Replication across O6-methylguanine activates futile cycling of DNA mismatch repair attempts assisted by the chromatin remodeling enzyme Smarcad1.

SN1-type alkylating reagents generate O6-methylguanine (meG) lesions that activate the mismatch repair (MMR) response. Since post-replicative MMR specifically targets the nascent strand, meG on the template strand is refractory to rectification by MMR and, therefore, can induce non-productive MMR reactions. The cycling of futile MMR attempts is proposed to cause DNA double-strand breaks in the subsequent S phase, leading to ATR-checkpoint-mediated G2 arrest and apoptosis.

Identification of a Novel Stomatal Opening Chemical, PP242, That Inhibits Early Abscisic Acid Signal Transduction in Guard Cells.

Plants control their stomatal apertures to optimize carbon dioxide uptake and water loss. Stomata open in response to light through the phosphorylation of the penultimate residue, Thr, of plasma membrane (PM) H+-ATPase in guard cells. Stomata close in response to drought and the phytohormone abscisic acid (ABA), and ABA suppresses the light-induced activation of PM H+-ATPase.

Peripheral Neuropathy in Systemic Sclerosis with Proximal Nerve Involvement: Diagnostic Challenges and Response to Corticosteroid Therapy.

Peripheral neuropathy is a complication in systemic sclerosis that is occasionally encountered in clinical settings. The mechanisms underlying this condition remain unclear and treatment strategies have not yet been established, making management challenging. Here, we report a case of peripheral neuropathy associated with systemic sclerosis that was successfully treated with corticosteroid therapy despite the absence of conventional inflammatory findings on histopathology or blood tests.

Efficacy and safety of risankizumab for the treatment of patients with plaque type psoriasis.

Risankizumab (Skyrizi, Abbvie, North Chicago, IL, USA) is a humanized immunoglobulin (Ig) G1 monoclonal antibody targeting the p19 subunit of IL-23, thereby inhibiting IL-23-dependent releasing of proinflammatory cytokines in plaque psoriasis. Risankizumab is licensed is most countries for the treatment of patients with moderate-to-severe plaque psoriasis, and in Japan for generalized pustular psoriasis, erythrodermic psoriasis and palmoplantar pustulosis. Risankizumab showed higher efficacy and favorable safety profiles in patients with moderate-to-severe plaque psoriasis, compared with adalimumab, secukinumab and ustekinumab in several randomized controlled phase 3 pivotal studies and among real-life data in large retrospective studies.

Influence of sewage effluent discharge on putative pathogen community in drinking water sources: insights from full-length 16S rRNA gene amplicon sequencing.

The discharge of sewage effluent is a major source of microbial contamination in drinking water sources, necessitating a comprehensive investigation of its impact on pathogenic bacterial communities. This study utilized full-length 16S rRNA gene amplicon sequencing to identify putative pathogenic bacteria and analyze their community structures in drinking water sources subjected to different levels of fecal pollution: urban rivers with low, moderate, and high sewage effluent mixing ratios, and mountain streams with minimal human impact. The sewage effluent itself was also analyzed.

Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons.

Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly , and encode the D- and D-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit.

Exploring the association between happy hypoxia and Coronavirus disease 2019 in the triage phase.

Background: Patients with severe coronavirus disease 2019 (COVID-19) have been reported to show hypoxia without displaying typical clinical signs or symptoms, called "happy hypoxia." To explore the potential of happy hypoxia as a distinctive symptom of COVID-19, we compared vital signs in the triage phase between patients with and without COVID-19.

Methods: We retrospectively identified emergency patients with and without COVID-19 admitted to Rakuwakai Marutamachi Hospital, Kyoto, Japan, between January 2021 and December 2021.

Relationship between volleyball spike jump height and lower limb kinetics is stronger for orientation leg than rear leg.

The orientation and rear legs have different roles in the spike jump (SPJ) in volleyball, yet the relationship between the jump height and kinetics of each leg remains underexplored. We aimed to clarify the relationships between jump height and kinetics of the orientation and rear legs in the SPJ. This study included 18 female college volleyball players.

Differences in kinematics, kinetics, and muscle activity between underwater dolphin kicking and flutter kicking: multiple approaches using three-dimensional motion analysis, electromyography, and hydrodynamic simulation.

It is well-known among swimmers and coaches that the swimming speed of the underwater dolphin kick (UDK) is higher than that of the underwater flutter kick (UFK). This study aimed to clarify the differences in swimming performance between the two kicking styles in terms of kinematics, kinetics and muscle activity. Eight male swimmers performed UDK and UFK in a water flume at same effort levels.

Ghrelin suppresses water intake with a different physiological significance from atrial natriuretic peptide in conscious seawater-acclimated eels.

In general, ghrelin is known as one of the orexigenic hormones in mammals. On the other hand, it has been shown that ghrelin inhibits water intake, which appear to be inconsistent with its role in the feeding response. In this study, the effect of ghrelin on water intake was comprehensively addressed using conscious seawater-acclimated eels known as an experimental model for water drinking behaviour.

Evaluation of Eye Alignment Before and After Refractive Surgery Using an Implantable Collamer Lens in Phakic Patients with Myopia.

Purpose: To investigate changes in eye alignment before and after ICL implantation in patients with myopia having corrected distance visual acuity (CDVA) of ≥0.0 logMAR.

Subjects And Methods: The medical records of 1012 patients without eye movement limitation who underwent bilateral ICL implantation were retrospectively reviewed a at the Eye Center of Sanno Hospital in Japan.

Impaired Resting State Functional Connectivity in CADASIL Mutant Mice.

Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most prevalent monogenic inherited cause of cerebral small-vessel disease. Despite its prevalence, there is currently no proven therapy to prevent or reverse the progression of the disease. This study aimed to characterize the functional integrity of long white matter tracts in CADASIL transgenic mice, both with and without focal white matter lesions in the corpus callosum added on, utilizing optical resting-state functional connectivity imaging alongside behavioral examinations.

XOR-Derived ROS in Tie2-Lineage Cells Including Endothelial Cells Promotes Aortic Aneurysm Progression in Marfan Syndrome.

Background: Marfan syndrome (MFS) is an inherited disorder caused by mutations in the gene encoding fibrillin-1, a matrix component of extracellular microfibrils. The main cause of morbidity and mortality in MFS is thoracic aortic aneurysm and dissection, but the underlying mechanisms remain undetermined.

Methods: To elucidate the role of endothelial XOR (xanthine oxidoreductase)-derived reactive oxygen species in aortic aneurysm progression, we inhibited in vivo function of XOR either by endothelial cell (EC)-specific disruption of the gene or by systemic administration of an XOR inhibitor febuxostat in MFS mice harboring the missense mutation p.

Prevalence and clinical impact of disseminated intravascular coagulation in acute aortic dissection: a nationwide cohort study.

Background: Acute aortic dissection is a life-threatening cardiovascular emergency with high mortality rates. Disseminated intravascular coagulation (DIC) is a critical complication in patients with acute aortic dissection; however, its incidence and impact on outcomes remain inconclusive.

Objectives: This study aimed to evaluate DIC prevalence and prognosis in patients with aortic dissection.

Effects of educational interventions for community pharmacists on promoting human papillomavirus vaccination: A randomized double-blind parallel group comparison trial.

Objective: Owing to persistent concerns about side effects, human papillomavirus (HPV) vaccination rates in Japan have remained low. Pharmacists are therefore encouraged to improve vaccination rates by providing accurate information. This study evaluated the impact of educational interventions on pharmacists' knowledge and willingness to recommend the HPV vaccine.

Barriers and facilitators for healthcare access among immigrants in Japan: a mixed methods systematic review and meta-synthesis.

Background: While Japan provides universal healthcare, immigrants may experience hampered access to healthcare. A comprehensive review of immigrant healthcare access is also lacking. This systematic review aims to examine barriers and facilitators of healthcare access among immigrants in Japan.

Treatment patterns and clinical profile in progressive pulmonary fibrosis: a Japanese cross-sectional survey.

Background: There is a paucity of real-world data on patients with interstitial lung diseases (ILDs) that are progressive, other than idiopathic pulmonary fibrosis (IPF), including treatment patterns and attitudes toward treatment. This study aimed to investigate the diagnosis, clinical characteristics, treatment paradigm and current decision-making practices of IPF and progressive pulmonary fibrosis (PPF) in a Japanese real-world setting.

Methods: Data were drawn from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey with retrospective data collection of pulmonologists and rheumatologists in Japan from April to October 2022.

Chemical etching of silicon assisted by graphene oxide under negative electric bias.

Chemical etching of silicon assisted by graphene oxide (GO) has been attracting attention as a new method to fabricate micro- or nano-structures. GO promotes the reduction of an oxidant, and holes are injected into silicon, resulting in the preferential dissolution of the silicon under GO. In the conventional etching method with GO, the selectivity of the etching was low due to the stain etching caused by nitric acid.

Reopenable clip over-the-line method in endoscopic full-thickness resection of gastric submucosal tumors: A historical control study.

Objectives: Endoscopic full-thickness resection for gastric submucosal tumors is gradually gaining popularity, and secure and amenable closure is key to its success. This study aimed to compare the reopenable clip over-the-line method with the purse-string method for defect closure after endoscopic full-thickness resection for gastric submucosal tumors.

Methods: This historical control trial included 37 consecutive patients with 37 gastric submucosal tumors, who underwent endoscopic full-thickness resection between January 2021 and July 2024.

Efficacy of e-learning using video content in improving trainees' biliary cannulation skills and understanding (with video).

Objectives: E-learning with video content was created to improve trainees' biliary cannulation techniques; this study aimed to evaluate its educational effect prospectively.

Methods: E-learning program was conducted using videos demonstrating biliary cannulation for 24 papillae, targeting trainees with 2-6 years of experience in endoscopic retrograde cholangiopancreatography. Ten consecutive cases of biliary cannulation for native papillae performed by trainees were prospectively assessed before and after the e-learning, respectively.

The Global Burden of Polycystic Ovary Syndrome in Women of Reproductive Age: Findings from the GBD 2019 Study.

Purpose: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the primary cause of anovulatory infertility among women aged 15-49 years. Despite its significance, it has been largely overlooked in global health discussions, with persistently high prevalence and incidence rates. This public health challenge necessitates attention both domestically and internationally.