25 research outputs found

    Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

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    Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

    Layer-by-Layer Self-Assembly Coating for Multi-Functionalized Fabrics: A Scientometric Analysis in CiteSpace (2005–2021)

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    Surface-engineered coatings have been increasingly applied to functionalize fabrics due to the ease of deposition of the coatings and their effectiveness in endowing the fabric with abundant properties. Among the surface modification methods, layer-by-layer (LbL) self-assembly has emerged as an important approach for creating multifunctional surfaces on fabrics. In this review, bibliometric analysis with the visualization analysis of LbL self-assembly coatings on fabrics was performed on publications extracted from the Web of Science (WOS) from 2005 to 2021 based on the CiteSpace software. The analysis results showed that research on LbL self-assembly coatings on fabrics has attracted much attention, and this technique has plentiful and flexible applications. Moreover, research on the LbL self-assembly method in the field of functionalization of fabrics has been summarized, which include flame retardant fabric, antibacterial fabric, ultraviolet resistant fabric, hydrophobic fabric and electromagnetic shielding fabric. It was found that the functionalization of the fabric has been changing from singularity to diversification. Based on the review, several future research directions can be proposed. The weatherability, comfort, cost and environmental friendliness should be considered when the multifunctional coatings are designed

    Novel heterozygous variant of ADPRHL2 causes pathogenic variation in CONDSIAS

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    Adprhl2 (OMIM: 610624) mutation associated stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS, OMIM: 618170) is a sporadic neurodegenerative disease with poor prognosis. ADPRHL2 encodes ADP-ribosylhydrolase 3 (ARH3), which participates in ADP-ribosylation to remove poly-ADP ribose (PAR). We found a new compound heterozygous mutation in the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A in a 30-month-old boy, who showed gait instability, abnormal EEG, and developmental delay after respiratory infection. He died of convulsions 4 months after onset. By constructing a mutant plasmid and using Western blot to detect the expression of ARH3 and PAR, it was demonstrated that the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A is pathogenic according to ACMG guidelines

    Trends of mitochondrial changes in AD: a bibliometric study

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    BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive progress and memory loss, which eventually develops into dementia. It can cause personality disorders and decreased quality of life of patients. Currently, AD patients account for 60–70% of global dementia patients and the incidence rate of AD is increasing annually. AD not only causes pain to patients but also brings a heavy burden to the entire family. Studies have found that there is a connection between mitochondrial dysfunction and other biochemical changes in AD like classical neuropathological hallmarks (β-amyloid and tau protein), inflammation pathways, oxidative stress, and so on. Evidence shows that early treatment targeted directly to mitochondria could extend the lifespan of model mice and decrease the relevant neuropathological markers. Therefore, research on the mitochondrial dysfunction of AD can be of potential significance for clinical treatment. To date, few bibliometric analysis articles related to mitochondrial dysfunction of AD have been published. Bibliometric analysis refers to quantitatively analyzing certain aspects of articles like publishers, authors, and countries by using statistical and mathematical methods. Combined with statistical software, a large number of papers can be converted to visualization figures and tables, which provide vital information such as keyword hotspots and the names of contributing authors. Through the bibliometric analysis method, our study aimed to provide study trends and keyword hotpots for researchers to conduct further relevant research in this field.MethodsWe used the Web of Science core collection database as a literature retrieval tool to obtain data related to mitochondrial changes in Alzheimer’s disease during the last 20 years. The retrieval type was [TS = (Alzheimer’s disease)] ND [TS = (mitochondrion)], ranging from January 1, 2000 to June 30, 2022. VOSviewer v1.6.18, Arcgis 10.8, and HistCite pro 2.1 were used to conduct data visualization analysis. VOSviewer v1.6.18 made relevant network visualization maps of the cooperative relationship between relevant countries, institutions, and authors (co-authorship), the frequency of different keywords appearing together (co-occurrence), and the frequency of different articles cited together (co-cited). Arcgis 10.8 created the world map of publications distribution in this field and Histcite pro 2.1 was used to count the local citation score (LCS) of references. In addition, Journal Citation Reports were used to consult the latest journal import factor and JCI quartile.ResultsAs of June 30, 2022, from the Web of Science core collection, we selected 2,474 original articles in English, excluding the document types of the news items, meeting abstracts, and some articles that had little relevance to our theme. The United States acted as the leader and enjoyed a high reputation in this field. The University of California System was the institution that made the greatest contribution (3.64% with 90 papers). Most articles were published in the Journal of Alzheimer’s Disease (8.21%, with 203 papers). The most frequently co-cited journal in Q1 was the Journal of Biological Chemistry (8,666 citations, TLS: 1039591). Russel H. Swerdlow (55 publications) was the most productive author and PH Reddy was the most co-cited author with 1,264 citations (TLS: 62971). The hotpots of mitochondrial dysfunction in AD were as follows: “oxidative stress,” “amyloid-beta-protein,” “tau,” “apoptosis,” “inflammation,” “autophagy,” “precursor protein,” “endoplasmic-reticulum,” “dynamics” and “mitochondrial unfolded protein response.”ConclusionThis bibliometric analysis research will help readers rapidly identify current hotpots and milestone studies related to directions of interest in AD research

    The Modulation of Laser Refractive Surgery on Sensory Eye Dominance of Anisometropia

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    Purpose. To evaluate the effect of laser refractive surgery on sensory eye dominance of anisometropia. Methods. A total of 156 subjects with nonanisometropic myopia and 70 subjects with anisometropic myopia were enrolled in the first part of the study. The dichoptic motion coherence threshold technique was applied to collect the normal dataset and distribution of sensory eye dominance. The second part of the study included 40 subjects with nonanisometropic myopia and 40 subjects with anisometropic myopia who received the femtosecond laser-assisted in situ keratomileusis (Fs-LASIK). A comprehensive ophthalmologic evaluation was performed with particular attention to sensory eye dominance preoperatively and one-week and one-month postoperatively. The ocular dominance index (ODI) was applied to evaluate the subject’s overall degree of sensory ocular dominance. Visual acuity, sighting eye dominance, and stereo acuity were also accessed. Results. In experiment one, the mean ODI in the nonanisometropic group and the anisometropic group was 1.48 ± 0.63 and 1.95 ± 1.07, respectively. The ODI values of the anisometropic group were significantly higher than those of the nonanisometropic group (Mann–Whitney U test, P<0.001). The demographics information and the distribution of ODI values in both groups are summarized in tables and figures. In experiment two, all LASIK procedures were uneventful and no postoperative complications were observed during the postoperative follow-up. Preoperatively, the ODI values of the anisometropic LASIK group were significantly higher than those of the nonanisometropic LASIK group, which was consistent with the results of part 1. However, one week after operation, the mean ODI values of the anisometropic LASIK group had significantly decreased from 1.89 ± 1.09 to 1.39 ± 0.44. And, the mean ODI values slightly increased to 1.65 ± 0.61 one-month postoperatively. In the nonanisometropic LASIK group, there were no statistically significant differences of ODI changes among preoperative, post-one-week and post-one-month visits. The demographics information and the changes of ODI of both LASIK groups are summarized in tables and figures. Conclusion. Stronger sensory eye dominance is seen in the subjects with anisometropic myopia compared to subjects with nonanisometropic myopia. The strong sensory dominance of anisometropia becomes more balanced at one week of postoperation but returns to the preoperative level after one month. Laser refractive surgery had a short-term modulation of sensory eye dominance

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    Novel Mechanism of Foxo1 Phosphorylation in Glucagon Signaling in Control of Glucose Homeostasis

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    Dysregulation of hepatic glucose production (HGP) serves as a major underlying mechanism for the pathogenesis of type 2 diabetes. The pancreatic hormone glucagon increases and insulin suppresses HGP, controlling blood glucose homeostasis. The forkhead transcription factor Foxo1 promotes HGP through increasing expression of genes encoding the rate-limiting enzymes responsible for gluconeogenesis. We previously established that insulin suppresses Foxo1 by Akt-mediated phosphorylation of Foxo1 at Ser256 in human hepatocytes. In this study, we found a novel Foxo1 regulatory mechanism by glucagon, which promotes Foxo1 nuclear translocation and stability via cAMP- and protein kinase A–dependent phosphorylation of Foxo1 at Ser276. Replacing Foxo1-S276 with alanine (A) or aspartate (D) to block or mimic phosphorylation, respectively, markedly regulates Foxo1 stability and nuclear localization in human hepatocytes. To establish in vivo function of Foxo1-Ser276 phosphorylation in glucose metabolism, we generated Foxo1-S273A and Foxo1-S273D knock-in (KI) mice. The KI mice displayed impaired blood glucose homeostasis, as well as the basal and glucagon-mediated HGP in hepatocytes. Thus, Foxo1-Ser276 is a new target site identified in the control of Foxo1 bioactivity and associated metabolic diseases

    A Qualitative Exploration of a User-Centered Model for Smartwatch Comfort Using Grounded Theory

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    Smartwatch comfort is a fundamental factor that significantly influences the user experience and provides crucial guidance for the evolution of wearable technology. However, there is currently a lack of a comprehensive theoretical model to describe the dimensions of smartwatch comfort and their corresponding influencing factors. Therefore, the present study employed a bottom-up grounded theory approach to construct a user-centered model for smartwatch comfort. Through the coding of in-depth interviews with 64 smartwatch users, we discovered that smartwatch comfort encompasses both physiological dimensions (e.g., pressure and foreign body sensation) and psychological dimensions (e.g., perceived intelligence and satisfaction of needs). Furthermore, the features of smartwatches, including physical attributes (e.g., size and material) and functionalities (e.g., interoperability and automation capabilities), directly impact the comfort experience. Additionally, individual and contextual factors can explain variations in the comfort experience of smartwatches. Users with different physiological characteristics (e.g., wrist size and body sensitivity) and psychological needs (e.g., utilitarian or hedonic needs) are influenced differently by the factors of smartwatches that affect their comfort experience. The adaptability of smartwatches across different contexts (including task context, social context, and temporal context) is also a significant influencing factor on comfort. This substantive grounded theory provides crucial guidance for the selection of core variables in future quantitative research and contributes to the development of smarter, more comfortable, and user-centric smartwatches.</p

    Deficiency of PKD2L1 (TRPP3) Exacerbates Pathological Cardiac Hypertrophy by Augmenting NCX1-Mediated Mitochondrial Calcium Overload

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    Summary: High salt intake is one independent risk factor for cardiac hypertrophy. Polycystic kidney disease 2-like 1 (PKD2L1, also called TRPP3) acts as a sour sensor in taste cells, and its possible role in the cardiovascular system is unknown. Here, we report that knockout of PKD2L1 exacerbated high-salt diet (HSD)-induced cardiac hypertrophy and fibrosis, accompanied by cardiac dysfunction and reduced cardiac mitochondrial oxidative phosphorylation and enzyme activity. Furthermore, knockdown of PKD2L1 led to more serious mitochondrial Ca2+ overload and reduced Ca2+ uptake in cardiomyocytes on high salt loading. Mechanistically, PKD2L1 deficiency increased p300-mediated acetylation of histone 3 lysine 27 on the promoter of sodium/calcium exchange 1 (NCX1) by repressing AMP-activated protein kinase (AMPK) activity, resulting in NCX1 overexpression and mitochondrial Ca2+ overload. These results reveal an inhibitory effect of PKD2L1 on cardiac hypertrophy and provide a mechanistic insight into the link between mitochondrial Ca2+ homeostasis and cardiac hypertrophy. : Lu et al. reveal a role of a mitochondria-localized TRPP member, PKD2L1, in high salt-induced cardiac hypertrophy. PKD2L1 knockout leads to overexpression of NCX1 through increasing the acetylation level of histone 3 lysine 27 on NCX1 promoter and thus exacerbates mitochondrial calcium overload by activating the reverse mode of NCX1 in cardiomyocytes. Keywords: high-salt diet, cardiac hypertrophy, PKD2L1, mitochondria, NCX

    Heterobimetallic Dinuclear Lanthanide Alkoxide Complexes as Acid–Base Difunctional Catalysts for Transesterification

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    A practical lanthanide­(III)-catalyzed transesterification of carboxylic esters, weakly reactive carbonates, and much less-reactive ethyl silicate with primary and secondary alcohols was developed. Heterobimetallic dinuclear lanthanide alkoxide complexes [Ln<sub>2</sub>Na<sub>8</sub>{(OCH<sub>2</sub>CH<sub>2</sub>NMe<sub>2</sub>)}<sub>12</sub>(OH)<sub>2</sub>] (Ln = Nd (<b>I</b>), Sm (<b>II</b>), and Yb (<b>III</b>)) were used as highly active catalysts for this reaction. The mild reaction conditions enabled the transesterification of various substrates to proceed in good to high yield. Efficient activation of transesterification may be endowed by the above complexes as cooperative acid–base difunctional catalysts, which is proposed to be responsible for the higher reactivity in comparison with simple acid/base catalysts
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