Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Depression and Anxiety in Patients with Chronic Kidney Disease and after Kidney Transplantation—A Comparative Analysis

Depression and anxiety are common among chronic kidney disease (CKD) patients but are rarely diagnosed and treated. Furthermore, the fraction of patients with depression is greater among hemodialyzed patients. The aim of the study was to assess the prevalence of depression symptoms, anxiety and assess the level of life satisfaction in three groups of patients based on the stage of CKD. The study group consisted of 283 patients—130 females and 153 males, mean aged was 54.7 (±15.3) with stage III–V chronic kidney disease and after kidney transplantation. The Beck Depression Inventory (BDI), the Satisfaction with Life Scale (SWLS), and the State-Trait Anxiety Inventory (STAI) were used. The highest percentage of patients with depressive symptoms was recorded in the group of dialysis patients with stage V CKD. The lowest percentage of patients with high satisfaction with life was noted in the pre-dialysis group. There was a significant relationship between BDI and STAI, SWLS in all groups while a significant relationship between BDI and handgrip strength was observed in dialysis and kidney transplantation patients. Anxiety as a trait was found to be the factor most significantly associated with depressive symptoms in each of the three patient groups. Screen testing and monitoring of the emotional state of patients with CKD are needed, regardless of the stage of the disease and treatment, including patients after kidney transplantation.
DL0410 Alleviates Memory Impairment in D-Galactose-Induced Aging Rats by Suppressing Neuroinflammation via the TLR4/MyD88/NF-κB Pathway

Oxidative stress and neuroinflammation have been demonstrated to be linked with Alzheimer's disease (AD). In this study, we examined the protective effects of DL0410 in aging rats and explored the underlying mechanism against oxidative damage and neuroinflammation, which was then validated in LPS-stimulated BV2 microglia. We firstly investigated the improvement effects of DL0410 on learning and memory abilities and explored the potential mechanisms in D-gal-induced aging rats. An 8-week treatment with DL0410 significantly improved the learning and cognitive function of D-gal-stimulated Alzheimer's-like rats in the Morris water maze test, step-down test, and novel object recognition test, and the therapeutic effect of DL0410 at 10 mg/kg was even better than that of donepezil. What is more, the results showed that DL0410 alleviated neuron injury, increased the number of synapses, and improved the level of postsynaptic density protein 95 (PSD95) in the hippocampus and cortex. Next, we examined the protective effects of DL0410 against oxidative damage and neuroinflammation. Our observations indicated that DL0410 reduced the production of harmful oxidation products and promoted the antioxidative system, decreased the levels of proinflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6), and increased anti-inflammatory cytokines IL-10. Moreover, DL0410 inhibited the activation of astrocytes and microglia and suppressed the activation of the TLR4/MyD88/NF-κB signaling pathway. The anti-inflammation effect of DL0410 was further confirmed in LPS-stimulated BV2 cells, and the results showed that DL0410 reduced the level of inflammatory factors and inhibited the activation of the TLR4/MyD88/TRAF6/NF-κB signaling pathway in BV2 microglia. Molecular docking results indicated that DL0410 occupied the LPS recognition site in the TLR4/MD2 complex. Furthermore, the enhanced expression of claudin-1, claudin-5, occludin, CX43, and ZO-1 indicated that DL0410 protected the blood-brain barrier (BBB) integrity. Together, these results suggest that DL0410 exerts neuroprotective effects against hippocampus and cortex injury induced by D-galactose, and the possible mechanisms include antioxidative stress, antineuroinflammation, improving synaptic plasticity, and maintaining BBB integrity, which is mediated by the TLR4/MyD88/NF-κB signaling pathway inhibition. We suggest that DL0410 is a promising candidate for AD treatment.
Alpha-1 Antitrypsin and Hepatocellular Carcinoma in Liver Cirrhosis: SERPINA1 MZ or MS Genotype Carriage Decreases the Risk

Heterozygotes for Z or S alleles of alpha-1-antrypsin (AAT) have low serum AAT levels. Our aim was to compare the risk of hepatocellular carcinoma (HCC) in patients with liver cirrhosis carrying the SERPINA1 MM, MZ and MS genotypes. The study groups consisted of 1119 patients with liver cirrhosis of various aetiologies, and 3240 healthy individuals served as population controls. The MZ genotype was significantly more frequent in the study group (55/1119 vs. 87/3240, p < 0.0001). The MS genotype frequency was comparable in controls (32/119 vs. 101/3240, p = 0.84). MZ and MS heterozygotes had lower serum AAT level than MM homozygotes (medians: 0.90 g/L; 1.40 g/L and 1.67 g/L; p < 0.001 for both). There were significantly fewer patients with HCC in the cirrhosis group among MZ and MS heterozygotes than in MM homozygotes (5/55 and 1/32 respectively, vs. 243/1022, p < 0.01 for both). The risk of HCC was lower in MZ and MS heterozygotes than in MM homozygotes (OR 0.3202; 95% CI 0.1361–0.7719 and OR 0.1522; 95% CI 0.02941–0.7882, respectively). Multivariate analysis of HCC risk factors identified MZ or MS genotype carriage as a protective factor, whereas age, male sex, BMI and viral aetiology of cirrhosis increased HCC risk.
Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty

Projected life expectancy continues to grow worldwide owing to the advancement of new treatments and technologies leading to rapid growth of geriatric population. Thus, age-associated diseases especially in the musculoskeletal system are becoming more common. Loss of bone (osteoporosis) and muscle (sarcopenia) mass are conditions whose prevalence is increasing because of the change in population distribution in the world towards an older mean age. The deterioration in the bone and muscle functions can cause severe disability and seriously affects the patients’ quality of life. Currently, there is no treatment to prevent and reverse age-related musculoskeletal frailty. Existing interventions are mainly to slow down and control the signs and symptoms. Mesenchymal stem cell (MSC) transplantation is a promising approach to attenuate age-related musculoskeletal frailty. This review compiles the present knowledge of the causes and changes of the musculoskeletal frailty and the potential of MSC transplantation as a regenerative therapy for age-related musculoskeletal frailty.
Probing the Suitability of Different Ca2+ Parameters for Long Simulations of Diisopropyl Fluorophosphatase

Organophosphate hydrolases are promising as potential biotherapeutic agents to treat poisoning with pesticides or nerve gases. However, these enzymes often need to be further engineered in order to become useful in practice. One example of such enhancement is the alteration of enantioselectivity of diisopropyl fluorophosphatase (DFPase). Molecular modeling techniques offer a unique opportunity to address this task rationally by providing a physical description of the substrate-binding process. However, DFPase is a metalloenzyme, and correct modeling of metal cations is a challenging task generally coming with a tradeoff between simulation speed and accuracy. Here, we probe several molecular mechanical parameter combinations for their ability to empower long simulations needed to achieve a quantitative description of substrate binding. We demonstrate that a combination of the Amber19sb force field with the recently developed 12-6 Ca2+ models allows us to both correctly model DFPase and obtain new insights into the DFP binding process.
Molecular and Metabolic Insights into Anthocyanin Biosynthesis for Leaf Color Change in Chokecherry (Padus virginiana)

Chokecherry (Padus virginiana L.) is an important landscaping tree with high ornamental value because of its colorful purplish-red leaves (PRL). The quantifications of anthocyanins and the mechanisms of leaf color change in this species remain unknown. The potential biosynthetic and regulatory mechanisms and the accumulation patterns of anthocyanins in P. virginiana that determine three leaf colors were investigated by combined analysis of the transcriptome and the metabolome. The difference of chlorophyll, carotenoid and anthocyanin content correlated with the formation of P. virginiana leaf color. Using enrichment and correlation network analysis, we found that anthocyanin accumulation differed in different colored leaves and that the accumulation of malvidin 3-O-glucoside (violet) and pelargonidin 3-O-glucoside (orange-red) significantly correlated with the leaf color change from green to purple-red. The flavonoid biosynthesis genes (PAL, CHS and CHI) and their transcriptional regulators (MYB, HD-Zip and bHLH) exhibited specific increased expression during the purple-red periods. Two genes encoding enzymes in the anthocyanin biosynthetic pathway, UDP glucose-flavonoid 3-O-glucosyl-transferase (UFGT) and anthocyanidin 3-O-glucosyltransferase (BZ1), seem to be critical for suppressing the formation of the aforesaid anthocyanins. In PRL, the expression of the genes encoding for UGFT and BZ1 enzymes was substantially higher than in leaves of other colors and may be related with the purple-red color change. These results may facilitate genetic modification or selection for further improvement in ornamental qualities of P. virginiana.
Is There a Link between Balance and Body Mass Composition in Children and Adolescents?

School-age children are particularly prone to disturbances in body composition, because this is a period of intensive growth and a period in which correct habits are shaped, especially in relation to diet. This is why it is so important to diagnose emerging disorders early so as to implement therapeutic or educational activities. The aim of this study was to assess the relationship between the factors of body mass composition and body mass index (BMI), as well as the balance parameters in children and adolescents. The study group consisted of 1137 children aged 7 to 15. There were 559 girls and 578 boys among the subjects. The study used the Tanita 780 body mass composition analyser and the Zebris stabilometric platform. It was found that girls were characterized by a significantly higher content of adipose tissue (24.37% vs. 20.45%), while boys were characterized by a higher content of lean tissue (32.99% vs. 30.43%), muscle tissue (31.23% vs. 28.86%) and water (24.15% vs. 22.28%). Interestingly, the girls had better balance than their peers in all analyzed parameters (COF TTL.—616.72 vs. 661.50; CEArea—73.63 vs. 112.24; COF HD—3.44 vs. 4.23; COF VD—4.52 vs. 5.12). It turned out that among children in adolescence, a higher adipose tissue content and a higher BMI correlated with a smaller surface area (p < 0.05) defined by the center of gravity and smaller deviations of the center of gravity in the horizontal plane (p < 0.05). Sex and adolescence play an important role in differentiating both body composition and body balance. The results of this study allow us to conclude that children with higher BMI values have better balance. Due to the fact that these conclusions are inconsistent with those of other researchers, it will be worth continuing the research (e.g., on a different population group) in order to confirm the results and to draw far-reaching conclusions.
Inhibition of NHE-1 Increases Smoke-Induced Proliferative Activity of Barrett’s Esophageal Cell Line

Several clinical studies indicate that smoking predisposes its consumers to esophageal inflammatory and malignant diseases, but the cellular mechanism is not clear. Ion transporters protect esophageal epithelial cells by maintaining intracellular pH at normal levels. In this study, we hypothesized that smoking affects the function of ion transporters, thus playing a role in the development of smoking-induced esophageal diseases. Esophageal cell lines were treated with cigarettesmoke extract (CSE), and the viability and proliferation of the cells, as well as the activity, mRNA and protein expression of the Na+/H+ exchanger-1 (NHE-1), were studied. NHE-1 expression was also investigated in human samples. For chronic treatment, guinea pigs were exposed to tobacco smoke, and NHE-1 activity was measured. Silencing of NHE-1 was performed by using specific siRNA. CSE treatment increased the activity and protein expression of NHE-1 in the metaplastic cells and decreased the rate of proliferation in a NHE-1-dependent manner. In contrast, CSE increased the proliferation of dysplastic cells independently of NHE-1. In the normal cells, the expression and activity of NHE-1 decreased due to in vitro and in vivo smoke exposure. Smoking enhances the function of NHE-1 in Barrett’s esophagus, and this is presumably a compensatory mechanism against this toxic agent.
DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures

G-quadruplex existence was proved in cells by using both antibodies and small molecule fluorescent probes. However, the G-quadruplex probes designed thus far are structure- but not conformation-specific. Recently, a core-extended naphthalene diimide (cex-NDI) was designed and found to provide fluorescent signals of markedly different intensities when bound to G-quadruplexes of different conformations or duplexes. Aiming at evaluating how the fluorescence behaviour of this compound is associated with specific binding modes to the different DNA targets, cex-NDI was here studied in its interaction with hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex models by biophysical techniques, molecular docking, and biological assays. cex-NDI showed different binding modes associated with different amounts of stacking interactions with the three DNA targets. The preferential binding sites were the groove, outer quartet, or intercalative site of the hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex, respectively. Interestingly, our data show that the fluorescence intensity of DNA-bound cex-NDI correlates with the amount of stacking interactions formed by the ligand with each DNA target, thus providing the rationale behind the conformation-sensitive properties of cex-NDI and supporting its use as a fluorescent probe of G-quadruplex structures. Notably, biological assays proved that cex-NDI mainly localizes in the G-quadruplex-rich nuclei of cancer cells.
Effects of Immersive and Non-Immersive Virtual Reality on the Static and Dynamic Balance of Stroke Patients: A Systematic Review and Meta-Analysis

(1) Background: The development of new technologies means that the use of virtual reality is increasingly being implemented in rehabilitative approaches for adult stroke patients. Objective: To analyze the existing scientific evidence regarding the application of immersive and non-immersive virtual reality in patients following cerebrovascular incidents and their efficacy in achieving dynamic and static balance. (2) Data sources: An electronic search of the databases Medline, Cochrane Library, PEDro, Scopus, and Scielo from January 2010 to December 2020 was carried out using the terms physiotherapy, physical therapy, virtual reality, immersive virtual reality, non-immersive virtual reality, stroke, balance, static balance, and dynamic balance. Selection of studies: Randomized controlled trials in patients older than 18 developed with an adult population (>18 years old) with balance disorders as a consequence of suffering a stroke in the previous six months before therapeutic intervention, including exercises harnessing virtual reality in their interventions and evaluations of balance and published in English or Spanish, were included. A total of two hundred twenty-seven articles were found, ten of which were included for review and of these, nine were included in the subsequent meta-analysis. (3) Data extraction: Two authors selected the studies and extracted their characteristics (participants, interventions, and validation instruments) and results. The methodological quality of the studies was evaluated using the PEDro scale, and the risk of bias was determined using the Cochrane risk-of-bias tool. Data synthesis: Of the selected studies, three did not show significant improvements and seven showed significant improvements in the intervention groups in relation to the variables. (4) Conclusions: Non-immersive virtual reality combined with conventional rehabilitation could be considered as a therapeutic option.
Prediction of the Interface Shear Strength between Ultra-High-Performance Concrete and Normal Concrete Using Artificial Neural Networks

The bond strength between ultra-high-performance concrete (UHPC) and normal-strength concrete (NC) plays an important role in governing the composite specimens’ overall behaviors. Unfortunately, there are still no widely accepted formulas targeting UHPC–NC interfacial strength, either in their specifications or in research papers. To this end, this study constructs an experimental database, consisting of 563 and 338 specimens for splitting and slant shear tests, respectively. Moreover, an additional 35 specimens for “improved” slant shear tests were performed, which could circumvent concrete crushing and trigger interfacial debonding. Additionally, for the first time in our tests, the effect of casting sequence on UHPC–NC bond strength was identified. Based on the database, an artificial neural network (ANN) model is proposed with the following inputs: namely, the normal stress perpendicular to the interface, the interface roughness, and the compressive strengths of the UHPC and NC materials. Based on the ANN analyses, the explicit expression of UHPC–NC bond strength is proposed, which significantly lowers the prediction error. To be fully compatible with the specifications, the conventional shear-friction formula is modified. By splitting the total force into adhesion and friction forces, the modified formula additionally takes the casting sequence into account. Although sacrificing accuracy to some extent compared to the ANN model, the modified formula relies on a solid physical basis and its accuracy is enhanced significantly compared to the existing formulas in specifications or research papers.
The Development of Filler Morphology in Dental Resin Composites: A Review

Dental resin composites (DRCs) with diverse fillers added are widely-used restorative materials to repair tooth defects. The addition of fillers brings an improvement in the mechanical properties of DRCs. In the past decade, diverse fillers have emerged. However, the change of emerging fillers mainly focuses on the chemical composition, while the morphologic characteristics changes are often ignored. The fillers with new morphologies not only have the advantages of traditional fillers (particles, fibrous filler, etc.), but also endow some additional functional characteristics (stronger bonding ability to resin matrix, polymerization resistance, and wear resistance, drug release control ability, etc.). Moreover, some new morphologies are closely related to the improvement of traditional fillers, porous filler vs. glass particles, core-sheath fibrous vs. fibrous, etc. Some other new morphology fillers are combinations of traditional fillers, UHA vs. HA particles and fibrous, tetrapod-like whisker vs. whisker and fibrous filler, mesoporous silica vs. porous and silica particles. In this review, we give an overall description and a preliminary summary of the fillers, as well as our perspectives on the future direction of the development of novel fillers for next-generation DRCs.
Beta 2 Adrenergic Receptor Antagonist Propranolol and Opioidergic Receptor Antagonist Naltrexone Produce Synergistic Effects on Breast Cancer Growth Prevention by Acting on Cancer Cells and Immune Environment in a Preclinical Model of Breast Cancer

Simple Summary Here, we show that propranolol, a beta blocker used to treat high blood pressure, and naltrexone, an opiate antagonist used for drug and alcohol dependence, when combined, produce marked inhibitory effects on tumor growth and tumor mass while improving the survival rate, increasing NK cell activity, and reducing inflammatory cytokine levels in plasma. These antitumor effects resulted from a reduction in tumor cell proliferation, the induction of cellular apoptosis, and the prevention of epithelial–mesenchymal transition in the tumor. Our data identify a novel treatment with a combination of approved classes of drugs in preclinical breast cancer models. Abstract Cancer progression is known to be promoted by increased body stress caused by elevated beta-adrenergic and opioidergic nervous system activities. The effects of β2-adrenergic blocker propranolol (PRO) and μ-opioid receptor antagonist naltrexone (NTX) were tested using a preclinical model of human breast cancer. These drugs, individually, and more potently when combined, inhibited the cell growth and progression of breast cancer cells in vitro in cultures, and in vivo in rat xenografts. The antitumor activities of these drugs were associated with direct cell intrinsic effects, including increased cell growth arrest, elevated levels of apoptotic proteins, and reduced production of epithelial–mesenchymal transition factors by the tumor cells, as well as effects on innate immune activation and reduced inflammatory cytokine levels in plasma. These data suggest that the combined treatments of PRO and NTX produce impressive antitumor effects in the preclinical breast cancer model, and thereby may provide a new combinatorial treatment strategy with more clinical treatment modalities.
A Comparative Study of 2-Hour Interface Pressure in Different Angles of Laterally Inclined, Supine, and Fowler’s Position

Insufficient research exists for position change intervals to eradicate pressure ulcers. We tried to provide evidence for the position change interval by comparing peak pressure, risk area ratio, and the time to reach 30 mmHg and 60 mmHg, and presented this in detail, according to the angle in the three positions. The study conducted RCTs on a total of 64 healthy adults. For two hours, interface pressure measurements were compared with 30° and 90° tilting at the inclined, 0° and 45° head-of-bed (HOB) elevation at the supine, and 30° and 45° HOB elevation at the Fowler’s position. The peak pressure on 30° tilting remained less than 60 mmHg for 2 h, unlike 90° tilting. To reach 60 mmHg took 78.18 min at 30° tilting, within 30 min at the 30° supine, 30° and 45° at the Fowler’s position, and 39.55 min at 0° supine. The pressure difference according to the angles was only significant at 30° and 90° tilting, with no difference in the other groups. To prevent pressure ulcers, position changes are required every 2 h in the 30° tilting position, every 1.5 to 2 h at 0° supine, and at least every 1.5 h for all the other positions.
Comparative Analysis of Genome Editors Efficiency on a Model of Mice Zygotes Microinjection

Genome editing is an indispensable tool for functional genomics. The caveat of the genome-editing pipeline is a prevalence of error-prone non-homologous end joining over homologous recombination, while only the latter is suitable to introduce particularly desired genetic variants. To overcome this problem, a toolbox of genome engineering was appended by a variety of improved instruments. In this work, we compared the efficiency of a number of recently suggested improved systems for genome editing applied to the same genome regions on a murine zygote model via microinjection. As a result, we observed that homologous recombination utilizing an ssDNA template following sgRNA directed Cas9 cleavage is still the method of choice for the creation of animals with precise genome alterations.