Miracle-dz/UniFAR-FTUs huggingface dataset:
The TLR9 2848C/T Polymorphism Is Associated with the CMV DNAemia among HIV/CMV Co-Infected Patients

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and are essential components of the host’s innate immune response. The aim of this study was to determine the TLR9 genotype frequency and investigate the association between TLR9 polymorphisms and cytomegalovirus (CMV) DNAemia in human immunodeficiency virus (HIV)/CMV co-infected patients. A total of 205 HIV/CMV co-infected adults were screened for the presence of the four TLR9 polymorphisms (−1237T/C, −1486T/C, 1174G/A, and 2848C/T) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutation presented in at least one allele of the TLR9 2848C/T single nucleotide polymorphism (SNP) was associated with the occurrence of CMV DNAemia among HIV-infected patients with CMV co-infection (p = 0.004). The level of CMV DNA was higher in patients who were homozygous recessive or heterozygous for the 2848C/T polymorphism compared with those who had a wild-type genotype for this polymorphism (p = 0.005). Mutation detected in at least one allele of this SNP was also associated with a lower interferon type β (IFN-β) concentration (p = 0.048), while no relationships between TLR9 −1237T/C, −1486T/C, and 1174G/A SNPs and CMV DNAemia were observed. Our findings suggest that the mutation present in at least one allele of the TLR9 2848C/T SNP may be associated with the active CMV infection in HIV/CMV co-infected subjects.
Inflammatory Bowel Disease and Neutrophil–Lymphocyte Ratio: A Systematic Scoping Review

Neutrophil–lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on NLR and inflammatory bowel disease (IBD). PubMed, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Specialized Register, DOAJ, PDQT, Biosis Citation Index, Scopus, and Web of Science were systematically searched. A total of 2621 citations yielding 62 primary studies were synthesized under four categories: distinguishing patients with IBD from controls, disease activity differentiation, clinical outcome prediction, and association of NLR with other IBD biomarkers. Thirty-eight studies employed receiver operating characteristic (ROC) curve analysis to generate optimal NLR cutpoints for applications including disease activity differentiation and prediction of response to treatment. Among the most promising findings, NLR may have utility for clinical and endoscopic disease activity differentiation and prediction of loss of response to infliximab (IFX). Overall findings suggest NLR may be a promising IBD biomarker. Assessment of NLR is non-invasive, low cost, and widely accessible given NLR is easily calculated from blood count data routinely and serially monitored in patients with IBD. Further research is justified to elucidate how evaluation of NLR in research and clinical practice would directly impact the quality and cost of care for patients living with IBD.
Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

A preliminary study of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines as new potential antimicrobial drugs was performed. Special emphasis was placed on the selection of the structure of target pyridine derivatives with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R2–R4 (with different lengths of LPS in its structure) were used. Studied target compounds were provided with yields ranging from 53% to 91% by the lipase-catalyzed one pot multicomponent reaction of various aromatic aldehydes with malononitrile, and thiols. The presented work showed that the antibacterial activity of the studied pyridines depends on their structure and affects the LPS of bacteria. Moreover, the influence of the pyridines on bacteria possessing smooth and rough LPS and oxidative damage to plasmid DNA caused by investigated compounds was indicated. Additionally, the modification of the bacterial DNA with the tested compounds was performed to detect new potential oxidative damages, which are recognized by the Fpg protein. The obtained damage modification values of the analyzed compounds were compared with the modifications after antibiotics were used in this type of research. The presented studies demonstrate that 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines can be used as substitutes for known antibiotics. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.
Molecular Dynamics Study of Ion Transport in Polymer Electrolytes of All-Solid-State Li-Ion Batteries

Atomistic analysis of the ion transport in polymer electrolytes for all-solid-state Li-ion batteries was performed using molecular dynamics simulations to investigate the relationship between Li-ion transport and polymer morphology. Polyethylene oxide (PEO) and poly(diethylene oxide-alt-oxymethylene), P(2EO-MO), were used as the electrolyte materials, and the effects of salt concentrations and polymer types on the ion transport properties were explored. The size and number of LiTFSI clusters were found to increase with increasing salt concentrations, leading to a decrease in ion diffusivity at high salt concentrations. The Li-ion transport mechanisms were further analyzed by calculating the inter/intra-hopping rate and distance at various ion concentrations in PEO and P(2EO-MO) polymers. While the balance between the rate and distance of inter-hopping was comparable for both PEO and P(2EO-MO), the intra-hopping rate and distance were found to be higher in PEO than in P(2EO-MO), leading to a higher diffusivity in PEO. The results of this study provide insights into the correlation between the nanoscopic structures of ion solvation and the dynamics of Li-ion transport in polymer electrolytes.
Study on the Efficacy and Mechanism of Lycium barbarum Polysaccharide against Lead-Induced Renal Injury in Mice

Lead is one of the most common heavy metal pollutants in the environment. Prolonged exposure to lead will induce oxidative stress, inflammation, and apoptosis in the kidneys, which in turn causes kidney injury. Lycium barbarum polysaccharide (LBP) is well known for its numerous pharmacological properties. This study aims to explore the efficacy and mechanism of LBP against lead-induced kidney damage in mice. Symptoms of renal injury were induced in mice by using 25 mg/kg lead acetate (PbAc2), and different doses of LBP (200, 400, and 600 mg/kg BW) were orally administrated to PbAc2-treated mice for five weeks. The results of the pharmacodynamics experiment showed that the renal pathological damages, serum creatinine (Cre), blood urea nitrogen (BUN), and kidney index of PbAc2-treated mice could be significantly alleviated by treatment with LBP. Further, LBP treatment significantly increased the weight and feed intake of PbAc2-treated mice. The dose effect results indicated that a medium dose of LBP was superior to high and low doses. The results of mechanistic experiments showed that LBP could attenuate oxidative stress, inflammation, and apoptosis in the kidneys of mice with lead toxicity by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.
High Diversity of Leptospira Species Infecting Bats Captured in the Urabá Region (Antioquia-Colombia)

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the genus Leptospira. This zoonotic disease affects humans, domestic animals and wild animals. Colombia is considered an endemic country for leptospirosis; Antioquia is the second department in Colombia, with the highest number of reported leptospirosis cases. Currently, many studies report bats as reservoirs of Leptospira spp. but the prevalence in these mammals is unknown. The goal of this study was to better understand the role of bats as reservoir hosts of Leptospira species and to evaluate the genetic diversity of circulating Leptospira species in Antioquia-Colombia. We captured 206 bats in the municipalities of Chigorodó (43 bats), Carepa (43 bats), Apartadó (39 bats), Turbo (40 bats), and Necoclí (41 bats) in the Urabá region (Antioquia-Colombia). Twenty bats tested positive for Leptospira spp. infection (20/206—9.70%) and the species of infected bats were Carollia perspicillata, Dermanura rava, Glossophaga soricina, Molossus molossus, Artibeus planirostris, and Uroderma convexum. These species have different feeding strategies such as frugivorous, insectivores, and nectarivores. The infecting Leptospira species identified were Leptospira borgpetersenii (3/20–15%), Leptospira alexanderi (2/20–10%), Leptospira noguchii (6/20–30%), Leptospira interrogans (3/20–15%), and Leptospira kirschneri (6/20–30%). Our results showed the importance of bats in the epidemiology, ecology, and evolution of Leptospira in this host-pathogen association. This is the first step in deciphering the role played by bats in the epidemiology of human leptospirosis in the endemic region of Urabá (Antioquia-Colombia).
Lavage, Simethicone, and Prokinetics—What to Swallow with a Video Capsule

The development of new capsules now allows endoscopic diagnosis in all segments of the gastrointestinal tract and comes with new needs for differentiated preparation regimens. Although the literature is steadily increasing, the results of the conducted trials on preparation are sometimes conflicting. The ingestion of simethicone before gastric and small bowel capsule endoscopy for prevention of air bubbles is established. The value of a lavage before small bowel capsule endoscopy (SBCE) is recommended, although not supported by all studies. Ingestion in the morning before the procedure seems useful for the improvement of mucosa visualization. Lavage after swallowing of the capsule seems to improve image quality, and in some studies also diagnostic yield. Prokinetics has been used with first generation capsules to shorten gastric transit time and increase the rate of complete small bowel visualization. With the massively prolonged battery capacity of the new generation small bowel capsules, prokinetics are only necessary in significantly delayed gastric emptying as documented by a real-time viewer. Lavage is crucial for an effective colon capsule or pan-intestinal capsule endoscopy. Mainly high or low volume polyethylene glycol (PEG) is used. Apart from achieving optimal cleanliness, propulsion of the capsule by ingested boosts is required to obtain a complete passage through the colon within the battery lifetime. Boosts with low volume sodium picosulfate (NaP) or diatrizoate (gastrografin) seem most effective, but potentially have more side effects than PEG. Future research is needed for more patient friendly but effective preparations, especially for colon capsule and pan-intestinal capsule endoscopy.
Probiotics and Achyranthes bidentata Polysaccharides Improve Growth Performance via Promoting Intestinal Nutrient Utilization and Enhancing Immune Function of Weaned Pigs

Simple Summary It is frequent to see that in-feed antibiotics are added to piglets diets because of their enteric problems after weaning. However, in-feed antibiotics have been forbidden to used in livestock production since 1 July 2020 in China. Therefore, it is urgent to develop some promising alternatives to in-feed antibiotics. Probiotics and plant extracts are considered to be the potential replacements, which have been studied or applied in animal production. In our study, we found that probiotic or Achyranthes bidentata polysaccharides used alone or in combination, the combination augmenting the positive effect more than the independent supplement, could improve piglets’ growth performance via promoting intestinal nutrient digestion and absorption and enhancing immune funtion, and the beneficial role was comparable to that of the selected in-feed antibiotics. Abstract The experiment aimed to investigate the effects of probiotics and Achyranthes bidentata polysaccharides on the growth performance, nutrients digestibility, and immune function of weaned pigs. One hundred and twenty weaned pigs (about 7 kg BW, 23 ± 2 d) were allotted to five dietary treatments (CON: antibiotics-free basal diet; ANT: CON + antibiotics; PRO: CON + probiotics; ABPS: CON + Achyranthes bidentata polysaccharides; P-ABPS: PRO + ABPS) for a 28-day trial. Compared with CON, pigs in ANT, PRO, ABPS, and P-ABPS had greater (p < 0.05) ADG, ATTD of CP and GE, serum ALB, IgA and IL-2, duodenal intraepithelial lymphocyte, ileal VH and jejunal mucosa sIgA, but lower (p < 0.05) fecal scores, serum BUN, and IL-1β. Meanwhile, ANT, PRO, ABPS, and P-ABPS exhibited similar beneficial roles on growth performance, nutrients digestibility, serum parameters, and immune function. Interestingly, P-ABPS effects were similar to those obtained with ANT rather than with PRO or ABPS. In conclusion, Dietary PRO or ABPS used alone or in combination (P-ABPS), the combination augmenting the positive effect more than the independent supplement, could improve piglets’ growth performance via promoting intestinal nutrient digestion and absorption and enhancing immune function, indicating it had the potential to act as an alternative to in-feed antibiotics used in piglet diets.
The Role of Copper in the Regulation of Ferroportin Expression in Macrophages

The critical function of ferroportin (Fpn) in maintaining iron homeostasis requires complex and multilevel control of its expression. Besides iron-dependent cellular and systemic control of Fpn expression, other metals also seem to be involved in regulating the Fpn gene. Here, we found that copper loading significantly enhanced Fpn transcription in an Nrf2-dependent manner in primary bone-marrow-derived macrophages (BMDMs). However, prolonged copper loading resulted in decreased Fpn protein abundance. Moreover, CuCl2 treatment induced Fpn expression in RAW 264.7 macrophages at both the mRNA and protein level. These data suggest that cell-type-specific regulations have an impact on Fpn protein stability after copper loading. Transcriptional suppression of Fpn after lipopolysaccharide (LPS) treatment contributes to increased iron storage inside macrophages and may result in anemia of inflammation. Here, we observed that in both primary BMDMs and RAW 264.7 macrophages, LPS treatment significantly decreased Fpn mRNA levels, but concomitant CuCl2 stimulation counteracted the transcriptional suppression of Fpn and restored its expression to the control level. Overall, we show that copper loading significantly enhances Fpn transcription in macrophages, while Fpn protein abundance in response to CuCl2 treatment, depending on macrophage type and factors specific to the macrophage population, can influence Fpn regulation in response to copper loading.
Spatial Learning in a Virtual Environment: The Role of Self-Efficacy Feedback and Individual Visuospatial Factors

We examined the roles self-efficacy plays in environmental learning in terms of self-efficacy feedback and task-specific (navigation-based) self-efficacy. We manipulated self-efficacy using positive and neutral feedback to investigate the relationship between receiving positive feedback and environmental learning performance and subsequent recall. A total of 231 participants were administered visuospatial tasks, where 117 received positive feedback, and 114 received neutral feedback. Then, we tested environmental learning using route retracing, pointing, and map-completion tasks. Before each environmental task, participants evaluated their task-specific self-efficacy. A series of spatial self-reported preferences were gathered as well. Mediation models showed that receiving positive feedback after a visuospatial task influences environmental recall performance through the mediation of task-specific self-efficacy. Moreover, after accounting for experimental manipulation and gender, we found that task-specific self-efficacy, sense of direction, and visuospatial abilities influence spatial-recall task performance, even with some differences as a function of the specific recall tasks considered. Overall, our findings suggest that among individual characteristics, task-specific self-efficacy can sustain environmental learning. Furthermore, giving positive feedback can improve spatial self-efficacy before conducting spatial-recall tasks.
Neuromuscular Adjustments Following Sprint Training with Ischemic Preconditioning in Endurance Athletes: Preliminary Data

This preliminary study examined the effect of chronic ischemic preconditioning (IPC) on neuromuscular responses to high-intensity exercise. In a parallel-group design, twelve endurance-trained males (VO2max 60.0 ± 9.1 mL·kg−1·min−1) performed a 30-s Wingate test before, during, and after 4 weeks of sprint-interval training. Training consisted of bi-weekly sessions of 4 to 7 supra-maximal all-out 30-s cycling bouts with 4.5 min of recovery, preceded by either IPC (3 × 5-min of compression at 220 mmHg/5-min reperfusion, IPC, n = 6) or placebo compressions (20 mmHg, PLA, n = 6). Mechanical indices and the root mean square and mean power frequency of the electromyographic signal from three lower-limb muscles were continuously measured during the Wingate tests. Data were averaged over six 5-s intervals and analyzed with Cohen’s effect sizes. Changes in peak power output were not different between groups. However, from mid- to post-training, IPC improved power output more than PLA in the 20 to 25-s interval (7.6 ± 10.0%, ES 0.51) and the 25 to 30-s interval (8.8 ± 11.2%, ES 0.58), as well as the fatigue index (10.0 ± 2.3%, ES 0.46). Concomitantly to this performance difference, IPC attenuated the decline in frequency spectrum throughout the Wingate (mean difference: 14.8%, ES range: 0.88–1.80). There was no difference in root mean square amplitude between groups. These preliminary results suggest that using IPC before sprint training may enhance performance during a 30-s Wingate test, and such gains occurred in the last 2 weeks of the intervention. This improvement may be due, in part, to neuromuscular adjustments induced by the chronic use of IPC.
Eradication of Mature Bacterial Biofilms with Concurrent Improvement in Chronic Wound Healing Using Silver Nanoparticle Hydrogel Treatment

Biofilm-associated infections are a major cause of impaired wound healing. Despite the broad spectrum of anti-bacterial benefits provided by silver nanoparticles (AgNPs), these materials still cause controversy due to cytotoxicity and a lack of efficacy against mature biofilms. Herein, highly potent ultrasmall AgNPs were combined with a biocompatible hydrogel with integrated synergistic functionalities to facilitate elimination of clinically relevant mature biofilms in-vivo combined with improved wound healing capacity. The delivery platform showed a superior release mechanism, reflected by high biocompatibility, hemocompatibility, and extended antibacterial efficacy. In vivo studies using the S. aureus wound biofilm model showed that the AgNP hydrogel (200 µg/g) was highly effective in eliminating biofilm infection and promoting wound repair compared to the controls, including silver sulfadiazine (Ag SD). Treatment of infected wounds with the AgNP hydrogel resulted in faster wound closure (46% closure compared to 20% for Ag SD) and accelerated wound re-epithelization (60% for AgNP), as well as improved early collagen deposition. The AgNP hydrogel did not show any toxicity to tissue and/or organs. These findings suggest that the developed AgNP hydrogel has the potential to be a safe wound treatment capable of eliminating infection and providing a safe yet effective strategy for the treatment of infected wounds.
MIDESP: Mutual Information-Based Detection of Epistatic SNP Pairs for Qualitative and Quantitative Phenotypes

Simple Summary The interactions between SNPs, which are known as epistasis, can strongly influence the phenotype. Their detection is still a challenge, which is made even more difficult through the existence of background associations that can hide correct epistatic interactions. To address the limitations of existing methods, we present in this study our novel method MIDESP for the detection of epistatic SNP pairs. It is the first mutual information-based method that can be applied to both qualitative and quantitative phenotypes and which explicitly accounts for background associations in the dataset. Abstract The interactions between SNPs result in a complex interplay with the phenotype, known as epistasis. The knowledge of epistasis is a crucial part of understanding genetic causes of complex traits. However, due to the enormous number of SNP pairs and their complex relationship to the phenotype, identification still remains a challenging problem. Many approaches for the detection of epistasis have been developed using mutual information (MI) as an association measure. However, these methods have mainly been restricted to case–control phenotypes and are therefore of limited applicability for quantitative traits. To overcome this limitation of MI-based methods, here, we present an MI-based novel algorithm, MIDESP, to detect epistasis between SNPs for qualitative as well as quantitative phenotypes. Moreover, by incorporating a dataset-dependent correction technique, we deal with the effect of background associations in a genotypic dataset to separate correct epistatic interaction signals from those of false positive interactions resulting from the effect of single SNP×phenotype associations. To demonstrate the effectiveness of MIDESP, we apply it on two real datasets with qualitative and quantitative phenotypes, respectively. Our results suggest that by eliminating the background associations, MIDESP can identify important genes, which play essential roles for bovine tuberculosis or the egg weight of chickens.
Anti-Inflammatory Effects of RTD-1 in a Murine Model of Chronic Pseudomonas aeruginosa Lung Infection: Inhibition of NF-κB, Inflammasome Gene Expression, and Pro-IL-1β Biosynthesis

Vicious cycles of chronic airway obstruction, lung infections with Pseudomonas aeruginosa, and neutrophil-dominated inflammation contribute to morbidity and mortality in cystic fibrosis (CF) patients. Rhesus theta defensin-1 (RTD-1) is an antimicrobial macrocyclic peptide with immunomodulatory properties. Our objective was to investigate the anti-inflammatory effect of RTD-1 in a murine model of chronic P. aeruginosa lung infection. Mice received nebulized RTD-1 daily for 6 days. Bacterial burden, leukocyte counts, and cytokine concentrations were evaluated. Microarray analysis was performed on bronchoalveolar lavage fluid (BALF) cells and lung tissue homogenates. In vitro effects of RTD-1 in THP-1 cells were assessed using quantitative reverse transcription PCR, enzyme-linked immunosorbent assays, immunoblots, confocal microscopy, enzymatic activity assays, and NF-κB-reporter assays. RTD-1 significantly reduced lung white blood cell counts on days 3 (−54.95%; p = 0.0003) and 7 (−31.71%; p = 0.0097). Microarray analysis of lung tissue homogenates and BALF cells revealed that RTD-1 significantly reduced proinflammatory gene expression, particularly inflammasome-related genes (nod-like receptor protein 3, Mediterranean fever gene, interleukin (IL)-1α, and IL-1β) relative to the control. In vitro studies demonstrated NF–κB activation was reduced two-fold (p ≤ 0.0001) by RTD-1 treatment. Immunoblots revealed that RTD-1 treatment inhibited proIL-1β biosynthesis. Additionally, RTD-1 treatment was associated with a reduction in caspase-1 activation (FC = −1.79; p = 0.0052). RTD-1 exhibited potent anti-inflammatory activity in chronically infected mice. Importantly, RTD-1 inhibits inflammasome activity, which is possibly a downstream effect of NF-κB modulation. These findings support that this immunomodulatory peptide may be a promising therapeutic for CF-associated lung disease.