Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 2.288
Filter
1.
J Environ Sci (China) ; 148: 88-106, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39095204

ABSTRACT

In this study, a string of Cr-Mn co-modified activated coke catalysts (XCryMn1-y/AC) were prepared to investigate toluene and Hg0 removal performance. Multifarious characterizations including XRD, TEM, SEM, in situ DRIFTS, BET, XPS and H2-TPR showed that 4%Cr0.5Mn0.5/AC had excellent physicochemical properties and exhibited the best toluene and Hg0 removal efficiency at 200℃. By varying the experimental gas components and conditions, it was found that too large weight hourly space velocity would reduce the removal efficiency of toluene and Hg0. Although O2 promoted the abatement of toluene and Hg0, the inhibitory role of H2O and SO2 offset the promoting effect of O2 to some extent. Toluene significantly inhibited Hg0 removal, resulting from that toluene was present at concentrations orders of magnitude greater than mercury's or the catalyst was more prone to adsorb toluene, while Hg0 almost exerted non-existent influence on toluene elimination. The mechanistic analysis showed that the forms of toluene and Hg0 removal included both adsorption and oxidation, where the high-valent metal cations and oxygen vacancy clusters promoted the redox cycle of Cr3+ + Mn3+/Mn4+ ↔ Cr6+ + Mn2+, which facilitated the conversion and replenishment of reactive oxygen species in the oxidation process, and even the CrMn1.5O4 spinel structure could provide a larger catalytic interface, thus enhancing the adsorption/oxidation of toluene and Hg0. Therefore, its excellent physicochemical properties make it a cost-effective potential industrial catalyst with outstanding synergistic toluene and Hg0 removal performance and preeminent resistance to H2O and SO2.


Subject(s)
Air Pollutants , Mercury , Oxides , Toluene , Toluene/chemistry , Oxides/chemistry , Air Pollutants/chemistry , Mercury/chemistry , Coke , Catalysis , Chromium/chemistry , Adsorption , Manganese/chemistry , Manganese Compounds/chemistry , Models, Chemical
2.
Int J Biol Macromol ; 277(Pt 3): 134485, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39102926

ABSTRACT

The blood glucose concentration in aquatic organisms, a crucial indicator reflecting their health status, holds significant importance for detecting glucose levels in serum in terms of processing and quality monitoring. In this study, a novel POD biomimetic enzyme (p-BEs) with horseradish peroxidase catalytic properties was designed, optimized, and its mechanism was discussed in detail. Based on this, a portable system has been developed capable of determining glucose levels in three ways: quantitatively analyzed through UV-Vis/MD, quantitatively analyzed on-site using a mobile phone RGB, and semi-quantitatively analyzed through a drip plate. Meanwhile, compared with other catalytic methods for detecting glucose, we achieved a lower limit of detection (0.03 µM) and shorter detection time (12 min), with high catalytic activity. This study provides new insights into the design of efficient and reliable cascade catalytic systems responsive to glucose, offering a low-cost, simplicity of operation method for glucose detection.

3.
Int J Biol Macromol ; 277(Pt 3): 134438, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39098676

ABSTRACT

Long-chain acyl-CoA synthetases (LACSs), belonging to the acyl-activating enzyme superfamily, play crucial roles in lipid biosynthesis and fatty acid catabolism. Here, we identified 11 LACS genes in the tomato reference genome, and these genes were clustered into six subfamilies. Gene structure and conserved motif analyses indicated that LACSs from the same subfamily shared conserved gene and protein structures. Expression analysis revealed that SlLACS1 was highly expressed in the outer epidermis of tomato fruits and leaves. Subcellular localization assay results showed that SlLACS1 was located in the endoplasmic reticulum. Compared with wild-type plants, the wax content on leaves and fruits decreased by 22.5-34.2 % in SlLACS1 knockout lines, confirming that SlLACS1 was involved in wax biosynthesis in both leaves and fruits. Water loss, chlorophyll extraction, water-deficit, and toluidine blue assays suggested that cuticle permeability was elevated in SlLACS1 knockout lines, resulting in reduction in both drought stress resistance and fruit shelf-life. Overall, our analysis of the LACSs in tomato, coupled with investigations of SlLACS1 function, yielded a deeper understanding of the evolutionary patterns of LACS members and revealed the involvement of SlLACS1 in wax accumulation contribute to drought resistance and extended fruit shelf-life in tomato.

4.
J Med Chem ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39134504

ABSTRACT

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/ß-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in ß-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

5.
JMIR Public Health Surveill ; 10: e50244, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39140280

ABSTRACT

Background: The evidence on the association of fine particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) with pulmonary tuberculosis (PTB) retreatment is limited. There are no data on whether greenness exposure protects air pollution-related PTB retreatment in patients with prior PTB. Objective: In a population-based retrospective study, we aimed to investigate the influence of PM2.5 and residential greenness on the risk of PTB retreatment. Methods: A total of 26,482 patients with incident PTB, registered in a mandatory web-based reporting system between 2012 and 2019 in Zhengzhou, China, were included in the analysis. The exposure to PM2.5 was assessed based on the China High Air Pollutants dataset, and the level of greenness was estimated using the Normalized Difference Vegetation Index (NDVI) values. The associations of PTB retreatment with exposure to PM2.5 and greenness were evaluated, respectively, considering the local socioeconomic level indicated by the nighttime light index. Results: Among the 26,482 patients (mean age 46.86, SD 19.52 years) with a median follow-up time of 1523 days per patient, 1542 (5.82%) PTB retreatments were observed between 2012 and 2019. Exposure to PM2.5 was observed to be significantly associated with the increased risk of PTB retreatment in fully adjusted models with a hazard ratio of 1.97 (95% CI 1.34-2.83) per 10 µg/m3 increase in PM2.5. Patients living in the regions with relatively high quartiles of NDVI values had a 45% lower risk of PTB retreatment than those living in the regions with the lowest quartile for the 500 m buffers (hazard ratio 0.55, 95% CI 0.40-0.77). Such a protective effect of residential greenness was more pronounced among patients living in lower nighttime light areas. The strength of the association between PM2.5 exposure and the risk of PTB retreatment was attenuated by greenness. No significant association was observed between NDVI and the incidence of drug resistance. Conclusions: Long-term exposure to PM2.5 might be a risk factor for PTB retreatment, while an increased level of residential greenness was found to be associated with reduced risks of PTB retreatment. Our results suggest strengthening the control of ambient air pollution and improving residential greenness may contribute to the reduction of PTB retreatment.


Subject(s)
Particulate Matter , Tuberculosis, Pulmonary , Humans , Retrospective Studies , Particulate Matter/analysis , Particulate Matter/adverse effects , Middle Aged , Female , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/drug therapy , Male , China/epidemiology , Adult , Air Pollution/adverse effects , Air Pollution/analysis , Environmental Exposure/adverse effects , Environmental Exposure/statistics & numerical data , Retreatment/statistics & numerical data , Aged , Risk Factors , Residence Characteristics/statistics & numerical data
6.
Sci Rep ; 14(1): 18171, 2024 08 06.
Article in English | MEDLINE | ID: mdl-39107400

ABSTRACT

Enhanced recovery after surgery (ERAS) has been successfully integrated into a diverse array of surgical fields to improve the quality and efficacy of treatment intervention. Nonetheless, the application of the ERAS protocol for patients with diabetic foot ulcer (DFU) subsequent to undergoing surgical procedures has not been previously explored. Therefore, this study aimed to investigate the effect of an enhanced recovery protocol on perioperative outcomes in patients with DFU following surgical procedures. A retrospective analysis was conducted on 112 patients with DFU who underwent surgery between January 2020 and December 2021 at a tertiary referral care center. In total, 57 patients received standard perioperative care (the non-ERAS group), and 55 patients received ERAS care (the ERAS group). The primary outcomes included the length of stay (LOS), wound healing time, patient satisfaction, and costs, serving as the basis for assessing the effectiveness of the two approaches. Secondary outcomes included preoperative anxiety (APAIS score), nutritional status (PG-SGA), pain (NRS score), the incidence of lower-extremity deep vein thrombosis (DVT), the reduction in lower-limb circumference, and the activity of daily living scale (Barthel Index). The ERAS group exhibited significantly shorter LOS (11.36 vs. 26.74 days; P < 0.001) and lower hospital costs (CNY 62,165.27 vs. CNY 118,326.84; P < 0.001), as well as a higher patient satisfaction score and Barthel Index score (P < 0.05). Additionally, we found a lower APAIS score, incidence of DVT, and circumference reduction in lower limbs in the ERAS group compared to the non-ERAS group (P < 0.05). In comparison, the wound healing time, nutritional status, and pain levels of participants in both groups showed no significant difference (P > 0.05). By reducing the LOS and hospital costs, and by minimizing perioperative complications, the ERAS protocol improves the quality and efficacy of treatment intervention in patients with DFU who underwent surgical procedures.Trial registration number: ChiCTR 2200064223 (Registration Date: 30/09/2022).


Subject(s)
Diabetic Foot , Enhanced Recovery After Surgery , Length of Stay , Humans , Male , Female , Retrospective Studies , Diabetic Foot/surgery , Middle Aged , Aged , Wound Healing , Patient Satisfaction , Perioperative Care/methods , Treatment Outcome
7.
J Biopharm Stat ; : 1-15, 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39127994

ABSTRACT

Dose optimization is a critical challenge in drug development. Historically, dose determination in oncology has followed a divergent path from other non-oncology therapeutic areas due to the unique characteristics and requirements in Oncology. However, with the emergence of new drug modalities and mechanisms of drugs in oncology, such as immune therapies, radiopharmaceuticals, targeted therapies, cytostatic agents, and others, the dose-response relationship for efficacy and toxicity could be vastly varied compared to the cytotoxic chemotherapies. The doses below the MTD may demonstrate similar efficacy to the MTD with an improved tolerability profile, resembling what is commonly observed in non-oncology treatments. Hence, alternate strategies for dose optimization are required for new modalities in oncology drug development. This paper delves into the historical evolution of dose finding methods from non-oncology to oncology, highlighting examples and summarizing the underlying drivers of change. Subsequently, a practical framework and guidance are provided to illustrate how dose optimization can be incorporated into various stages of the development program. We provide the following general recommendations: 1) The objective for phase I is to identify a dose range rather than a single MTD dose for subsequent development to better characterize the safety and tolerability profile within the dose range. 2) At least two doses separable by PK are recommended for dose optimization in phase II. 3) Ideally, dose optimization should be performed before launching the confirmatory study. Nevertheless, innovative designs such as seamless II/III design can be implemented for dose selection and may accelerate the drug development program.

8.
Mol Plant ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39095994

ABSTRACT

Understanding how maize (Zea mays L.) responds to cold stress is crucial for facilitating breeding programs of cold-tolerant varieties. Despite the extensive utilization of the genome-wide association study (GWAS) approach in exploring favorable natural alleles associated with maize cold tolerance, there are few reports that have successfully identified the candidate genes contributing to maize cold tolerance. In this study, by employing a diverse panel of maize inbred lines collected from different germplasm sources, we conducted a GWAS on the variation of the relative injured area of maize true leaves during cold stress-a trait most closely correlated with maize cold tolerance-and identified HSF21, encoding a B-class heat shock transcription factor, which positively regulates cold tolerance at both seedling and germination stages. The natural variations within the promoter of the cold-tolerant HSF21Hap1 allele led to increased HSF21 expression under cold stress by inhibiting the binding of bZIP68 transcription factor, a negative regulator of cold tolerance. Through integrated transcriptome deep sequencing, DNA affinity purification sequencing, and targeted lipidomic analysis, we unveiled the function of HSF21 in regulating lipid metabolism homeostasis for modulating cold tolerance in maize. Additionally, HSF21 confers maize cold tolerance without incurring yield penalties. This study thereby establishes HSF21 as a key regulator that enhances cold tolerance in maize, thus providing valuable genetic resources for the breeding of cold-tolerant maize varieties.

9.
Int J Med Sci ; 21(10): 1806-1813, 2024.
Article in English | MEDLINE | ID: mdl-39113891

ABSTRACT

Background: Roxadustat is commonly used to treat renal anemia. However, the potential effects of roxadustat on metabolism and organs other than the kidneys have recently attracted increased attention. Objective: This study aimed to examine the regulatory effects of roxadustat on thyroid hormones and blood lipid metabolism in patients with end-stage kidney disease (ESKD) undergoing hemodialysis. Methods: Eighty ESKD patients on hemodialysis and taking roxadustat were enrolled. Hemoglobin, thyroid hormones (TSH, FT3, FT4), and blood lipid profiles (TC, LDL-C, TG, HDL-C) were assessed before and after treatment. Changes in these parameters were compared, and relevant causative factors were analyzed. Results: Roxadustat significantly increased Hb, lowered TSH, FT4, TC, and LDL-C levels (all P<0.001). Patients were categorized into three groups based on post-treatment TSH inhibition percentage: Q1(≥70%), Q2(30%-70%), Q3(≤30%). Pre-treatment TSH decreased with reduced TSH inhibition (P<0.05). Post-treatment, TC, LDL-C, TSH, FT3, and FT4 increased with reduced TSH inhibition (all P<0.05).TC and LDL-C significantly decreased post-treatment in Q1 and Q2 (P<0.05). Correlation analysis showed a positive correlation between ΔTSH and pre-treatment TSH levels (r=0.732, P<0.001). The proportion of patients with ≥70% TSH inhibition increased with higher pre-treatment TSH levels (P for trend <0.05). ΔLDL-C and ΔTSH were positively correlated (r=0.278, P<0.05), with ΔTSH identified as an influencing factor in multiple linear regression (ß=0.133, 95% CI [0.042, 0.223], P<0.05). Conclusion: Roxadustat effectively improves anemia in ESKD patients while inhibiting TSH and FT4 secretion and reducing TC and LDL-C levels. Decreases in TSH levels correlate with baseline TSH levels, and lowered blood lipid levels are associated with decreased TSH levels.


Subject(s)
Glycine , Isoquinolines , Kidney Failure, Chronic , Lipid Metabolism , Renal Dialysis , Thyroid Hormones , Humans , Male , Female , Renal Dialysis/adverse effects , Middle Aged , Retrospective Studies , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Aged , Glycine/analogs & derivatives , Glycine/therapeutic use , Lipid Metabolism/drug effects , Thyroid Hormones/blood , Isoquinolines/therapeutic use , Isoquinolines/administration & dosage , Lipids/blood , Adult , Thyrotropin/blood
10.
Adv Sci (Weinh) ; : e2403845, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120071

ABSTRACT

Magnetron-sputtered thermoelectric thin films have the potential for reproducibility and scalability. However, lattice mismatch during sputtering can lead to increased defects in the epitaxial layer, which poses a significant challenge to improving their thermoelectric performance. In this work, nanocrystalline n-type Bi2Te3 thin films with an average grain size of ≈110 nm are prepared using high-temperature sputtering and post-annealing. Herein, it is demonstrated that high-temperature treatment exacerbates Te evaporation, creating Te vacancies and electron-like effects. Annealing improves crystallinity, increases grain size, and reduces defects, which significantly increases carrier mobility. Furthermore, the pre-deposited Ti additives are ionized at high temperatures and partially diffused into Bi2Te3, resulting in a Ti doping effect that increases the carrier concentration. Overall, the 1 µm thick n-type Bi2Te3 thin film exhibits a room temperature resistivity as low as 3.56 × 10-6 Ω∙m. Notably, a 5 µm thick Bi2Te3 thin film achieves a record power factor of 6.66 mW mK-2 at room temperature, which is the highest value reported to date for n-type Bi2Te3 thin films using magnetron sputtering. This work demonstrates the potential for large-scale of high-quality Bi2Te3-based thin films and devices for room-temperature TE applications.

11.
Plant Physiol ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052943

ABSTRACT

Drought stress poses a substantial challenge to plant growth and agricultural productivity worldwide. Upon water depletion, plants activate an abscisic acid (ABA) signaling pathway, leading to stomatal closure to reduce water loss. The MYB family of transcription factors plays diverse roles in growth, development, stress responses and biosynthesis, yet their involvement in stomatal regulation remains unclear. Here, we demonstrate that ABA significantly upregulates the expression of MYB41, MYB74, and MYB102, with MYB41 serving as a key regulator that induces the expression of both MYB74 and MYB102. Through luciferase assays, chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSA), we reveal that MYB41 engages in positive feedback regulation by binding to its own promoter, thus amplifying its transcription in Arabidopsis (Arabidopsis thaliana). Furthermore, our investigation showed that MYB41 recruits BRAHMA (BRM), the core ATPase subunit of the SWI/SNF complex, to the MYB41 promoter, facilitating the binding of HISTONE DEACETYLASE 6 (HDA6). This recruitment triggers epigenetic modifications, resulting in reduced MYB41 expression characterized by elevated H3K27me3 levels and concurrent decreases in H3ac, H3K27ac, and H3K14ac levels in wild-type plants compared to brm knockout mutant plants. Our genetic and molecular analyses show that ABA mediates autoregulation of the MYB41-BRM module, which intricately modulates stomatal movement in A. thaliana. This discovery sheds light on a drought response mechanism with the potential to greatly enhance agricultural productivity.

12.
ISME J ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39073917

ABSTRACT

Acidimicrobiia are widely distributed in nature and suggested to be autotrophic via the Calvin-Benson-Bassham (CBB) cycle. However, direct evidence of chemolithoautotrophy in Acidimicrobiia is lacking. Here, we report a chemolithoautotrophic enrichment from a saline lake, and the subsequent isolation and characterization of a chemolithoautotroph, Salinilacustristhrix flava EGI L10123T, which belongs to a new Acidimicrobiia family. Although strain EGI L10123T is autotrophic, neither its genome nor Acidimicrobiia metagenome-assembled genomes (MAGs) from the enrichment culture encode genes necessary for the CBB cycle. Instead, genomic, transcriptomic, enzymatic, and stable-isotope probing data hinted at the activity of the reversed oxidative TCA (roTCA) coupled with the oxidation of sulfide as the electron donor. Phylogenetic analysis and ancestral character reconstructions of Acidimicrobiia suggested that the essential CBB gene rbcL was acquired through multiple horizontal gene transfer events from diverse microbial taxa. In contrast, genes responsible for sulfide- or hydrogen-dependent roTCA carbon fixation were already present in the last common ancestor of extant Acidimicrobiia. These findings imply the possibility of roTCA carbon fixation in Acidimicrobiia and the ecological importance of Acidimicrobiia. Further research in the future is necessary to confirm whether these characteristics are truly widespread across the clade.

13.
Rev Cardiovasc Med ; 25(4): 119, 2024 Apr.
Article in English | MEDLINE | ID: mdl-39076536

ABSTRACT

It has been rarely reported that a stuck optical coherence tomography (OCT) catheter can lead to longitudinal stent deformation (LSD). This complication can result in incomplete stent apposition and dissection after stent implantation. In this study, we present a case where a bailout stent was implanted in the distal segment of the left anterior descending artery (LAD) after longitudinal stent deformation caused by a stuck OCT catheter. This approach was taken to prevent acute stent thrombosis, subacute stent thrombosis, in-stent restenosis (ISR), and death. The patients were followed up for one year, and no adverse events were observed.

14.
Rev Cardiovasc Med ; 25(3): 95, 2024 Mar.
Article in English | MEDLINE | ID: mdl-39076931

ABSTRACT

With the development of drug-eluting stents, intimal re-endothelialisation is significantly inhibited by antiproliferative drugs, and stent restenosis transforms from smooth muscle cell proliferation to neoatherosclerosis (NA). As a result of the development of intravascular imaging technology, the incidence and characteristics of NA can be explored in vivo, with some progress made in illustrating the mechanisms of NA. Experimental studies have shed light on the molecular characteristics of NA. More critically, sufficient evidence proves NA as a significant cause of late stent failure. Treatments for NA are still being explored. In this review, we summarise the histopathological characteristics of different types of stent NA, explore the potential relationship of NA with native atherosclerosis and discuss the clinical significance of NA in late stent failure and the promising present and future prevention and treatment strategies.

15.
Sci Total Environ ; 949: 174871, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038672

ABSTRACT

Vegetated coastal ecosystems (VCE), encompassing tidal marshes, mangroves, and seagrasses, serve as significant 'blue' carbon (C) sinks. Improving our understanding of VCE soils and their spatial and temporal dynamics is essential for conservation efforts. Conventional methods to characterise the dynamics and provenance of VCE soils and measure their total organic carbon (TOC) and inorganic carbon (TIC) contents are cumbersome and expensive. We recorded the mid-infrared (MIR) spectra and measured the TOC and TIC content of 323 subsamples across consistent depths from 106 soil core samples. Using the spectra of each VCE, we determined their mineral and organic composition by depth. We then used a regression tree algorithm, cubist, to model TOC and TIC contents. We rigorously validated the models to test their performance with a 10-fold cross-validation, bootstrapping, and a separate random test dataset. Our analysis revealed distinct mineralogical and organic MIR signatures in VCE soils that correlated with their position within the seascape. The spectra showed decreased clay minerals and increased quartz and carbonate with distance from freshwater inputs. The mineralogy of tidal marsh and mangrove soils differed with depth, showing larger absorptions due to carbonate and quartz and weakening clay minerals and organics absorptions. The mineralogy of the seagrass soils remained the same with depth. The cubist models to estimate TOC and TIC content were accurate (Lin's concordance correlation, ρc≥ 0.92 and 0.93 respectively) and interpretable, confirming our understanding of C in these systems. These findings shed light on the provenance of the soils and help quantify the flux and accumulation of TOC and TIC, which is crucial for informing VCE conservation. Moreover, our results indicate that MIR spectroscopy could help scale the measurements cost-effectively, for example, in carbon crediting schemes and to improve inventories. The approach will help advance blue C science and contribute to the conservation and protection of VCE.

16.
J Immunother Cancer ; 12(7)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39060025

ABSTRACT

BACKGROUND: The high metastasis rate is one of the main reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC). Coagulation factor Xa (FXa) and its receptor proteinase-activated receptor-2 (PAR-2) proven to promote tumor metastasis in other forms of cancer. Here, we explore the role and mechanism of FXa in the regulation of resistance of anoikis and immune escape of HCC. METHODS: In vitro and in vivo experiments were conducted to explore the role of FXa in HCC metastasis and its potential mechanism. The effects of FXa inhibitor rivaroxaban on HCC immunotherapy were evaluated using intrahepatic metastasis animal models and clinical trial (No. ChiCTR20000040540). We investigated the potential of FXa inhibition as a treatment for HCC. RESULTS: FXa was highly expressed in HCC and promoted metastasis by activating PAR-2. Mechanistically, FXa-activated PAR-2 endows HCC cells with the ability of anoikis resistance to survive in the circulating blood by inhibiting the extrinsic apoptosis pathway. Furthermore, suspension stimulation-induced phosphorylation of STAT2, which promotes programmed death-ligand 1 (PD-L1) transcription and inhibits the antitumor effects of immune cells by inhibiting the infiltration of CD8+T cells in tumors and the levels of secreted cytokines. In vivo inhibition of FXa with rivaroxaban reduced HCC metastasis by decreasing PD-L1 expression and exhausting tumor-infiltrating lymphocytes. Notably, the combination of rivaroxaban and anti-programmed death-1 monoclonal antibody (anti-PD-1) programmed Death-1 monoclonal antibody (anti-PD-1) induced synergistic antitumor effects in animal models. Most importantly, rivaroxaban improved the objective response rate of patients with HCC to immune checkpoint inhibitors and prolonged overall survival time. CONCLUSIONS: FXa-activated PAR-2 promotes anoikis resistance and immune escape in HCC, suggesting the potential for combining coagulation inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance the therapeutic efficacy of HCC.


Subject(s)
Anoikis , B7-H1 Antigen , Carcinoma, Hepatocellular , Immunotherapy , Liver Neoplasms , Receptor, PAR-2 , Tumor Escape , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Humans , Receptor, PAR-2/metabolism , Animals , Mice , Immunotherapy/methods , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Factor Xa/metabolism , Factor Xa/pharmacology , Factor Xa/therapeutic use , Male , Female , Cell Line, Tumor , Factor Xa Inhibitors/pharmacology , Factor Xa Inhibitors/therapeutic use
17.
Oncogene ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060439

ABSTRACT

Gastric cancer (GC) is a substantial global health concern, and the development of liver metastasis (LM) in GC represents a critical stage linked to unfavorable patient prognoses. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the immune landscape of GC liver metastasis, revealing several immuno-suppressive components within the tumor immune microenvironment (TIM). Our findings unveiled an increased presence of cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cell (MDSC)-like macrophages, tumor-associated macrophage (TAM)-like macrophages, and naive T cells, while conventional dendritic cells (cDCs) and effector CD8 T cells declined in LM. Additionally, we identified two distinct natural killer (NK) cell clusters exhibiting differential cytotoxicity-related gene expression, with cytotoxic NK cells notably reduced in LM. Strikingly, TGFß was identified as an inducer of NK cell dysfunction, potentially contributing to immune evasion and tumor metastasis. In preclinical LM models, the combined approach of inhibiting TGFß and transferring NK cells exhibited a synergistic impact, resulting in a significant reduction in liver metastasis. This work highlights the importance of understanding the complex immune dynamics within GC liver metastasis and presents a promising strategy combining TGFß inhibition and NK-based immunotherapy to improve patient outcomes.

18.
Food Sci Nutr ; 12(7): 4810-4818, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39055212

ABSTRACT

Quinoa is a full-nutrition food; however, its poor flavor and small size make it not the best food option for direct consumption. In this study, a quinoa snack (QS, a cake) was developed, and the aroma profile of the products was improved by adding jujube fruit powder (made from dried jujube fruits, from 5% to 30%). Gas chromatography mass spectrum (GC-MS) combined with electronic nose (e-nose) was applied for characterizing the aroma profiles of QS samples. Results showed a total of 26 aroma compounds were identified in QS samples by GC-MS, and 3-methylbutanol (from 1525 µg/kg in QS-30 to 3487 µg/kg in QS-0), ethanol (from 1126 µg/kg in QS-0 to 3581 µg/kg in QS-30), hexanal (from 125.6 µg/kg in QS-30 to 984.1 µg/kg in QS-0), and acetaldehyde (from 531.9 µg/kg in QS-30 to 191.1 µg/kg in QS-0) were common. The e-nose response of W1S (sensitive to methane, from 17.50 of QS-0 to 93.85 of QS-30) and W1W (sensitive to sulfur-organic compounds of e-nose, from 15.57 of QS-0 to 39.50 of QS-30) were significantly higher, and significant differences were presented among QS samples. In conclusion, the aroma profile of the QS sample was significantly (p < .05) enhanced by the addition of jujube powder, and QS-30 with the highest jujube content (30%) presented the strongest aroma profile. Moreover, QS samples with different additions of jujube powders could be well distinguished by principal component analysis (PCA), and the combination of e-nose and GC-MS was effective in the volatile profile analysis of QS samples.

19.
Front Plant Sci ; 15: 1428752, 2024.
Article in English | MEDLINE | ID: mdl-39055354

ABSTRACT

Introduction: In the invaded areas, it is believed that invasive species reduce their investment in defense due to the absence of natural enemies. Methods: By field investigation and a series of laboratory assays, This study explored the defense strategies of invasive plants. Results: Field investigation indicated that invasive plants have a antifeedant effect on herbivorous pests, and the distribution frequency of wormholes of native plants shows a peak at a distance of 2-3 m from the invasive species. The feeding preference experiment conducted with two generalist herbivorous insects (native insect Spodoptera litura and invasive insect Spodoptera frugiperda) showed that the invasive plants have a stronger antifeedant effect than native plants. By analyzing the content of secondary metabolites in the leaves of three invasive plants (Sphagneticola trilobata, Mikania micrantha, Ipomoea cairica) and three native plants (Ipomoea nil, Paederia foetida, Polygonum chinense), the leaves of invasive plants had higher concentrations of substances associated with defenses, including total phenols, flavonoids, jasmonic acid, tannin, H2O2, and total antioxidant capacity (TAC), and lower soluble protein concentrations than native plants. After leaf damage, compared to native plants, the leaves of invasive plants showed an overall increase in substances associated with defense, except for soluble sugar. Discussion: These results suggest that invasive plants maintain active defense strategies in invaded areas, leading to changes in the distribution patterns of herbivorous insects in a manner that facilitates invasion.

20.
Cardiovasc Toxicol ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008240

ABSTRACT

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.

SELECTION OF CITATIONS
SEARCH DETAIL