Stress granule-localized USP8 potentiates cGAS-mediated type I interferonopathies through deubiquitination of DDX3X.

Cyclic GMP-AMP synthase (cGAS) undergoes liquid-liquid phase separation (LLPS) to trigger downstream signaling upon double-stranded DNA (dsDNA) stimulation, and the condensed cGAS colocalizes with stress granules (SGs). However, the molecular mechanism underlying the modulation of cGAS activation by SGs remains elusive. In this study, we show that USP8 is localized to SGs upon dsDNA stimulation and potentiates cGAS-stimulator of interferon genes (STING) signaling. A USP8 inhibitor ameliorates pathological inflammation in Trex1-/- mice. Systemic lupus erythematosus (SLE) databases indicate a positive correlation between USP8 expression and SLE. Mechanistic study shows that the SG protein DDX3X promotes cGAS phase separation and activation in a manner dependent on its intrinsic LLPS. USP8 cleaves K27-linked ubiquitin chains from the intrinsically disordered region (IDR) of DDX3X to enhance its condensation. In conclusion, we demonstrate that USP8 catalyzes the deubiquitination of DDX3X to facilitate cGAS condensation and activation and that inhibiting USP8 is a promising strategy for alleviating cGAS-mediated autoimmune diseases.

C1q/Tumor Necrosis Factor-Related Protein-9 Enhances Macrophage Cholesterol Efflux and Improves Reverse Cholesterol Transport via AMPK Activation.

Cholesterol efflux from foam cells in atherosclerotic plaques is crucial for reverse cholesterol transport (RCT), an important antiatherogenic event. ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1, are key receptors in the cholesterol efflux pathway. C1q/tumor necrosis factor-related protein-9 (CTRP9) is a newly discovered adipokine and exhibits an atheroprotective activity. However, the role of CTRP9 in RCT still remains unknown. In this work, we investigated the effect of subcutaneous administration of CTRP9 protein on RCT and atherosclerotic lesion formation in ApoE-/- mice fed with a high-fat diet. CTRP9-dependent regulation of cholesterol efflux and ABC transporters in RAW 264.7 foam cells was determined. Our results showed that CTRP9 protein decreased atherosclerotic lesions, increased cholesterol efflux, and upregulated liver ABCA1 and ABCG1 expression in ApoE-/- mice. CTRP9 treatment dose-dependently increased mRNA and protein expression of ABCA1, ABCG1, and LXR-α in RAW 264.7 foam cells. Moreover, the expression and phosphorylation of AMPK was potentiated upon CTRP9 treatment. Notably, CTRP9-induced cholesterol efflux and upregulation of ABCA, ABCG1, and LXR-α were impaired when AMPK was knocked down. AMPK depletion restored cholesterol accumulation in CTRP9-treated RAW 264.7 cells. Taken together, subcutaneous injection is an effective novel delivery route for CTRP9 protein, and exogenous CTRP9 can facilitate cholesterol efflux and promote RCT in an animal model of atherosclerosis. The atheroprotective activity of CTRP9 is mediated through the activation of AMPK signaling.

The Shear-Accelerated II-I Phase Transition of Isotactic Poly(1-Butene).

The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces are introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (Tc) and shear temperature (Tshear) on crystallization and phase transition are explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high Tc (105 °C). Besides, the shear-induced Form II can transit to Form I faster than the unsheared one. In addition, the phase transition rate increases as the Tshear decreases, with the fastest rate occurring at Tshear of 120 °C. The half transition time (t1/2) is measured as 6.3 h when Tc = 105 °C, Tshear = 120 °C, which is much shorter than the 20.7 h required for unsheared samples. The accelerated phase transition of iPBu can be attributed to the stretching of molecular chains, resulting from shear treatment. This study provides a quantitative analysis of the influence of the shear treatment and the Tshear on the II-I phase transition rate. It also presents a cost-effective and straightforward approach for expediting the phase transition process.

A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-containing therapy.

Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2-13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4-13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223-0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268-0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506-0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184-0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566-0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516-0.816), 0.654 (95% CI: 0.470-0.823), and 0.675 (95% CI: 0.491-0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response.

Magnetically driven Janus conical vertical array for all-weather freshwater collection.

The engineering of multifunctional structures with special surface wettability is highly desirable for all-weather freshwater production, but relevant research is scarce. In this study, a Janus conical vertical array was designed and fabricated via a magnetically driven spray-coating method for the first time. Benefiting from the special structure and wettability enhancement of the array in terms of solar absorption, fog capture and merging, droplet movement and evaporation area, all-weather freshwater production consisting of high-quality daytime solar vapor generation (water evaporation rate approximately 2.43 kg m-2 h-1, 1 kW m-2) and nighttime fog collection (water collection rate approximately 3.536 g cm-2 h-1) can be realized concurrently. When the designed array is employed for outdoor environments (114°35'E, 30°38'N, average daily temperature 34.9 °C, average daily humidity 64.0%), reliable and efficient daily pure water yields of 19.13 kg m-2-26.09 kg m-2 are obtainable. We believe that the proposed strategy for fabricating a Janus conical vertical array is novel in the integration of solar vapor generation and fog collection, which has great significance for all-weather freshwater production.

Fabrication of Dual-Functional Bacterial-Cellulose-Based Composite Anion Exchange Membranes with High Dimensional Stability and Ionic Conductivity.

Anion exchange membranes (AEMs) are increasingly becoming a popular research area due to their ability to function with nonprecious metals in electrochemical devices. Nevertheless, there is a challenge to simultaneously optimize the dimensional stability and ionic conductivity of AEMs due to the "trade-off" effect. Herein, we adopted a novel strategy of combining filling and cross-linking using functionalized bacterial cellulose (PBC) as a dual-functional porous support and brominated poly(phenylene oxide) (Br-PPO) as the cross-linking agent and filler. The PBC nanofiber framework together with cross-linking can provide a reliable mechanical support for the subsequent filled polymer, thus improving the mechanical properties and effectively limiting the size change of the final quaternized-PPO (QPPO)-filled PBC composite membrane. The composite membrane showed a very low swelling ratio of only 10.35%, even at a high water uptake (81.83% at 20 °C). Moreover, the existence of multiple -NR3+ groups in the cross-link bonds between BC and Br-PPO can provide extra OH- ion transport sites, contributing to the increase in ionic conductivity. The final membrane demonstrated a hydroxide ion conductivity of 62.58 mS cm-1, which was remarkably higher than that of the pure QPPO membrane by up to 235.93% (80 °C). The successful preparation of the PBC3/QPPO membrane provides an effective avenue to tackle the trade-off effect through a dual-functional strategy.

Astragaloside IV alleviates LPS-induced cardiomyocyte hypertrophy and collagen expression associated with CCL2-mediated activation of NF-κB signaling pathway.

Cardiac remodeling (CR), characterized by cardiac hypertrophy and fibrosis, leads to the development and progression of heart failure (HF). Nowadays, emerging evidence implicated that inflammation plays a vital role in the pathogenesis of CR and HF. Astragaloside IV (AS-IV), an effective component of Astragalus membranaceus, exerts cardio-protective and anti-inflammatory effects, but the underlying mechanism remains not fully elucidated. This present study aimed to investigate the effects of AS-IV on cardiac hypertrophy and fibrosis in cultured H9C2 cells stimulated with LPS, as well as explore its underlying mechanisms. As a result, we found AS-IV could reduce the cell surface size, ameliorate cardiac hypertrophy and fibrosis in LPS-induced H9C2 cells. To specify which molecules or signaling pathways play key roles in the process, RNA-seq analysis was performed. After analyzing the transcriptome data, CCL2 has captured our attention, of which expression was sharply increased in model group and reversed by AS-IV treatment. The results also indicated that AS-IV could ameliorate the inflammatory response by down-regulating NF-κB signaling pathway. Additionally, a classical inhibitor of CCL2 (bindarit) were used to further explore whether the anti-inflammatory effect of AS-IV was dependent on this chemokine. Our results indicated that AS-IV could exert a potent inhibitory effect on CCL2 expression and down-regulated NF-κB signaling pathway in a CCL2-dependent manner. These findings provided a scientific basis for promoting the treatment of HF with AS-IV.

Composite proton exchange membrane for fuel cells based on chitosan modified by acid-base amphoteric nanoparticles.

Currently, achieving a simultaneous improvement in proton conductivity and mechanical properties is a key challenge in using chitosan (CS) as a proton exchange membrane (PEM) substrate in direct methanol fuel cells (DMFCs). Herein, a novel nanofiller-zwitterionic molecule, (3-(3-aminopropyl) dimethylammonio) propane-1-sulfonate, ADPS)-modified polydopamine (PDA) (PDA-ADPS) was synthesized by the Michael addition reaction and was incorporated into a CS matrix to prepare CS/PDA-ADPS composite membranes. PDA-ADPS, which contains an acid-based ion pair can create new proton conduction channels in the composite membrane, improving proton conductivity. The proton conductivity of the CS/PDA-ADPS composite membrane was as high as 38.4 mS cm-1 at 80 °C. Moreover, due to the excellent compatibility and dispersibility of PDA-ADPS in the CS matrix, the obtained CS/PDA-ADPS composite membranes exhibited favorable mechanical properties. Such outstanding proton conductivity and mechanical properties guarantee good performance of the composite membranes in fuel cells. The peak power density of the CS/PDA-ADPS composite membranes was 30.2 mW cm-2 at 70 °C. This work provides a new strategy for fabricating high-performance CS based PEMs for DMFCs.

Macro-porous structured aerogel with enhanced ab/desorption kinetics for sorption-based atmospheric water harvesting.

Sorption-based atmospheric water harvesting (SAWH) has been proven to be a promising method to alleviate the impact of the water crisis on human activities. However, the low water-sorption capacity and sluggish ab/desorption kinetics of current SAWH materials make it difficult to achieve high daily water production. In this study, a photothermal porous sodium alginate-tannic acid-5/Fe3+@lithium chloride aerogel (SA-TA-5/Fe3+@LiCl) with macroporous structure (average pore diameter ∼43.67 µm) and high solar absorbance (∼98.4 %) was fabricated via Fe3+-induced crosslinking and blackening methods. When it is employed for SAWH, moisture can enter the inner space of the aerogel and contact highly hygroscopic lithium chloride (LiCl) more easily via macroporous channels, resulting in the water uptake for the SA-TA-5/Fe3+@LiCl aerogel reaching approximately 1.229 g g-1 under dry conditions (relative humidity (RH) âˆ¼ 45 %, 25 °C) after a short time (4 h) moisture absorption, and releasing as much as 97.7 % of the absorbed water under 1 sun irradiation within 2 h. As a proof of concept, it is estimated that the daily water yield of the fabricated SA-TA/Fe3+@LiCl aerogel can reach approximately 4.65 kg kg-1 in conditions close to the real outdoor environment (RH âˆ¼ 45 %, 25 °C), which satisfies the daily minimum water consumption of two adults. This study demonstrates a novel strategy for developing advanced solar-driven SAWH materials with enhanced ab/desorption kinetics and efficient water sorption-desorption properties.

Regulation of SARS-CoV-2 infection and antiviral innate immunity by ubiquitination and ubiquitin-like conjugation.

A global pandemic COVID-19 resulting from SARS-CoV-2 has affected a significant portion of the human population. Antiviral innate immunity is critical for controlling and eliminating the viral infection. Ubiquitination is extensively involved in antiviral signaling, and recent studies suggest that ubiquitin-like proteins (Ubls) modifications also participate in innate antiviral pathways such as RLR and cGAS-STING pathways. Notably, virus infection harnesses ubiquitination and Ubls modifications to facilitate viral replication and counteract innate antiviral immunity. These observations indicate that ubiquitination and Ubls modifications are critical checkpoints for the tug-of-war between virus and host. This review discusses the current progress regarding the modulation of the SARS-CoV-2 life cycle and antiviral innate immune pathways by ubiquitination and Ubls modifications. This paper emphasizes the arising concept that ubiquitination and Ubls modifications are powerful modulators of virus and host interaction and potential drug targets for treating the infection of SARS-CoV-2.

miR-926-3p influences myocardial injury in septic mice through regulation of mTOR signaling pathway by targeting TSC1.

BACKGROUND: The purpose of this study is to investigate the influence of miR-926-3p on myocardial injury and its mechanisms. METHODS: An animal model of sepsis was constructed by CLP, and animals were randomly divided into 4 groups: C group, miR-926-3p inhibitor group, CLP + NC group, and CLP + miR-926-3p inhibitor group. RESULTS: Compared with those in C group, echocardiographic parameters remarkably declined in CLP + NC group. Compared with CLP + NC group, miR-926-3p inhibitor group indicated elevated echocardiographic parameters in mice, pathological improvement tendency of myocardial tissues and distinct reduction in cardiomyocyte apoptosis. It could be observed by electron microscopy that the number of lysosomes in miR-926-3p inhibitor group was greatly increased relative to CLP + NC group. Immunofluorescence exhibited that the number of green fluorescent puncta was significantly higher in miR-926-3p inhibitor group as compared to that in CLP + NC group. The autophagic flow was verified by observing the relative expression of LC3II at different times. The results of Western blotting manifested that miR-926-3p inhibitor up-regulated mTOR-related protein expressions and down-regulated the protein expression of p-mTOR. LPS was adopted to induce cardiomyocyte injury in vitro, and the results confirmed that, identical to in vivo experiments, miR-926-3p inhibitor was able to up-regulate the protein expressions of mTOR-related protein and down-regulate p-mTOR protein expression in cardiomyocytes. After addition of MHY1485, The expression of mTOR-related proteins changes in each group. CONCLUSION: Inhibition of miR-926-3p enhances autophagy through regulation of the mTOR signaling pathway, thus ameliorating myocardial injury in septic mice.

Spermine-starch nanoparticles with antisense vicR suppress Streptococcus mutans cariogenicity.

Dental caries of permanent teeth is a common public health concern and has the second-highest incidence among global diseases. The exopolysaccharides (EPS) synthesized by Streptococcus mutans (S. mutans) are the principal virulence factor for cariogenic etiology. We previously discovered that an endogenous antisense vicR RNA (ASvicR) could significantly inhibit EPS synthesis in S. mutans and reduce its cariogenicity. However, ASvicR cannot be directly applied in the oral environment. An appropriate vector is of great need to protect ASvicR from being degraded by nucleases for effective gene delivery to S. mutans. Functionally modified starches shed light on this field because of their excellent biocompatibility and biodegradability. In this study, a biocompatible and biodegradable spermine-starch nanocomposite (SSN) was constructed for ASvicR delivery. Starch was cationically functionalized by grafting endogenous spermine to closely bind with the recombinant ASvicR plasmid. The SSN not only protected the recombinant ASvicR plasmid from DNase I but also achieved highly efficient gene transformation to S. mutans via the hydrolysis of α-amylase in the saliva. In addition, SSN-ASvicR was shown to endow ASvicR with an increasing transformation efficiency approximately four times that of the naked ASvicR plasmid, as well as allowing for targeting specificity to the transcription of the vicR gene and the suppression of biofilm organization via EPS digestion. In particular, SSN-ASvicR nanoparticles exhibited excellent biological safety and maintained oral microbiota homeostasis in vivo. The SSN can be prepared in a ready-to-use formulation for targeting cariogenic bacteria, thus demonstrating important prospects in the prevention of dental caries.

Minocycline and Pyrrolidine Dithiocarbamate Attenuate Hypertension via Suppressing Activation of Microglia in the Hypothalamic Paraventricular Nucleus.

Proinflammatory cytokines, reactive oxygen species and imbalance of neurotransmitters are involved in the pathophysiology of angiotensin II-induced hypertension. The hypothalamic paraventricular nucleus (PVN) plays a vital role in hypertension. Evidences show that microglia are activated and release proinflammatory cytokines in angiocardiopathy. We hypothesized that angiotensin II induces PVN microglial activation, and the activated PVN microglia release proinflammatory cytokines and cause oxidative stress through nuclear factor-kappa B (NF-κB) pathway, which contributes to sympathetic overactivity and hypertension. Male Sprague-Dawley rats (weight 275-300 g) were infused with angiotensin II to induce hypertension. Then, rats were treated with bilateral PVN infusion of microglial activation inhibitor minocycline, NF-κB activation inhibitor pyrrolidine dithiocarbamate or vehicle for 4 weeks. When compared to control groups, angiotensin II-induced hypertensive rats had higher mean arterial pressure, PVN proinflammatory cytokines, and imbalance of neurotransmitters, accompanied with PVN activated microglia. These rats also had more PVN gp91phox (source of reactive oxygen species production), and NF-κB p65. Bilateral PVN infusion of minocycline or pyrrolidine dithiocarbamate partly or completely ameliorated these changes. This study indicates that angiotensin II-induced hypertensive rats have more activated microglia in PVN, and activated PVN microglia release proinflammatory cytokines and result in oxidative stress, which contributes to sympathoexcitation and hypertensive response. Suppression of activated PVN microglia by minocycline or pyrrolidine dithiocarbamate attenuates inflammation and oxidative stress, and improves angiotensin II-induced hypertension, which indicates that activated microglia promote hypertension through activated NF-κB. The findings may offer hypertension new strategies.

Long noncoding RNA THRIL promotes foam cell formation and inflammation in macrophages.

Tumor necrosis factor-α (TNF-α) and heterogenous nuclear ribonucleoprotein L (hnRNPL)-related immunoregulatory lincRNA (THRIL) is a long noncoding RNA (lncRNA) involved in various inflammatory diseases. However, its role in atherosclerosis is not known. In this study, we aimed to investigate the function of THRIL in mediating macrophage inflammation and foam cell formation. The expression of THRIL was quantified in THP-1 macrophages after treatment with oxidized low-density lipoprotein (oxLDL). The effect of THRIL overexpression and knockdown on oxLDL-induced inflammatory responses and lipid accumulation was determined. THRIL-associated protein partners were identified by RNA pull-down and RNA immunoprecipitation assays. We show that THRIL is upregulated in macrophages after oxLDL treatment. Knockdown of THRIL blocks oxLDL-induced expression of interleukin-1ß (IL-1ß), IL-6, and TNF-α and lipid accumulation. Conversely, ectopic expression of THRIL enhances inflammatory gene expression and lipid deposition in oxLDL-treated macrophages. Moreover, THRIL depletion increases cholesterol efflux from macrophages and the expression of ATP-binding cassette transporter (ABC) A1 and ABCG1. FOXO1 is identified as a protein partner of THRIL and promotes macrophage inflammation and lipid accumulation. Furthermore, overexpression of FOXO1 restores lipid accumulation and inflammatory cytokine production in THRIL-depleted macrophages. In conclusion, our data suggest a model where THRIL interacts with FOXO1 to promote macrophage inflammation and foam cell formation. THRIL may represent a therapeutic target for atherosclerosis.

Identification of immune subtypes and their prognosis and molecular implications in colorectal cancer.

Immune composition is commonly heterogeneous and varies among colorectal cancer (CRC) patients. A comprehensive immune classification may act as important characteristics to predict CRC prognosis. Thus, we aimed to identify novel immune specific subtypes to guide future therapies. Unsupervised clustering was used to classify CRC samples into different immune subtypes based on abundances of immune cell populations, during which TCGA and GSE17536 datasets were used as training and validation sets, respectively. The associations between the immune subtypes and patient prognosis were investigated. Further, we identified differentially expressed genes (DEGs) between immune high and low subtypes, followed by functional enrichment analyses of DEGs. The expression levels of 74 immunomodulators (IMs) across immune subtypes were analyzed. As a result, we clustered CRC samples into three distinct immune subtypes (immune high, moderate, and low). Patients with immune-high subtype showed the best prognosis, and patients with immune-low subtype had the worst survival in both TCGA and GSE17536 cohorts. A group of 2735 up-regulated DEGs were identified across immune high and low subtypes. The main DEGs were the members of complement components, chemokines, immunoglobulins, and immunosuppressive genes that are involved in immune modulation-related pathways (e.g., cytokine-cytokine receptor interaction) or GO terms (e.g., adaptive immune response and T cell activation). The expression levels of 63 IMs were significantly varied across immune subtypes. In conclusion, this study provides a conceptual framework and molecular characteristics of CRC immune subtypes, which may accurately predict prognosis and offer novel targets for personalized immunotherapy through modifying subtype-specific tumor immune microenvironment.

Super-enhancers in esophageal carcinoma: Transcriptional addictions and therapeutic strategies.

The tumorigenesis of esophageal carcinoma arises from transcriptional dysregulation would become exceptionally dependent on specific regulators of gene expression, which could be preferentially attributed to the larger non-coding cis-regulatory elements, i.e. super-enhancers (SEs). SEs, large genomic regulatory entity in close genomic proximity, are underpinned by control cancer cell identity. As a consequence, the transcriptional addictions driven by SEs could offer an Achilles' heel for molecular treatments on patients of esophageal carcinoma and other types of cancer as well. In this review, we summarize the recent findings about the oncogenic SEs upon which esophageal cancer cells depend, and discuss why SEs could be seen as the hallmark of cancer, how transcriptional dependencies driven by SEs, and what opportunities could be supplied based on this cancer-specific SEs.

Endoscopic resection of upper gastrointestinal lymphangioma: A single-center experience.

Objective: Lymphagioma, which in most cases as benign tumors, occurs in head, neck, axilla, and mediastinum. Lymphangioma is exceedingly rare in the upper gastrointestinal tract including esophagus, stomach, and duodenum. However, the clinical characteristics, natural history, and recurrence rate after endoscopic resection remain unclear. This study aims to evaluate the characteristic findings and assess the efficacy of endoscopic techniques in the management of this disease. Methods: In this systematic retrospective analysis, we evaluated all 24 cases of upper gastrointestinal lymphangioma resected by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and diagnosed by histopathology at our hospital from January 2012 to May 2021. We analyzed the results of endoscopy, endoscopic ultrasonography (EUS), CT, histologic examination, and follow-up assessments. Results: 9 male and 15 female patients with esophageal lymphangioma were enrolled in this study, with a mean age of 54.17 ± 11.60 years (range 30-71 years). The lesions' size varied from 2.20 to 40.10 mm, with the median size of 7.83 mm. All patients were evaluated preoperatively, whose endoscopic appearance typically appears as dilated lymphatic channels beneath the surface epithelium of the protrude mucosal or sub-mucosal lesion. Endoscopic ultrasonography revealed the presence of a honeycomb-like or grid-like mass with a heterogeneous echo pattern, and a clear boundary between the lesion and the muscularis propria layer may be helpful for the primary diagnosis of this disease. 22 patients underwent EMR and 2 patient were treated with ESD. Histologic examination revealed that the lesions contained many dilated lymphatic vessels, which confirmed the initial diagnosis of lymphangioma in all patients. No major adverse events were found during the operation or a median follow-up of 43 months (range 13-92). Conclusions: Endoscopic ultrasonography has important clinical value for the primary diagnosis of lymphangioma in the upper gastrointestinal tract. This study also suggests that endoscopic resection should be considered as a more minimally invasive, safe, feasible, and effective therapeutic option comparing to laparoscopic surgery.

Low-Temperature Oxidation of Heavy Oil Asphaltene with and without Catalyst.

In this study, the asphaltene extracted from Luntai heavy oil was oxidized by a mixture of propionic anhydride and hydrogen peroxide without and with a catalyst. Elemental analysis and infrared spectroscopy results indicated the occurrence of oxygen addition, condensation, and side chain cleavage reactions in the oxidation process. Oxidation products were divided into methanol solubles and methanol insolubles. The H/C and O/C atomic ratios of the MeOHS in the oxidation products without a catalyst were higher than those of the Luntai asphaltene. MeOHS had fewer aromatic rings than Luntai asphaltene. Compared with the oxidative reaction without a catalyst, the total mass of oxidation products and the proportion of MeOHS in oxidation products both increased after catalytic oxidation. This low-temperature oxidation technology can be used to upgrade asphaltenes, and thus can promote the exploitation and processing of heavy oil.

A change of PD-1/PD-L1 expression on peripheral T cell subsets correlates with the different stages of Alzheimer's Disease.

BACKGROUND: Immune checkpoints are a set of costimulatory and inhibitory molecules that maintain self-tolerance and regulate immune homeostasis. The expression of immune checkpoints on T cells in malignancy, chronic inflammation, and neurodegenerative diseases has gained increasing attention. RESULTS: To characterize immune checkpoints in neurodegenerative diseases, we aimed to examine the expression of the immune checkpoint PD-1/PD-L1 in peripheral T cells in different Alzheimer's disease (AD) patients. To achieve this aim, sixteen AD patients and sixteen age-matched healthy volunteers were enrolled to analyze their CD3+ T cells, CD3+CD56+ (neural cell adhesion molecule, NCAM) T cells, CD4+/CD8+ T cells, and CD4+/CD8+CD25+ (interleukin-2 receptor alpha, IL-2RA) T cells in this study. The expression of PD-1 on T cells was similar between the AD patients and healthy volunteers, but increased expression of PD-L1 on CD3+CD56+ T cells (natural killer T cells, NKT-like), CD4+ T cells (helper T cells, Th), CD4+CD25+ T cells, and CD8+ T cells (cytotoxic T lymphocytes, CTL) was detected in the AD patients. In addition, we found negative correlations between the AD patients' cognitive performance and both CD8+ T cells and CD8+CD25+ T cells. To identify CD8+ T-cell phenotypic and functional characteristic differences between the healthy volunteers and AD patients in different stages, a machine learning algorithm, t-distributed stochastic neighbor embedding (t-SNE), was implemented. Using t-SNE enabled the above high-dimensional data to be visualized and better analyzed. The t-SNE analysis demonstrated that the cellular sizes and densities of PD-1/PD-L1 on CD8+ T cells differed among the healthy, mild AD, and moderate AD subjects. CONCLUSIONS: Our results suggest that changes in PD-1/PD-L1-expressing T cells in AD patients' peripheral blood could be a potential biomarker for monitoring disease and shed light on the AD disease mechanism. Moreover, these findings indicate that PD-1/PD-L1 blockade treatment could be a novel choice to slow AD disease deterioration.