Miracle-dz/UniFAR-FTUs huggingface dataset:
Requirements for Terpene Cyclizations inside the Supramolecular Resorcinarene Capsule: Bound Water and its Protonation Determine the Catalytic Activity.

The elucidation of the requirements for efficient catalysis within supramolecular host systems is an important prerequisite for developing novel supramolecular catalysts. The resorcinarene hexamer has recently been shown to be the first supra-molecular catalyst to promote the tail-to-head terpene cyclization in a biomimetic fashion. We herein present the synthesis of a number of resorcinarene-based macrocycles capable of self-assembly, and compare the corresponding assemblies regarding their catalytic activity in the cyclization of monoterpenes. The assemblies were investigated in detail with respect to a number of properties including the encapsulation of substrate, and ion pairs, the structural incorporation of water and the response to externally added acid (HCl). The results obtained strongly indicate that water incorporated into the hydrogen bond network of the self-assembled structure plays an integral role for catalysis, effectively acting as a proton shuttle to activate the encapsulated substrate. These findings are also supported by molecular dynamics simulations, providing further insight into the protonation pathway and the relative energies of the intermediates involved.
Sex-Specific Differences in Motor-Unit Remodeling in a Mouse Model of ALS

Abstract Progressive loss of neuromuscular junctions (NMJs) is an early event in amyotrophic lateral sclerosis (ALS), preceding the global degeneration of motor axons and being accompanied by new axonal sprouting within the same axonal arbor. Some aspects of ALS onset and progression seem to be affected by sex in animal models of the disease. However, whether there are sex-specific differences in the pattern or time course of NMJ loss and repair within single motor axons remains unknown. We performed further analysis of a previously published in vivo dataset, obtained from male and female SOD1G37R mice. We found that NMJ losses are as frequent in male and female motor axons but, intriguingly, axonal sprouting is more frequent in female than male mice, resulting in a net increase of axonal arborization. Interestingly, these numerous new axonal branches in female mice are associated with a slightly faster decline in grip strength, increased NMJ denervation, and reduced α-motor neuron survival. Collectively, these results suggest that excessive axonal sprouting and motor-unit (MU) expansion in female SOD1G37R mice are maladaptive during ALS progression.
Fabrication of Cellulose Nanocrystal-g-Poly(Acrylic Acid-Co-Acrylamide) Aerogels for Efficient Pb(II) Removal

In this work, cellulose nanocrystals (CNCs) obtained by the acid hydrolysis of waste bamboo powder were used to synthesize cellulose nanocrystal-g-poly(acrylic acid-co-acrylamide) (CNC-g-P(AA/AM)) aerogels via graft copolymerization followed by freeze-drying. The structure and morphology of the resulting aerogels were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), and the CNC-g-P(AA/AM) aerogels exhibited excellent absorbent properties and adsorption capacities. Subsequent Pb(II) adsorption studies showed that the kinetic data followed the pseudo-second-order equation, while the adsorption isotherms were best described using the Langmuir model. The maximum Pb(II) adsorption capacity calculated by the Langmuir model reached up to 366.3 mg/g, which is a capacity that outperformed that of the pure CNC aerogel. The CNC-g-P (AA/AM) aerogels become structurally stable through chemical cross-linking, which enabled them to be easily regenerated in HCl solution and retain the adsorption capacity after repeated use. The aerogels were found to maintain 81.3% removal efficiency after five consecutive adsorption–desorption cycles. Therefore, this study demonstrated an effective method for the fabrication of an aerogel adsorbent with an excellent reusability in the effective removal of Pb(II) from aqueous solutions.
Arsenic Toxicity: Molecular Targets and Therapeutic Agents

High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.
Effect of copper concentration on the structure and properties of Al–Cu–Fe and Al–Cu–Ni melts

We address a relationship between properties of liquid and solid states by comparing structural characteristics and viscosity in Al–Cu–Fe and Al–Cu–Ni melts. The former system forms an equilibrium quasicrystalline phase but the latter does not. We show that the concentration behavior of the viscosity, melting temperature and characteristics of the chemical short-range order correlate with each other. The main structural differences between the melts are related to the peculiarities of their electronic structure, which is the same for liquid and solid states near the melting temperature.
Stem Cell-Derived Exosomes in Autism Spectrum Disorder

Neurodevelopmental lifelong pathologies defined by problems with social interaction, communication capacity and presence of repetitive/stereotyped clusters of behavior and interests are grouped under the definition of autism spectrum disorder (ASD). ASD prevalence is still increasing, indicating the need to identify specific biomarkers and novel pharmacotherapies. Neuroinflammation and neuro-immune cross-talk dysregulation are specific hallmarks of ASD, offering the possibility of treating these disorders by stem cell therapy. Indeed, cellular strategies have been postulated, proposed and applied to ASD. However, less is known about the molecular action mechanisms of stem cells. As a possibility, the positive and restorative effects mediated by stem cells could be due to their paracrine activity, by which stem cells produce and release several ameliorative and anti-inflammatory molecules. Among the secreted complex tools, exosomes are sub-organelles, enriched by RNA and proteins, that provide cell-to-cell communication. Exosomes could be the mediators of many stem cell-associated therapeutic activities. This review article describes the potential role of exosomes in alleviating ASD symptoms.
The utility of elastography during EBUS‐TBNA in a population with a high prevalence of anthracosis

Ultrasound elastography, is a pioneer sonographic modality that is conducted during endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) in order to increase the accuracy of sampling location. The current study aims to evaluate the usefulness of elastography during EBUS‐TBNA in a population with a high prevalence of anthracosis.
IbBBX24 Promotes the Jasmonic Acid Pathway and Enhances Fusarium Wilt Resistance in Sweet Potato

BBX24 regulates the jasmonic acid pathway, Fusarium wilt resistance, and storage root yield in sweet potato, providing a candidate target gene for enhancing pathogen resistance without yield penalty. Cultivated sweet potato (Ipomoea batatas) is an important source of food for both humans and domesticated animals. Here, we show that the B-box (BBX) family transcription factor IbBBX24 regulates the jasmonic acid (JA) pathway in sweet potato. When IbBBX24 was overexpressed in sweet potato, JA accumulation increased, whereas silencing this gene decreased JA levels. RNA sequencing analysis revealed that IbBBX24 modulates the expression of genes involved in the JA pathway. IbBBX24 regulates JA responses by antagonizing the JA signaling repressor IbJAZ10, which relieves IbJAZ10’s repression of IbMYC2, a JA signaling activator. IbBBX24 binds to the IbJAZ10 promoter and activates its transcription, whereas it represses the transcription of IbMYC2. The interaction between IbBBX24 and IbJAZ10 interferes with IbJAZ10’s repression of IbMYC2, thereby promoting the transcriptional activity of IbMYC2. Overexpressing IbBBX24 significantly increased Fusarium wilt disease resistance, suggesting that JA responses play a crucial role in regulating Fusarium wilt resistance in sweet potato. Finally, overexpressing IbBBX24 led to increased yields in sweet potato. Together, our findings indicate that IbBBX24 plays a pivotal role in regulating JA biosynthesis and signaling and increasing Fusarium wilt resistance and yield in sweet potato, thus providing a candidate gene for developing elite crop varieties with enhanced pathogen resistance but without yield penalty.
Influence of Pore Size and Fatigue Loading on NaCl Transport Properties in C-S-H Nanopores: A Molecular Dynamics Simulation

The transport properties of chloride ions in cement-based materials are one of the major deterioration mechanisms for reinforced concrete (RC) structures. This paper investigates the influence of pore size and fatigue loading on the transport properties of NaCl in C-S-H nanopores using molecular dynamics (MD) simulations. Molecular models of C-S-H, NaCl solution, and C-S-H nanopores with different pore diameters are established on a microscopic scale. The distribution of the chloride ion diffusion rate and the diffusion coefficient of each particle are obtained by statistically calculating the variation of atomic displacement with time. The results indicate that the chloride ion diffusion rate perpendicular to C-S-H nanopores under fatigue loading is 4 times faster than that without fatigue loading. Moreover, the diffusion coefficient of water molecules and chloride ions in C-S-H nanopores increases under fatigue loading compared with those without fatigue loading. The diffusion coefficient of water molecules in C-S-H nanopores with a pore size of 3 nm obtained from the MD simulation is 1.794 × 10−9 m2/s, which is slightly lower than that obtained from the experiment.
PD-1+ stemlike CD8 T cells are resident in lymphoid tissues during persistent LCMV infection

Significance T cell immunity is important in the control of chronic viral infections and cancer. Recent studies have identified a population of programmed cell death 1 (PD-1+) stemlike CD8 T cells that provide the proliferative burst after PD-1–directed immunotherapy. In this study, we have examined the migratory properties of these stemlike CD8 T cells using the mouse model of chronic lymphocytic choriomeningitis virus infection. We show that these quiescent stemlike CD8 T cells do not circulate and are resident in lymphoid tissues, providing a protective niche for their maintenance during chronic infection. These results raise important questions regarding the role of specialized niches within lymphoid tissues and for developing new immunotherapeutic approaches targeting these PD-1+ stemlike CD8 T cells. The migratory patterns of virus-specific CD8 T cells during chronic viral infection are not well understood. To address this issue, we have done parabiosis experiments during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. We found that despite the high frequency of virus-specific CD8 T cells in both lymphoid and nonlymphoid tissues there was minimal migration of virus-specific CD8 T cells between the chronically infected conjoined parabiont mice. This was in contrast to parabionts between mice that had undergone an acute LCMV infection where virus-specific CD8 T cells established equilibrium demonstrating circulation of memory T cells generated after viral clearance. We have identified a population of PD-1+ TCF1+CXCR5+Tim-3- stemlike virus-specific CD8 T cells that reside in lymphoid tissues and act as resource cells for maintaining the T cell response during chronic infection. These are the cells that proliferate and give rise to the more terminally differentiated PD-1+ CXCR5-Tim-3+ CD8 T cells. Both the stemlike CD8 T cells and their terminally differentiated progeny showed minimal migration during chronic infection and the few LCMV-specific CD8 T cells that were present in circulation were the recently emerging progeny from the stemlike CD8 T cells. The PD-1+ TCF1+CXCR5+ stemlike CD8 T cells were truly resident in lymphoid tissues and did not circulate in the blood. We propose that this residency in specialized niches within lymphoid tissues is a key aspect of their biology and is essential for maintaining their quiescence and stemlike program under conditions of a chronic viral infection.
Risk for Colorectal Neoplasia in Patients With Helicobacter pylori Infection: A Systematic Review and Meta-analysis

OBJECTIVES: Helicobacter pylori may reportedly be associated with extragastric malignancy beyond gastric cancer. The present study aimed to evaluate the association between H. pylori infection and colorectal neoplasia through a systematic review and meta-analysis. METHODS: The literature search aimed to retrieve all relevant studies published up to September 2019 that examined the risk for colorectal neoplasia including colorectal adenoma, advanced adenoma, and cancer in patients with H. pylori infection. Meta-analysis was performed to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). If publication bias was observed, the pooled OR was adjusted using the trim-and-fill method. RESULTS: Forty-eight studies including 171,045 patients were evaluated, of which 24, 8, and 31 reported H. pylori-associated risk for adenoma, advanced adenoma, and cancer, respectively. H. pylori infection was associated with a significantly higher risk for colorectal adenoma (pooled OR 1.49 [95% CI 1.37–1.62]). H. pylori infection was also associated with a higher risk for advanced colorectal adenoma (pooled OR 1.50 [95% CI 1.28–1.75]). The risk for colorectal cancer in patients with H. pylori infection was also identified (pooled OR 1.44 [95% 1.26–1.65]). Although publication bias was identified in the analysis for colorectal adenoma, the pooled estimate was not significantly changed after adjustment (pooled OR 1.39 [95% CI 1.27–1.52]). DISCUSSION: Although this meta-analysis based on the observational studies could not show causality, it demonstrated that colorectal adenoma, advanced adenoma, and cancer were all associated with H. pylori infection.
RNA decay during gammaherpesvirus infection reduces RNA polymerase II occupancy of host promoters but spares viral promoters

In mammalian cells, widespread acceleration of cytoplasmic mRNA degradation is linked to impaired RNA polymerase II (Pol II) transcription. This mRNA decay-induced transcriptional repression occurs during infection with gammaherpesviruses including Kaposi’s sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), which encode an mRNA endonuclease that initiates widespread RNA decay. Here, we show that MHV68-induced mRNA decay leads to a genome-wide reduction of Pol II occupancy at mammalian promoters. This reduced Pol II occupancy is accompanied by down-regulation of multiple Pol II subunits and TFIIB in the nucleus of infected cells, as revealed by mass spectrometry-based global measurements of protein abundance. Viral genes, despite the fact that they require Pol II for transcription, escape transcriptional repression. Protection is not governed by viral promoter sequences; instead, location on the viral genome is both necessary and sufficient to escape the transcriptional repression effects of mRNA decay. We propose a model in which the ability to escape from transcriptional repression is linked to the localization of viral DNA within replication compartments, providing a means for these viruses to counteract decay-induced transcript loss.
JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing

In healthy individuals, the healing of soft tissues such as skin after pathological insult or post injury follows a relatively predictable and defined series of cell and molecular processes to restore tissue architecture and function(s). Healing progresses through the phases of hemostasis, inflammation, proliferation, remodeling, and concomitant with re-epithelialization restores barrier function. Soft tissue healing is achieved through the spatiotemporal interplay of multiple different cell types including neutrophils, monocytes/macrophages, fibroblasts, endothelial cells/pericytes, and keratinocytes. Expressed in most cell types, c-Jun N-terminal kinases (JNK) are signaling molecules associated with the regulation of several cellular processes involved in soft tissue wound healing and in response to cellular stress. A member of the mitogen-activated protein kinase family (MAPK), JNKs have been implicated in the regulation of inflammatory cell phenotype, as well as fibroblast, stem/progenitor cell, and epithelial cell biology. In this review, we discuss our understanding of JNKs in the regulation of cell behaviors related to tissue injury, pathology, and wound healing of soft tissues. Using models as diverse as Drosophila, mice, rats, as well as human tissues, research is now defining important, but sometimes conflicting roles for JNKs in the regulation of multiple molecular processes in multiple different cell types central to wound healing processes. In this review, we focus specifically on the role of JNKs in the regulation of cell behavior in the healing of skin, cornea, tendon, gingiva, and dental pulp tissues. We conclude that while parallels can be drawn between some JNK activities and the control of cell behavior in healing, the roles of JNK can also be very specific modes of action depending on the tissue and the phase of healing.
VisBicluster: A Matrix-Based Bicluster Visualization of Expression Data

One of the main methods to analyze gene expression data is biclustering, a nonsupervised technique, which consists of selection subgroups of genes that co-expressed under subgroups of experimental conditions. A large number of biclustering algorithms have been developed to classify gene expression data. These algorithms can give as output a large number of overlapped biclusters, whose visualization still requires deeper studies. We present VisBicluster, a web-based interactive visualization tool for displaying biclustering results. The developed visualization technique consists of laying out the generated biclusters in a two-dimensional matrix where each bicluster is represented as a column and each overlap between a set of biclusters is represented as a row. A search interface for the user is developed to query the matrix of bicluster intersection and visualize the results matching the queries. Our tool supports many interactive features such as sorting, zooming, and details-on-demand. We proved the usefulness of VisBicluster with biclustering results from real and synthetic datasets. Besides, we performed a user study with 14 participants to illustrate the clarity and simplicity of overlap representation with our tool.
A Bayesian Formulation of Coherent Point Drift

Coherent point drift is a well-known algorithm for solving point set registration problems, i.e., finding corresponding points between shapes represented as point sets. Despite its advantages over other state-of-the-art algorithms, theoretical and practical issues remain. Among theoretical issues, (1) it is unknown whether the algorithm always converges, and (2) the meaning of the parameters concerning motion coherence is unclear. Among practical issues, (3) the algorithm is relatively sensitive to target shape rotation, and (4) acceleration of the algorithm is restricted to the use of the Gaussian kernel. To overcome these issues and provide a different and more general perspective to the algorithm, we formulate coherent point drift in a Bayesian setting. The formulation brings the following consequences and advances to the field: convergence of the algorithm is guaranteed by variational Bayesian inference; the definition of motion coherence as a prior distribution provides a basis for interpretation of the parameters; rigid and non-rigid registration can be performed in a single algorithm, enhancing robustness against target rotation. We also propose an acceleration scheme for the algorithm that can be applied to non-Gaussian kernels and that provides greater efficiency than coherent point drift.
MORTALITY OF PATIENTS WITH UVEAL MELANOMA DETECTED BY DIABETIC RETINOPATHY SCREENING.

PURPOSE To investigate whether early detection and treatment of uveal melanoma by screening was associated with a lower mortality rate. METHODS Retrospective assessment of prospectively collected data comparing 132 patients with uveal melanoma referred by the National Diabetic Screening Service with 608 control patients referred through other means. RESULTS Mean tumor diameter was smaller in the diabetic screening group (11.1 mm vs. 12.5 mm) as was tumor thickness (3.4 mm vs. 5.4 mm). The prevalence of high-risk monosomy 3 was also lower (17/40, 43% vs. 62/110, 56%). Despite a higher rate of systemic comorbidities in the patients diagnosed through screening and despite older age at diagnosis, the 5-year all-cause mortality was similar in both groups (17% vs. 20%); however, the metastatic mortality was lower in the diabetic screening group (11/132, 8% vs. 95/608, 16%). CONCLUSION Despite higher rates of comorbidities, the patients detected at diabetic screening had a lower 5-year mortality rate. The diabetic screening programme enabled detection and treatment of posterior uveal melanomas at an earlier stage. However, the confounding factors of lead and length time bias are not to be ignored.
Interventions for Couples.

Because relationship discord and dissolution are common and costly, interventions are needed to treat distressed couples and to prevent distress among vulnerable couples. We review meta-analytic evidence showing that 60-80% of distressed couples benefit from behavioral and emotion-focused approaches to couple therapy, but we also note that treatment effects are weaker in actual clinical practice than in controlled studies, dissipate following treatment for about half of all couples, and may be explained by factors that are common across models. Meta-analyses of prevention programs reveal reliable but smaller effects, reflecting a need to know more about whether and how communication mediates effects, about how risk and diversity moderate effects, and about how technology-enabled interventions can reduce attrition in vulnerable populations. Interventions for couples are improving and expanding, but critical questions remain about how and for whom they work. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 16 is May 7, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.