Ionomer and Membrane Designs for Low-Temperature CO2 and CO Electrolysis.

Low-temperature electroreduction of CO2 and CO (CO(2)RR) into valuable chemicals and fuels offers a promising pathway to reduce greenhouse gas emissions and achieve carbon neutrality. Today's low-temperature CO(2)RR technology relies on the use of ionomers, polymers with ionized groups, primarily as catalyst layer (CL) additives. In the meantime, ionomers can assemble into ion-exchange membranes (IEMs), serving as important components of electrolyzers. According to the ion-exchange functions, ionomer additives are classified as cation-exchange ionomers (CEIs) and anion-exchange ionomers (AEIs); similarly, IEMs are divided into cation-exchange membranes (CEMs) and anion-exchange membranes (AEMs), as well as the multilayer polymer electrolytes (MPEs). Recent studies show that ionomer additives can regulate the catalytic microenvironment and thereby enhance performance towards desired products. This Review discusses the roles of ionomer additives and IEMs in CO2 and CO reduction reactions, highlighting the latest mechanistic insights and performance advances. It outlines challenges in designing ionomer additives and IEMs to improve product selectivity, energy efficiency (EE), and operational lifetime of CO(2)RR electrolyzers, while also providing perspectives on future research directions. The aim is to connect the current status of ionomer and membrane development with performance metrics analysis, offering insights for the advancement of commercially relevant low-temperature CO(2)RR electrolyzers.

Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection.

IL-1ß represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1ß in the process of ferroptosis. However, the relationship between IL-1ß and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1ß induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1ß is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1ß playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

Neutrophils in the premetastatic niche: key functions and therapeutic directions.

Metastasis has been one of the primary reasons for the high mortality rates associated with tumours in recent years, rendering the treatment of current malignancies challenging and representing a significant cause of recurrence in patients who have undergone surgical tumour resection. Halting tumour metastasis has become an essential goal for achieving favourable prognoses following cancer treatment. In recent years, increasing clarity in understanding the mechanisms underlying metastasis has been achieved. The concept of premetastatic niches has gained widespread acceptance, which posits that tumour cells establish a unique microenvironment at distant sites prior to their migration, facilitating their settlement and growth at those locations. Neutrophils serve as crucial constituents of the premetastatic niche, actively shaping its microenvironmental characteristics, which include immunosuppression, inflammation, angiogenesis and extracellular matrix remodelling. These characteristics are intimately associated with the successful engraftment and subsequent progression of tumour cells. As our understanding of the role and significance of neutrophils in the premetastatic niche deepens, leveraging the presence of neutrophils within the premetastatic niche has gradually attracted the interest of researchers as a potential therapeutic target. The focal point of this review revolves around elucidating the involvement of neutrophils in the formation and shaping of the premetastatic niche (PMN), alongside the introduction of emerging therapeutic approaches aimed at impeding cancer metastasis.

Pre-metastatic niche: formation, characteristics and therapeutic implication.

Distant metastasis is a primary cause of mortality and contributes to poor surgical outcomes in cancer patients. Before the development of organ-specific metastasis, the formation of a pre-metastatic niche is pivotal in promoting the spread of cancer cells. This review delves into the intricate landscape of the pre-metastatic niche, focusing on the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The discussion encompasses cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells, in addition to molecular factors like secreted substances from tumors and extracellular vesicles, within the framework of pre-metastatic niche formation. Insights into the temporal mechanisms of pre-metastatic niche formation such as epithelial-mesenchymal transition, immunosuppression, extracellular matrix remodeling, metabolic reprogramming, vascular permeability and angiogenesis are provided. Furthermore, the landscape of pre-metastatic niche in different metastatic organs like lymph nodes, lungs, liver, brain, and bones is elucidated. Therapeutic approaches targeting the cellular and molecular components of pre-metastatic niche, as well as interventions targeting signaling pathways such as the TGF-ß, VEGF, and MET pathways, are highlighted. This review aims to enhance our understanding of pre-metastatic niche dynamics and provide insights for developing effective therapeutic strategies to combat tumor metastasis.

Clinicopathological and prognostic significance of TIMP1 expression in gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The research on the associations between tissue inhibitors of metalloproteinase-1 (TIMP1) expression and the clinicopathological characteristics and prognosis of patients with gastric cancer (GC) have resulted in contradictory findings. Exploring the associations between TIMP1 and clinicopathological parameters and the prognosis of GC patients is essential. METHODS: We searched the literature in the databases according to the inclusion and exclusion criteria. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the relationships between TIMP1 expression and the clinicopathological parameters and prognosis of GC patients. RESULTS: Nine studies with 1,200 GC patients were included. Our results indicated that TIMP1 expression was not related to sex, age, TNM stage, depth of invasion, lymph node metastasis, or tumor size in GC patients. However, TIMP1 expression was associated with the differentiation of GC. Furthermore, TIMP1 expression was associated with poor prognosis in GC patients. CONCLUSION: TIMP1 expression was related to tumor differentiation and poor prognosis but not sex, age, TNM stage, depth of invasion, lymph node metastasis or tumor size.

Galloyl-boosted gold nanorods: Unleashing personalized cancer immunotherapy potential.

Cancer immunotherapy has emerged as a potent treatment strategy by harnessing the host immune system to target cancer cells. However, challenges including low tumor vaccine immunogenicity and tumor heterogeneity hinder its clinical efficacy. To address these issues, we propose a novel nanoplatform integrating photothermal material gold nanorods (GNRs) with polyphenols for enhanced immunotherapy efficacy via photothermal therapy. Polyphenols, natural compounds with phenolic hydroxyl groups, are known for their ability to bind tightly to various molecules, making them ideal for antigen capture. We synthesized GNRs modified with polyphenols (GNR-PA and GNR-GA) and demonstrated their ability to induce immunogenic cell death upon laser irradiation, releasing tumor-associated antigens (TAAs). The surface polyphenols on GNRs effectively captured released TAAs to shield them from clearance. In vivo studies confirmed increased accumulation of GNR-GA in lymph nodes and enhanced dendritic cell maturation, leading to promoted effector T cell infiltration into tumors. Furthermore, treatment combined with PD-1/PD-L1 pathway blockade demonstrated potent tumor regression and systemic immunotherapy efficacy. Our findings highlight the potential of this photothermal nanoplatform as a promising strategy to overcome the limitations of current cancer immunotherapy approaches and improve therapeutic outcomes.

Elemental Design of Alkali-Activated Materials with Solid Wastes Using Machine Learning.

Understanding the strength development of alkali-activated materials (AAMs) with fly ash (FA) and granulated blast furnace slag (GBFS) is crucial for designing high-performance AAMs. This study investigates the strength development mechanism of AAMs using machine learning. A total of 616 uniaxial compressive strength (UCS) data points from FA-GBFS-based AAM mixtures were collected from published literature to train four tree-based machine learning models. Among these models, Gradient Boosting Regression (GBR) demonstrated the highest prediction accuracy, with a correlation coefficient (R-value) of 0.970 and a root mean square error (RMSE) of 4.110 MPa on the test dataset. The SHapley Additive exPlanations (SHAP) analysis revealed that water content is the most influential variable in strength development, followed by curing periods. The study recommends a calcium-to-silicon ratio of around 1.3, a sodium-to-aluminum ratio slightly below 1, and a silicon-to-aluminum ratio slightly above 3 for optimal AAM performance. The proposed design model was validated through laboratory experiments with FA-GBFS-based AAM mixtures, confirming the model's reliability. This research provides novel insights into the strength development mechanism of AAMs and offers a practical guide for elemental design, potentially leading to more sustainable construction materials.

Clinicopathological and prognostic significance of stromal cell derived factor 2 in the patients with gastric cancer.

BACKGROUND: The stromal cell derived factor 2 (SDF2) relates closely to the occurrence and development of several kind of cancers. There are few studies to investigate the clinicopathological and prognostic significance of SDF2 in gastric cancer (GC) patients. METHODS: We detected SDF2 expression in GC and normal gastric tissues using bioinformatics, western blot and immunohistochemistry. Furthermore, we tested the relationship between SDF2 expression and clinicopathological characteristics and prognosis of GC patients. RESULTS: Bioinformatics, western blot and immunohistochemistry results showed that SDF2 expression in GC tissue was higher than that in normal gastric tissue (P < 0.01). SDF2 expression was associated with Borrmann classification III-IV (χ2 = 6.484, P = 0.011), depth of infiltration T3-T4 (χ2 = 9.140, P = 0.003), positive lymph node metastasis (χ2 = 24.945, P = 0.000) and TNM III-IV stage (χ2 = 9.945, P = 0.002) of GC patients. The Cox regression analysis indicated that distant metastasis M1 stage (HR = 6.026, 95% CI: 1.880-19.318, P = 0.003), TNM III-IV (HR = 1.833, 95% CI: 1.023-3.287, P = 0.042) and SDF2 high expression (HR = 2.091, 95% CI: 1.064-4.108, P = 0.032) were independent risk factors for OS of GC patients. Kaplan-Meier test showed that the OS of GC patients with SDF2 high expression was much poorer than that of GC patients with SDF2 low-expression (χ2 = 22.925, P = 0.000). CONCLUSION: SDF2 expression is high in GC tissue and is correlated with Borrmann classification III-IV, tumor infiltration depth, positive lymph node metastasis and TNM III-IV stage of GC patients. GC patients with SDF2 high-expression have significantly poor OS.

Current status and quality of prognosis prediction models of non-small cell lung cancer constructed using computed tomography (CT)-based radiomics: a systematic review and radiomics quality score 2.0 assessment.

Background: Radiomics extracts specific quantitative data from medical images and explores the characteristics of tumors by analyzing these representations and making predictions. The purpose of this paper is to review computed tomography (CT)-based radiomics articles related to prognostic outcomes in non-small cell lung cancer (NSCLC), assess their scientificity and quality by the latest radiomics quality score (RQS) 2.0 scoring criteria, and provide references for subsequent related studies. Methods: CT-based radiomics studies on NSCLC prognosis published from 1 November 2012 to 30 November 2022 in English were screened through the databases of the Cochrane Library, Embase, and PubMed. By excluding criteria such as non-original studies, small sample sizes studies, positron emission tomography (PET)/CT only, and methodological studies only, 17 studies in English were included. The RQS proposed in 2017 is a quality evaluation index specific to radiomics following the PRISMA guidelines, and the latest update of RQS 2.0 has improved the scientificity and completeness of the score. Each checkpoint either belongs to handcrafted radiomics (HCR), deep learning, or both. Results: The 17 included studies covered most treatments for NSCLC, including radiotherapy, chemotherapy, surgery, radiofrequency ablation, immunotherapy, and targeted therapy, and predicted outcomes such as overall survival (OS), progression-free survival (PFS), distant metastases, and disease-free survival (DFS). The median score rate for the included studies was 28%, with a range of 12% to 44%. The quality of studies in HCR is not high, and only 4 studies have been validated with independent cohorts. Conclusions: The value of radiomics studies needs to be increased, such that clinical application will be possible, and the field of radiomics still has much room for growth. To make prediction models more reliable and stable in forecasting the prognosis of NSCLC and advancing the individualized treatment of NSCLC patients, more clinicians must participate in their development and clinical testing.

Arteriovenous Fistula Caused by Ruptured Abdominal Aortoiliac Aneurysm.

Teaching point: A ruptured aorto-iliac aneurysm, complicated by an iliac arteriovenous fistula, is rare but has a possibly fatal outcome and requires prompt diagnosis and appropriate treatment.

Distributed Vibration Sensing Based on a Forward Transmission Polarization-Generated Carrier.

For distributed fiber-optic sensors, slowly varying vibration signals down to 5 mHz are difficult to measure due to low signal-to-noise ratios. We propose and demonstrate a forward transmission-based distributed sensing system, combined with a polarization-generated carrier for detection bandwidth reduction, and cross-correlation for vibration positioning. By applying a higher-frequency carrier signal using a fast polarization controller, the initial phase of the known carrier frequency is monitored and analyzed to demodulate the vibration signal. Only the polarization carrier needs to be analyzed, not the arbitrary-frequency signal, which can lead to hardware issues (reduced detection bandwidth and less noise). The difference in arrival time between the two detection ends obtained through cross-correlation can determine the vibration position. Our experimental results demonstrate a sensitivity of 0.63 mrad/µÎµ and a limit of detection (LoD) of 355.6 pε/Hz1/2 at 60 Hz. A lock-in amplifier can be used on the fixed carrier to achieve a minimal LoD. The sensing distance can reach 131.5 km and the positioning accuracy is 725 m (root-mean-square error) while the spatial resolution is 105 m. The tested vibration frequency range is between 0.005 Hz and 160 Hz. A low frequency of 5 mHz for forward transmission-based distributed sensing is highly attractive for seismic monitoring applications.

Imaging Dissolution Dynamics of Individual NaCl Nanoparticles during Deliquescence with In Situ Transmission Electron Microscopy.

Water vapor condensation on hygroscopic aerosol particles plays an important role in cloud formation, climate change, secondary aerosol formation, and aerosol aging. Conventional understanding considers deliquescence of nanosized hygroscopic aerosol particles a nearly instantaneous solid to liquid phase transition. However, the nanoscale dynamics of water condensation and aerosol particle dissolution prior to and during deliquescence remain obscure due to a lack of high spatial and temporal resolution single particle measurements. Here we use real time in situ transmission electron microscopy (TEM) imaging of individual sodium chloride (NaCl) nanoparticles to demonstrate that water adsorption and aerosol particle dissolution prior to and during deliquescence is a multistep dynamic process. Water condensation and aerosol particle dissolution was investigated for lab generated NaCl aerosols and found to occur in three distinct stages as a function of increasing relative humidity (RH). First, a < 100 nm water layer adsorbed on the NaCl cubes and caused sharp corners to dissolve and truncate. The water layer grew to several hundred nanometers with increasing RH and was rapidly saturated with solute, as evidenced by halting of particle dissolution. Adjacent cube corners displayed second-scale curvature fluctuations with no net particle dissolution or water layer thickness change. We propose that droplet solute concentration fluctuations drove NaCl transport from regions of high local curvature to regions of low curvature. Finally, we observed coexistence of a liquid water droplet and aerosol particle immediately prior to deliquescence. Particles dissolved discretely along single crystallographic directions, separated by few second lag times with no dissolution. This work demonstrates that deliquescence of simple pure salt particles with sizes in the range of 100 nm to several microns is not an instantaneous phase transition and instead involves a range of complex dissolution and water condensation dynamics.

Cancer immunotherapy and its facilitation by nanomedicine.

Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches.

Trilayer Polymer Electrolytes Enable Carbon-Efficient CO2 to Multicarbon Product Conversion in Alkaline Electrolyzers.

The electrochemical CO2 reduction reaction (CO2RR) is an appealing method for carbon utilization. Alkaline CO2 electrolyzers exhibit high CO2RR activity, low full-cell voltages, and cost-effectiveness. However, the issue of CO2 loss caused by (bi)carbonate formation leads to excessive energy consumption, rendering the process economically impractical. In this study, we propose a trilayer polymer electrolyte (TPE) comprising a perforated anion exchange membrane (PAEM) and a bipolar membrane (BPM) to facilitate alkaline CO2RR. This TPE enables the coexistence of high alkalinity near the catalyst surface and the H+ flux at the interface between the PAEM and the cation exchange layer (CEL) of the BPM, conditions favoring both CO2 reduction to multicarbon products and (bi)carbonate removal in KOH-fed membrane electrode assembly (MEA) reactors. As a result, we achieve a Faradaic efficiency (FE) of approximately 46 % for C2H4, corresponding to a C2+ FE of 64 % at 260 mA cm-2, with a CO2-to-C2H4 single-pass conversion (SPC) of approximately 32 % at 140 mA cm-2-nearly 1.3 times the limiting SPC in conventional AEM-MEA electrolyzers. Furthermore, coupling CO2 reduction with formaldehyde oxidation reaction (FOR) in the TPE-MEA electrolyzer reduces the full-cell voltage to 2.3 V at 100 mA cm-2 without compromising the C2H4 FE.

Association of the PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study.

BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

Functional analysis of the CaPIPLC5 gene in the regulation of the fertility restoration in pepper.

Cytoplasmic male sterility (CMS) is a very important factor to produce hybrid seeds, and the restoration of fertility involves the expression of many fertility-related genes. Our previous study showed that the expression of CaPIPLC5 was significantly up-regulated in pepper restorer accessions and minimally expressed in sterile accessions, speculating that CaPIPLC5 is related to the restoration of fertility. In this study, we further validated the function of CaPIPLC5 in the restoration of fertility. The results showed that CaPIPLC5 was specifically expressed in the anthers of the restorer accessions with the subcellular localization in the cytoplasm. Furthermore, the expression of CaPIPLC5 was significantly higher in restorer lines and restorer combinations than that in CMS lines and their maintainer lines. Silencing CaPIPLC5 led to the number of pollen decreased, pollen grains wrinkled, and the ratio of pollen germination reduced. In addition, the joint analysis of Yeast One-Hybrid (Y1H) and Dual-Luciferase (dual-LUC) assays suggested that transcription factors such as CaARF5, CabZIP24 and CaMYB-like1, interacted with the promoter regions of CaPIPLC5, which regulated the expression of CaPIPLC5. The present results provide new insights into the study of CaPIPLC5 involved in the restoration of fertility in pepper.

Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y14 Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

Glucocorticoids promote joint microenvironment alteration of GABBR1 expression associated with mitigating rheumatoid arthritis.

GABBR1 receptors have been implicated in the progression of rheumatoid arthritis (RA), and p38 MAP kinase (MAPK) was shown to be downregulated by GABA and result in unchecked production of pro-inflammatory cytokine. GABBR1 is a member of GABA receptors, and it is known to be upregulated and plays a vital role in RA. Glucocorticoids are efficient therapeutics in rheumatoid arthritis (RA) and are known to regulate GABA actions; therefore, we intended to investigate the potential of glucocorticoids in RA concerning the potential pathway GABBR1/MAPK. Joint specimens were obtained from collagen-induced arthritis mouse model. A double-blind semi-quantitative analysis of vascularity, cell infiltration, as well as lining thickness by help of a 4-point scale setting was used to assess joint inflammation. Expression of GABBR1 and p38 was evaluated immunohistochemically. In vitro peripheral blood (PB), synovial fluid (SF), and mononuclear cells (MCs) were acquired from RA mice. Western blotting was used for detecting expression of GABBR1 and p38 proteins. The presence of high levels of GABBR1 and p38 was prevalent in RA joints relative to healthy joints and related to the inflammation level. Glucocorticoid treatment alters GABBR1 along with p38 protein expression in joints while reducing joint inflammation. Ex vivo and in vitro assays revealed glucocorticoids have a direct impact on p38, such as the decreased GABBR1 expression level after dexamethasone incubation with SFMC. GABBR1 together with p38 expression in RA joints depends on local inflammation and can be targeted by glucocorticoids.