Generating a mirror-image monobody targeting MCP-1 via TRAP display and chemical protein synthesis.

Biologically produced protein drugs are generally susceptible to degradation by proteases and often exhibit immunogenicity. To address this issue, mirror-image peptide/protein binders consisting of D-amino acids have been developed so far through the mirror-image phage display technique. Here, we develop a mirror-image protein binder derived from a monobody, one of the promising protein scaffolds, utilizing two notable technologies: chemical protein synthesis and TRAP display, an improved version of mRNA display.

Role of anthropogenic forcing in Antarctic sea ice variability simulated in climate models.

Antarctic sea ice extent has seen a slight increase over recent decades, yet since 2016, it has undergone a sharp decline, reaching record lows. While the precise impact of anthropogenic forcing remains uncertain, natural fluctuations have been shown to be important for this variability. Our study employs a series of coupled model experiments, revealing that with constant anthropogenic forcing, the primary driver of interannual sea ice variability lies in deep convection within the Southern Ocean, although it is model dependent.

Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus.

To explore the potential efficacy of early initiation of intravenous cyclophosphamide (IVCPA), we reviewed consecutive four cases of super-refractory cryptogenic-new onset refractory status epilepticus (C-NORSE) between 2015 and 2023. We compared functional outcomes at 3 months and 1 year after the onset between patients who received IVCPA within 20 days (early-treated) and those who received it later (late-treated). All patients (median age: 43 years) had a prodromal fever.

Cervical Mesonephric Adenocarcinoma Treated with Neoadjuvant Chemotherapy: A Case Report and a Literature Review.

Introduction: Cervical mesonephric ductal adenocarcinoma (MA) is an HPV-independent adenocarcinoma that occurs in middle-aged women. MA originates from remnants of the Wolffian duct that usually regress in females once the induction of sex differentiation is activated. MA is a rare disease that accounts for less than 1% of all cervical adenocarcinomas.

Effects of ipragliflozin on skeletal muscle adiposity in patients with diabetes and metabolic dysfunction-associated steatotic liver disease.

Objective Myosteatosis affects the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and may be a potential therapeutic target. This study aimed to examine the effects of ipragliflozin on myosteatosis in patients with type 2 diabetes mellitus (T2D) and MASLD. Methods Patients were treated with ipragliflozin (IPR group) or a control (CTR group) for 72 weeks in a randomized trial.

Adenoid glioblastoma: Stromal hypovascularity and secretion of chondromodulin-I by tumor cells.

The case of a 75-year-old man with a glioblastoma of the right frontal lobe showing features of adenoid glioblastoma is reported. The tumor consisted of two components: the adenoid component, in which large, cohesive, polygonal cells with vesicular nuclei and abundant basophilic cytoplasm showed nest-like, trabecular, or tubular growth on the myxoid matrix and formed a multinodular configuration; and the subsidiary component, in which short spindle cells showed compact fascicular growth. The features of ordinary glioblastoma were also found in a small area.

Clinical manifestations and outcomes associated with a high 2HELPS2B score in patients with acute impaired consciousness.

Purpose: The 2HELPS2B score is an invaluable tool for assessing seizure risk in critically ill patients with unconsciousness. However, this can be challenging for non-epileptologists to use owing to its reliance on electroencephalogram (EEG) analysis. Thus, identifying clinical manifestations associated with high 2HELPS2B scores is crucial.

H3 K27-altered diffuse midline glioma of the thalamus with formation of glio-fibrillary globular structures.

A case of diffuse midline glioma (DMG), H3 K27-altered, that arose in the right thalamus of a 14-year-old boy is reported. The patient died of tumor spread after a progressive clinical course of approximately 13 months. Histopathologically, the tumor consisted of a mixture of loose proliferation of stellate cells and compact fascicular growth of spindle cells showing a "piloid" feature.

Environment-Mediated Vertical Transmission Fostered Uncoupled Phylogenetic Relationships between Longicorn Beetles and Their Symbionts.

The Coleoptera Cerambycidae (longicorn beetles) use wood under different states (living healthy, freshly snapped, completely rot, etc.) in a species-specific manner for their larval diet. Larvae of some Cerambycidae groups have mycetomes, accessory organs associated with the midgut that harbor fungal symbiont cells.

Structure-Activity Relationship Study of CYM51010, an agonist for the µ-δ Opioid Receptor Heterodimer.

Although opioid analgesics are indispensable in treating pain, these drugs are accompanied by life-threatening side effects. While clinically relevant opioid drugs target the µ opioid receptor (MOR), a heterodimer between the MOR and the δ opioid receptor (DOR) has emerged as another target to develop safer analgesics. Although some heterodimer-preferring agonists have been reported so far, it is still difficult to activate the MOR/DOR heterodimer selectively in the presence of MOR or DOR monomers/homodimers.

First Measurement of ν_{e} and ν_{μ} Interaction Cross Sections at the LHC with FASER's Emulsion Detector.

The first results of the study of high-energy electron neutrino (ν_{e}) and muon neutrino (ν_{μ}) charged-current interactions in the FASERν emulsion-tungsten detector of the FASER experiment at the LHC are presented. A 128.8 kg subset of the FASERν volume was analyzed after exposure to 9.

Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings.

Chemical Synthesis of Interleukin-6 for Mirror-Image Screening.

Interleukin-6 (IL-6), a multifunctional cytokine, is an attractive therapeutic target for immunological and inflammatory diseases. We investigated the chemical synthesis of IL-6 and its enantiomer (d-IL-6) using a sequential N-to-C native chemical ligation strategy from six peptide segments. Solubilizing Trt-K tags improved the intermediate solubility and served as protecting groups during the metal-free desulfurization to facilitate the synthesis of full-length IL-6 protein.

Impact of an unprecedented marine heatwave on extremely hot summer over Northern Japan in 2023.

Possible local influence of an extreme marine heatwave is investigated on unprecedentedly hot summer around northern Japan in 2023. Sea-surface temperatures (SSTs) and subsurface ocean temperatures around northern Japan were also unprecedentedly high in the summer. This was especially the case off the east coast of Japan, where cool Oyashio water was replaced with much warmer water due to a striking poleward meander of the Kuroshio Extension persistent from the spring.

Cognitive behavioral therapy for a Japanese woman with olfactory reference disorder (ORD) comorbid with schizophrenia: A case study.

Background: Olfactory reference disorder (ORD) is a mental illness in which individuals overestimate their sense of smell and worry about the negative impact of odors. Little is known about its successful treatment. A new cognitive behavioral model was developed based on cognitive behavioral therapy (CBT) for obsessive-compulsive disorder.

The Inhibition of TREK-1 K Channels via Multiple Compounds Contained in the Six Kamikihito Components, Potentially Stimulating Oxytocin Neuron Pathways.

Oxytocin, a significant pleiotropic neuropeptide, regulates psychological stress adaptation and social communication, as well as peripheral actions, such as uterine contraction and milk ejection. Recently, a Japanese Kampo medicine called Kamikihito (KKT) has been reported to stimulate oxytocin neurons to induce oxytocin secretion. Two-pore-domain potassium channels (K2P) regulate the resting potential of excitable cells, and their inhibition results in accelerated depolarization that elicits neuronal and endocrine cell activation.

Engineering a Low-Immunogenic Mirror-Image VHH against Vascular Endothelial Growth Factor.

Immunogenicity is a major caveat of protein therapeutics. In particular, the long-term administration of protein therapeutic agents leads to the generation of antidrug antibodies (ADAs), which reduce drug efficacy while eliciting adverse events. One promising solution to this issue is the use of mirror-image proteins consisting of d-amino acids, which are resistant to proteolytic degradation in immune cells.