: Prenatal diagnosis rates were unavailable. Mothers of infants with CLP had higher psychological distress than controls at 27 weeks of pregnancy (prevalence ratio [PR] = 1.36, 95% CI: 1.06-1.74) and postnatal depression at 1 month after birth (PR = 2.21, 95% CI: 1.53-3.19). Mothers of infants with CP showed heightened psychological distress at 27 weeks of pregnancy (PR = 1.62, 95% CI: 1.21-2.17) and postnatal depression 6 months after birth (PR = 1.86, 95% CI: 1.01-3.43). There was no significant association between CL and maternal psychological status. At 12 months after birth, no differences in distress were found between mothers of infants with a cleft and controls. Conclusions: Mothers of infants with orofacial clefts may need psychosocial support, particularly during pregnancy and the first year after birth.
Spectral–Spatial Features Integrated Convolution Neural Network for Breast Cancer Classification

Cancer identification and classification from histopathological images of the breast depends greatly on experts, and computer-aided diagnosis can play an important role in disagreement of experts. This automatic process has increased the accuracy of the classification at a reduced cost. The advancement in Convolution Neural Network (CNN) structure has outperformed the traditional approaches in biomedical imaging applications. One of the limiting factors of CNN is it uses spatial image features only for classification. The spectral features from the transform domain have equivalent importance in the complex image classification algorithm. This paper proposes a new CNN structure to classify the histopathological cancer images based on integrating the spectral features obtained using a multi-resolution wavelet transform with the spatial features of CNN. In addition, batch normalization process is used after every layer in the convolution network to improve the poor convergence problem of CNN and the deep layers of CNN are trained with spectral–spatial features. The proposed structure is tested on malignant histology images of the breast for both binary and multi-class classification of tissue using the BreaKHis Dataset and the Breast Cancer Classification Challenge 2015 Datasest. Experimental results show that the combination of spectral–spatial features improves classification accuracy of the CNN network and requires less training parameters in comparison with the well known models (i.e., VGG16 and ALEXNET). The proposed structure achieves an average accuracy of 97.58% and 97.45% with 7.6 million training parameters on both datasets, respectively.
Curcumin and Quercetin-Loaded Nanoemulsions: Physicochemical Compatibility Study and Validation of a Simultaneous Quantification Method

Biphasic oil/water nanoemulsions have been proposed as delivery systems for the intranasal administration of curcumin (CUR) and quercetin (QU), due to their high drug entrapment efficiency, the possibility of simultaneous drug administration and protection of the encapsulated compounds from degradation. To better understand the physicochemical and biological performance of the selected formulation simultaneously co-encapsulating CUR and QU, a stability test of the compound mixture was firstly carried out using X-ray powder diffraction and thermal analyses, such as differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The determination and quantification of the encapsulated active compounds were then carried out being an essential parameter for the development of innovative nanomedicines. Thus, a new HPLC–UV/Vis method for the simultaneous determination of CUR and QU in the nanoemulsions was developed and validated. The X-ray diffraction analyses demonstrated that no interaction between the mixture of active ingredients, if any, is strong enough to take place in the solid state. Moreover, the thermal analysis demonstrated that the CUR and QU are stable in the nanoemulsion production temperature range. The proposed analytical method for the simultaneous quantification of the two actives was selective and linear for both compounds in the range of 0.5–12.5 µg/mL (R2 > 0.9997), precise (RSD below 3%), robust and accurate (recovery 100 ± 5 %). The method was validated in accordance with ICH Q2 R1 “Validation of Analytical Procedures” and CDER-FDA “Validation of chromatographic methods” guideline. Furthermore, the low limit of detection (LOD 0.005 µg/mL for CUR and 0.14 µg/mL for QU) and the low limit of quantification (LOQ 0.017 µg/mL for CUR and 0.48 µg/mL for QU) of the method were suitable for the application to drug release and permeation studies planned for the development of the nanoemulsions. The method was then applied for the determination of nanoemulsions CUR and QU encapsulation efficiencies (> 99%), as well as for the stability studies of the two compounds in simulated biological fluids over time. The proposed method represents, to our knowledge, the only method for the simultaneous quantification of CUR and QU in nanoemulsions.
Regular exercise and branched‐chain amino acids prevent ischemic acute kidney injury‐related muscle wasting in mice

Acute kidney injury (AKI) causes glucose and protein metabolism abnormalities that result in muscle wasting, thereby affecting the long‐term prognosis of critical illness survivors. Here, we examined whether early intervention with treadmill exercise and branched‐chain amino acids (BCAA) can prevent AKI‐related muscle wasting and reduced physical performance in mice. Unilateral 15 min ischemia‐reperfusion injury was induced in contralateral nephrectomized mice, and muscle histological and physiological changes were assessed and compared with those of pair‐fed control mice, since AKI causes severe anorexia. Mice exercised for 30 min each day and received oral BCAA for 7 days after AKI insult. By day 7, ischemic AKI significantly decreased wet weight, myofiber cross‐sectional area, and central mitochondrial volume density of the anterior tibialis muscle, and significantly reduced maximal exercise time. Regular exercise and BCAA prevented AKI‐related muscle wasting and low physical performance by suppressing myostatin and atrogin‐1 mRNA upregulation, and restoring reduced phosphorylated Akt and PGC‐1α mRNA expression in the muscle. Ischemic AKI induces muscle wasting by accelerating muscle protein degradation and reducing protein synthesis; however, we found that regular exercise and BCAA prevented AKI‐related muscle wasting without worsening kidney damage, suggesting that early rehabilitation with nutritional support could prevent AKI‐related muscle wasting.
Oral delivery of liraglutide-loaded Poly-N-(2-hydroxypropyl) methacrylamide/chitosan nanoparticles: Preparation, characterization, and pharmacokinetics

The delivery of peptides or protein drugs via the oral route has always presented a significant challenge. Here, nanoparticles for the oral delivery of liraglutide are prepared. The nanoparticles are composed of the biodegradable carrier materials chitosan and poly-N-(2-hydroxypropyl) methacrylamide (pHPMA). In addition, CSKSSDYQC (CSK) and hemagglutinin-2 (HA2) are introduced into the particles to improve the in vivo bioavailability of liraglutide. The size of the nanoparticles is less than 200 nm, and the encapsulation efficiency is approximately 80%. Compared with the subcutaneously injected liraglutide solution group (100%), the relative bioavailability of the nanoparticle group modified with CSK and HA2 reached 10.12%, which is 2.53 times that of the oral liraglutide solution group. In vivo imaging results showed that pHPMA/HA2-CSK chitosan nanoparticles (pHPMA/HA-CCNPs) are retained in the gastrointestinal tract for up to 12 h, which is beneficial for oral absorption. CSK and HA2 modified pHPMA/chitosan nanoparticles significantly improved liraglutide oral bioavailability and therefore have the potential to be applied for oral administration of peptides and proteins.
Construction and Analysis of Fosmid Library of Rumen Microbiota of Hu Sheep

A Fosmid library of uncultured microorganism from Hu sheep rumen was constructed to explore the potential of the ruminants’ gut ecosystem,and the library storage capacity,stability and the functionality was also analyzed. A total of 12 704 clones were acquired from the Fosmid library. Restriction analysis by Xho Ⅰ and BamH Ⅰ revealed a high level of diversity of the cloned DNA fragments. The insert size of clone ranged from 17 to 55 kb,with average insert size of 30.9 kb,which mostly distributed between 36～40 kb and 26～30 kb. The capacity of this Fosmid library was 393 Mb. It was demonstrated by restriction analysis with Hind Ⅲ that the Fosmid library clones cultured for 100 generations still showed good stability. With the Congo red stain analysis,18 clones had been acquired with the activity of xylanase. It was suggested that the constructed Fosmid library had good storage capacity,stability and the functionality,and could be used for further research on exploration of enzyme resource.
Holographic Photopolymer Material with High Dynamic Range (∆n) via Thiol-ene Click Chemistry.

A high-performance holographic recording media was developed based on a unique combination of photoinitiated thiol-ene click chemistry and functional, linear polymers used as binders. Allyl reactive sites were incorporated along the backbone of the linear polymer binder to enable facile film casting and to facilitate crosslinking by photopolymerization of the thiol-ene monomers that also serve as the writing monomers in this distinctive approach to holographic materials. The allyl content and the ratio of the linear polymer to the writing monomers were varied to maximize and control the refractive index contrast. A blade-coating-based film preparation method was developed to form films from the mixture of linear polymer and the thiol-ene monomers. This approach results in a holographic material with a peak to mean index contrast (∆n) that reaches 0.04. The refractive index contrast was stable for at least two weeks. Haze in holograms with a high writing monomer loading was significantly reduced when a higher allyl content was incorporated into the binder, resulting in the lowest haze around 0.2%. Finally, the media exhibits high resolution, as demonstrated by the ability to record reflection holograms with 140 nm pitch and diffraction efficiency in excess of 90%.
Effect of γ-Aminobutyric Acid (GABA) on the Metabolome of Two Strains of Lasiodiplodia theobromae Isolated from Grapevine

The effect of γ-aminobutyric acid (GABA) on the metabolome of two strains of Lasiodiplodia theobromae isolated from grapevine that hold a different degree of virulence to the host plant (LA-SOL3 (more virulent), LA-SV1 (less virulent)) was investigated. The culture filtrates and crude extracts from the two strains grown in the presence and absence of 10 mM of GABA were tested for phytotoxicity on tomato plant cuttings and leaves, respectively. Considering the opportunistic nature of this fungus for humans, crude extracts were also tested for cytotoxicity on mammalian cell lines. We found that culture filtrates and crude extracts have a decreased toxicity in the presence of GABA. Metabolomic analysis, conducted on both strains at both growth conditions, revealed the production of several compounds, such as indole-3-carboxylic acid (ICA, which is the main compound produced by L. theobromae), 3-indolecarboxyaldehyde, (3R,4S)-botryodiplodin, (R)-mellein. Finally, data demonstrate that GABA both induces a decrease in the amount of ICA, and a diversification of the metabolites produced by L. theobromae.
Design, Optimization, Manufacture and Characterization of Efavirenz-Loaded Flaxseed Oil Nanoemulsions

The formation, manufacture and characterization of low energy water-in-oil (w/o) nanoemulsions prepared using cold pressed flaxseed oil containing efavirenz was investigated. Pseudo-ternary phase diagrams were constructed to identify the nanoemulsion region(s). Other potential lipid-based drug delivery phases containing flaxseed oil with 1:1 m/m surfactant mixture of Tween® 80, Span® 20 and different amounts of ethanol were tested to characterize the impact of surfactant mixture on emulsion formation. Flaxseed oil was used as the oil phase as efavirenz exhibited high solubility in the vehicle when compared to other vegetable oils tested. Optimization of surfactant mixtures was undertaken using design of experiments, specifically a D-optimal design with the flaxseed oil content set at 10% m/m. Two solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, physical and chemical stability. Metastable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and significant isotropic gel (semisolid) and o/w emulsions were observed during phase behavior studies. Droplet sizes ranged between 156 and 225 nm, zeta potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487.
Effects of Pyramid Resistance-Training System with Different Repetition Zones on Cardiovascular Risk Factors in Older Women: A Randomized Controlled Trial

This study analyzed the effects of the pyramidal resistance training (RT) system with two repetition zones on cardiovascular risk factors in older women (≥60 years old). Fifty-nine older women were randomly assigned in three groups: non-exercise control (CON, n = 19), narrow-pyramid system (NPR, n = 20), and wide-pyramid system (WPR, n = 20). Training was performed for eight weeks (eight exercises for the whole-body, 3x/week) in which NPR and WPR performed three sets of 12/10/8 and 15/10/5 repetitions, respectively. Regional body fat was estimated by dual-energy X-ray absorptiometry, and blood parameters related to glycemic, lipid, and inflammatory profiles were assessed. After the training period, although no difference was observed for the magnitude of the changes between NPR and WPR, significant group by time interactions indicated benefits with RT compared to CON for reducing body fat (mainly android body fat; −7%) and improving glucose, HDL-C, LDL-C and C-reactive protein (p < 0.05). Composite z-score of cardiovascular risk, created by the average of the intervention effects on the outcomes, indicate similar responses between NPR and WPR, differing from CON (p < 0.001). Results indicate that both the repetition zones of the pyramidal RT reduced similarly the cardiovascular risk in older women.
Contribution of mobile sources to secondary formation of carbonyl compounds

ABSTRACT In the 2014 National Air Toxics Assessment (NATA), the carbonyl compounds formaldehyde and acetaldehyde were identified as key cancer risk drivers and acrolein was identified as one of the three air toxics that drive most of the noncancer risk. In this assessment, averaged across the Continental United States, about 75% of ambient formaldehyde and acetaldehyde, and about 18% of acrolein, is formed secondarily. This study was conducted to estimate the potential contribution to these secondarily formed carbonyl compounds from mobile sources. To develop such estimates, we conducted several CMAQ runs, where emissions are set to zero for different mobile source sectors, to determine their potential contribution. Although zeroing out emissions from an individual sector can offer only a rough approximation of how the sector might contribute to overall secondary concentrations, our results suggest that across the U. S. , mobile sources contribute about 6–18% to secondary formaldehyde, 0–10% to secondary acetaldehyde, and 0–70% to secondary acrolein, depending on location. Implications: Photochemical modeling of carbonyl compounds was conducted with emissions set to zero for various mobile source sectors to determine their contribution to secondary concentrations. Results indicated mobile sources contributed to total and secondary concentrations of formaldehyde, acetaldehyde, and acrolein in many locations across the U.S. with acrolein the dominant contributor in some locations. However, biogenic sources dominated secondary formaldehyde and acetaldehyde, and fires dominated secondary acrolein.
Site-Specific Tryptophan Labels Reveal Local Microsecond–Millisecond Motions of Dihydrofolate Reductase

Many enzymes are known to change conformations during their catalytic cycle, but the role of these protein motions is not well understood. Escherichia coli dihydrofolate reductase (DHFR) is a small, flexible enzyme that is often used as a model system for understanding enzyme dynamics. Recently, native tryptophan fluorescence was used as a probe to study micro- to millisecond dynamics of DHFR. Yet, because DHFR has five native tryptophans, the origin of the observed conformational changes could not be assigned to a specific region within the enzyme. Here, we use DHFR mutants, each with a single tryptophan as a probe for temperature jump fluorescence spectroscopy, to further inform our understanding of DHFR dynamics. The equilibrium tryptophan fluorescence of the mutants shows that each tryptophan is in a different environment and that wild-type DHFR fluorescence is not a simple summation of all the individual tryptophan fluorescence signatures due to tryptophan–tryptophan interactions. Additionally, each mutant exhibits a two-phase relaxation profile corresponding to ligand association/dissociation convolved with associated conformational changes and a slow conformational change that is independent of ligand association and dissociation, similar to the wild-type enzyme. However, the relaxation rate of the slow phase depends on the location of the tryptophan within the enzyme, supporting the conclusion that the individual tryptophan fluorescence dynamics do not originate from a single collective motion, but instead report on local motions throughout the enzyme.
[Application of restricted cube spline in cox regression model].

Restricted cubic spline Cox proportional hazard regression model analysis is an important method of epidemiological multivariate survival analysis. By comparing the typical Cox regression model and the restricted cubic spline Cox regression model, this study expounds the limitations of the typical Cox regression model, and explains the basic principles and implementation process of the restricted cubic spline Cox proportional hazard regression model. When the follow‑up data does not meet the application conditions of the typical Cox regression model, this method can be used to realize the correlation analysis between continuous exposure and outcomes.