Discovery of a Hidden Spermidine Synthase Binding Site and Inhibitors through , and X-ray Crystallography.

In drug discovery research, the selection of promising binding sites and understanding the binding mode of compounds are crucial fundamental studies. The current understanding of the proteins-ligand binding model extends beyond the simple lock and key model to include the induced-fit model, which alters the conformation to match the shape of the ligand, and the pre-existing equilibrium model, selectively binding structures with high binding affinity from a diverse ensemble of proteins. Although methods for detecting target protein binding sites and virtual screening techniques using docking simulation are well-established, with numerous studies reported, they only consider a very limited number of structures in the diverse ensemble of proteins, as these methods are applied to a single structure.

Crystallographic Study of Product Phases of Carbothermic Reduction and Nitridation of Hafnium Dioxide.

Details of the carbothermic reduction/nitridation to synthesize hafnium nitride (HfN) and hafnium carbide (HfC) are scarce in the literature. Therefore, this current study was carried out to evaluate two pathways for synthesizing these two refractory materials: direct nitridation and carbothermic reduction/nitridation. Two mixtures of hafnium dioxide and carbon with C/HfO molar ratios of 2.

Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism.

Background: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation.

Objectives: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal.

Methods: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference.

A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America.

Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults. Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen, has been proven effective in this patient subgroup.

Efficacy and safety following two or more years of vagus nerve stimulation (VNS Therapy) in pediatric patients with drug-resistant epilepsy enrolled in a Russian VNS Registry.

Introduction: Following approval in 2009 of vagus nerve stimulation (VNS Therapy) for drug-resistant epilepsy (DRE) in the Russian Federation, this is the first multicenter study across Russia to evaluate the safety and efficacy of adjunctive VNS Therapy.

Methods: The retrospective, observational registry included 58 pediatric patients with DRE (5-17 years old at implantation) who had ≥2 years of VNS. To ensure a robust evaluation process, changes in seizure frequency were evaluated for all seizure types as well as "most disabling" seizures (defined as seizures accompanied by falls, physical trauma, and/or incontinence in the absence of preventative measures).

Hominoid SVA-lncRNA AK057321 targets human-specific SVA retrotransposons in SCN8A and CDK5RAP2 to initiate neuronal maturation.

SINE-VNTR-Alu (SVA) retrotransposons arose and expanded in the genome of hominoid primates concurrent with the slowing of brain maturation. We report genes with intronic SVA transposons are enriched for neurodevelopmental disease and transcribed into long non-coding SVA-lncRNAs. Human-specific SVAs in microcephaly CDK5RAP2 and epilepsy SCN8A gene introns repress their expression via transcription factor ZNF91 to delay neuronal maturation.

Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms.

Azacitidine is a mainstay of therapy for myelodysplastic syndrome (MDS)-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their posttreatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms.

UBE3A and transsynaptic complex NRXN1-CBLN1-GluD1 in a hypothalamic VMHvl-arcuate feedback circuit regulates aggression.

The circuit origins of aggression in autism spectrum disorder remain undefined. Here we report -expressing glutamatergic neurons in ventrolateral division of ventromedial hypothalamus (VMHvl) drive intermale aggression. Aggression is increased due to increases of gene dosage in the VMHvl neurons when modeling autism due to maternal 15q11-13 triplication.

A Healthy Vaginal Microbiota Remains Stable during Oral Probiotic Supplementation: A Randomised Controlled Trial.

The primary objective of this randomised, placebo-controlled, triple-blind study was to assess whether orally consumed La-14 (La-14) and HN001 (HN001) colonise a healthy human vagina. Furthermore, potential effects on vaginal microbiota and immune markers were explored. Fifty women devoid of vaginal complaints (Nugent score 0-3 and vaginal pH ≤ 4.

Dynamic changes in clinical biomarkers of cardiometabolic diseases by changes in exercise behavior, and network comparisons: a community-based prospective cohort study in Korea.

Objectives: Lifestyles, including exercise behaviors, change continually over time. This study examined whether the clinical biomarkers (CBs) related to cardiometabolic diseases (CMDs) and their relationships differed with changes in exercise behavior.

Methods: The Ansan-Ansung cohort study (third to fifth phases; n=2,668) was used in the current study.

Developing a Novel Method for the Analysis of Spinal Cord-Penile Neurotransmission Mechanisms.

Sexual dysfunction can be caused by impaired neurotransmission from the peripheral to the central nervous system. Therefore, it is important to evaluate the input of sensory information from the peripheral genital area and investigate the control mechanisms in the spinal cord to clarify the pathological basis of sensory abnormalities in the genital area. However, an in vivo evaluation system for the spinal cord-penile neurotransmission mechanism has not yet been developed.

MRI-visible Perivascular Spaces in the Neonatal Brain.

Background Mounting evidence suggests that perivascular spaces (PVSs) visible at MRI reflect the function of the glymphatic system. Understanding PVS burden in neonates may guide research on early glymphatic-related pathologic abnormalities. Purpose To perform a visual and volumetric evaluation of PVSs that are visible at MRI in neonates and to evaluate potential associations with maturation, sex, and preterm birth.

Hyaluronan driven by epithelial aPKC deficiency remodels the microenvironment and creates a vulnerability in mesenchymal colorectal cancer.

Mesenchymal colorectal cancer (mCRC) is microsatellite stable (MSS), highly desmoplastic, with CD8 T cells excluded to the stromal periphery, resistant to immunotherapy, and driven by low levels of the atypical protein kinase Cs (aPKCs) in the intestinal epithelium. We show here that a salient feature of these tumors is the accumulation of hyaluronan (HA) which, along with reduced aPKC levels, predicts poor survival. HA promotes epithelial heterogeneity and the emergence of a tumor fetal metaplastic cell (TFMC) population endowed with invasive cancer features through a network of interactions with activated fibroblasts.

Efficacy and Safety of a Novel Hemostatic Peptide Solution During Endoscopic Submucosal Dissection: A Multicenter Randomized Controlled Trial.

Introduction: To compare the effectiveness of the novel hemostatic peptide, TDM-621, with that of conventional hemostatic methods in treating intraoperative blood oozing during endoscopic submucosal dissection (ESD).

Methods: This multicenter, open-label, randomized controlled trial involved 227 patients with gastric and rectal epithelial tumors in whom ESD was indicated. Patients in whom the source of blood oozing was difficult to identify with waterjet washing during the procedure and required hemostasis with hemostatic forceps were randomly assigned to the TDM-621 and control groups.

Minimal residual disease in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation.

Improved biomarkers are required to guide the optimal use of autologous stem cell transplantation (ASCT) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples, post-ASCT peripheral blood mononuclear cell (PBMC), and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples.

MRI-visible Dilated Perivascular Space in the Brain by Age: The Human Connectome Project.

Background Dilated perivascular spaces (dPVS) are associated with aging and various disorders; however, the effect of age on dPVS burden in young populations and normative data have not been fully evaluated. Purpose To investigate the dPVS burden and provide normative data according to age in a healthy population, including children. Materials and Methods In this retrospective study, three-dimensional T2-weighted brain MRI scans from the Human Connectome Project data sets were used for visual grading (grade 0, 1, 2, 3, 4 for 0, 1-10, 11-20, 21-40, and >40 dPVS on a single section of either hemispheric region) and automated volumetry of dPVS in basal ganglia (BGdPVS) and white matter (WMdPVS).

The synergetic effect of lanthanide (La and Ce) and N co-doping of ZnO NPs for high-rate photocatalytic phenol degradation.

Simultaneously, lanthanide and N-modified ZnO NPs were synthesized and applied for the photocatalytic phenol degradation under LED irradiation. Among La and Ce, Ce-doped ZnO exhibited more efficiently photocatalytic activity. XRD analysis confirmed that most of Ce was oxidized to CeO/CeO over the photocatalyst surface as a secondary phase.

Enhancing Sweat Rate Using a Novel Device for the Treatment of Congestion in Heart Failure.

Background: Current treatment of fluid retention in heart failure relies primarily on diuretics. However, adequate decongestion is not achieved in many patients. We aimed to study the feasibility and short-term performance of a novel approach to remove fluids and sodium directly from the interstitial compartment by enhancing sweat rate.

NaPON Doping of NaPS Glass and Its Effects on the Structure and Properties of Mixed Oxy-Sulfide-Nitride Phosphate Glass.

The preparation, properties, and short-range order (SRO) structures of glasses in the series (1-)[2/3NaS + 1/3PS] + [1/3NaS + 2/3NaPON] = NaPSON, where 0 ≤ ≤ 0.5 (NaPSON), are reported on. In this study, these mixed oxy-sulfide-nitride (MOSN) glasses were prepared by adding the nitrided material NaPON; = 0.

Edaravone Administered Orally and Via Nasogastric Tube in Healthy Adults: A Comparative Bioavailability Phase 1 Study.

Intravenous edaravone is used to treat patients with amyotrophic lateral sclerosis. This randomized, open-label, two-way crossover, single-dose phase 1 study compared the relative bioavailability of a newly developed edaravone oral suspension when administered orally and via a nasogastric tube (NGT) as a model of percutaneous endoscopic gastrostomy tube administration in healthy adult subjects. Thirty-six subjects were randomly assigned to one of two groups, with 18 per group.

Usefulness of Bifidobacterium longum BB536 in Elderly Individuals With Chronic Constipation: A Randomized Controlled Trial.

Introduction: Few reports exist regarding the therapeutic effects of probiotics on chronic constipation in elderly individuals. This study evaluated the effects of Bifidobacterium longum BB536 in elderly individuals with chronic constipation.

Methods: This was a randomized, double-blind placebo-controlled, parallel-group superiority trial in Japan (UMIN 000033031).

Metabologenomic Approach Reveals Intestinal Environmental Features Associated with Barley-Induced Glucose Tolerance Improvements in Japanese: A Randomized Controlled Trial.

(1) Background: Consumption of barley has been known to exert beneficial effects on glucose tolerance; however, it has also been reported that there are inter-individual differences in these responses. Recent evidence has suggested that these individual differences are mediated by the gut microbiota. (2) Methods: In the present study, we aimed to understand the relationship between the intestinal environment, including intestinal microbiome and their metabolome, and glucose tolerance.