Methyl scanning approach for enhancing the biological activity of the linear peptidic natural product, efrapeptin C.

Efrapeptin C (1a) is a large peptidic natural product comprising a 15-mer linear sequence and exerts potent anticancer activity by inhibiting mitochondrial FF-ATP synthase. Residues 1-6 and 9-15 of 1a fold into two 3-helical domains and interact with ATP synthase, while the central β-Ala-7-Gly-8 region functions as a flexible linker of the two domains. To enhance the function of 1a by minimally modifying its structure, we envisioned attaching one small methyl group to the β-Ala-7-Gly-8 and designed six methylated analogues 1b-1g, differing only in the position and configuration of the methyl group.

Association of Placental Pathology with Physical and Neuronal Development of Infants: A Narrative Review and Reclassification of the Literature by the Consensus Statement of the Amsterdam Placental Workshop Group.

The placenta is the largest fetal organ, which connects the mother to the fetus and supports most aspects of organogenesis through the transport of nutrients and gases. However, further studies are needed to assess placental pathology as a reliable predictor of long-term physical growth or neural development in newborns. The Consensus Statement of the Amsterdam Placental Workshop Group (APWGCS) on the sampling and definition of placental lesions has resulted in diagnostic uniformity in describing the most common pathological lesions of the placenta and contributed to the international standardization of descriptions of placental pathology.

Predictors of Major Adverse Cardiovascular and Cerebrovascular Events After Acute Coronary Syndromes: A Retrospective Observational Study Using YoMDB Database.

Objectives: Despite the rapid aging of the population in Japan, clinical predictors for major adverse cerebrovascular and cardiovascular events (MACCE) in patients with new onset of acute coronary syndromes (ACS) have not been well studied. This study therefore aimed to identify the predictors of MACCE in the first onset of ACS patients requiring care.

Materials And Methods: Using the Yokohama Original Medical Database, we identified 3,373 patients who experienced a first onset of ACS and had certified care information from April 2014 to March 2016.

Interleukin-23 levels in umbilical cord blood are associated with neurodevelopmental trajectories in infancy.

Our previous study, which aimed to understand the early neurodevelopmental trajectories of children with and without neurodevelopmental disorders, identified five classes of early neurodevelopmental trajectories, categorized as high normal, normal, low normal, delayed, and markedly delayed. This investigation involved measurement using the Mullen Scale of Early Learning in a representative sample of Japanese infants followed up from the age of 0 to 2 years (Nishimura et al., 2016).

Investigation of optimal weight gain during pregnancy: A retrospective analysis of the Japanese perinatal registry database.

Aim: This study aimed to determine the weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy body mass index (BMI) and make recommendations for optimal weight gain in Japan.

Methods: The Japan Society of Obstetrics and Gynecology perinatal database for 2015-2017 was used. From the 719 723 deliveries included in this database, parturients with underlying diseases or missing data were excluded, and 419 114 deliveries were analyzed.

Molecular Editing Enhances Oxidation Resistance of Menaquinone-Targeting Antibiotics Lysocin E and WAP-8294A2.

Lysocin E (1 a) and WAP-8294A2 (2 a) are peptidic natural products with 37- and 40-membered macrocycles, respectively. Compounds 1 a and 2 a have potent antibacterial activities against Gram-positive bacteria and share a unique mode of action. The electron-rich indole ring of d-Trp-10 of 1 a and 2 a interacts with the electron-deficient benzoquinone ring of menaquinone, which is a co-enzyme in the bacterial respiratory chain.

Interaction of genetic liability for attention deficit hyperactivity disorder (ADHD) and perinatal inflammation contributes to ADHD symptoms in children.

Objective: Genetic and environmental factors contribute to the development of Attention Deficit/Hyperactivity Disorder (ADHD). Perinatal inflammation is one of the promising environmental risk factors for ADHD, but the relationship between the genetic risk for ADHD and perinatal inflammation requires further examination.

Methods: A possible gene-environmental interaction between perinatal inflammation and ADHD polygenic risk score (ADHD-PRS) on ADHD symptoms was investigated in children aged 8-9 from the Hamamatsu Birth Cohort for Mothers and Children (N = 531).

Massive platelet-rich thrombus formation in small pulmonary vessels in amniotic fluid embolism: An autopsy study.

Objective: To identify pulmonary/uterine thrombus formation in amniotic fluid embolism (AFE).

Design: Retrospective, observational.

Setting: Nationwide.

C-Terminal modification of polytheonamide B uncouples its dual functions in MCF-7 cancer cells.

Polytheonamide B (1) is an exceptionally large peptide that forms a transmembrane ion channel. The potent cytotoxicity of 1 against MCF-7 cancer cells originates from its two ion transport functions. Compound 1 depolarizes the plasma membrane and neutralizes acidic lysosomes.

Identifying Active Progeny Virus Particles in Formalin-Fixed, Paraffin-Embedded Sections Using Correlative Light and Scanning Electron Microscopy.

Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissue blocks is routinely used to identify virus-infected cells. However, detecting virus particles in FFPE sections using light microscopy is difficult because of the light diffraction resolution limitations of an optical microscope. In this study, light microscopy and field emission scanning electron microscopy were performed to observe 3-dimensional virus particles in FFPE sections in a nondestructive manner using NanoSuit or osmium conductive treatment methods.

Outdoor Play as a Mitigating Factor in the Association Between Screen Time for Young Children and Neurodevelopmental Outcomes.

Importance: Whether the association between higher screen time in infancy and later suboptimal neurodevelopment can be mitigated by frequency of outdoor play is unknown.

Objective: To investigate whether higher screen time at age 2 years is associated with neurodevelopmental outcomes at age 4 years and whether this association is mediated by frequency of outdoor play at age 2 years 8 months.

Design, Setting, And Participants: Participants were a subsample of the Hamamatsu Birth Cohort Study for Mothers and Children (HBC Study, N = 1258).

Association between serum concentrations of perfluoroalkyl substances and global DNA methylation levels in peripheral blood leukocytes of Japanese women: A cross-sectional study.

Global DNA methylation levels in peripheral blood leukocytes can be a biomarker for cancer risk; however, levels can be changed by various factors such as environmental pollutants. We investigated the association between serum concentrations of perfluoroalkyl substances (PFASs) and global DNA methylation levels of leukocytes in a cross-sectional study using the control group of a Japanese breast cancer case-control study [397 women with a mean age of 54.1 (SD 10.

Development of the Japanese version of the Depression Literacy Scale.

Background: Depression is a major social concern in Japan. It is therefore necessary to develop a scale in Japanese that can assess depression literacy.

Aims: The present study aimed to develop the Japanese version of the Depression Literacy Scale (D-Lit-J), and examined its validity and reliability.

Gramicidin A accumulates in mitochondria, reduces ATP levels, induces mitophagy, and inhibits cancer cell growth.

Gramicidin A (1) is a linear 15-mer peptidic natural product. Because of its sequence of alternating d- and l-chirality, 1 folds into a β-helix in a lipid bilayer and forms a head-to-head dimer to function as a transmembrane channel for monovalent cations (H, Na, and K). The potent anticancer activity of 1 was believed to be mainly attributed to the free ion diffusion across the plasma membrane.

[Total Synthesis and Functional Analysis of Complex Peptidic Natural Products and Their Artificial Analogues].

This review focuses on a new solid-phase synthetic strategy for an anticancer natural product yaku'amide B (1) and its target identification and structure-function relationship study using synthetic analogues and probes. To realize the Fmoc-based solid-phase synthesis of 1, we developed new synthetic methods for enamide formation. Namely, modified traceless Staudinger ligation using alkenyl azides and newly designed phosphinophenol esters enabled stereoselective construction of the (E)- and (Z)-ΔIle moieties.