Akkermansia muciniphila: a deworming partner independent of type 2 immunity.

The gut microbiota has coevolved with the host for hundreds of millions of years, playing a beneficial role in host health. Human parasitic helminths are widespread and pose a pervasive global public health issue. Although Type 2 immunity provides partial resistance to helminth infections, the composition of the gut microbiota can change correspondingly. Therefore, it raises the question of what role the gut microbiota plays during helminth infection. Akkermansia muciniphila has emerged as a notable representative of beneficial microorganisms in the gut microbiota. Recent studies indicate that A. muciniphila is not merely associated with helminth infection but is also causally linked to infection. Here, we provide an overview of the crosstalk between A. muciniphila and enteric helminth infection. Our goal is to enhance our understanding of the interplay among A. muciniphila, helminths, and their hosts while also exploring the potential underlying mechanisms.

Ceramides and metabolic profiles of patients with acute coronary disease: a cross-sectional study.

Metabolic Syndrome (MS) is a rapidly growing medical problem worldwide and is characterized by a cluster of age-related metabolic risk factors. The presence of MS increases the likelihood of developing atherosclerosis and significantly raises the morbidity/mortality rate of acute coronary syndrome (ACS) patients. Early detection of MS is crucial, and biomarkers, particularly blood-based, play a vital role in this process. This cross-sectional study focused on the investigation of certain plasma ceramides (Cer14:0, Cer16:0, Cer18:0, Cer20:0, Cer22:0, and Cer24:1) as potential blood biomarkers for MS due to their previously documented dysregulated function in MS patients. A total of 695 ACS patients were enrolled, with 286 diagnosed with MS (ACS-MS) and 409 without MS (ACS-nonMS) serving as the control group. Plasma ceramide concentrations were measured by LC-MS/MS assay and analyzed through various statistical methods. The results revealed that Cer18:0, Cer20:0, Cer22:0, and Cer24:1 were significantly correlated with the presence of MS risk factors. Upon further examination, Cer18:0 emerged as a promising biomarker for early MS detection and risk stratification, as its plasma concentration showed a significant sensitivity to minor changes in MS risk status in participants. This cross-sectional observational study was a secondary analysis of a multicenter prospective observational cohort study (Chinese Clinical Trial Registry, https://www.who.int/clinical-trials-registry-platform/network/primary-registries/chinese-clinical-trial-registry-(chictr), ChiCTR-2200056697), conducted from April 2021 to August 2022.

Non-linear association between aspartate aminotransferase to alanine aminotransferase ratio and mortality in critically ill older patients: A retrospective cohort study.

BACKGROUND: The aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio has been shown to be associated with poor clinical outcomes across various patient groups. However, little is unclear about the association between the two in critically ill older patients. Therefore, we aim to investigate the association of the AST/ALT ratio with hospital mortality in this special population. METHODS: In this retrospective cohort study, we extracted elderly patients (age ≥ 65 years) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was in-hospital mortality. The association between the AST/ALT ratio and hospital mortality was studied using univariable and multivariable Cox regression analysis, as well as restricted cubic splines (RCS). Survival analysis was performed using the Kaplan-Meier (KM) method according to the AST/ALT ratio. RESULTS: Among the 13,358 eligible patients, the mean age was 77.6 years, 7,077 patients (52.9%) were male, and 2,511 patients (18.8%) died in hospital. The AST/ALT ratio was found to be independently associated with in-hospital mortality (HR = 1.05, 95% CI: 1.01-1.09, P = 0.022) after adjusting for potential confounders. Furthermore, a non-linear relationship and saturation effect were observed between them, with the inflection point being 1.80. When the AST/ALT ratio was less than 1.80, we found that every 1 unit increase in the AST/ALT ratio resulted in a 39% increased risk of in-hospital mortality (HR = 1.39, 95% CI: 1.18-1.64, P < 0.001). However, when the AST/ALT ratio was greater than 1.80, the association became saturated (HR = 1.01, 95% CI: 0.96-1.07, P = 0.609). Sensitivity and subgroup analyses showed the results were robust. CONCLUSION: In critically ill older patients, the association between the AST/ALT ratio and in-hospital mortality was non-linear and showed a saturation effect. An elevated AST/ALT ratio was significantly associated with increased in-hospital mortality when the AST/ALT ratio was less than 1.80.

Association of age-adjusted Charlson comorbidity index with adverse outcomes in patients undergoing transcatheter aortic valve replacement: A retrospective cohort study.

Patients undergoing transcatheter aortic valve replacement (TAVR) have a high comorbid burden. Our objective was to assess the association between the age-adjusted Charlson comorbidity index (Age-CCI) and mortality and readmission rates within 1-year post-TAVR. Data were extracted from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version 2.0). The primary endpoint was a composite outcome of all-cause mortality or readmission within 1-year after TAVR. To examine the associations of Age-CCI with outcomes, we used multivariable Cox proportional hazards regression, restricted cubic spline (RCS), and Kaplan-Meier curves. A total of 785 patients (52.9% male) with a median age of 84.0 years were assessed. More than half of our patients had an Age-CCI ≥ 7. After adjustment for potential confounders, we found that a 1 unit increase in Age-CCI was associated with a 10% increase in mortality and readmission rates after TAVR (HR = 1.10, 95% CI: 1.04-1.17, P < .001). High Age-CCI (Age-CCI ≥ 7) compared with the low Age-CCI (Age-CCI < 7) showed a 36% increase of mortality and readmission rates (HR = 1.36, 95% CI: 1.07-1.73, P = .013). The RCS curve analysis showed a continuous linear relationship between Age-CCI and the composite outcome risk (P for non-linearity = .671). The Kaplan-Meier survival analysis showed that patients with Age-CCI ≥ 7 had a poorer prognosis than those with Age-CCI < 7 (log-rank P < .001). Subgroup analyses showed the results remained stable. Age-CCI is independently associated with all-cause mortality and readmission in patients treated with TAVR, which may help clinicians risk-stratify patients and offer an opportunity to improve patient outcomes.

Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming.

T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells. At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. Our findings also bear clinical significance, as metabolic engineering of chimeric antigen receptor (CAR) T cells is a promising strategy to enhance the stemness and functionality of Tpex cells for cancer immunotherapy.

Macroalgae culture-induced carbon sink in a large cultivation area of China.

Macroalgae culture-induced carbon sink in sediments has been little investigated. Here, total organic carbon (TOC), total nitrogen (TN), and δ13C were examined in sediments in a cultivation field of macroalgae (kelp and Gracilariopsis lemaneiformis) in Sansha Bay, Southeast China. Both proxies of C/N (TOC to TN ratio) and δ13C indicated a multisource of TOC. Based on a three-endmember model, macroalgae-derived TOC (TOCma) accounted for < 35% of the total TOC, averaging 16 ± 9% (mean ± SD). On average, terrestrial and phytoplankton-derived TOC showed much higher percentages of 24 ± 17% and 60 ± 20%, respectively (t-test, p < 0.02). A preliminary estimate suggested that TOCma represents a carbon sink of 8.2 × 103 tons per year, corresponding to about 22% of the sink associated with phytoplankton and macroalgae and 8 ± 6% of the macroalgae carbon production in Sansha Bay. Considering its production magnitude, the macroalgae-induced carbon sink seems to be insignificant, on a national or global scale, to phytoplankton, though it should be taken into account given the small cultivation area.

The splicing isoform Foxp3Δ2 differentially regulates tTreg and pTreg homeostasis.

Foxp3 is the master transcription factor for regulatory T cells (Tregs). Alternative splicing of human Foxp3 results in the expression of two isoforms: the full length and an exon 2-deleted protein. Here, AlphaFold2 predictions and in vitro experiments demonstrate that the N-terminal domain of Foxp3 inhibits DNA binding by moving toward the C terminus and that this movement is mediated by exon 2. Consequently, we find that Foxp3Δ2-bearing thymus-derived Tregs (tTregs) in the peripheral lymphoid organ are less sensitive to T cell receptor (TCR) stimulation due to the enhanced binding of Foxp3Δ2 to the Batf promoter and are hyporesponsive to interleukin-2 (IL-2). In contrast, among RORγt+ peripherally induced Tregs (pTregs) in the large intestine, Foxp3Δ2 pTregs express many more RORγt-related genes, conferring a competitive advantage. Together, our results reveal that alternative splicing of exon 2 generates an active form of Foxp3, which plays a differential role in regulating tTreg and pTreg homeostasis.

Changes in the carbon source and storage in a cultivation area of macro-algae in Southeast China.

Macro-algae culture has recently attracted attention in China because of its capability to sequester carbon. Here, radionuclides, total organic carbon (TOC), and nitrogen (TN) were examined in a cultivation area of macro-algae in Southeast China. At the reference site, the ratio of TOC to TN (C/N, 8.1 ± 0.2, mean ± SD) did not exhibit discernible variation over the past 70 years. In contrast, in the cultivation area, C/N descended from 9.0 ± 0.2 around 1960 to 8.3 ± 0.2 between 1960 and 1990 and 7.6 ± 0.2 after 1990, coincident with the recorded kelp production in this area, indicating an influence of macro-algae culture-associated activities on carbon origin. Using a model, algal culture-associated activities contributed 23 ± 7 % between 1963 and 1990 and 53 ± 8 % between 1990 and 2022 to TOC. The burial of culture-associated TOC varied from 0.15 to 1.23 mg-C cm-2 yr-1, implying the unneglectable influence on carbon storage.

Combining immune checkpoint blockade with ATP-based immunogenic cell death amplifier for cancer chemo-immunotherapy.

Amplifying "eat me signal" during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary "eat me signal" for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe2+) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H2O2 concentration would induce hydroxyl radical (·OH) and oxygen (O2) generation through Fenton reaction by Fe2+. DOX and ATP would be released from the amplifier, which could induce ICD effect and "ICD adjuvant" to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.

A phenolic based tumor-permeated nano-framework for immunogenic cell death induction combined with PD-L1 immune checkpoint blockade.

A critical obstacle for programmed death ligand 1 (PD-L1) immune checkpoint blockade immunotherapy is the insufficient T cell infiltration and low immunogenicity of tumor cells. Improving tumor immunogenicity through immunogenic cell death (ICD) can make tumor sensitive to PD-L1 checkpoint blockade immunotherapy. Herein, a phenolic based tumor-permeated nano-framework (EGPt-NF) was fabricated by cross-linking phenylboric acid modified platinum nanoparticles (PBA-Pt, ICD inducer) and epigallocatechin-3-O-gallate (EGCG, PD-L1 inhibitor) via pH-reversible borate ester. In particular, PBA-Pt could not only induce ICD cascade but also relieve tumor hypoxia. Consequently, EGPt-NF could effectively promote dendritic cell maturation and downregulate PD-L1 expression in tumor cells. Furthermore, EGPt-NF could also relieve tumor hypoxia to facilitate cytotoxic T lymphocyte infiltration and IFN-γ secretion. The synergistic effect of EGPt-NF could effectively improve tumor immunogenicity and amplify the therapeutic outcomes of cancer immunotherapy, resulting in a strong antitumor immune response in primary tumor and metastasis inhibition. Our simple approach expands the application of platinum-based drug delivery systems for cancer immunotherapy.

A Self-amplifying ROS-sensitive prodrug-based nanodecoy for circumventing immune resistance in chemotherapy-sensitized immunotherapy.

Circumventing immune resistance and boosting immune response is the ultimate goal of cancer immunotherapy. Herein, we reported a tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle for specifically inducing immunogenic cell death (ICD) in combination with TAM depletion. A versatile ROS-cleavable camptothecin (CPT) prodrug (DCC) was synthesized through a thioacetal linker between CPT and the ROS generator cinnamaldehyde (CA), which could self-assemble into a uniform prodrug nanoparticle to realize a positive feedback loop of "ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation." This DCC was further modified with the TAM membrane (abbreviated as DCC@M2), which could not only target both primary tumors and lung metastasis nodules through VCAM-1/α4ß1 integrin interaction but also absorb CSF-1 secreted by tumor cells to disturb the interaction between TAMs and cancer cells. Our nanodecoy could effectively induce ICD cascade and deplete TAMs for priming tumor-specific effector T cell infiltration for antitumor immune response activation, which represents a versatile approach for cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle was fabricated for the first time. This ROS-cleavable camptothecin (CPT)/cinnamaldehyde (CA) prodrug (DCC) could self-assemble into a uniform nanoparticle to realize the positive feedback loop of "ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation." After TAM membrane coating, this system (DCC@M2) could not only target both primary tumors and lung metastatic nodules but also scavenge CSF-1 secreted by tumor cells for TAM depletion for sufficient chemotherapy-sensitized immunotherapy.

Watson-Crick Base Pairing-Inspired Laser/GSH Activatable miRNA-Coordination Polymer Nanoplexes for Combined Cancer Chemo-Immuno-Photothermal Therapy.

The tumor immunosuppressive microenvironment (TIM) greatly hindered the efficacy of cancer immunotherapy. Overexpressed indoleamine 2,3-dioxygenase-1 (IDO1) in tumor tissues plays a vital role in TIM generation, and downregulation of IDO1 expression may reverse TIM. Inspired by the Watson-Crick base-pairing rule, a versatile noncationic miRNA vector (miDAC@PDA) is developed for cancer immunotherapy. Doxorubicin (DOX), adenosine triphosphate (ATP), and copper ions (Cu2+) are coassembled into coordination polymer nanoparticles (DAC) and bind miRNA via the hydrogen bond interaction (miDAC) between adenine residues (ATP) and uracil residues (miRNA). Polydopamine (PDA) is deposited onto the surface of miDAC for photothermal therapy. miDAC@PDA can efficiently accumulate into tumor tissues for cellular uptake. Under laser irradiation and high intracellular GSH levels, the PDA shell of miDAC@PDA can dissociate from miDAC for miRNA release due to local hyperthermia. Cu2+-mediated GSH consumption and intracellular ATP release can amplify the DOX-based immunogenic cell death (ICD) cascade, together with miR-448-mediated IDO1 inhibition, and these versatile nanoplexes will not only restrain primary tumor growth but also display a remarkable abscopal effect on distant tumors. Collectively, our study provides a unique strategy for intracellular gene delivery and an inspirational approach for multimechanism cancer management.

Binary regulation of the tumor microenvironment by a pH-responsive reversible shielding nanoplatform for improved tumor chemo-immunotherapy.

The limited infiltration of specific T cells in an immunosuppressive microenvironment is a major challenge for cancer immunotherapy. Reversing tumor microenvironment and inducing an antitumor immune response are crucial for cancer therapy. Here, phenylboronic acid (PBA) derivative-stabilized ultrasmall platinum nanoparticles (PBA-Pt) and dextran-coated BLZ-945 nanoparticles (DNPs) were co-assembled through a pH-responsive borate ester bond to construct a versatile reversible shielding multifunctional nanoplatform (Pt@DNPs) for the first time. Pt@DNPs dissociated into two individual components, namely PBA-Pt and DNPs, in the tumor acid microenvironment. Both in vitro and in vivo studies revealed that Pt@DNPs induced immunogenic cell death (ICD) (through multimechanisms involving PtⅡ release and a multienzyme catalytic process by PBA-Pt) and relieved immunosuppressive microenvironment (depletion of tumor-associated macrophages by BLZ-945), which led to tumor-associated antigen release, maturation of dendritic cells, and infiltration of cytotoxic T cells for efficient antitumor immune response against both primary tumor and pulmonary metastatic tumor nodules. Therefore, Pt@DNPs is a promising option for cancer chemo-immunotherapy. STATEMENT OF SIGNIFICANCE: A versatile reversible shielding multifunctional nanoplatform (Pt@DNPs) was engineered for the first time for combinational cancer chemo-immunotherapy. Multimechanisms involving induction of immunogenic cell death by PBA-Pt and sufficient TAM depletion by DNPs could efficiently relieve tumor immunosuppressive microenvironment and activate the antitumor immune response. The synergistic effect not only increased the infiltration of specific T cells in primary tumor, but it also induced a strong immune response against pulmonary metastatic nodules. Collectively, this nanoplatform may represent a promising strategy for combinational chemo-immunotherapy for cancers.

Design and Fabrication of a Microfluidic Chip for Particle Size-Exclusion and Enrichment.

Based on the size of particles, a microfluidic chip integrating micro particles capture, controlled release and counting analysis was designed and fabricated in this paper. The chip is composed of a polydimethylsiloxane (PDMS) cover sheet and a PDMS substrate. The PDMS substrate is made of a sample inlet, microfluidic channels, a micropillar array, a three-dimensional (3D) focusing channel, and a sample outlet. The chip was fabricated by the multistep SU-8 lithography and PDMS molding method in this study. The micropillar array and channels in the chip can be molded in one step and can be replicated multiple times, which reduces the production cost and increases the practicability of the chip. Using a homemade electromagnetic drive device, the detection function of the chip was tested using a deionized water solution containing 22 µm polyethylene particles. The results showed that under the action of electromagnetic force, the chip enriched polyethylene particles; when the electromagnetic force disappeared, the enriched polyethylene particles were released by injecting buffer solution, and it was looked at as new sample solution. The flow rate of the sample solution and the sheath flow solution (deionized water) was injected into the three-dimensional focusing channel at a flow rate ratio of 1:4, and the polyethylene particles sample solution was focused, which could be used for the counting and analysis of polyethylene particles. The work of this paper can provide a reference for the subsequent detection of circulating tumor cells (CTCs).

Semi-enclosed bays serve as hotspots for black carbon burial: A case study in Jiaozhou Bay, western Yellow Sea.

The provenance of black carbon (BC) and its role in affecting contaminant cycling in both the atmosphere and aquatic environments have been extensively studied. However, the fate and cycling dynamics of BC, particularly in marine environments, are poorly understood. Herein, soot BC was determined in the semi-enclosed Jiaozhou Bay to examine the seasonal variability, residence timescale in seawater, and settling flux to sediments, together with particle-reactive 234Th. Soot BC ranged from 0.39 to 4.26 µmol-C L-1. On average, spring produced the highest value of 1.88 ± 0.31 µmol-C L-1, followed by winter (1.59 ± 0.18 µmol-C L-1), summer (0.94 ± 0.09 µmol-C L-1), and autumn (0.90 ± 0.09 µmol-C L-1). The seasonality of soot BC was similar to the activity concentration of particulate 234Th (i.e., 234ThP). The close relationships between soot BC and 234ThP (p < 0.01) provide the basis for the application of 234Th to trace the fate of soot BC. Based on the 234Th deficit with respect to 238U, the residence times of soot BC were estimated to be 41 ± 6 d and 36 ± 5 d for May-August and August-November, respectively. The shorter residence times of soot BC than that of seawater indicated that soot BC delivered to Jiaozhou Bay settled in the local sediments. Furthermore, soot BC concentrations were higher in the inflow seawater from the Yellow Sea than the outflow water from Jiaozhou Bay, implying a net input of soot BC from the Yellow Sea to Jiaozhou Bay. The soot BC fluxes were 0.266 ± 0.035 mmol-C m-2 d-1 and 0.0472 ± 0.0065 mmol-C m-2 d-1 for May-August and August-November, respectively. From the bay-scale perspective, Jiaozhou Bay had buried 0.101 ± 0.010 Gg of soot BC each year. These results indicate that the semi-enclosed Jiaozhou Bay acts as an effective trap for soot BC and particle-reactive contaminants.

Stimuli-Responsive and Highly Penetrable Nanoparticles as a Multifunctional Nanoplatform for Boosting Nonsmall Cell Lung Cancer siRNA Therapy.

In cancer therapy, it is acknowledged that large-size nanoparticles stay in the circulation system for a long time, but their permeability to tumor tissues is poor. To address the conflicting need for prolonging circulation time and favorable tumor tissue penetration ability, a charge conversional multifunctional nanoplatform was strategically designed to improve the efficacy of small interfering RNA (siRNA) therapy against nonsmall cell lung cancer (NSCLC). The development of nanodrug delivery systems (NDDSs) was constructed by loading siRNA on polyamidoamine (PAMAM) dendrimers to build small-sized PAM/siRNA via electrostatic interaction and then capped with a pH-triggered copolymer poly(ethylene glycol) methyl ether (mPEG)-poly-l-lysine (PLL)-2,3-dimethylmaleic anhydride (DMA) (shorted as PLM) under physiological conditions. While in the tumor microenvironment, the acidic reaction of the PLM copolymer changes from negative charge to positive charge due to the cleavable amide bond between mPEG-PLL and DMA, leading to large-size nanoparticles (NPs) with a negative charge that turns into a positive charge and small NPs with a high tumor-penetrating ability. All of the in vitro and in vivo studies validated that PLM/PAM/siRNA NPs possess desirable features including excellent biocompatibility, a prolonged circulation time, significant pH sensitivity, high tumor tissue penetration ability, and sufficient endo-/lysosomal escape. Taken together, all results suggest tremendous potential of the gene therapy based on the stimuli-sensitive PLM/PAM/siRNA NPs, providing a profound application prospective treatment strategy in cancer gene therapy.

EEG theta responses induced by emoji semantic violations.

This study investigated emoji semantic processing by measuring changes in event-related electroencephalogram (EEG) power. The last segment of experimental sentences was designed as either words or emojis consistent or inconsistent with the sentential context. The results showed that incongruent emojis led to a conspicuous increase of theta power (4-7 Hz), while incongruent words induced a decrease. Furthermore, the theta power increase was observed at midfrontal, occipital and bilateral temporal lobes with emojis. This suggests a higher working memory load for monitoring errors, difficulty of form recognition and concept retrieval in emoji semantic processing. It implies different neuro-cognitive processes involved in the semantic processing of emojis and words.

Combined glycoprotein IIb/IIIa inhibitor therapy with ticagrelor for patients with acute coronary syndrome.

This study was to compare the efficacy and safety of combined glycoprotein IIb/IIIa inhibitor (GPI) and ticagrelor versus ticagrelor in patients with acute coronary syndrome (ACS). An observational study was conducted using the Improving Care for Cardiovascular Disease in China-ACS project. Totally, 13,264 patients with ACS and received combination therapy or ticagrelor therapy were analyzed. The primary outcome was the composite of major cardiovascular events (MACE: all-cause mortality, myocardial infarction [MI], stent thrombosis, cardiogenic shock, and ischemic stroke), and secondary outcomes included all-cause mortality, MI, stent thrombosis, cardiogenic shock, and ischemic stroke. The multivariable adjusted analysis indicated that combination therapy was associated with an increased risk of major cardiovascular events (MACE) (P = 0.001), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, the multivariable adjusted for propensity score-matched (PSM) analysis suggested that combination therapy produced additional risk of MACE (P = 0.014), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, PSM analysis suggested that combination therapy was associated with greater risk of stent thrombosis (P = 0.012) and intracranial bleeding (P = 0.020). Combined GPI and ticagrelor therapies did not have any beneficial effects on MACE, stent thrombosis, intracranial bleeding, any bleeding, or major bleeding.

Processing network emojis in Chinese sentence context: An ERP study.

As network emojis play an increasingly important role in modern communications, the question of how semantic processing of emojis is performed in the context arises. By comparing the N400 and P600 effects of emojis and words in contextually incongruent conditions, we investigated the neural basis of semantic processing of emojis. We found that incongruent words elicited robust N400 and P600 effects, while emojis only generated a more conspicuous and sustained N400 effect. This suggests that emojis may have more difficult semantic retrieval versus words in the context, with potentially inefficient semantic integration. These data suggest that the semantic processing of network emojis in context is not the same as words and the meaning of emojis is more difficult to process at sentence level.

Interleukin-18 Expression Increases in the Aorta and Plasma of Patients with Acute Aortic Dissection.

BACKGROUND: Interleukin- (IL-) 18 is a proinflammatory cytokine related to cardiovascular diseases, including hypertension and atherosclerosis. This study is aimed at determining whether IL-18 is related to aortic dissection (AD) and identifying the underlying mechanisms. METHODS: IL-18 expression in human aorta samples from AD (n = 8) and non-AD (NAD, n = 7) patients was measured. In addition, the IL-18, IL-6, interferon- (IFN-) γ, and IL-18-binding protein (IL-18BP) concentrations in plasma samples collected from the NAD and AD patients were detected. The effects of IL-18 on macrophage differentiation and smooth muscle cell (SMC) apoptosis were investigated in vitro. RESULTS: IL-18 expression was significantly increased in the aorta samples from the AD patients compared with those from the NAD patients, especially in the torn section. Aortic IL-18 was mainly derived from macrophages and also partly derived from CD4+ T lymphocytes and vascular SMCs. Plasma IL-18, IFN-γ, and IL-6 levels were significantly higher in the AD group than in the NAD group, and the IL-18 levels were positively correlated with the IFN-γ and IL-6 levels. In addition, plasma IL-18BP and free IL-18 levels were also elevated in the AD group. Linear regression analysis showed that the IL-18 level was independently associated with the presence of AD. In addition, anti-mouse IL-18-neutralizing monoclonal antibodies (anti-IL-18 nAb) inhibited angiotensin II-induced M1 macrophage differentiation and SMC apoptosis in vitro. CONCLUSION: IL-18 may participate in AD by regulating macrophage differentiation and macrophage-induced SMC apoptosis.