Development of an environmentally responsive fluorescent ligand for vitamin D receptor.

Vitamin D receptor (VDR) plays a critical role in regulating multiple biological processes, including bone metabolism and cell differentiation, by mediating transcriptional activation in response to ligand binding. We have constructed an environmentally fluorescent probe 2 for VDR to facilitate real-time observation of its ligand-dependent conformational changes in living cells. This probe 2 was synthesized by introducing a dansyl fluorophore via an ethynyl group at the C11 position of 1α,25(OH)2D3.

Covalent Plant Natural Product that Potentiates Antitumor Immunity.

Despite the unprecedented therapeutic potential of immune checkpoint antibody therapies, their efficacy is limited partly by the dysfunction of T cells within the cancer microenvironment. Combination therapies with small molecules have also been explored, but their clinical implementation has been met with significant challenges. To search for antitumor immunity activators, the present study developed a cell-based system that emulates cancer-attenuated T cells.

d-Galactose-Esterification of a Fungal Polyketide Catalyzed by a Carnitine Acyltransferase Domain.

While sugar-containing natural products are commonly biosynthesized via glycosyltranferases using sugar-UDP as the electrophile, nature has evolved alternative strategies of glyco-modification to expand the diversity of natural products. Hydroxyl groups on sugars can serve as nucleophiles in the release of polyketide products from polyketide synthases. Herein, we demonstrate a highly reducing polyketide synthase (HRPKS) from the biocontrol fungus Trichoderma afroharzianum T22, which is terminated with a carnitine acyltransferase (cAT) domain, catalyzes the biosynthesis of a d-galactose esterified polyketide named as trichogalactin.

A rare case of endotracheal tube cuff leakage with no detectable decrease in cuff pressure.

Background: Common causes of air leakage around an endotracheal tube include insufficient endotracheal tube cuff inflation and damage to the cuff, while damage to the pilot balloon or pilot balloon tubing is relatively rare.

Case Presentation: A 74-year-old female with vertebral osteomyelitis was scheduled for an extreme lateral interbody fusion followed posterior fixation. A fiber-optic light was utilized as part of the surgical illuminator.

Topology-selective photo-crosslinking of G-quadruplexes dual G-quartet and groove recognition.

The novel photo-crosslinking ligand 6OTD-Bp, bearing an alkylamine benzophenone (Bp) with macrocyclic hexaoxazole (6OTD), was shown to preferentially ligate with hybrid G4s through recognizing both G-quartets and their characteristic wide groove. Higher crosslinking yield was observed for hybrid G4 with wider grooves.

Unique characteristics of bone union at the infected vertebrae after minimally invasive posterior fixation without bone grafting in thoracolumbar pyogenic spondylitis: a retrospective multicenter cohort study.

Background: The current study aimed to evaluate the bone union rate between infected vertebrae after minimally invasive posterior fixation without bone grafting in thoracolumbar pyogenic spondylitis.

Methods: This retrospective multicenter cohort study evaluated 75 patients of posterior fixation for thoracolumbar pyogenic spondylitis that have been recorded at six relevant institutions from January 2016 to December 2022. Data on age, sex, location of infected vertebrae, number of infected disks, comorbidity, Pola classification, number of vertebrae fixed according to surgery, implant failure requiring revision surgery, and distance according to the type of infected vertebrae after surgery were evaluated.

Discovery and Structural Analysis of Metabolites of Vitamin D Lactones.

25-Hydroxyvitamin D-23,26-lactone (1) and 1α,25-dihydroxyvitamin D-23,26-lactone (2) have long been considered as among the end metabolites of vitamin D. Recently, however, we found that these lactones exhibit biological activity related to the β-oxidation of fatty acids. We hypothesized that a metabolic pathway might exist to inactivate their physiological activity.

The prebiotic effect of 1-kestose in low-birth-weight neonates taking bifidobacteria: a pilot randomized trial in comparison with lactulose.

Probiotics such as bifidobacteria have been given to low-birth-weight neonates (LBWNs) at risk for a disrupted gut microbiota leading to the development of serious diseases such necrotizing enterocolitis. Recently prebiotics such as lactulose are used together with bifidobacteria as synbiotics. However, faster and more powerful bifidobacteria growth is desired for better LBWN outcomes.

Prospective hospital-based cohort studies of Respiratory Syncytial Virus (RSV) infections in infants under one year during and after the SARS-CoV-2 pandemic in Japan.

Objectives: In Japan, population-based epidemiological data on respiratory syncytial virus (RSV) infections are limited. To elucidate the epidemiology of RSV before the introduction of new prophylactic drugs, we conducted a population-based study during and after the SARS-CoV-2 pandemic.

Methods: This study was performed in four hospitals in Chiba City and three hospitals in Ichihara City.

Synthesis of Saxitoxin Biosynthetic Intermediates: Reveal the Mechanism for Formation of its Tricyclic Skeleton in Biosynthesis.

The synthesis and biosynthesis of the complex saxitoxin (STX) structure have garnered significant interest. Previously, we hypothesized that the tricyclic skeleton of STX originates from the monocyclic precursor 11-hydroxy-IntC'2 during biosynthesis, although direct evidence has been lacking. In this study, we identified conditions to synthesize a proposed tricyclic biosynthetic intermediate, 12,12-dideoxy-decarbamoyloxySTX (dd-doSTX), along with its 6-epimer (6-epi-dd-doSTX) and a bicyclic compound, in a single step from di-Boc protected 11-hydroxy-IntC'2.

Effectiveness of isavuconazole in invasive cerebral aspergillosis during hematopoietic stem cell transplantation in a pediatric patient with myelodysplastic syndrome: A case report.

Pediatric myelodysplasia syndrome is often characterized by hypoplastic bone marrow morphology and predisposition to infection. Invasive aspergillosis during hematopoietic stem cell transplantation poses a significant threat and often requires voriconazole (VRCZ) therapy. However, difficulties in achieving appropriate VRCZ blood levels due to drug interactions have prompted the exploration of alternative treatments, such as isavuconazole (ISCZ).

Insights into ADAR gene complement, expression patterns, and RNA editing landscape in Chlamys farreri.

Adenosine Deaminases Acting on RNA (ADARs) are evolutionarily conserved enzymes known to convert adenosine to inosine in double-stranded RNAs and participate in host-virus interactions. Conducting a meta-analysis of available transcriptome data, we identified and characterised eight ADAR transcripts in Chlamys farreri, a farmed marine scallop susceptible to Acute viral necrosis virus (AVNV) infections and mortality outbreaks. Accordingly, we identified six ADAR genes in the Zhikong scallop genome, revised previous gene annotations, and traced alternative splicing variants.

Altered Expression of Astrocytic ATP Channels and Ectonucleotidases in the Cerebral Cortex and Hippocampus of Chronic Social Defeat Stress-Susceptible BALB/c Mice.

The increasing number of patients with depressive disorder is a serious socioeconomic problem worldwide. Although several therapeutic agents have been developed and used clinically, their effectiveness is insufficient and thus discovery of novel therapeutic targets is desired. Here, focusing on dysregulation of neuronal purinergic signaling in depressive-like behavior, we examined the expression profiles of ATP channels and ectonucleotidases in astrocytes of cerebral cortex and hippocampus of chronic social defeat stress (CSDS)-susceptible BALB/c mice.

Pedicle screw insertion into infected vertebrae reduces operative time and range of fixation in minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis: a multicenter retrospective cohort study.

Background: Minimally invasive posterior fixation surgery for pyogenic spondylitis is known to reduce invasiveness and complication rates; however, the outcomes of concomitant insertion of pedicle screws (PS) into the infected vertebrae via the posterior approach are undetermined. This study aimed to assess the safety and efficacy of PS insertion into infected vertebrae in minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis.

Methods: This multicenter retrospective cohort study included 70 patients undergoing minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis across nine institutions.

Discovery and Characterization of Pyridoxal 5'-Phosphate-Dependent Cycloleucine Synthases.

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are the most versatile biocatalysts for synthesizing nonproteinogenic amino acids. α,α-Disubstituted quaternary amino acids, such as 1-aminocyclopentane-1-carboxylic acid (cycloleucine), are useful building blocks for pharmaceuticals. In this study, starting with the biosynthesis of fusarilin A, we discovered a family of PLP-dependent enzymes that can facilitate tandem carbon-carbon forming steps to catalyze an overall [3 + 2]-annulation.

Survival benefits of interventional radiology and surgical teams collaboration during primary trauma surveys: a single-centre retrospective cohort study.

Background: A team approach is essential for effective trauma management. Close collaboration between interventional radiologists and surgeons during the initial management of trauma patients is important for prompt and accurate trauma care. This study aimed to determine whether trauma patients benefit from close collaboration between interventional radiology (IR) and surgical teams during the primary trauma survey.

Alteration of Sweet and Bitter Taste Sensitivity with Development of Glucose Intolerance in Non-insulin-Dependent Diabetes Mellitus Model OLETF Rats.

Patients with diabetes exhibit altered taste sensitivity, but its details have not been clarified yet. Here, we examined alteration of sweet taste sensitivity with development of glucose intolerance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of non-insulin-dependent diabetes mellitus. Compared to the cases of Long Evans Tokushima Otsuka (LETO) rats as a control, glucose tolerance of OLETF rats decreased with aging, resulting in development of diabetes at 36-weeks-old.

Global cognition and executive functions of older adults with type 1 diabetes mellitus without dementia.

Aims/introduction: This study aimed to characterize the global cognition and executive functions of older adults with type 1 diabetes mellitus in comparison with type 2 diabetes mellitus.

Materials And Methods: This study included 37 patients with type 1 diabetes mellitus aged ≥65 years and 37 age- and sex-matched patients with type 2 diabetes mellitus. Patients with dementia scoring <24 on the Mini-Mental State Examination were excluded.

Suppressive Effects of Neuromedin U Receptor 2-Selective Peptide Agonists on Appetite and Prolactin Secretion in Mice.

Neuromedin U receptor 2 (NMUR2), which is expressed in the central nervous system (CNS) including the hypothalamus, has been noted as a therapeutic target against obesity. We previously reported that intranasal administration of CPN-219, a NMUR2-selective hexapeptide agonist, suppresses body weight gain in mice; however, there is no detailed information regarding its CNS effects. Recently, in addition to appetite suppression, stress responses and regulation of prolactin (PRL) secretion have also attracted attention.

Epidermal loss of Bcl6 exacerbates MC903-induced atopic dermatitis-like skin inflammation.

Atopic dermatitis (AD) is a chronic inflammatory skin disease where Th2-type immune responses are dominant. In the lesional skin of AD, keratinocytes show differentiation defects and secrete proinflammatory cytokines and chemokines, amplifying Th2-type responses in AD. We previously reported that inducible loss of B-cell lymphoma 6 (Bcl6), a transcription repressor and a master transcriptional regulator of follicular helper T cells and germinal center B cells, in the whole body results in upregulation of Th2-related cytokines in mouse skin.

Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

Aims/introduction: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state.

Materials And Methods: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques.

Sub-chronic and mild social defeat stress exposure to C57BL/6J mice increases visceral fat mass and causes accumulation of cholesterol and bile acids in the liver.

Major depressive disorder is accompanied by a high metabolic illness comorbidity and patients with atypical depression are a subgroup with particularly high risk of obesity, dyslipidemia, and metabolic syndrome; however, the underlying mechanisms have not been fully elucidated. In this study, we examined visceral fat deposition, lipid profiles in the liver, and gut microbiota in sub-chronic and mild social defeat stress (sCSDS)-exposed C57BL/6J mice, which exhibit atypical depression-like phenotypes, i.e.