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Background: This systematic review and meta‐analysis aimed to assess the effectiveness of non‐invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192). Objective: We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients. Methods: The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta‐analysis was performed. Results: Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = −2.49, [95% confidence interval: −3.34, −1.64]) and ICARS (−5.27 [−7.06, −3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia. Conclusion: Non‐invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high‐quality RCTs are required. [ABSTRACT FROM AUTHOR]

Despite advanced therapeutics, esophageal squamous cell carcinoma (ESCC) remains one of the deadliest cancers. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and MK1775 (WEE1 inhibitor) as a treatment for ESCC. This study demonstrates that trifluridine induces single‐strand DNA damage in ESCC cells, as evidenced by phosphorylated replication protein 32. The DNA damage response includes cyclin‐dependent kinase 1 (CDK1) (Tyr15) phosphorylation as CDK1 inhibition and a decrease of the proportion of phospho‐histone H3 (p‐hH3)‐positive cells, indicating cell cycle arrest at the G2 phase before mitosis entry. The WEE1 inhibitor remarkedly suppressed CDK1 phosphorylation (Try15) and reactivated CDK1, and also increased the proportion of p‐hH3‐positive cells, which indicates an increase of the number of cells into mitosis. Trifluridine combined with a WEE1 inhibitor increased trifluridine‐mediated DNA damage, namely DNA double‐strand breaks, as shown by increased γ‐H2AX expression. Moreover, the combination treatment with trifluridine/tipiracil and a WEE1 inhibitor significantly suppressed tumor growth of ESCC‐derived xenograft models. Hence, our novel combination treatment with trifluridine/tipiracil and a WEE1 inhibitor is considered a candidate treatment strategy for ESCC. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a 19-year-old Japanese female who experienced prolonged toxic encephalopathy with electroencephalogram (EEG) abnormalities following an overdose of dextromethorphan (DXM), a widely used cough suppressant. The patient ingested a high dosage of DXM in a suicide attempt, along with other over-the-counter medications. She had a history of intermittent DXM abuse, which resulted in mood elevation and hallucinations. The patient exhibited symptoms such as coma, dilated pupils, tachycardia, and hyperthermia. Her consciousness gradually improved after transfer to the psychiatric unit, and she was discharged without any apparent sequelae. The article highlights the potential psychiatric and neurological outcomes of recreational DXM abuse and emphasizes the need for clinicians to remain vigilant. [Extracted from the article]

Background: Niemann–Pick disease type C (NPC) is a fatal neurodegenerative disorder caused by abnormal intracellular cholesterol trafficking. Cyclodextrins (CDs), the most promising therapeutic candidates for NPC, but with concerns about ototoxicity, are cyclic oligosaccharides with dual functions of unesterified cholesterol (UC) shuttle and sink that catalytically enhance the bidirectional flux and net efflux of UC, respectively, between the cell membrane and the extracellular acceptors. However, the properties of CDs that regulate these functions and how they could be used to improve treatments for NPC are unclear. Methods: We estimated CD–UC complexation for nine CD derivatives derived from native α‐, β‐, and γ‐CD with different cavity sizes, using solubility and molecular docking analyses. The stoichiometry and complexation ability of the resulting complexes were investigated in relation to the therapeutic effectiveness and toxicity of each CD derivative in NPC experimental models. Findings: We found that shuttle and sink activities of CDs are dependent on cavity size‐dependent stoichiometry and substituent‐associated stability of CD–UC complexation. The ability of CD derivatives to form 1:1 and 2:1 complexes with UC were correlated with their ability to normalize intracellular cholesterol trafficking serving as shuttle and with their cytotoxicity associated with cellular UC efflux acting as sink, respectively, in NPC model cells. Notably, the ability of CD derivatives to form an inclusion complex with UC was responsible for not only efficacy but ototoxicity, while a representative derivative without this ability negligibly affected auditory function, underscoring its preventability. Conclusions: Our findings highlight the importance of strategies for optimizing the molecular structure of CDs to overcome this functional dilemma in the treatment of NPC. [ABSTRACT FROM AUTHOR]

Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma that selectively affects small blood vessels. We report a patient who presented with dyspnea and weight loss as well as refractory shock and multiple‐organ dysfunction. The postmortem revealed disseminated involvement of an IVL but no evidence of infection. [ABSTRACT FROM AUTHOR]

Summary: Wounding triggers de novo organogenesis, vascular reconnection and defense response but how wound stress evoke such a diverse array of physiological responses remains unknown.We previously identified AP2/ERF transcription factors, WOUND INDUCED DEDIFFERENTIATION1 (WIND1) and its homologs, WIND2, WIND3 and WIND4, as key regulators of wound‐induced cellular reprogramming in Arabidopsis. To understand how WIND transcription factors promote downstream events, we performed time‐course transcriptome analyses after WIND1 induction.We observed a significant overlap between WIND1‐induced genes and genes implicated in cellular reprogramming, vascular formation and pathogen response. We demonstrated that WIND transcription factors induce several reprogramming genes to promote callus formation at wound sites. We, in addition, showed that WIND transcription factors promote tracheary element formation, vascular reconnection and resistance to Pseudomonas syringae pv. tomato DC3000.These results indicate that WIND transcription factors function as key regulators of wound‐induced responses by promoting dynamic transcriptional alterations. This study provides deeper mechanistic insights into how plants control multiple physiological responses after wounding. [ABSTRACT FROM AUTHOR]

Background and Purpose: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with disrupted intracellular cholesterol trafficking. A cyclic heptasaccharide, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), is a cholesterol solubilizer that is being developed to treat NPC, but its ototoxicity and pulmonary toxicity remain important issues. We have characterized 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), a cyclic octasaccharide with a larger cavity than HP-β-CD, as a candidate drug to treat NPC. However, the molecular target of HP-γ-CD with respect to NPC and its potential for clinical application are still unclear.Experimental Approach: We investigated the mode of interaction between HP-γ-CD and cholesterol by phase-solubility analysis, proton NMR spectroscopy and molecular dynamics simulations. We then evaluated the therapeutic effects of HP-γ-CD compared with HP-β-CD using cellular and murine NPC models. Mouse auditory and pulmonary function tests were also conducted.Key Results: HP-γ-CD solely formed a 1:1 inclusion complex with cholesterol with an affinity similar to that of HP-β-CD. In vitro, HP-γ-CD and HP-β-CD amelioration of NPC-related manifestations was almost equivalent at lower concentrations. However, at higher concentrations, the cholesterol inclusion mode of HP-β-CD shifted to the highly soluble 2:1 complex whereas that of HP-γ-CD maintained solely the 1:1 complex. The constant lower cholesterol solubilizing ability of HP-γ-CD conferred it with significantly reduced toxicity compared with HP-β-CD, but equal efficacy in treating a mouse model of NPC.Conclusions and Implications: HP-γ-CD can serve as a fine-tuned cholesterol solubilizer for the treatment of NPC with a wider safety margin than HP-β-CD in terms of ototoxicity and pulmonary toxicity. [ABSTRACT FROM AUTHOR]

The development of an efficient and cost‐effective method for monitoring animal populations or biodiversity is urgently needed, and invertebrate‐derived DNA (iDNA) may offer a promising tool for assessing the diversity and other ecological information of vertebrates. We studied the host species of a hematophagous leech (Haemadipsa japonica) in Yakushima by genetic barcoding and compared the results with those for mammal composition revealed by camera trapping. We analyzed 119 samples using two sets of primers by Sanger sequencing and one set of primer by next generation sequencing. The proportion of the samples that were successfully sequenced and identified to at least one species was 11.8–24.3%, depending on the three different methods. In all of these three methods, most of the samples were identified as sika deer (18/20, 6/15 and 16/29) or human (2/20, 7/15 and 21/29). The nonhuman mammal host species composition was significantly different from that estimated by camera trapping. Sika deer was the main host, which may be related with their high abundance, large body size and terrestriality. Ten samples included DNA derived from multiple species of vertebrates. This may be due to the contamination of human DNA, but we also found DNA from deer, Japanese macaque and a frog in the same samples, suggesting the mixture of the two meals in the gut of the leech. Using H. japonica‐derived iDNA would not be suitable to make an inventory of species, but it may be useful to collect genetic information on the targeted species, due to their high host selectivity. [ABSTRACT FROM AUTHOR]

Summary: The post‐embryonic growth of plants requires the activities of apical meristems and lateral meristems. In the meristems, self‐proliferation and differentiation of stem cells is tightly modulated by plant hormone signaling networks and specific transcription factors. Despite extensive studies on stem cell maintenance in plants, the mechanism by which stem cells are initially established is largely unknown. Vascular stem cells consisting of procambial/cambial cells give rise to xylem and phloem cells. In this study, we analyzed the establishment of procambial cells using the in vitro culture system VISUAL, in which mesophyll cells rapidly differentiate into xylem tracheary elements and phloem sieve elements via procambial cells. We found that procambial cell formation in VISUAL is initiated by light, which can be replaced by application of gibberellin (GA). Gibberellin was able to promote procambial cell formation through degradation of DELLA, whereas light did not elevate the endogenous GA content. Indeed, light in combination with bikinin reduced the accumulation of DELLA protein in VISUAL. Consistently, overexpression of a constitutively active DELLA protein repressed vascular cell differentiation even under light. These combined results suggest that DELLA signaling suppresses procambial cell formation during vascular development in VISUAL. [ABSTRACT FROM AUTHOR]

Novel glass light guide plate was developed by set total approach of improving both glass and peripheral technologies, and was mass-produced by float process. Besides the excellent mechanical properties compared with PMMA, improved brightness and small chromaticity difference will provide new possibility, such as to realize the perfect 'zero-bezel', one of the ultimate TV designed. [ABSTRACT FROM AUTHOR]

Glass light guide plate has been fabricated by a mass-production line. Backlight characteristics are equivalent to those of PMMA. Glass light guide plate itself can be a body of television without additional supporting members, which results in ultrathin and light-weight television with a flat back and is suitable for wallmounted television. [ABSTRACT FROM AUTHOR]

ABSTRACT Human induced pluripotent stem cells (hiPSCs) are a promising cell source for drug screening. For this application, self-renewal or differentiation of the cells is required, and undefined factors in the culture conditions are not desirable. Microfluidic perfusion culture allows the production of small volume cultures with precisely controlled microenvironments, and is applicable to high-throughput cellular environment screening. Here, we developed a microfluidic perfusion culture system for hiPSCs that uses a microchamber array chip under defined extracellular matrix (ECM) and culture medium conditions. By screening various ECMs we determined that fibronectin and laminin are appropriate for microfluidic devices made out of the most popular material, polydimethylsiloxane (PDMS). We found that the growth rate of hiPSCs under pressure-driven perfusion culture conditions was higher than under static culture conditions in the microchamber array. We applied our new system to self-renewal and differentiation cultures of hiPSCs, and immunocytochemical analysis showed that the state of the hiPSCs was successfully controlled. The effects of three antitumor drugs on hiPSCs were comparable between microchamber array and 96-well plates. We believe that our system will be a platform technology for future large-scale screening of fully defined conditions for differentiation cultures on integrated microfluidic devices. Biotechnol. Biotechnol. Bioeng. 2014;111: 937-947. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Cell division and differentiation of stem cells are controlled by non-cell-autonomous signals in higher organisms. The plant vascular meristem is a stem-cell tissue comprising procambial cells that produce xylem cells on one side and phloem cells on the other side. Recent studies have revealed that TDIF (tracheary element differentiation inhibitory factor)/CLE41/CLE44 peptide signal controls the procambial cell fate in a non-cell-autonomous manner. TDIF produced in and secreted from phloem cells is perceived by TDR/PXY, a leucine-rich repeat receptor kinase located in the plasma membrane of procambial cells. This signal suppresses xylem cell differentiation of procambial cells and promotes their proliferation. In addition to TDIF, some other CLE peptides play roles in vascular development. Here, we summarize recent advances in CLE signaling governing vascular development. [ABSTRACT FROM AUTHOR]

Embedded processors are increasingly being used in digital consumer appliances such as cellular phones, digital still/video cameras, and car navigation systems. They must therefore deliver high performance within a reasonable area and power consumption level, and be flexible to meet a wide range of requirements for various applications. In this paper, we introduce our latest processor core SH-X developed under the above background. The low-power version of the SH-X core achieves 360 MIPS with a power of 80 mW resulting in the high power-performance ratio of 4500 MIPS/W. The standard version achieves 720 MIPS with a power of 250 mW, 2.8 GFLOPS, and 36M polygons/s graphics performance. The leak currents in the resume standby and U-standby modes are 100 and 10µA, respectively. The resume standby mode can return the status before the standby in only 3 ms, while the U-standby mode requires reset sequence to restart. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(3): 10–19, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20450 [ABSTRACT FROM AUTHOR]

The female Truljalia hibinonis ingests metanotal secretions of the male during copulation. The effect of ingestion on oviposition behavior was compared between three female groups: females that copulated once with an intact male (a male that had not been manipulated; M group); females that copulated once with a male from which most of the metanotal secretion had been removed (NO group); and females that copulated once with an intact male followed by being artificially supplied with metanotal secretion three times (MS group). There were no obvious differences in female fecundity across the three groups. However, within the MS group, intake of an optimal amount of metanotal secretion increased the number of eggs laid. This effect appeared quickly after ingestion and was most effective on the first bout (eggs laid during the first few days after copulation) after ingestion of the metanotal secretion. In contrast, the number of eggs laid had a negative correlation with the amount of metanotal secretion ingested when the amount exceeded the optimal in this experimental arrangement. [ABSTRACT FROM AUTHOR]

AbstractBackground and Aims: The relationship between peptic ulcer, autonomic activity and the incidence of Helicobacter pylori infection in untreated hypertensive patients complicated with peptic ulcer were evaluated. Methods: Ten hypertensive patients with peptic ulcer (HT-PU group), 15 untreated essential hypertensive patients without peptic ulcer (HT group) and 10 normal subjects (N group) were enrolled, and a power spectral analysis was performed in each subject. A biopsy urease test was used to detect infection by H. pylori. Results: No significant differences were observed in the values of mean low-frequency (LF) power between the three groups. However, the mean high-frequency (HF) power in the HT-PU group was significantly greater than those of the HT and N groups (P < 0.01). The mean LF/HF ratios in the HT-PU and HT groups were significantly greater than that of the N group (P < 0.01). With respect to H. pylori infection, no significant differences between the three groups were observed. Sympathetic activity (LF power) was increased in the HT and HT-PU groups. Furthermore, parasympathetic activity (HF power) was increased in the HT-PU group. Conclusions: These findings suggest the participation of increased parasympathetic activity in peptic ulcer patients. Therefore, it is suggested that new techniques, such as spectral analysis of heart rate variability, as used in this study, will clarify the relationship between peptic ulcer and autonomic nervous function. [ABSTRACT FROM AUTHOR]