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Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real‐world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process. [ABSTRACT FROM AUTHOR]

In this study, we demonstrate breakdown voltage at 1500 V of GaN on a QST power device. The high breakdown voltage and low current collapse performance can be attributed to the higher quality of GaN buffer layers grown on QST substrates. This is primarily due to the matched coefficient of thermal expansion (CTE) with GaN and the enhanced mechanical strength. Based on computer-aided design (TCAD) simulations, the strong electric-field-induced trap-assisted thermionic field emissions (TA-TFEs) in the GaN on QST could be eliminated in the GaN buffer. This demonstration showed the potential of GaN on QST, and promises well-controlled performance and reliability under high-power operation conditions. [ABSTRACT FROM AUTHOR]

(1) Background: An asthma exacerbation that is not relieved with medication typically requires an emergency room visit (ERV). The coronavirus disease 2019 (COVID-19) pandemic began in Taiwan in January of 2020. The influence of the COVID-19 pandemic on pediatric ERVs in Taiwan was limited. Our aim was to survey pediatric asthma ERVs in the COVID-19 era; (2) Methods: Data were collected from the health quality database of the Taiwanese National Health Insurance Administration from 2019 to 2021. Air pollution and climatic factors in Taipei were used to evaluate these relationships. Changes in the rates of pediatric asthma ERVs were assessed using logistic regression analysis. Poisson regression was used to evaluate the impact of air pollution and climate change; (3) Results: The rate of pediatric asthma ERVs declined in different areas and at different hospital levels including medical centers, regional and local hospitals. Some air pollutants (particulate matter ≤ 2.5 µm, particulate matter ≤ 10 µm, nitrogen dioxide, and carbon monoxide) reduced during the COVID-19 lockdown. Ozone increased the relative risk (RR) of pediatric asthma ERVs during the COVID-19 period by 1.094 (95% CI: 1.095–1.12) per 1 ppb increase; (4) Conclusions: The rate of pediatric asthma ERVs declined during the COVID-19 pandemic and ozone has harmful effects. Based on these results, the government could reduce the number of pediatric asthma ERVs through healthcare programs, thereby promoting children's health. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether the efficiency, precision, and validity of computerized adaptive testing (CAT) could be improved by assessing confidence differences in knowledge that examinees possessed. We proposed a novel polytomous CAT model called the confidence-weighting computerized adaptive testing (CWCAT), which combined a confidence-weighting scoring scheme with the graded response model (GRM). The CWCAT provided a more interactive testing environment by focusing on the examinees' confidence in their responses. An experiment was conducted to evaluate the comparison between the CWCAT and conventional CAT in terms of efficiency, precision, and validity. As expected, the polytomous method provided better discrimination among individual differences in the confidence in knowledge and required fewer items per examinee. Results also showed that CWCAT yielded ability estimates that were higher and better correlated to examinees' performance in English learning. Furthermore, the ability measured by CWCAT was not as likely to be affected by guessing as on conventional CAT, and, therefore, was more consistent with examinees' true ability. (Contains 9 tables and 9 figures.)

Aim: Periodontitis (PD) is the sixth most prevalent disease around the world and is involved in the development and progression of multiple systemic diseases. Previous studies have reported that PD may aggravate liver injuries. The objective of this study was to investigate whether and how PD affects liver fibrosis. Materials and Methods: Ligature‐induced PD (LIP) was induced in male C57/B6J mice, and sub‐gingival plaques (PL) from patients with PD were applied to mouse teeth. Liver fibrosis was induced by carbon tetrachloride (CCl4) injection. The mice were randomly divided into six groups: Oil, Oil+LIP, Oil+LIP+PL, CCl4, CCl4+LIP, and CCl4+LIP+PL. Alveolar bone resorption was evaluated by methylene blue staining. Hepatic function was analysed by serum alanine aminotransferase and hepatic hydroxyproline. Picrosirius red and α‐smooth muscle actin (SMA) staining were used to evaluate the fibrotic area. RNA sequencing and quantitative RT‐PCR were used to measure gene expression. Western blotting was used to measure protein levels. Flow cytometry was used to analyse the accumulation of immune cells. Mouse microbiota were analysed using 16S rRNA gene sequencing. Results: Mice in the CCl4+LIP+PL group displayed higher serum alanine aminotransferase and hepatic hydroxyproline as well as more Picrosirius red‐positive and α‐SMA‐positive areas in liver samples than those of the CCl4 group, suggesting that PD (LIP+PL) aggravated CCl4‐induced hepatic dysfunction and liver fibrosis. Consistently, the expression of fibro‐genic genes and the protein levels of transforming growth factor β were much higher in the CCl4+LIP+PL group than in the CCl4 group. Flow cytometry revealed that PD increased the accumulation of immune cells, including Kupffer cells, B cells, and Th17 cells, in the liver of mice with CCl4 treatment. PD also increased the expression of inflammatory genes and activated pro‐inflammatory nuclear factor‐kappa B pathway in the livers of CCl4‐injected mice. Moreover, PD altered both oral and liver microbiota in CCl4‐injected mice. Conclusions: PD aggravates CCl4‐induced hepatic dysfunction and fibrosis in mice, likely through the increase of inflammation and alteration of microbiota in the liver. [ABSTRACT FROM AUTHOR]

The wavelength-routed optical network on chip (WRONoC) is a promising solution for signal transmission in modern System-on-Chip (SoC) designs. Previous works do not simultaneously handle all the following four main issues for WRONoCs: 1) correlations between the topological structure and physical layout; 2) tradeoffs between the maximum insertion loss and the number of wavelengths; 3) runtime scalability of wavelength assignment scheme; and 4) a fully automated flow to generate predictable designs. As a result, their insertion loss estimation is inaccurate, their wavelength assignment is inefficient, and thus, only suboptimal results are obtained. To remedy these disadvantages, we present a fully automated topological structure and a physical layout co-design flow with improved wavelength assignment schemes to minimize the maximum insertion loss and the laser power simultaneously with a significant speedup. The experimental results show that our co-design flow significantly outperforms state-of-the-art works in the maximum insertion loss, laser power, and runtimes. [ABSTRACT FROM AUTHOR]

Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17+ γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4+ T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials. [ABSTRACT FROM AUTHOR]

The title inorganic-organic hybrid material containing a mixed anion, [BzIQl]2[Zn(NCS)2Br2] (1) (BzIQl = benzyl isoquinolinium, NCS− = isothiocyanate), crystallizes with a benzyl isoquinolinium cation and half of a bis(bromo)-bis(isothiocyanate)zinc(II) anion in the asymmetric unit. It was characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), electrospray ionization mass spectrometry (ESI-MS), and powder and single crystal X-ray diffraction (PXRD and SC-XRD). The organic cation exhibits a Λ-shaped configuration in which two aromatic rings form an inclined dihedral angle of 90.12°. The ZnII ion in the anion is coordinated by two Br ions and two isothiocyanate ions, and two contiguous anions forms a dimer through S···Br interactions. The thermal stability of the hybrid crystal analyzed by thermogravimetric-differential thermal analysis (TG-DTA) reveals that the title crystal was stable up to 170 °C. The PXRD study confirms the phase purity of the crystalline sample. The band gap energy between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) explains the eventual charge transfer interaction that take place mainly between the anion and [BzIQl]+ cation, and the low value (0.46 ev) indicates the suitability of the crystal for optical application. The first hyperpolarizability predicted using density functional theory (DFT) is more than 720 times that of the reference potassium dihydrogen phosphate crystal (KDP). [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy. [ABSTRACT FROM AUTHOR]

Abstract Background Fibronectin (FN) is known to be a large multifunction glycoprotein with binding sites for many substances, including N-terminal and C-terminal heparin-binding domains. We investigated the effects of highly purified rhFNHN29 and rhFNHC36 polypeptides originally cloned from the two heparin-binding domains on the adhesion and invasion of highly metastatic human hepatocellular carcinoma cells (MHCC97H) and analyzed the underlying mechanism involved. Methods The MHCC97H cells that adhered to FN in the presence of various concentrations of rhFNHN29 and rhFNHC36 polypeptides were stained with crystal violet and measured, and the effects of rhFNHN29 and rhFNHC36 on the invasion of the MHCC97H cells were then detected using the Matrigel invasion assay as well as a lung-metastasis mouse model. The expression level of integrins and focal adhesion kinase (FAK) phosphotyrosyl protein was examined by Western blot, and the activity of matrix metalloproteinases (MMPs) and activator protein 1 (AP-1) was analyzed by gelatin zymography and the electrophoretic mobility band-shift assay (EMSA), respectively. Results Both of the polypeptides rhFNHN29 and rhFNHC36 inhibited adhesion and invasion of MHCC97H cells; however, rhFNHC36 exhibited inhibition at a lower dose than rhFNHN29. These inhibitory effects were mediated by integrin αvβ3 and reversed by a protein tyrosine phosphatase inhibitor. Polypeptides rhFNHN29 and rhFNHC36 abrogated the tyrosine phosphorylation of focal adhesion kinase (p-FAK) and activation of activator protein 1 (AP-1), resulting in the decrease of integrin αv, β3 and β1 expression as well as the reduction of MMP-9 activity. Conclusions Polypeptides rhFNHN29 and rhFNHC36 could potentially be applicable to human liver cancer as anti-adhesive and anti-invasive agents.

The vector graphics with gradient mesh can be attributed to their compactness and scalability; however, they tend to fall short when it comes to real-time editing due to a lack of real-time rasterization and an efficient editing tool for image details. In this paper, we encode global manipulation geometries and local image details within a hybrid vector structure, using parametric patches and detailed features for localized and parallelized thin-plate spline interpolation in order to achieve good compressibility, interactive expressibility, and editability. The proposed system then automatically extracts an optimal set of detailed color features while considering the compression ratio of the image as well as reconstruction error and its characteristics applicable to the preservation of structural and irregular saliency of the image. The proposed real-time vector representation makes it possible to construct an interactive editing system for detail-maintained image magnification and color editing as well as material replacement in cross mapping, without maintaining spatial and temporal consistency while editing in a raster space. Experiments demonstrate that our representation method is superior to several state-of-the-art methods and as good as JPEG, while providing real-time editability and preserving structural and irregular saliency information. [ABSTRACT FROM AUTHOR]

Objectives. Stroke is a common condition after a transient ischemic attack (TIA) or minor ischemic stroke (IS). Adding clopidogrel to aspirin may yield more beneficial outcomes than aspirin mono-therapy; meanwhile, the risk of bleeding in the acute phase remains poorly understood. Therefore, there is increasing emphasis on the risks and benefits of clopidogrel with aspirin compared with aspirin mono-therapy in an effort to treat TIA/IS. Design. We searched several electronic databases, including PubMed, Cochrane, and Embase, to identify eligible randomized controlled trials (RCTs) based on the index words comparing dual-antiplatelet therapy to aspirin mono-therapy for secondary stroke prevention updated to December, 2018. Results. A total of 11 RCTs met our inclusion criteria. The pooled analysis showed that clopidogrel plus aspirin was associated with a trend toward a reduction in recurrent IS (RR = 0.72, 95%CI = 0.65-0.81, p < .001), but not the recurrent stroke rate (RR = 0.81, 95% CI = 0.63-1.03, p = .09) than aspirin mono-therapy. There were differences in bleeding episodes (RR = 1.81, 95%CI = 1.65-1.99, p < .001), moderate-severe major bleeding (RR = 1.64, 95% CI = 1.24-2.16, p = .0005), or mild bleeding (RR = 2.25, 95%CI = 1.54-3.31, p < .001) between the study groups. Meanwhile, no benefit of reducing the risk of intracranial hemorrhage with dual-antiplatelet therapy was found in TIA/IS patients (RR = 1.44, 95% CI = 0.95-2.19, p = .09). Conclusions. The addition of clopidogrel to aspirin for patients with TIA or IS appeared to significantly reduce the risk of IS recurrence with a possible increase in the risk of bleeding compared with aspirin alone. [ABSTRACT FROM AUTHOR]

Although the small bowel mesentery was slightly bruised, the herniated small bowel was otherwise healthy and viable, and no bowel resection was necessary. Surg. 1964; 159: 382 - 4. 3 Kheok SW, Haja Mohideen SM, Lim JW, Santhosh Raj SR. Intramesosigmoid hernia complicated by strangulated small-bowel obstruction. The clinical suspicion was either a congenital adhesion band or an internal hernia causing the small bowel obstruction. [Extracted from the article]

A novel design for T-shaped and Π-shaped transmission lines on dual-band bandpass filters are proposed to efficiently suppress high-frequency harmonic. The dual-band can be designed using stepped-impedance resonators. The harmonic suppression of the proposed dual-band bandpass filter is extended to 12 GHz with a rejection level higher than −20 dB. The measured results concur with the full-wave simulation results. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:547-551, 2015 [ABSTRACT FROM AUTHOR]

Abstract: Two series of raw materials were adopted to form TiAl/Ti2AlC composites: Ti/Al/TiC and Ti/Al/C. Differential thermal analysis (DTA) of starting powers and X-ray diffraction (XRD) of samples sintered at different temperatures from 600°C to 1300°C by hot pressing were utilized to analyze the phase transformation and the mechanism of synthesis. Scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy (EDS) was utilized to investigate the morphology characteristics of the products. The experimental results showed that Ti reacted with Al to form TiAl intermetallics below 900°C; and above 900°C, TiAl reacted with TiC to produce dense TiAl/Ti2AlC composites. The products sintered at 1200°C had fine crystals and dense fibres, and the distribution of Ti2AlC particles in TiAl matrix was homogeneous. [Copyright &y& Elsevier]

Abstract: Adsorption of ammonia (NH3) onto activated carbons prepared from palm shells impregnated with sulfuric acid (H2SO4) was investigated. The effects of activation temperature and acid concentration on pore surface area development were studied. The relatively large micropore surface areas of the palm-shell activated carbons prepared by H2SO4 activation suggest their potential applications in gas adsorption. Adsorption experiments at a fixed temperature showed that the amounts of NH3 adsorbed onto the chemically activated carbons, unlike those prepared by CO2 thermal activation, were not solely dependent on the specific pore surface areas of the adsorbents. Further adsorption tests for a wide range of temperatures suggested combined physisorption and chemisorption of NH3. Desorption tests at the same temperature as adsorption and at an elevated temperature were carried out to confirm the occurrence of chemisorption due to the interaction between NH3 and some oxygen functional groups via hydrogen bonding. The surface functional groups on the adsorbent surface were detected by Fourier transform infrared spectroscopy. The amounts of NH3 adsorbed by chemisorption were correlated with the contents of elemental oxygen present in the adsorbents. Mechanisms for chemical activation and adsorption processes are proposed based on the observed phenomena. [Copyright &y& Elsevier]

Abstract: Adsorption of hydrogen sulphide (H2S) onto activated carbons derived from oil palm shell, an abundant solid waste from palm oil processing mills, by thermal or chemical activation method was investigated in this paper. Dynamic adsorption in a fixed bed configuration showed that the palm-shell activated carbons prepared by chemical activation (KOH or H2SO4 impregnation) performed better than the palm-shell activated carbon by thermal activation and a coconut-shell-based commercial activated carbon. Static equilibrium adsorption studies confirmed this experimental result. An intra-particle Knudsen diffusion model based on a Freundlich isotherm was developed for predicting the amount of H2S adsorbed. Desorption tests at the same temperature as adsorption (298K) and at an elevated temperature (473K) were carried out to confirm the occurrence of chemisorption and oxidation of H2S on the activated carbon. Surface chemistries of the palm-shell activated carbons were characterized by Fourier transform infrared spectroscopy and Boehm titration. It was found that uptaking H2S onto the palm-shell activated carbons was due to different mechanisms, e.g. physisorption, chemisorption and/or H2S oxidation, depending on the activation agent and activation method. [Copyright &y& Elsevier]

Background:  Oral cavity cancers requiring excision of the oral commissure and free flap reconstruction often requires commissuroplasty to manage oral incontinence. We aimed to evaluate the implications of primary versus delayed commissuroplasty on drooling, and interincisal distance outcomes in this cohort., Methods:  A retrospective query of head and neck cancer patients operated by a single surgeon from 2017 to 2020 was performed. Patients were included if they underwent free flap reconstruction of the oral commissure, had an immediate or delayed commissuroplasty, and had 2 years of follow-up data including Thomas-Stonell and Greenberg drooling rating scales and interincisal distance measurements., Results:  Thirty-five patients were included in the review. Twelve patients received immediate commissuroplasty and 23 patients had delayed commissuroplasty. Interincisal distance was similar at baseline, although significantly varied between immediate and delayed commissuroplasty groups at 1 month and 2 years postoperative. Drooling scores were significantly elevated in the group treated with delayed commissuroplasty, but eventually normalized after staged surgery and follow-up. Patients treated with adjunct radiation therapy had lower interincisal distance than patients who did not have radiation., Conclusion:  Delayed commissuroplasty increased interincisal distance and normalize drooling in patients who required full-thickness excision of the buccal mucosa and oral commissure and free tissue reconstruction. The presented data can help to educate patients on expected postoperative outcomes and likely advocates for a second-stage procedure after completion of adjunct radiotherapy to achieve optimal commissural placement and oral competence., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China., Methods: Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up., Results: The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05)., Conclusions: Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF., (© 2023 JGC All rights reserved; www.jgc301.com.)

Background: Fibrosis is a core pathological factor of ligamentum flavum hypertrophy (LFH) resulting in degenerative lumbar spinal stenosis. Autophagy plays a vital role in multi-organ fibrosis. However, autophagy has not been reported to be involved in the pathogenesis of LFH., Methods: The LFH microarray data set GSE113212, derived from Gene Expression Omnibus, was analyzed to obtain differentially expressed genes (DEGs). Potential autophagy-related genes (ARGs) were obtained with the human autophagy regulator database. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to elucidate the underlying biological pathways of autophagy regulating LFH. Protein-protein interaction (PPI) network analyses was used to obtain hub ARGs. Using transmission electron microscopy, quantitative RT-PCR, Western blotting, and immunohistochemistry, we identified six hub ARGs in clinical specimens and bipedal standing (BS) mouse model., Results: A total of 70 potential differentially expressed ARGs were screened, including 50 up-regulated and 20 down-regulated genes. According to GO enrichment and KEGG analyses, differentially expressed ARGs were mainly enriched in autophagy-related enrichment terms and signaling pathways related to autophagy. GSEA and GSVA results revealed the potential mechanisms by demonstrating the signaling pathways and biological processes closely related to LFH. Based on PPI network analysis, 14 hub ARGs were identified. Using transmission electron microscopy, we observed the autophagy process in LF tissues for the first time. Quantitative RT-PCR, Western blotting, and immunohistochemistry results indicated that the mRNA and protein expression levels of FN1, TGFβ1, NGF, and HMOX1 significantly higher both in human and mouse with LFH, while the mRNA and protein expression levels of CAT and SIRT1 were significantly decreased., Conclusion: Based on bioinformatics analysis and further experimental validation in clinical specimens and the BS mouse model, six potential ARGs including FN1 , TGFβ1 , NGF , HMOX1 , CAT , and SIRT1 were found to participate in the fibrosis process of LFH through autophagy and play an essential role in its molecular mechanism. These potential genes may serve as specific therapeutic molecular targets in the treatment of LFH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Fei, Chen, Chen, Lai, Tan, Yu, Xiang, Dong, Zhang, Wang and Zhang.)

Alterations of protein glycosylation are closely related with pathophysiological regulation. Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome. Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides. In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions. The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions. Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO 2 and ZIC-HILIC, respectively. To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type. Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R. The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.

Background: Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer's disease (AD). Dysregulation of the endosomal-autophagic-lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction., Methods: We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4-7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis. To further explore the mechanism of EAL dysregulation in AD, components of the class III phosphatidylinositol 3-kinase (PI3KC3) complex, activators of Rab7 (Beclin1 and UVRAG), and the negative regulator of Rab7 (Rubicon) were also measured in this two brain regions., Results: In 7-month-old APP/PS1 brain that amyloid beta initiated to accumulate intracellularly, EAL pathway, and related PI3KC3 members, UVRAG and Beclin1 were upregulated both in cortex and hippocampus (all P < 0.05). By the age of 12 months old, when abundant amyloid plaques formed, EAL markers, UVRAG, and Beclin1 were also upregulated in the cortex (all P < 0.05). However, Rab7 was decreased significantly (P = 0.0447), accompanied by a reduction of its activating PI3KC complex component Beclin1 (P = 0.0215) and enhancement of its inhibiting component Rubicon (P = 0.0055) in the hippocampus., Conclusions: Our study implies that EAL pathway, represented as Rab7 and its PI3KC3 regulators' expressions, showed temporal and spatial variation in brains at different stages of AD. It provides new insights into the role of EAL pathway in pathogenesis and indicates potential therapeutic targets in neurodegenerative diseases.

BACKGROUND Torsion of an intra-abdominal lipoma is rarely the cause of acute abdominal pain. Most of the previously reported cases of intra-abdominal lipoma torsion originated in the mesentery or omentum. However, an antimesenteric lipoma of the ileum with torsion has not been reported before. CASE REPORT A 67-year-old man presented to the emergency department with acute abdominal pain. Contrast-enhanced computed tomography (CECT) of the abdomen and pelvis only showed a giant fat-containing, soft-tissue, intra-abdominal tumor, suspected to be a lipoma. Laparotomy was performed, and the presence of torsion of the antimesenteric lipoma of the ileum was confirmed. Beside tumor resection, en bloc segmental resection of the ileum with end-to-end anastomosis was performed to avoid bowel stricture and obtain tumor-free margins. CONCLUSIONS CECT is the modality of choice to detect an intra-abdominal lipoma. Urgent surgical intervention should be considered if the symptoms persist and torsion cannot be excluded. If simple excision is not adequate because of poor accessibility of the tumor stalk, en bloc segmental resection with end-to-end anastomosis should be considered.