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After a large-scale radiological or nuclear event, hundreds of thousands of people may be exposed to ionizing radiation and require subsequent medical management. Acute exposure to moderate doses (2-6 Gy) of radiation can lead to the hematopoietic acute radiation syndrome, in which the bone marrow (BM) is severely compromised, and severe hemorrhage and infection are common. Previously, we have developed a panel of intracellular protein markers (FDXR, ACTN1, DDB2, BAX, p53 and TSPYL2), designed to reconstruct absorbed radiation dose from human peripheral blood (PB) leukocyte samples in humanized mice up to 3 days after exposure. The objective of this work was to continue to use the humanized mouse model to evaluate biomarker dose-/time- kinetics in human PB leukocytes in vivo, at an earlier (day 2) and later (day 7) time point, after exposure to total-body irradiation (TBI) doses of 0 to 2 Gy of X rays. In addition, to assess hematological sensitivity and radiation-induced injury, PB leukocyte cell counts, human BM hematopoietic stem cell (HSC) and progenitor cell [multipotent progenitor (MPP), common myeloid progenitor (CMP), granulocyte myeloid progenitor (GMP), megakaryocyte/erythrocyte progenitor (MEP) and multi-lymphoid progenitor (MLP)] levels were measured, and their correlation was also examined as the BM damages are difficult to assess by routine tests. Peripheral blood B-cells were significantly lower after TBI doses of 0.5 Gy on day 2 and 2 Gy on days 2 and 7; T-cells were significantly reduced only on day 2 after 2 Gy TBI. Bone marrow HSCs and MPP cells showed a dose-dependent depletion after irradiation with 0.5 Gy and 2 Gy on day 2, and after 1 Gy and 2 Gy on day 7. Circulating B cells correlated with HSCs, MPP and MLP cells on day 2, whereas T cells correlated with MPP, and myeloid cells correlated with MLP cells. On day 7, B cells correlated with MPP, CMP, GMP and MEP, while myeloid cells correlated with CMP, GMP and MEP. The intracellular leukocyte biomarkers were able to discriminate unirradiated and irradiated samples at different time points calculated by receiver operating characteristic (ROC) curve. Using machine learning algorithm methods, combining ACTN1, p53, TSPYL2 and PB-T cell and PB-B cell counts served as a strong predictor (area under the ROC >0.8) to distinguish unirradiated and irradiated samples independent of the days after TBI. The results further validated our biomarker-based triage assay and additionally evaluated the radiation sensitivity of the hematopoietic system after TBI exposures.
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INTRODUCTION: Heart failure is a common chronic illness associated with high readmission rates and death. Comprehensive nursing care, management of symptoms, and psychological support are increasingly seen as critical components of successful heart failure therapy. OBJECTIVE: This systematic review and meta-analysis aimed to determine the effect of comprehensive nursing care on clinical outcomes and quality of life in heart failure patients. METHODS: We searched electronic databases (Pubmed, PROSPERO, and Web of Science) for randomised controlled trials and observational studies on comprehensive nursing care treatments for heart failure patients. Data on readmission rates, mortality rates and quality of life were obtained and examined. RESULTS: 693 studies satisfied the inclusion criteria. A meta-analysis found that comprehensive nursing care reduced heart failure-related readmissions considerably when compared to conventional therapy (odds ratio (OR) 0.77 (95% CI 0.66-0.88, P =.0002). There was a significant difference in all-cause mortality (OR 0.76 (95% CI: 0.60-0.97, P=.03), but comprehensive treatment enhanced quality of life and functional status (Standardised Mean Difference -0.05, 95% CI -0.21 to 0.10, P =.49). CONCLUSION: Comprehensive nursing care improves clinical outcomes and quality of life for heart failure patients. This study stresses the need to add comprehensive nurse interventions in normal heart failure treatment programmes.
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The piezoelectric properties of two-dimensional semiconductor nanobubbles present remarkable potential for application in flexible optoelectronic devices, and the piezoelectric field has emerged as an efficacious pathway for both the separation and migration of photogenerated electron-hole pairs, along with inhibition of recombination. However, the comprehension and control of photogenerated carrier dynamics within nanobubbles still remain inadequate. Hence, this study is dedicated to underscore the importance of in situ detection and detailed characterization of photogenerated electron-hole pairs in nanobubbles to enrich understanding and strategic manipulation in two-dimensional semiconductor materials. Utilizing frequency modulation kelvin probe force microscopy (FM-KPFM) and strain gradient distribution techniques, the existence of a piezoelectric field in monolayer WS2 nanobubbles was confirmed. Combining w/o and with illumination FM-KPFM, second-order capacitance gradient technique and in situ nanoscale tip-enhanced photoluminescence characterization techniques, the interrelationships among the piezoelectric effect, interlayer carrier transfer, and the funneling effect for photocarrier dynamics process across various nanobubble sizes were revealed. Notably, for a WS2/graphene bubble height of 15.45 nm, a 0 mV surface potential difference was recorded in the bubble region w/o and with illumination, indicating a mutual offset of piezoelectric effect, interlayer carrier transfer, and the funneling effect. This phenomenon is prevalent in transition metal dichalcogenides materials exhibiting inversion symmetry breaking. The implication of our study is profound for advancing the understanding of the dynamics of photogenerated electron-hole pair in nonuniform strain piezoelectric systems, and offers a reliable framework for the separation and modulation of photogenerated electron-hole pair in flexible optoelectronic devices and photocatalytic applications.
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Photoelectrochemical (PEC) water splitting provides a scalable and integrated platform to harness renewable solar energy for green hydrogen production. The practical implementation of PEC systems hinges on addressing three critical challenges: enhancing energy conversion efficiency, ensuring long-term stability, and achieving economic viability. Metal-insulator-semiconductor (MIS) heterojunction photoelectrodes have gained significant attention over the last decade for their ability to efficiently segregate photogenerated carriers and mitigate corrosion-induced semiconductor degradation. This review discusses the structural composition and interfacial intricacies of MIS photoelectrodes tailored for PEC water splitting. The application of MIS heterostructures across various semiconductor light-absorbing layers, including traditional photovoltaic-grade semiconductors, metal oxides, and emerging materials, is presented first. Subsequently, this review elucidates the reaction mechanisms and respective merits of vacuum and non-vacuum deposition techniques in the fabrication of the insulator layers. In the context of the metal layers, this review extends beyond the conventional scope, not only by introducing metal-based cocatalysts, but also by exploring the latest advancements in molecular and single-atom catalysts integrated within MIS photoelectrodes. Furthermore, a systematic summary of carrier transfer mechanisms and interface design principles of MIS photoelectrodes is presented, which are pivotal for optimizing energy band alignment and enhancing solar-to-chemical conversion efficiency within the PEC system. Finally, this review explores innovative derivative configurations of MIS photoelectrodes, including back-illuminated MIS photoelectrodes, inverted MIS photoelectrodes, tandem MIS photoelectrodes, and monolithically integrated wireless MIS photoelectrodes. These novel architectures address the limitations of traditional MIS structures by effectively coupling different functional modules, minimizing optical and ohmic losses, and mitigating recombination losses.
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Xylanases have broad applications in the food industry to decompose the complex carbohydrate xylan. This is applicable to enhance juice clarity, improve dough softness, or reduce beer turbidity. It can also be used to produce prebiotics and increase the nutritional value in foodstuff. However, the low yield and poor stability of most natural xylanases hinders their further applications. Therefore, it is imperative to explore higher-quality xylanases to address the potential challenges that appear in the food industry and to comprehensively improve the production, modification, and utilization of xylanases. Xylanases, due to their various sources, exhibit diverse characteristics that affect production and activity. Most fungi are suitable for solid-state fermentation to produce xylanases, but in liquid fermentation, microbial metabolism is more vigorous, resulting in higher yield. Fungi produce higher xylanase activity, but bacterial xylanases perform better than fungal ones under certain extreme conditions (high temperature, extreme pH). Gene and protein engineering technology helps to improve the production efficiency of xylanases and enhances their thermal stability and catalytic properties.
Subject(s)
Endo-1,4-beta Xylanases , Fermentation , Food Industry , Fungi , Endo-1,4-beta Xylanases/metabolism , Endo-1,4-beta Xylanases/genetics , Fungi/enzymology , Fungi/genetics , Bacteria/enzymology , Bacteria/genetics , Protein Engineering , Enzyme Stability , Fungal Proteins/metabolism , Fungal Proteins/genetics , Xylans/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/geneticsABSTRACT
Developing a high-performance activator is crucial for the practical application of peroxymonosulfate-based advanced oxidation processes (PMS-AOPs). High-entropy oxides (HEOs) have attracted increasing attention due to their stable crystal structure, flexible composition and unique functionality. However, research into the mechanisms by which HEOs function as PMS activators for degrading organic pollutants remains insufficient, and the relationship between entropy and the catalytic performance of HEOs has yet to be clarified. In this study, we synthesized NiMgZnCuCoOx with different levels of entropy as PMS activators for acetaminophen (APAP) degradation, and observed a significant effect for entropy on the catalytic performance. Sulfate radicals (SO4â¢â) were identified as the primary reactive oxygen species (ROS), while hydroxyl radicals (â¢OH) and singlet oxygen (1O2) act as secondary ROS during APAP degradation. Both the Co2+ contents and the oxygen vacancy concentration in NiMgZnCuCoOx are found to increase with the entropy. An increase in the Co2+ sites leads to more activation sites for PMS activation, while excessive oxygen vacancies consume PMS, producing weak oxidation species, and affect the electron-donating ability of Co2+. Consequently, the NiMgZnCuCoOx with middle level of entropy exhibits the optimal performance with APAP degradation rate and mineralization rate reaching 100% and 74.22%, respectively. Furthermore, the degradation intermediates and their toxicities were assessed through liquid chromatography-mass spectrometry and quantitative structure-activity relationship analysis. This work is expected to provide critical insight into the impact of the HEOs entropy on the PMS activation and guide the rational design of highly efficient peroxymonosulfate activators for environmental applications.
Subject(s)
Acetaminophen , Entropy , Oxidation-Reduction , Oxides , Peroxides , Acetaminophen/chemistry , Catalysis , Peroxides/chemistry , Oxides/chemistry , Reactive Oxygen Species/metabolism , Sulfates/chemistryABSTRACT
SnPb solder was widely used in electronic packaging for aerospace devices due to its high reliability. However, its creep resistance is poor and can be improved by adding alloying elements. The effects of Sb content on the microstructure, tensile, and creep properties of eutectic SnPb solder were investigated. Sb addition effectively improved the mechanical properties of the SnPb solder. When Sb content exceeds 1.7 wt.%, SbSn intermetallic compounds (IMCs) occurred. And increasing the Sb content increased the tensile strength. Furthermore, Sb addition decreased the steady-state creep rate and increased the stress exponent n, suggesting that the creep resistance had been enhanced, which may be attributed to the hindrance of dislocation movement by SbSn IMCs, as well as the reduction in phase boundaries, which consequently reduced grain boundary sliding.
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Pear residue, a byproduct of pear juice extraction, is rich in soluble sugar, vitamins, minerals, and cellulose. This study utilized Monascus anka in liquid fermentation to extract dietary fiber (DF) from pear residue, and the structural and functional characteristics of the DF were analyzed. Soluble DF (SDF) content was increased from 7.9/100 g to 12.6 g/100 g, with a reduction of average particle size from 532.4 to 383.0 nm by fermenting with M. anka. Scanning electron microscopy and infrared spectroscopic analysis revealed more porous and looser structures in Monascus pear residue DF (MPDF). Water-, oil-holding, and swelling capacities of MPDF were also enhanced. UV-visible spectral analysis showed that the yield of yellow pigment in Monascus pear residue fermentation broth (MPFB) was slightly higher than that in the Monascus blank control fermentation broth. The citrinin content in MPFB and M. anka seed broth was 0.90 and 0.98 ug/mL, respectively. Therefore, liquid fermentation with M. anka improved the structural and functional properties of MPDF, suggesting its potential as a functional ingredient in food.
Subject(s)
Dietary Fiber , Fermentation , Monascus , Pyrus , Monascus/metabolism , Monascus/chemistry , Dietary Fiber/analysis , Pyrus/chemistry , Pigments, Biological/analysis , Citrinin/analysis , Fruit/chemistry , Microscopy, Electron, Scanning , Particle SizeABSTRACT
Hippocampal neural stem/progenitor cells (NSPCs) are highly vulnerable to different stress stimuli, resulting in adult neurogenesis decline and eventual cognitive defects. Our previous study demonstrated that NOD-like receptor family pyrin domain-containing 6 (Nlrp6) highly expressed in NSPCs played a critical role in sustaining hippocampal neurogenesis to resist stress-induced depression, but the underlying mechnistms are still unclear. Here, we found that Nlrp6 depletion led to cognitive defects and hippocampal NSPC loss in mice. RNA-sequencing analysis of the primary NSPCs revealed that Nlrp6 deficiency altered gene expression profiles of mitochondrial energy generation and ferroptotic process. Upon siNlrp6 transfection, as well as corticosterone (CORT) exposure, downregulation of Nlrp6 suppressed retinoic acid-inducible gene I (RIG-1)/mitochondrial antiviral signaling proteins (MAVS)-mediated autophagy, but drove NSPC ferroptotic death. More interesting, short chain fatty acids (SCFAs) upregulated Nlrp6 expression and promoted RIG-1/MAVS-mediated mitophagy, preventing CORT-induced NSPC ferroptosis. Our study further demonstrates that Nlrp6 should be a sensor for RIG-1/MAVS-mediated mitophagy and play a critical role in maintain mitochondrial homeostasis of hippocampal NSPCs. These results suggests that Nlrp6 should be a potential drug target to combat neurodegenerative diseases relative with chronic stress.
Subject(s)
Adaptor Proteins, Signal Transducing , Corticosterone , DEAD Box Protein 58 , Ferroptosis , Mitophagy , Neural Stem Cells , Animals , Mice , DEAD Box Protein 58/metabolism , DEAD Box Protein 58/genetics , Corticosterone/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Neural Stem Cells/metabolism , Hippocampus/metabolism , Mitochondria/metabolism , Signal Transduction , Receptors, Cell SurfaceABSTRACT
BACKGROUND AND AIMS: The potential influence of left atrial size on the relationship between uric acid and atrial fibrillation has not been fully investigated. This study aims to evaluate the interaction effect of left atrial size on the association between uric acid and atrial fibrillation in patients with coronary artery disease. METHODS AND RESULTS: This retrospective cohort study, conducted from January 2018 to October 2022, included 2004 patients undergoing Drug-Eluting Stent implantation for coronary artery disease. Utilizing logistic regression models with the product of left atrial enlargement (LAE) and uric acid, interaction effects were assessed. Among the participants, 383 had LAE, and 159 experienced atrial fibrillation. After adjusting for covariates, continuous uric acid levels were associated with an increased risk of atrial fibrillation in patients without LAE (OR:1.631, 95% CI: 1.284-2.072), but not in those with LAE (OR:1.069, 95% CI: 0.848-1.348). A significant interaction of uric acid levels was observed between groups with and without LAE (p = 0.046). Restricted cubic spline curves indicated a J-shaped relationship between uric acid and atrial fibrillation in the absence of LAE. However, the association between uric acid levels and atrial fibrillation in the LAE group remained unchanged with increasing uric acid levels. CONCLUSION: The study suggested that left atrial size modified the association between uric acid and atrial fibrillation in patients with coronary artery disease. Uric acid serves as a potential biomarker for atrial fibrillation risk, especially in individuals without LAE.
Subject(s)
Atrial Fibrillation , Biomarkers , Coronary Artery Disease , Heart Atria , Uric Acid , Humans , Atrial Fibrillation/blood , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Uric Acid/blood , Male , Female , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Middle Aged , Retrospective Studies , Aged , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Risk Factors , Biomarkers/blood , Risk Assessment , Percutaneous Coronary Intervention/adverse effects , Hyperuricemia/blood , Hyperuricemia/diagnosis , Hyperuricemia/epidemiology , Drug-Eluting Stents , Atrial Remodeling , Atrial Function, LeftABSTRACT
We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.
Subject(s)
Neuroendocrine Tumors , Pituitary Neoplasms , Humans , Panobinostat/pharmacology , Panobinostat/therapeutic use , NF-E2-Related Factor 2/genetics , Neuroendocrine Tumors/drug therapy , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Signal TransductionABSTRACT
The non-free radical oxidation pathway (PMS-NOPs) of peroxymonosulfate (PMS) holds significant promise for practical wastewater treatment applications, owing to its low oxidation potential, high PMS utilization rate, and robust anti-interference capability in the degradation of pollutants. A novel activator copper nitrogen co-doped porous biochar (Cu-N-BC) with rich defect edges and functional groups was obtained by adding Cu and N to the biochar matrix generated by sodium alginate through pyrolysis in this study. Under the condition of 1 mM PMS, 30 mg/L activator was used to activate PMS and achieve efficient degradation of 10 mg/L paracetamol (PCT) within 15 min, with a high reaction rate constants (kobs) of 0.391 min-1. The activation mechanism of the Cu-N-BC/PMS/PCT system was a non-radical activation pathway with the dominance of singlet oxygen (1O2) and the presence of catalyst-mediated electron transfer. The graphite nitrogen, pyridine nitrogen, and Cu-N coordination introduced by Cu/N co-doping, as well as the carbon skeleton and CO functional group of biochar, were considered active sites that promote the 1O2 generation. The Cu-N-BC/PMS system exhibits strong stability, eco-friendliness, effective mineralization, and interference resistance across diverse pH levels (3-11) and interfering ions, including Cl-, H2PO4-, NO3-, SO42-, and humic acid. Remarkably, it efficiently degrades PCT in tap and lake water, achieving a notable 63.73% TOC mineralization rate, with leached copper ions below 0.02 mg/L. This research introduces a novel method for obtaining metal nitrogen carbon activators and enhances understanding of PMS non-radical activation pathways and active sites.
Subject(s)
Acetaminophen , Charcoal , Copper , Nitrogen , Oxidation-Reduction , Peroxides , Singlet Oxygen , Water Pollutants, Chemical , Charcoal/chemistry , Copper/chemistry , Acetaminophen/chemistry , Water Pollutants, Chemical/chemistry , Singlet Oxygen/chemistry , Nitrogen/chemistry , Peroxides/chemistry , Electron Transport , Wastewater/chemistry , CatalysisABSTRACT
BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. METHODS: The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. RESULTS: The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. CONCLUSIONS: In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.
Subject(s)
Macrophages , Neuroendocrine Tumors , Pituitary Neoplasms , Single-Cell Analysis , Transcriptome , Tumor Microenvironment , Humans , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/immunology , Neuroendocrine Tumors/metabolism , Pituitary Neoplasms/genetics , Pituitary Neoplasms/immunology , Pituitary Neoplasms/pathology , Pituitary Neoplasms/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Animals , Mice , Macrophages/metabolism , Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Phenotype , Apoptosis/genetics , Cell Lineage/geneticsABSTRACT
We propose using physical-informed neural network (PINN) for power evolution prediction in bidirectional Raman amplified WDM systems with Rayleigh backscattering (RBS). Unlike models based on data-driven machine learning, PINN can be effectively trained without preparing a large amount of data in advance and can learn the potential rules of power evolution. Compared to previous applications of PINN in power prediction, our model considers bidirectional Raman pumping and RBS, which is more practical. We experimentally demonstrate power evolution prediction of 200â km bidirectional Raman amplified wavelength-division multiplexed (WDM) system with 47 channels and 8 pumps using PINN. The maximum prediction error of PINN compared to experimental results is only 0.38â dB, demonstrating great potential for application in power evolution prediction. The power evolution predicted by PINN shows good agreement with the results simulated by traditional numerical method, but its efficiency is more suitable for establishing models and calculating noise, providing convenience for subsequent power configuration optimization.
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Dendrobium officinale is an important traditional Chinese medicinal herb containing bioactive polysaccharides and alkaloids. This study characterized metabolite differences between jiaosu (fermented plant product) from Dendrobium flowers versus stems using untargeted metabolomics. The jiaosu was fermented by mixed fermentation of Saccharomyces cerevisiae, Lactobacillus bulgaricus and Streptococcus thermophilus. Liquid chromatography-mass spectrometry analysis identified 476 differentially expressed metabolites between the two Jiaosu products. Key results showed downregulation of flavonoid metabolism in Dendrobium Stems Edible Plant Jiaosu (SEP) but increased flavonoid synthesis in Dendrobium Flowers Edible Plant Jiaosu (FEP), likely an antioxidant response. SEP displayed upregulation of lignin metabolites with potential antioxidant properties. The findings demonstrate significant metabolite profile differences between SEP and FEP, providing the basis for developing functional jiaosu products targeting specific health benefits.
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BACKGROUND: How to comprehensively evaluate the rationality of drug use is a challenging issue. OBJECTIVE: To establish the evaluation index of the effective use of tislelizumab, so as to ensure its higher rationality and normalization in clinical application. METHODS: Based on the indications, drug instructions, and relevant guidelines of the National Basic Medical Insurance Restriction Catalogue, a retrospective analysis and evaluation of 286 cases of using tislelizumab injection in our hospital from January to December 2022 were conducted using the weighted technique for order of preference by similarity to ideal solution (TOPSIS) method. RESULTS: Among the 286 medical records evaluated, the main irrational manifestations were inappropriate indications (90 cases, 31.47%), auxiliary examination and laboratory examination did not meet the minimum requirements of combination chemotherapy drugs (40 cases, 13.99%), the drug course was not standard (39 cases, 13.64%). Among the included cases, 57.34% were reasonable cases (Ci⩾ 0.8), 10.84% were basic reasonable cases (0.6 ⩽Ci< 0.8), and 31.82% were unreasonable cases (Ci< 0.6). CONCLUSION: The TOPSIS method, with its attribute hierarchical model (AHM)-weighted approach, can be employed as the rational assessment technique for the injection of tislelizumab. The clinical application of tislelizumab in our hospital is still insufficient, which needs to be further improved management.
Subject(s)
Antibodies, Monoclonal, Humanized , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Retrospective Studies , Female , Male , Middle Aged , Drug Utilization/statistics & numerical data , Adult , AgedABSTRACT
Metal oxide semiconductor hetero- and homojunctions are commonly constructed to improve the performance of hydrogen sensors at room temperature. In this study, a simple two-step hydrothermal method was employed to prepare TiO2 films with homojunctions of rutile and anatase phases (denoted as TiO2-R/A). Then, the microstructure of anatase-phase TiO2 was altered by controlling the amount of hydrochloric acid to realize a more favorable porous structure for charge transport and a larger surface area for contact with H2. The sensor used a Pt interdigital electrode. At an optimal HCl dosage (25 mL), anatase-phase TiO2 uniformly covered rutile-phase TiO2 nanorods, resulting in a greater response to H2 at 2500 ppm compared with that of a rutile TiO2 nanorod sensor by a factor of 1153. The response time was 21 s, mainly because the homojunction formed by the TiO2 rutile and anatase phases increased the synergistic effect of the charge transfer and potential barrier between the two phases, resulting in the formation of more superoxide (O2-) free radicals on the surface. Furthermore, the porous structure increased the surface area for H2 adsorption. The TiO2-R/A-based sensor exhibited high selectivity, long-term stability, and a fast response. This study provides new insights into the design of commercially competitive hydrogen sensors.
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According to recent research, metabolic-associated fatty liver disease (MAFLD) has emerged as an important underlying etiology of hepatocellular carcinoma (HCC). However, the molecular mechanism of MAFLD-HCC is still unclear. Tumor necrosis factor receptor-associated factor 2 (TRAF2) is the key molecule to mediate the signal of inflammatory NF-κB pathway. This study aims to investigate the potential dysregulation of TRAF2 and its biological function in MAFLD-HCC. Huh7 TRAF2-/- demonstrated increased tumor formation ability compared to huh7 TRAF2+/+ when stimulated with transforming growth factor-ß (TGF-ß). The decisive role of TGF-ß in the development of MAFLD-HCC was confirmed through the specific depletion of TGF-ß receptor II gene in the hepatocytes (Tgfbr2ΔHep) of mice. In TRAF2-/- cells treated with TGF-ß, both the glycolysis rate and lipid synthesis were enhanced. We proved the signal of the mechanistic target of rapamycin complex 1 (mTORC1) could be activated in the presence of TGF-ß, and was enhanced in TRAF2-/- cells. The coimmunoprecipitation (co-IP) experiments revealed that TRAF2 fortified the Smurf2-mediated ubiquitination degradation of AXIN1. Hence, TRAF2 depletion resulted in increased Smad7 degradation induced by AXIN1, thus promoting the TGF-ß signal. We also discovered that PLX-4720 could bind with AXIN1 and restrained the tumor proliferation of TRAF2-/- in mice fed with high-fat diet (HFD). Our findings indicate that TRAF2 plays a significant role in the pathogenesis of MAFLD-HCC. The reduction of TRAF2 expression leads to the enhancement of the TGF-ß-mTORC1 pathway by facilitating AXIN1-mediated Smad7 degradation.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Mice , Animals , Carcinoma, Hepatocellular/metabolism , Transforming Growth Factor beta/metabolism , TNF Receptor-Associated Factor 2/genetics , TNF Receptor-Associated Factor 2/metabolism , Liver Neoplasms/metabolism , Hepatocytes/metabolism , Smad7 Protein/genetics , Smad7 Protein/metabolismABSTRACT
Recycled PET (rPET) is gaining popularity for use in the production of new food contact materials (FCMs) under the context of circular economy. However, the limited information on contaminants in rPET from China and concerns about their potential risk are major obstacles to their use in FCM in China. Fifty-five non-volatile compounds were tentatively identified in 126 batches of hot-washed rPET flakes aimed for food packaging applications in China. Although the 55 substances are not necessarily migratable and may not end up in the contacting media, their presence indicates a need for proper management and control across the value chain. For this reason, the 55 substances prioritized on the basis of level of concerns and in-silico genotoxicity profiler. Among them, dimethoxyethyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate were classified as level V substances, and Michler's ketone and 4-nitrophenol were both categorized as level V substances and had the genotoxic structure alert, while 2,4,5-trimethylaniline was specified with genotoxic structure alert. The above substances have high priority and may pose a potential risk to human health, therefore special attention should be paid to their migration from rPET. Aside from providing valuable information on non-volatile contaminants present in hot-washed rPET flakes coming from China, this article proposed a prioritization workflow that can be of great help to identify priority substances deserving special attention across the value chain.
Subject(s)
Dibutyl Phthalate , Food Contamination , Humans , China , Dibutyl Phthalate/analysis , Food Contamination/analysis , RecyclingABSTRACT
Intestinal injury is one of the most debilitating side effects of many chemotherapeutic agents, such as irinotecan hydrochloride (CPT-11). Accumulating evidence indicates that neutrophil extracellular traps (NETs) play a critical role in the symptoms of ischemia and inflammation related to chemotherapy. The present study investigated the effects and possible mechanisms of phenethyl isothiocyanate (PEITC) in inhibiting NETs and alleviating chemotherapeutic intestinal injury. CPT-11 induced robust neutrophil activation, as evidenced by increased NETs release, intestinal ischemia, and mRNA expression of inflammatory factors. PEITC prolonged the clotting time of chemotherapeutic mice, improved the intestinal microcirculation, inhibited the expression of inflammatory factors, and protected the tight junctions of the intestinal epithelium. Both in vivo and in vitro experiments revealed that PEITC directly suppresses CPT-11-induced NETs damage to intestinal cells, resulting in significant attenuation of epithelial injury. These results suggest that PEITC may be a novel agent to relieve chemotherapeutic intestinal injury via inhibition of NETs.