Miracle-dz/UniFAR-FTUs huggingface dataset:
Subconjunctival Injection of Regulatory T Cells Potentiates Corneal Healing Via Orchestrating Inflammation and Tissue Repair After Acute Alkali Burn

Purpose This study aimed to investigate the therapeutic effects and underlying mechanisms of locally delivered regulatory T cells (Tregs) on acute corneal wound healing after alkali burn. Methods After corneal alkali burn, the mice were injected subconjunctivally with regulatory T cells (Tregs) isolated from syngeneic mice. The wound healing process was monitored by clinical manifestation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). As amphiregulin (Areg) was significantly upregulated, its reparative function in injured corneas was suggested. The hypothesis was further verified via loss- and gain-of-function experiments by administrating the antibody of Areg (anti-Areg) and recombinant Areg (rmAreg). Results Subconjunctivally injected Tregs rapidly migrated to injured corneas. The mice treated with Tregs showed prominently reduced corneal opacity, alleviated edema, and faster re-epithelialization compared with the control group. Mechanistically, Treg treatment led to suppressed infiltration of inflammatory cells, along with improved proliferation and inhibited apoptosis of corneal epithelial cells. Tregs expressed upregulated functional markers, including Areg. Expectantly, the levels of Areg in corneas were dramatically higher in the Treg injection group, in line with better corneal restoration. Additional experiments showed that the administration of anti-Areg blunted the reparative effect of Tregs, while exogenous Areg enhanced it. Treg-treated corneas also exhibited less neovascularization and fibrosis at a later reconstruction stage of corneal repair. Conclusions The findings showed that the subconjunctival injection of Tregs effectively promoted corneal wound healing by inhibiting excessive inflammation and enhancing epithelial regeneration, with an indispensable reparative role of Areg. Subsequent complications of corneal vascularization and fibrosis were therefore reduced.
Flow behaviour of erythrocytes - I. Rotation and deformation in dilute suspensions

The behaviour of individual human red cells and rouleaux were studied under the microscope in suspensions of < 2% haematocrit: (i) in Poiseuille flow by tracking the particles in glass tubes, and (ii) in Couette flow by observing cells in the stationary layer between counter-rotating glass disks. At shear stresses ≪ 0.1 N m-2, the rotations of red cells in plasma were in accord with theory applicable to rigid disks. At shear stresses > 0.1 N m-2, especially in viscous isotonic Dextran solutions, the cells oriented themselves at a constant angle to the flow and their membrane appeared to rotate about the interior. Although this behaviour was analogous to that of liquid drops, the concavity was still present in the deformed erythrocytes, whose mean major diameters in plasma increased by 1.05 µm as the shear stress increased from 0 to 0.4 N m-2. Deformation, through bending, was also observed with linear rouleaux of > 6 cells, here, at even the lowest shear stresses. By contrast, glutaraldehyde hardened cells and rouleaux rotated, without deforming, as rigid disks and rods respectively.
Tissue Engineering and Three-Dimensional Printing in Periodontal Regeneration: A Literature Review

The three-dimensional printing of scaffolds is an interesting alternative to the traditional techniques of periodontal regeneration. This technique uses computer assisted design and manufacturing after CT scan. After 3D modelling, individualized scaffolds are printed by extrusion, selective laser sintering, stereolithography, or powder bed inkjet printing. These scaffolds can be made of one or several materials such as natural polymers, synthetic polymers, or bioceramics. They can be monophasic or multiphasic and tend to recreate the architectural structure of the periodontal tissue. In order to enhance the bioactivity and have a higher regeneration, the scaffolds can be embedded with stem cells and/or growth factors. This new technique could enhance a complete periodontal regeneration. This review summarizes the application of 3D printed scaffolds in periodontal regeneration. The process, the materials and designs, the key advantages and prospects of 3D bioprinting are highlighted, providing new ideas for tissue regeneration.
DeMaSk: a deep mutational scanning substitution matrix and its use for variant impact prediction

Abstract Motivation Accurately predicting the quantitative impact of a substitution on a protein’s molecular function would be a great aid in understanding the effects of observed genetic variants across populations. While this remains a challenging task, new approaches can leverage data from the increasing numbers of comprehensive deep mutational scanning (DMS) studies that systematically mutate proteins and measure fitness. Results We introduce DeMaSk, an intuitive and interpretable method based only upon DMS datasets and sequence homologs that predicts the impact of missense mutations within any protein. DeMaSk first infers a directional amino acid substitution matrix from DMS datasets and then fits a linear model that combines these substitution scores with measures of per-position evolutionary conservation and variant frequency across homologs. Despite its simplicity, DeMaSk has state-of-the-art performance in predicting the impact of amino acid substitutions, and can easily and rapidly be applied to any protein sequence. Availability and implementation https://demask.princeton. edu generates fitness impact predictions and visualizations for any user-submitted protein sequence. Supplementary information Supplementary data are available at Bioinformatics online.
Influence of the Grain Boundaries and Intragrain Defects on the Performance of Poly‐Si Thin Film Transistors

The influence of grain boundaries and intragrain defects on poly-Si thin-film transistors (TFTS) was investigated by examining the crystallinity of poly-Si films formed by solid phase crystallization (SPC) and excimer laser annealing (ELA), and the electrical characteristics of transistors fabricated on the poly-Si films were examined. The increase in grain size by SPC improves field effect mobility (μ Fe ) due to the increase in the emission current over the potential barrier height at the grain boundary. The decrease in intragrain defect densities by an oxide thinning process improves the threshold voltage (V h ) and subthreshold voltage swing (S). On the contrary, in spite of the small grain size of 800 A, polv-Si TFTs fabricated by ELA exhibit good characteristics with a high μ FE low V th and low S, and good uniformity. It is found that since the realization of excellent performance and good uniformity in poly-Si TFTs depends on a low trap state density at the grain boundaries and a low intragrain defect density, poly-Si films formed by ELA are well suited for the application to poly-Si TFT liquid crystal display with peripheral integrated circuits.
Proteomic Analysis of the Protective Effect of Early Heat Exposure against Chronic Heat Stress in Broilers

Simple Summary Heat stress affects the livestock industry, especially in poultry. Screening for metabolic changes after early and chronic heat exposure in poultry would be beneficial in resolving the production issues. In this study, we identified differentially expressed proteins that affected early heat exposure during chronic heat stress. Chronic heat stress affected 277 proteins, of which 95 differed in expression by early heat exposure. Differentially expressed proteins were related to actin metabolism and also involved in carbohydrate and carbon metabolism. According to our results, early heat exposed liver of broilers activates the different physiological mechanisms for protection from later heat stress. Abstract The increasing trend of global warming has affected the livestock industry through the heat stress, especially in poultry. Therefore, a better understanding of the mechanisms of heat stress in poultry would be helpful for maintaining the poultry production. Three groups were designed to determine early heat stress effects during chronic heat stress: CC, raised at a comfortable temperature; CH, chronic heat exposure at 35 °C for 21–35 days continuously; and HH, early heat exposure at 40 °C for 24 h at 5 days old with 35 °C temperature for 21–35 days continuously. In this study, proteome analysis was carried out to identify differentially expressed proteins in the liver tissue of broilers under chronic and early heat exposure. There were eight differentially expressed proteins from early heat stress during chronic heat exposure, which were related to actin metabolism. According to KEGG (Kyoto encyclopedia of genes and genomes) analysis, the proteins involved in carbohydrate metabolism were expressed to promote the metabolism of carbohydrates under chronic heat stress. Early heat reduced the heat stress-induced expression changes of select proteins. Our study has shown that early heat exposure suggests that the liver of broilers has various physiological mechanisms for regulating homeostasis to aid heat resistance.
Trimethyllysine: From Carnitine Biosynthesis to Epigenetics

Trimethyllysine is an important post-translationally modified amino acid with functions in the carnitine biosynthesis and regulation of key epigenetic processes. Protein lysine methyltransferases and demethylases dynamically control protein lysine methylation, with each state of methylation changing the biophysical properties of lysine and the subsequent effect on protein function, in particular histone proteins and their central role in epigenetics. Epigenetic reader domain proteins can distinguish between different lysine methylation states and initiate downstream cellular processes upon recognition. Dysregulation of protein methylation is linked to various diseases, including cancer, inflammation, and genetic disorders. In this review, we cover biomolecular studies on the role of trimethyllysine in carnitine biosynthesis, different enzymatic reactions involved in the synthesis and removal of trimethyllysine, trimethyllysine recognition by reader proteins, and the role of trimethyllysine on the nucleosome assembly.
Strategy for Encapsulation of CdS Quantum Dots into Zeolitic Imidazole Frameworks for Photocatalytic Activity

Encapsulating CdS quantum dots (QDs) into zeolitic imidazole framework-8 (ZIF-8) can offer several advantages for photocatalysis. Various types of capping agents have been used to encapsulate QDs into ZIF-8 nanopores. An effective method for encapsulating CdS QDs into ZIF-8 is to use 2-mercaptoimidazole as the capping agent. This is because 2-mercaptoimidazole is similar to the imidazolate ligands of ZIFs and can used for capping active species with simultaneous encapsulation during the crystal growth of ZIF-8. Compared to other widely used capping agents such as polyvinylpyrrolidone (PVP), using 2-mercaptoimidazole for encapsulating CdS QDs into ZIF-8 revealed photocatalytic effects along with the molecular sieving effect when using differently sized molecular redox mediators such as methyl viologen (MV2+) and diquat (DQ2+).
Age-Related Decline of Sensorimotor Integration Influences Resting-State Functional Brain Connectivity

Age-related decline in sensorimotor integration involves both peripheral and central components related to proprioception and kinesthesia. To explore the role of cortical motor networks, we investigated the association between resting-state functional connectivity and a gap-detection angle measured during an arm-reaching task. Four region pairs, namely the left primary sensory area with the left primary motor area (S1left–M1left), the left supplementary motor area with M1left (SMAleft–M1left), the left pre-supplementary motor area with SMAleft (preSMAleft–SMAleft), and the right pre-supplementary motor area with the right premotor area (preSMAright–PMdright), showed significant age-by-gap detection ability interactions in connectivity in the form of opposite-sign correlations with gap detection ability between younger and older participants. Morphometry and tractography analyses did not reveal corresponding structural effects. These results suggest that the impact of aging on sensorimotor integration at the cortical level may be tracked by resting-state brain activity and is primarily functional, rather than structural. From the observation of opposite-sign correlations, we hypothesize that in aging, a “low-level” motor system may hyper-engage unsuccessfully, its dysfunction possibly being compensated by a “high-level” motor system, wherein stronger connectivity predicts higher gap-detection performance. This hypothesis should be tested in future neuroimaging and clinical studies.
Genome-Wide Analysis of Off-Target CRISPR/Cas9 Activity in Single-Cell-Derived Human Hematopoietic Stem and Progenitor Cell Clones

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)-mediated genome editing holds remarkable promise for the treatment of human genetic diseases. However, the possibility of off-target Cas9 activity remains a concern. To address this issue using clinically relevant target cells, we electroporated Cas9 ribonucleoprotein (RNP) complexes (independently targeted to two different genomic loci, the CXCR4 locus on chromosome 2 and the AAVS1 locus on chromosome 19) into human mobilized peripheral blood-derived hematopoietic stem and progenitor cells (HSPCs) and assessed the acquisition of somatic mutations in an unbiased, genome-wide manner via whole genome sequencing (WGS) of single-cell-derived HSPC clones. Bioinformatic analysis identified >20,000 total somatic variants (indels, single nucleotide variants, and structural variants) distributed among Cas9-treated and non-Cas9-treated control HSPC clones. Statistical analysis revealed no significant difference in the number of novel non-targeted indels among the samples. Moreover, data analysis showed no evidence of Cas9-mediated indel formation at 623 predicted off-target sites. The median number of novel single nucleotide variants was slightly elevated in Cas9 RNP-recipient sample groups compared to baseline, but did not reach statistical significance. Structural variants were rare and demonstrated no clear causal connection to Cas9-mediated gene editing procedures. We find that the collective somatic mutational burden observed within Cas9 RNP-edited human HSPC clones is indistinguishable from naturally occurring levels of background genetic heterogeneity.
Thalamic Deep Brain Stimulation in Essential Tremor Plus Is as Effective as in Essential Tremor

The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn–Tolosa–Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show that DBS is similarly effective in ET-p compared to ET. TRS scores were higher in ET-p preoperatively, and higher stimulation parameters were needed for tremor reduction compared to ET. The latter may be related to a more dorsal location of active electrode contacts in the ET-p group of this cohort. Prospective studies are warranted to investigate DBS in ET-p further.
Immunotherapy Advances for Epithelial Ovarian Cancer

Simple Summary The overall five-year survival rate in epithelial ovarian cancer is 44% and has only marginally improved in the past two decades. Despite an initial response to standard treatment consisting of chemotherapy and surgical removal of tumor, the lesions invariably recur, and patients ultimately die of chemotherapy resistant disease. New treatment modalities are needed in order to improve the prognosis of women diagnosed with ovarian cancer. One such modality is immunotherapy, which aims to boost the capacity of the patient’s immune system to recognize and attack the tumor cells. We performed a retrospective study to identify some of the most promising immune therapies for epithelial ovarian cancer. Special emphasis was given to immuno-oncology clinical trials. Abstract New treatment modalities are needed in order to improve the prognosis of women diagnosed with epithelial ovarian cancer (EOC), the most aggressive gynecologic cancer type. Most ovarian tumors are infiltrated by immune effector cells, providing the rationale for targeted approaches that boost the existing or trigger new anti-tumor immune mechanisms. The field of immuno-oncology has experienced remarkable progress in recent years, although the results seen with single agent immunotherapies in several categories of solid tumors have yet to extend to ovarian cancer. The challenge remains to determine what treatment combinations are most suitable for this disease and which patients are likely to benefit and to identify how immunotherapy should be incorporated into EOC standard of care. We review here some of the most promising immune therapies for EOC and focus on those currently tested in clinical trials.
Protective Effects of a Strawberry Ellagitannin-Rich Extract against Pro-Oxidative and Pro-Inflammatory Dysfunctions Induced by a High-Fat Diet in a Rat Model

Due to the demonstrated intestinal microbial transformation of strawberry ellagitannins (ET) into bioactive metabolites, in the current study on rats, we hypothesised that the dietary addition of a strawberry ET-rich extract (S-ET) to a high-fat diet (HFD) would attenuate disturbances in the redox and lipid status as well as in the inflammatory response. We randomly distributed 48 Wistar rats into six groups and used two-way analysis of variance (ANOVA) to assess the effects of two main factors—diet type (standard and high-fat) and ET dosage (without, low, and 3× higher)—applied to rats for 4 weeks. In relation to the hypothesis, irrespective of the dosage, the dietary application of ET resulted in the desired attenuating effects in rats fed a HFD as manifested by decreased body weight gain, relative mass of the epididymal pad, hepatic fat, oxidized glutathione (GSSG), triglycerides (TG), total cholesterol (TC), and thiobarbituric acid-reactive substances (TBARS) concentrations as well as desired modifications in the blood plasma parameters. These beneficial changes were enhanced by the high dietary addition of ET, which was associated with considerably higher concentrations of ET metabolites in the urine and plasma of rats. The results indicated that S-ET could be effectively used for the prevention and treatment of metabolic disturbances associated with obesity, dyslipidaemia, redox status imbalance, and inflammation.
An Improved Representative Equation for the Dynamic Viscosity of Water Substance

Experimental evidence for steam and other fluids has demonstrated the existence of an anomalous enhancement of the dynamic viscosity in the close vicinity of the critical point. A re‐analysis of the experimental evidence for the viscosity of steam indicates that the observed behavior of the critical viscosity enhancement is consistent with current theoretical predictions. An interpolating equation for the dynamic viscosity of water substance is presented which is in good agreement with the experimental viscosity data in a large range of temperatures and pressures. The equation contains a smaller number of coefficients than the current international equation for the viscosity of water substance and incorporates the enhancement of the viscosity in the close vicinity of the critical point.
Simulating Absorption Spectra of Flavonoids in Aqueous Solution: A Polarizable QM/MM Study

We present a detailed computational study of the UV/Vis spectra of four relevant flavonoids in aqueous solution, namely luteolin, kaempferol, quercetin, and myricetin. The absorption spectra are simulated by exploiting a fully polarizable quantum mechanical (QM)/molecular mechanics (MM) model, based on the fluctuating charge (FQ) force field. Such a model is coupled with configurational sampling obtained by performing classical molecular dynamics (MD) simulations. The calculated QM/FQ spectra are compared with the experiments. We show that an accurate reproduction of the UV/Vis spectra of the selected flavonoids can be obtained by appropriately taking into account the role of configurational sampling, polarization, and hydrogen bonding interactions.
EEG-Based BCI System to Detect Fingers Movements

The advancement of assistive technologies toward the restoration of the mobility of paralyzed and/or amputated limbs will go a long way. Herein, we propose a system that adopts the brain-computer interface technology to control prosthetic fingers with the use of brain signals. To predict the movements of each finger, complex electroencephalogram (EEG) signal processing algorithms should be applied to remove the outliers, extract features, and be able to handle separately the five human fingers. The proposed method deals with a multi-class classification problem. Our machine learning strategy to solve this problem is built on an ensemble of one-class classifiers, each of which is dedicated to the prediction of the intention to move a specific finger. Regions of the brain that are sensitive to the movements of the fingers are identified and located. The average accuracy of the proposed EEG signal processing chain reached 81% for five subjects. Unlike the majority of existing prototypes that allow only one single finger to be controlled and only one movement to be performed at a time, the system proposed will enable multiple fingers to perform movements simultaneously. Although the proposed system classifies five tasks, the obtained accuracy is too high compared with a binary classification system. The proposed system contributes to the advancement of a novel prosthetic solution that allows people with severe disabilities to perform daily tasks in an easy manner.