ABSTRACT
Claudin18.2 (CLDN18.2) is overexpressed in cancers of the digestive system, rendering it an ideal drug target for antibody-drug conjugates (ADCs). Despite many CLDN18.2-directed ADCs undergoing clinical trials, the inconclusive underlying mechanisms pose a hurdle to extending the utility of these agents. In our study, αCLDN18.2-MMAE, an ADC composed of an anti-CLDN18.2 monoclonal antibody and the tubulin inhibitor MMAE, induced a dose-dependent apoptosis via the cleavage of caspase-9/PARP proteins in CLDN18.2-positive gastric cancer cells. It was worth noting that autophagy was remarkably activated during the αCLDN18.2-MMAE treatment, which was characterized by the accumulation of autophagosomes, the conversion of autophagy marker LC3 from its form I to II, and the complete autophagic flux. Inhibiting autophagy by autophagy inhibitor LY294002 remarkably enhanced αCLDN18.2-MMAE-induced cytotoxicity and caspase-mediated apoptosis, indicating the cytoprotective role of autophagy in CLDN18.2-directed ADC-treated gastric cancer cells. Combination with an autophagy inhibitor significantly potentiated the in vivo antitumoral efficacy of αCLDN18.2-MMAE. Besides, the Akt/mTOR pathway inactivation was demonstrated to be implicated in the autophagy initiation in αCLDN18.2-MMAE-treated gastric cancer cells. In conclusion, our study highlighted a groundbreaking investigation into the mechanism of the CLDN18.2-directed ADC, focusing on the crucial role of autophagy, providing a novel insight to treat gastric cancer by the combination of CLDN18.2-directed ADC and autophagy inhibitor.
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Danggui Buxue (DGBX) decoction is a classical prescription composed of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), used to enrich blood, and nourish Qi in Chinese medicine, with the potential to recover energy and stimulate metabolism. Chronic inflammation is a risk factor in the development of inflammatory bowel disease (IBD)-related colorectal cancer (CRC). More importantly, AR and ASR have anti-inflammatory and anti-cancer activities, as well as prefiguring a potential effect on inflammation-cancer transformation. We, therefore, aimed to review the immunometabolism potential of DGBX decoction and its components in this malignant transformation, to provide a helpful complement to manage the risk of IBD-CRC. The present study investigates the multifaceted roles of DGBX decoction and its entire components AR and ASR, including anti-inflammation effects, anti-cancer properties, immune regulation, and metabolic regulation. This assessment is informed by a synthesis of scholarly literature, with more than two hundred articles retrieved from PubMed, Web of Science, and Scopus databases within the past two decades. The search strategy employed utilized keywords such as "Danggui Buxue", "Astragali Radix", "Angelicae Sinensis Radix", "Inflammation", and "Metabolism", alongside the related synonyms, with a particular emphasis on high-quality research and studies yielding significant findings. The potential of DGBX decoction in modulating immunometabolism holds promise for the treatment of IBD-related CRC. It is particularly relevant given the heterogeneity of CRC and the growing trend towards personalized medicine, but the precise and detailed mechanism necessitate further in vivo validation and extensive clinical studies to substantiate the immunometabolic modulation and delineate the pathways involved.
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Background: Previous studies have indicated a strong link between blood metabolites and hypertension, however the causality of metabolites and hypertension is unknown. Methods: Two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between 486 blood metabolites and essential hypertension (EHT). Blood metabolite GWAS data was utilized as the exposure, with EHT GWAS data as the outcome. To further verify the results, another different source of EHT GWAS data was repeatedly analyzed. The major MR analytic approach used to determine causality was inverse variance weighted (IVW), with MR-Egger, Weighted Median, and MR-PRESSO models serving as supplements. We used the Cochran Q test to examine heterogeneity. Horizontal pleiotropy was examined using MR-Egger intercept and MR-PRESSO global test. The MR Steiger test confirmed the causal relationship between blood metabolites and EHT. Results: In this study, nine blood metabolites associated with EHT were preliminarily identified by MR analysis, including four known metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid, creatine, hexadecanedioate) and five unknown metabolites. Then another source of EHT GWAS data was repeatedly analyzed for further verification, and two overlapped metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid) were found. There was a negative correlation between N-acetylornithine and EHT (OR = 0.987, 95% CI = 0.980-0.993, P = 1.01 × 10-4), Cochran's Q test suggested there was no heterogeneity (Q = 31.7586, P = 0.1331), MR-Egger intercept and MR-PRESSO global test suggested there was no horizontal pleiotropy (P > 0.05), Leave-one-out analysis indicated that no single single-nucleotide polymorphism (SNP) had a significant effect on the results, and MR Steiger test confirmed that the direction of causality was correct (P < 0.001). There was a negative correlation between X-12510-2-aminooctanoic acid and EHT (OR = 0.982, 95% CI = 0.972-0.993, P = 0.0017), and there was no evidence of heterogeneity or pleiotropy in multiple sensitivity analyses. Conclusion: The study discovered some blood metabolites causally linked to EHT, which might lead to new understandings of the pathophysiology of hypertension.
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In previous studies, iron-based nanomaterials, especially biochar (BC)-supported sulfidized nanoscale zero-valent iron (S-nZVI/BC), have been widely used for the remediation of soil contaminants. However, its potential risks to the soil ecological environment are still unknown. This study aims to explore the effects of 3% added S-nZVI/BC on soil environment and microorganisms during the remediation of Cd contaminated yellow-brown soil of paddy field. The results showed that after 49 d of incubation, S-nZVI/BC significantly reduced physiologically based extraction test (PBET) extractable Cd concentration (P < 0.05), and increased the immobilization efficiency of Cd by 16.51% and 17.43% compared with S-nZVI and nZVI/BC alone, respectively. Meanwhile, the application of S-nZVI/BC significantly increased soil urease and sucrase activities by 0.153 and 0.446 times, respectively (P < 0.05), improving the soil environmental quality and promoting the soil nitrogen cycle and carbon cycle. The results from the analysis of the 16S rRNA genes indicated that S-nZVI/BC treatment had a minimal effect on the bacterial community and did not appreciably alter the species of the original dominant bacterial phylum. Importantly, compared to other iron-based nanomaterials, incorporating S-nZVI/BC significantly increased the soil organic carbon (OC) content and decreased the excessive release of iron (P < 0.05). This study also found a significant negative correlation between OC content and Fe(II) content (P < 0.05). It might originate from the reducing effect of Fe-reducing bacteria, which consumed OC to promote the reduction of Fe(III). Accompanying this process, the redistribution of Cd and Fe mineral phases in the soil as well as the generation of secondary Fe(II) minerals facilitated Cd immobilization. Overall, S-nZVI/BC could effectively reduce the bioavailability of Cd, increase soil nutrients and enzyme activities, with less toxic impacts on the soil microorganisms.
Subject(s)
Cadmium , Charcoal , Iron , Soil Microbiology , Soil Pollutants , Charcoal/chemistry , Cadmium/chemistry , Iron/chemistry , Oryza , Soil/chemistry , Bacteria/metabolism , Environmental Restoration and Remediation/methods , RNA, Ribosomal, 16S , Biodegradation, EnvironmentalABSTRACT
Hepatocellular carcinoma (HCC), as one of the most lethal cancers, significantly impacts human health. Attempts in this area tends to develop novel technologies with sensitive and multiplexed detection properties for early diagnosis. Here, we present novel hydrogel photonic crystal (PhC) barcodes with tyramine deposition amplified enzyme-linked immunosorbent assay (ELISA) for highly sensitive and multiplexed HCC biomarker screening. Because of the abundant amino groups of acrylic acid (AA) component, the constructed hydrogel PhC barcodes with inverse opal structure could facilitate the loading of antibody probes for subsequent detection of tumor markers. By integrating tyramine deposition amplified ELISA on the barcode, the detection signal of tumor markers has been enhanced. Based on these features, it is demonstrated that the hydrogel PhC barcodes with tyramine deposition amplified ELISA could realize highly sensitive and multiplexed detection of HCC-related biomarkers. It was found that this method is flexible, sensitive and accurate, suitable for multivariate analysis of low abundance tumor markers and future cancer diagnosis. These features make the newly developed PhC barcodes an innovation platform, which possesses tremendous potential for practical application of low abundance targets.
Subject(s)
Biosensing Techniques , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Hydrogels/chemistry , Carcinoma, Hepatocellular/diagnosis , Biosensing Techniques/methods , Liver Neoplasms/diagnosis , Biomarkers, Tumor , Enzyme-Linked Immunosorbent Assay , TyramineABSTRACT
A pig inventory is a crucial component of achieving precise and large-scale farming. In complex pigsty environments, due to pigs' stress reactions and frequent obstructions, it is challenging to count them accurately and automatically. This difficulty contrasts with most current deep learning studies, which rely on overhead views or static images for counting. This research proposes a video-based dynamic counting method, combining YOLOv7 with DeepSORT. By utilizing the YOLOv7 network structure and optimizing the second and third 3 × 3 convolution operations in the head network ELAN-W with PConv, the model reduces the computational demand and improves the inference speed without sacrificing accuracy. To ensure that the network acquires accurate position perception information at oblique angles and extracts rich semantic information, we introduce the coordinate attention (CA) mechanism before the three re-referentialization paths (REPConv) in the head network, enhancing robustness in complex scenarios. Experimental results show that, compared to the original model, the improved model increases the mAP by 3.24, 0.05, and 1.00 percentage points for oblique, overhead, and all pig counting datasets, respectively, while reducing the computational cost by 3.6 GFLOPS. The enhanced YOLOv7 outperforms YOLOv5, YOLOv4, YOLOv3, Faster RCNN, and SSD in target detection with mAP improvements of 2.07, 5.20, 2.16, 7.05, and 19.73 percentage points, respectively. In dynamic counting experiments, the improved YOLOv7 combined with DeepSORT was tested on videos with total pig counts of 144, 201, 285, and 295, yielding errors of -3, -3, -4, and -26, respectively, with an average accuracy of 96.58% and an FPS of 22. This demonstrates the model's capability of performing the real-time counting of pigs in various scenes, providing valuable data and references for automated pig counting research.
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Research and development on Nectin-4 antibody-drug conjugates (ADC) have been greatly accelerated since the approval of enfortumab vedotin to treat uroepithelial cancer. During the course of this study, we identified that autophagy serves as a cytoprotective mechanism during Nectin-4-MMAE treatment and proposed a strategy to enhance the antitumor effects of Nectin-4-MMAE in bladder cancer. Nectin-4-MMAE rapidly internalized into bladder cancer cells in 30 minutes and released MMAE, inducing the onset of caspase-mediated apoptosis and leading to the inhibition of tumor cell growth. Transcriptomics showed significant alterations in autophagy-associated genes in bladder cancer cells treated with Nectin-4-MMAE, which suggested autophagy was activated by Nectin-4-MMAE. Furthermore, autophagy activation was characterized by ultrastructural analysis of autophagosome accumulation, immunofluorescence of autophagic flux, and immunoblotting autophagy marker proteins SQSTM1 and LC3 I/II. Importantly, inhibiting autophagy by LY294002 and chloroquine significantly enhances the cytotoxicity effects of Nectin-4-MMAE in bladder cancer cells. Additionally, we detected the participation of the AKT/mTOR signaling cascade in the induction of autophagy by Nectin-4-MMAE. The combination of Nectin-4-MMAE and an autophagy inhibitor demonstrated enhanced antitumor effects in the HT1376 xenograft tumor model. After receiving a single dose of Nectin-4-MMAE, the group that received the combination treatment showed a significant decrease in tumor size compared to the group that received only one type of treatment. Notably, one mouse in the combination treatment group achieved complete remission of the tumor. The combination group exhibited a notable rise in apoptosis and necrosis, as indicated by H&E staining and immunohistochemistry (cleaved caspase-3, ki67). These findings demonstrated the cytoprotective role of autophagy during Nectin-4-MMAE treatment and highlighted the potential of combining Nectin-4-MMAE with autophagy inhibitors for bladder cancer treatment.
Subject(s)
Autophagy , Cell Adhesion Molecules , Morpholines , Nectins , Urinary Bladder Neoplasms , Autophagy/drug effects , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/genetics , Humans , Animals , Cell Line, Tumor , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Mice , Morpholines/pharmacology , Morpholines/therapeutic use , Xenograft Model Antitumor Assays , Oligopeptides/pharmacology , Apoptosis/drug effects , Mice, Nude , Chromones/pharmacology , Chloroquine/pharmacology , Chloroquine/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Proliferation/drug effects , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Mice, Inbred BALB C , Female , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.
Subject(s)
Neoplasms , Stomach Neoplasms , Animals , Humans , CD47 Antigen , Disease Models, Animal , Immunotherapy , Leukocytes, Mononuclear/metabolism , Neoplasm Recurrence, Local , Phagocytosis , Vascular Endothelial Growth Factor AABSTRACT
Sulfidized nanoscale zero-valent iron (S-nZVI) showed excellent removal capacity for cadmium (Cd) in aqueous phase. However, the remediation effects of S-nZVI on Cd-contaminated sediment and its interactions with microorganisms in relation to Cd fate remain unclear. The complexity of the external environment posed a challenge for Cd remediation. This study synthesized S-nZVI with different S and Fe precursors to investigate the effect of precursors and applied the optimal material to immobilize Cd in sediments. Characterization analysis revealed that the precursor affected the morphology, Fe0 crystallinity, and the degree of oxidation of the material. Incubation experiments demonstrated that the immobilization efficiency of Cd using S-nZVIFe3++S2- (S/Fe = 0.14) reached the peak value of 99.54%. 1% and 5% dosages of S-nZVI significantly reduced Cd concentration in the overlying water, DTPA-extractable Cd content, and exchangeable (EX) Cd speciation (P < 0.05). Cd leaching in sediment and total iron in the overlying water remained at low levels during 90 d of incubation. Notably, each treatment maintained a high Cd immobilization efficiency under different pH, water/sediment ratio, organic acid, and coexisting ion conditions. Sediment physicochemical properties, functional bacteria, and a range of adsorption, complexation and precipitation of CdS effects dominated Cd immobilization.
Subject(s)
Iron , Water Pollutants, Chemical , Iron/chemistry , Cadmium/chemistry , Water Pollutants, Chemical/chemistry , Water , AdsorptionABSTRACT
Antibiotics and antibiotic resistance genetic pollution have become a global environmental and health concern recently, with frequent detection in various environmental media. Therefore, finding ways to control antibiotics and antibiotic resistance genes (ARGs) is urgently needed. Nano zero-valent iron (nZVI) has shown a positive effect on antibiotics degradation and restraining ARGs, making it a promising solution for controlling antibiotics and ARGs. However, given the current increasingly fragmented research focus and results, a comprehensive review is still lacking. In this work, we first introduce the origin and transmission of antibiotics and ARGs in various environmental media, and then discuss the affecting factors during the degradation of antibiotics and the control of ARGs by nZVI and modified nZVI, including pH, nZVI dose, and oxidant concentration, etc. Then, the mechanisms of antibiotic and ARGs removal promoted by nZVI are also summarized. In general, the mechanism of antibiotic degradation by nZVI mainly includes adsorption and reduction, while promoting the biodegradation of antibiotics by affecting the microbial community. nZVI can also be combined with persulfates to degrade antibiotics through advanced oxidation processes. For the control of ARGs, nZVI not only changes the microbial community structure, but also affects the proliferation of ARGs through affecting the fate of mobile genetic elements (MGEs). Finally, some new ideas on the application of nZVI in the treatment of antibiotic resistance are proposed. This paper provides a reference for research and application in this field.
Subject(s)
Anti-Bacterial Agents , Water Pollutants, Chemical , Anti-Bacterial Agents/pharmacology , Iron/chemistry , Oxidation-Reduction , Drug Resistance, Microbial/genetics , Adsorption , Water Pollutants, Chemical/chemistryABSTRACT
The pollution of antibiotics, specifically ciprofloxacin (CIP), has emerged as a significant issue in the aquatic environment. Advanced oxidation processes (AOPs) are capable of achieving stable and efficient removal of antibiotics from wastewater. In this work, biochar-supported sulfidized nanoscale zero-valent iron (S-nZVI/BC) was adopted to activate persulfate (PS) for the degradation of CIP. The impacts of different influencing factors such as S/Fe molar ratios, BC/S-nZVI mass ratios, PS concentration, S-nZVI/BC dosage, CIP concentration, initial pH, coexisting anions, and humic acid on CIP degradation efficiency were explored by batch experiments. The results demonstrated that the highest degradation ability of S-nZVI/BC was achieved when the S/Fe molar ratio was 0.07 and the BC/S-nZVI mass ratio was 1:1. Under the experimental conditions with 0.6 g/L S-nZVI/BC, 2 mmol/L PS, and 10 mg/L CIP, the degradation rate reached 97.45% after 90 min. The S-nZVI/BC + PS system showed significant degradation in the pH range from 3 to 9. The coexisting anions affected the CIP degradation efficiency in the following order: CO32- > NO3- > SO42- > Cl-. The radical quenching experiments and electron paramagnetic resonance (EPR) revealed that oxidative species, including SO4â¢-, HOâ¢, â¢O2-, and 1O2, all contribute to the degradation of CIP, in which â¢O2- plays a particularly prominent role. Furthermore, the probable degradation pathway of CIP was explored according to the 12 degradation intermediates identified by LC-MS. This study provides a new idea for the activation method of PS and presents a new approach for the treatment of aqueous antibiotics with highly catalytic active nanomaterials.
Subject(s)
Charcoal , Ciprofloxacin , Water Pollutants, Chemical , Iron , Water Pollutants, Chemical/analysis , Anti-Bacterial Agents , WaterABSTRACT
BACKGROUND: Autophagy is essential for the homeostasis and function of the cardiovascular system. Citespace is a visual analysis software developed in the context of scientometrics and data visualization. The purpose of this study is to use Citespace software to conduct bibliometric and visual analysis of the research on autophagy in cardiovascular diseases, identify the current status, hot spots and trends in this field, help researchers clarify the future research focus and direction of autophagy in cardiovascular diseases, and provide more positive and broader ideas for the treatment and drug development of cardiovascular diseases. METHODS: In the Web of Science Core Collection database to download the data from 2004 to 2022 regarding autophagy in cardiovascular research. CitespaceV was used to collect the research status, hotspots and development trends for visual analysis. RESULTS: The 3568 articles were published by 547 authors from 397 institutions in 75 countries. From 2004 to 2021, the annual publications increased over time. The top 3 productive nations were China, the United States, and Germany. The leading institution was China's Fudan University. The most cited paper is Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). The research hotpots include monitoring methods for autophagy activity, changes in autophagy levels in different types of cardiovascular diseases, autophagy signal transduction mechanism in cardiovascular diseases, etc. CONCLUSION: Bibliometric analysis provided valuable information for autophagy research in cardiovascular disease, which is full of opportunities and challenges. The research of autophagy in the field of cardiovascular diseases is still worthy of in-depth exploration. A challenge with autophagy-targeted therapies is their dichotomy in which the goal is to target maladaptive autophagy while maintaining a baseline level of cell survival to optimize a beneficial outcome. It is necessary for scientists to develop new methods to evaluate the level of autophagy from basic application to human body and reveal the signaling mechanism of autophagy in different types of cardiovascular diseases.
Subject(s)
Cardiovascular Diseases , Cardiovascular System , Humans , Bibliometrics , Autophagy , Biological AssayABSTRACT
Nanoscale zerovalent iron (Fe0)-based materials have been demonstrated to be a effective method for the U(VI) removal. However, limited research has been conducted on the long-term immobilization efficiency and mechanism of Fe0-based materials for U(VI), which are essential for achieving safe handling and disposal of U(VI) on a large scale. In this study, the prepared carboxymethyl cellulose (CMC) and sulfurization dual stabilized Fe0 (CMC-Fe0/FeS) exhibited excellent long-term immobilization performances for U(VI) under both anoxic and oxic conditions, with the immobilization efficiencies were respectively reached over 98.0 % and 94.8 % after 180 days of aging. Most importantly, different from the immobilization mechanisms of the fresh CMC-Fe0/FeS for U(VI) (the adsorption effect of -COOH and -OH groups, coordination effect with sulfur species, as well as reduction effect of Fe0), the re-mobilized U(VI) were finally re-immobilized by the formed FeOOH and Fe3O4 on the aged CMC-Fe0/FeS. Under anoxic conditions, more Fe3O4 was produced, which may be the main reason for the long-term immobilization U(VI). Under oxic conditions, the production of Fe3O4 and FeOOH were relatively high, which both played significant roles in re-immobilizing U(VI) through surface complexation, reduction and incorporation effects.
Subject(s)
Uranium , Carboxymethylcellulose Sodium , Iron , AdsorptionABSTRACT
The improvement in the overall efficiency of thin-film composite (TFC) reverse osmosis (RO) membranes is limited by their low permeability and sensitivity to degradation by chlorine. In the present study, polypiperazine (PIP), the commonly used amine monomer in preparing commercial TFC nanofiltration (NF) membranes, was used to regulate the m-phenylenediamine (MPD) based interfacial polymerization (IP) process. The results showed that addition of PIP optimized the micro-structure and surface properties of the polyamide (PA) layer. When the MPD and PIP mass ratio was 1 : 1, the TFCW-1:1 membrane exhibited 70% flux enhancement compared to pure MPD-based TFCW-1:0 membranes. Besides, the TFCW-1:1 membrane exhibited better chlorine-resistant performance since the NaCl rejection declined to just 3.8% while it was 11.3% for TFCW-1:0 membranes after immersion in 500 ppm NaClO solution for 48 h. Such improvement can be attributed to the increased number of unreacted amine groups and the thickness of the PA layer that PIP brought, which provided a sacrificial protective layer to consume the active chlorine, and thus maintain the integrity of the inner rejection layer. In all, the novelty and purpose of the present work is to find a more simple and scalable method to fabricate high-performance TFC RO membranes by using commonly, cheaply and frequently used materials.
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BACKGROUND: Atrial fibrillation (AF) is a very common arrhythmia with significant incidence rate and mortality. Several studies have shown a notable correlation between non-alcoholic fatty liver disease (NAFLD) and AF. It has been observed that serum cholinesterase (SChE) levels are elevated in individuals with fatty liver. However, the relationship between the SChE index and AF is still unclear. Therefore, the purpose of this study is to explore the association between the SChE index and the prevalence of AF in patients with hypertension. METHOD: We collected cross-sectional data from January 2018 to April 2021 based on a retrospective study of cardiovascular disease. A total of 748 patients with hypertension were included, of whom 165 had AF. We used logistic regression models to test the relationship between SChE and the prevalence of AF in hypertensive patients. RESULT: In hypertensive patients, the SChE index was significantly associated with AF (OR = 0.723, P < 0.001). After adjusting for potential confounding factors, this correlation was still significant (OR = 0.778, P < 0.001). The stability of the model was verified by adjusting the variable type of SChE. The data were further stratified according to whether the patient had fatty liver. In the stratified data, the correlation between SChE and atrial fibrillation was still significant (P < 0.05). CONCLUSION: Our study showed that SChE was significantly negatively correlated with the occurrence of AF in patients with hypertension. And this correlation was not affected by whether the patient had fatty liver.
Subject(s)
Atrial Fibrillation , Cholinesterases , Hypertension , Humans , Atrial Fibrillation/complications , Cholinesterases/blood , Cross-Sectional Studies , East Asian People , Hypertension/complications , Hypertension/epidemiology , Prevalence , Retrospective Studies , Risk FactorsABSTRACT
Modified nanoscale zero-valent iron (NZVI) exhibited great potential for the remediation of heavy metal contaminated river sediments, but its mechanisms and environmental risks are still unclear. This study systematically discussed the performance and the mechanisms of modified NZVI materials, i.e., sodium alginate-coated NZVI (SNZVI), rhamnolipid-coated NZVI (RNZVI), and graphene oxide-loaded NZVI (GNZVI), for the stabilization of Cd in sediment, with the exploration of their stability to Cd at various pH values and Fe dissolution rate. Compared with the control, the toxicity characteristic leaching procedure (TCLP) leachable Cd decreased by 52.66-96.28%, and the physiologically based extraction test (PBET) extractable Cd decreased by 44.68-70.21% after 56 days of incubation with the immobilization efficiency varying according to GNZVI > RNZVI > SNZVI > NZVI. Besides, the adsorption behavior of Cd on materials was fitted with the Freundlich model and classified as an endothermic, spontaneous, and chemical adsorption process. SEM-EDX, XRD, and FTIR results verified that the stabilization mechanisms of Cd were principally based on the adsorption, complexation of Cd2+ with secondary Fe minerals (including Fe2O3, γ-Fe2O3, and γ-FeOOH) and precipitation (Cd(OH)2). From the risk assessment results, it was observed that the materials were favorable for Cd stabilization at a pH range from 7 to 11, meanwhile, the leaching concentration of Fe in the overlying water was detected below the limit value. These findings pave the way to developing an effective strategy to remediate Cd contaminated river sediments.
Subject(s)
Environmental Restoration and Remediation , Metals, Heavy , Water Pollutants, Chemical , Iron , Cadmium , Rivers , AdsorptionABSTRACT
Background: Tanshinone IIA, derived from Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge), constitutes a significant component of this traditional Chinese medicine. Numerous studies have reported positive outcomes regarding its influence on cardiac function. However, a comprehensive comprehension of the intricate mechanisms responsible for its cardioprotective effects is still lacking. Methods: A rat model of heart failure (HF) induced by acute myocardial infarction (AMI) was established via ligation of the left anterior descending coronary artery. Rats received oral administration of tanshinone IIA (1.5 mg/kg) and captopril (10 mg/kg) for 8 weeks. Cardiac function was assessed through various evaluations. Histological changes in myocardial tissue were observed using staining techniques, including Hematoxylin and Eosin (HE), Masson, and transmission electron microscopy. Tunel staining was used to detect cell apoptosis. Serum levels of NT-pro-BNP, IL-1ß, and IL-18 were quantified using enzyme-linked immunosorbent assay (ELISA). Expression levels of TLR4, NF-κB p65, and pyroptosis-related proteins were determined via western blotting (WB). H9C2 cardiomyocytes underwent hypoxia-reoxygenation (H/R) to simulate ischemia-reperfusion (I/R) injury, and cell viability and apoptosis were assessed post treatment with different tanshinone IIA concentrations (0.05 µg/ml, 0.1 µg/ml). ELISA measured IL-1ß, IL-18, and LDH expression in the cell supernatant, while WB analysis evaluated TLR4, NF-κB p65, and pyroptosis-related protein levels. NF-κB p65 protein nuclear translocation was observed using laser confocal microscopy. Results: Tanshinone IIA treatment exhibited enhanced cardiac function, mitigated histological cardiac tissue damage, lowered serum levels of NT-pro-BNP, IL-1ß, and IL-18, and suppressed myocardial cell apoptosis. Moreover, tanshinone IIA downregulated the expression of TLR4, NF-κB p65, IL-1ß, pro-IL-1ß, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in myocardial tissue. Additionally, it bolstered H/R H9C2 cardiomyocyte viability, curbed cardiomyocyte apoptosis, and reduced the levels of TLR4, NF-κB p65, IL-1ß, pro-IL-1ß, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in H/R H9C2 cells. Furthermore, it hindered NF-κB p65 protein nuclear translocation. Conclusion: These findings indicate that tanshinone IIA enhances cardiac function and alleviates myocardial injury in HF rats following AMI. Moreover, tanshinone IIA demonstrates potential suppression of cardiomyocyte pyroptosis. These effects likely arise from the inhibition of the TLR4/NF-κB p65 signaling pathway, presenting a promising therapeutic target.
ABSTRACT
Over the past decade, sulfidized nanoscale zero-valent iron (S-nZVI) has been developed as a promising tool for the remediation of contaminated soil, sediment, and water. Although most studies have focused on applying S-nZVI for clean-up purposes, there is still a lack of systematic summary and discussion from its synthesis, application, to toxicity assessment. This review firstly summarized and compared the properties of S-nZVI synthesized from one-step and two-step synthesis methods, and the modification protocols for obtaining better stability and reactivity. In the context of environmental remediation, this review outlined an update on the latest development of S-nZVI for removal of heavy metals, organic pollutants, antibiotic resistance genes (ARGs), and antibiotic resistant bacteria (ARB) and also discussed the underlying removal mechanisms. Environmental factors affecting the remediation performance of S-nZVI (e.g., humic acid, coexisting ions, S/Fe molar ratio, pH, and oxygen condition) were highlighted. Besides, the application potential of S-nZVI in advanced oxidation processes (AOP), especially in activating persulfate, was also evaluated. The toxicity impacts of S-nZVI on the environmental microorganism were described. Finally, the future challenges and remaining restrains to be resolved for better applicability of S-nZVI are also proposed. This review could provide guidance for the environmental remediation with S-nZVI-based technology from theoretical basis and practical perspectives.
ABSTRACT
Immunotherapies including adaptive immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have developed the treatment of cancer in clinic, and most of them focus on activating T cell immunity. Although these strategies have obtained unprecedented clinical responses, only limited subsets of cancer patients could receive long-term benefits, highlighting the demand for identifying novel targets for the new era of tumor immunotherapy. Innate immunity has been demonstrated to play a determinative role in the tumor microenvironment (TME) and influence the clinical outcomes of tumor patients. A thorough comprehension of the innate immune cells that infiltrate tumors would allow for the development of new therapeutics. In this review, we outline the role and mechanism of innate immunity in TME. Moreover, we discuss innate immunity-based cancer immunotherapy in basic and clinical studies. Finally, we summarize the challenges in sufficiently motivating innate immune responses and the corresponding strategies and measures to improve anti-tumor efficacy. This review could aid the comprehension of innate immunity and inspire the creation of brand-new immunotherapies for the treatment of cancer.
Subject(s)
Neoplasms , Humans , Neoplasms/pathology , Immunity, Innate , Immunotherapy , T-Lymphocytes , Biology , Tumor MicroenvironmentABSTRACT
BACKGROUND: Biomarker of insulin resistance, namely triglyceride-glucose index, is potentially useful in identifying critically ill patients at high risk of hospital death. However, the TyG index might have variations over time during ICU stay. Hence, the purpose of the current research was to verify the associations between the dynamic change of the TyG index during the hospital stay and all-cause mortality. METHODS: The present retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV) critical care dataset, which included data from 8835 patients with 13,674 TyG measurements. The primary endpoint was 1-year all-cause mortality. Secondary outcomes included in-hospital all-cause mortality, the need for mechanical ventilation during hospitalization, length of stay in the hospital. Cumulative curves were calculated using the Kaplan-Meier method. Propensity score matching was performed to reduce any potential baseline bias. Restricted cubic spline analysis was also employed to assess any potential non-linear associations. Cox proportional hazards analyses were performed to examine the association between the dynamic change of TyG index and mortality. RESULTS: The follow-up period identified a total of 3010 all-cause deaths (35.87%), of which 2477 (29.52%) occurred within the first year. The cumulative incidence of all-cause death increased with a higher quartile of the TyGVR, while there were no differences in the TyG index. Restricted cubic spline analysis revealed a nearly linear association between TyGVR and the risk of in-hospital all-cause mortality (P for non-linear = 0.449, P for overall = 0.004) as well as 1-year all-cause mortality (P for non-linear = 0.909, P for overall = 0.019). The area under the curve of all-cause mortality by various conventional severity of illness scores significantly improved with the addition of the TyG index and TyGVR. The results were basically consistent in subgroup analysis. CONCLUSIONS: Dynamic change of TyG during hospital stay is associated with in-hospital and 1-year all-cause mortality, and may be superior to the effect of baseline TyG index.