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On 1 January 2024, a massive earthquake struck the Noto Peninsula in Japan, and the resulting tsunami significantly damaged the nearby coasts. This study focuses on Iida Bay, located on the peninsula that suffered severe coastal damage. We observed a tsunami waveform in Iida Bay from video analysis owing to the lack of instrument data. This, combined with the waveform observed outside the bay, was used to correct the initial sea‐surface displacements produced by a prior source model. We successfully reproduced the observed waveforms with corrected displacements and investigated how the tsunami propagated and amplified in the bay. Alongshore wave propagation and superposition were identified as crucial factors in this tsunami event. Plain Language Summary: On 1 January 2024, a large earthquake struck the Noto Peninsula in Japan, generating a tsunami that significantly impacted the nearby coasts. Post‐event surveys revealed severe damage to Iida Bay, located on the peninsula. To investigate tsunami propagation and amplification, we analyzed the images of the recorded video of the tsunami along with a numerical simulation. According to our results, the tsunami maximized during the subsequent waves rather than during the primary wave in the bay. Waves propagating along the shore developed after the primary wave of the tsunami, and some of these waves propagating from opposite sides of the bay overlapped at a specific location in the bay, where significant inundation was observed ∼20 min after the arrival of the primary wave. Key Points: Generation, propagation, and amplification characteristics of a tsunami following the 2024 Noto Peninsula Earthquake were investigatedSignificant sea‐surface displacements were concentrated in the northeastern part of the source areaWaves propagating in alongshore directions and their superposition greatly contributed to coastal damage in Iida Bay [ABSTRACT FROM AUTHOR]

The amyloid β peptide (Aβ), starting with pyroglutamate (pE) at position 3 and ending at position 42 (Aβ3pE-42), predominantly accumulates in the brains of Alzheimer's disease. Consistently, donanemab, a therapeutic antibody raised against Aβ3pE-42, has been shown to be effective in recent clinical trials. Although the primary Aβ produced physiologically is Aβ1-40/42, an explanation for how and why this physiological Aβ is converted to the pathological form remains elusive. Here, we present experimental evidence that accounts for the aging-associated Aβ3pE-42 deposition: Aβ3pE-42 was metabolically more stable than other Aβx-42 variants; deficiency of neprilysin, the major Aβ-degrading enzyme, induced a relatively selective deposition of Aβ3pE-42 in both APP transgenic and App knock-in mouse brains; Aβ3pE-42 deposition always colocalized with Pittsburgh compound B-positive cored plaques in APP transgenic mouse brains; and under aberrant conditions, such as a significant reduction in neprilysin activity, aminopeptidases, dipeptidyl peptidases, and glutaminyl-peptide cyclotransferase-like were up-regulated in the progression of aging, and a proportion of Aβ1-42 may be processed to Aβ3pE-42. Our findings suggest that anti-Aβ therapies are more effective if given before Aβ3pE-42 deposition., (© 2024 Iwata et al.)

Alzheimer's disease (AD) involves reduced glutathione levels, causing oxidative stress and contributing to neuronal cell death. Our prior research identified diminished glutamate-cysteine ligase catalytic subunit (GCLC) as linked to cell death. However, the effect of GCLC on AD features such as amyloid and tau pathology remained unclear. To address this, we investigated amyloid pathology and tau pathology in mice by combining neuron-specific conditional GCLC knockout mice with amyloid precursor protein (App) knockin (KI) or microtubule-associated protein tau (MAPT) KI mice. Intriguingly, GCLC knockout resulted in an increased Aβ42/40 ratio. Additionally, GCLC deficiency in MAPT KI mice accelerated the oligomerization of tau through intermolecular disulfide bonds. These findings suggest that the decline in glutathione levels, due to aging or AD pathology, may contribute to the progression of AD., (© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

A 73-year-old woman underwent a descending colectomy for descending colon cancer. The tumor was graded as pStage Ⅲb(pT3[SS], pN1b, pM0, Cur A), according to the 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma. Postoperative treatment of adjuvant chemotherapy comprised oral tegafur/uracil and Leucovorin for 6 months with no evident recurrence. However, contrast-enhanced CT and FDG-PET/CT examination 8 years and 7 months after surgery revealed a 30 mm irregular recurrent tumor in the left iliac fossa. Since the tumor was adjacent to the left psoas muscle, it was considered that RM0(no tumor identified at the radial margin)could not be achieved in that region. Owing to the patient's good general condition, systemic chemotherapy with CAPOX+bevacizumab was administered. Although adverse events prompted discontinuation of the treatment during the first course, the recurrent tumor had significantly regressed. Systemic chemotherapy with mFOLFOX6+bevacizumab as selected subsequent treatment achieved a significant tumor shrinkage to date. Although a recurrence more than 5 years after curative resection of colorectal cancer is extremely rare, the possibility of late recurrence must be considered in patients with well-differentiated tumors who received adjuvant chemotherapy and had negative vascular invasion.

Rational synthetic expansion of photoresponsive ligands is important for photopharmacological studies. Adenosine A 2A receptor (A 2A R) is stimulated by adenosine and related in Parkinson's disease and other diseases. Here, we report the crystal structure of the A 2A R in complex with the novel photoresponsive ligand photoNECA (blue) at 3.34 Å resolution. PhotoNECA (blue) was designed for this structural study and the cell-based assay showed a photoresponsive and receptor selective characteristics of photoNECA (blue) for A 2A R. The crystal structure explains the binding mode, photoresponsive mechanism and receptor selectivity of photoNECA (blue). Our study would promote not only the rational design of photoresponsive ligands but also dynamic structural studies of A 2A R., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Accumulating evidence suggests that glutathione loss is closely associated with the progression of neurodegenerative disorders. Here, we found that the neuronal conditional-knockout (KO) of glutamyl-cysteine-ligase catalytic-subunit (GCLC), a rate-limiting enzyme for glutathione synthesis, induced brain atrophy accompanied by neuronal loss and neuroinflammation. GCLC-KO mice showed activation of C1q, which triggers engulfment of neurons by microglia, and disease-associated-microglia (DAM), suggesting that activation of microglia is linked to the neuronal loss. Furthermore, gasdermins, which regulate inflammatory form of cell death, were upregulated in the brains of GCLC-KO mice, suggesting the contribution of pyroptosis to neuronal cell death in these animals. In particular, GSDME-deficiency significantly attenuated the hippocampal atrophy and changed levels of DAM markers in GCLC-KO mice. Finally, we found that the expression of GCLC was decreased around amyloid plaques in App NL-G-F AD model mice. App NL-G-F mouse also exhibited inflammatory events similar to GCLC-KO mouse. We propose a mechanism by which a vicious cycle of oxidative stress and neuroinflammation enhances neurodegenerative processes. Furthermore, GCLC-KO mouse will serve as a useful tool to investigate the molecular mechanisms underlying neurodegeneration and in the development of new treatment strategies to address neurodegenerative diseases., (© 2023. The Author(s).)