Energy-intensive industries are a priority for achieving low-carbon economic growth in China, and a large number of government R&D subsidies have been injected into energy-intensive firms to support ...green innovation in recent years. Most of the existing literature has studied the impacts of R&D subsidies on the general innovation of high-tech firms or emerging enterprises. This paper explores the impacts of government R&D subsidies on the green innovation of energy-intensive firms. By employing propensity score matching with 527 samples of listed companies from 2010 to 2015, the empirical results show that government R&D subsidies increase the green innovation of energy-intensive firms, specifically their tendency and performance, by 107.3% and 54.1%, respectively. Heterogeneity analyses show that the impact is stronger in state-owned enterprises and in small and medium enterprises. Finally, some practical implications are put forward that may help to improve the efficiency of government R&D subsidies and promote the green innovation of energy-intensive firms.
•The impacts of government R&D subsidies on the green innovation of energy-intensive firms are analyzed.•The firm-level impacts are investigated.•The firm-level impacts are investigated.Government R&D subsidies significantly increase the green innovation tendency and performance of energy-intensive firms.•The impact is stronger in state-owned enterprises and in small and medium enterprises (SMEs).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although 5-fluorouracil (5-FU) is the primary chemotherapy treatment for colorectal cancer (CRC), its efficacy is limited by drug resistance. Ferroptosis activation is a promising treatment for ...5-FU-resistant cancer cells; however, potential therapeutic targets remain elusive. This study investigated ferroptosis vulnerability and dihydroorotate dehydrogenase (DHODH) activity using stable, 5-FU-resistant CRC cell lines and xenograft models. Ferroptosis was characterized by measuring malondialdehyde levels, assessing lipid metabolism and peroxidation, and using mitochondrial imaging and assays. DHODH function is investigated through gene knockdown experiments, tumor behavior assays, mitochondrial import reactions, intramitochondrial localization, enzymatic activity analyses, and metabolomics assessments. Intracellular lipid accumulation and mitochondrial DHODH deficiency led to lipid peroxidation overload, weakening the defense system of 5-FU-resistant CRC cells against ferroptosis. DHODH, primarily located within the inner mitochondrial membrane, played a crucial role in driving intracellular pyrimidine biosynthesis and was redistributed to the cytosol in 5-FU-resistant CRC cells. Cytosolic DHODH, like its mitochondrial counterpart, exhibited dihydroorotate catalytic activity and participated in pyrimidine biosynthesis. This amplified intracellular pyrimidine pools, thereby impeding the efficacy of 5-FU treatment through molecular competition. These findings contribute to the understanding of 5-FU resistance mechanisms and suggest that ferroptosis and DHODH are promising therapeutic targets for patients with CRC exhibiting resistance to 5-FU.
Intracellular lipid accumulation leads to lipid peroxidation overload, while mitochondrial DHODH deficiency weakens the ferroptosis defense system. This dual vulnerability makes 5-FU-resistant CRC cells susceptible to ferroptosis. Moreover, the redistribution of mitochondrial DHODH to the cytosol increases intracellular pyrimidine pools, impairing the effectiveness of 5-FU through molecular competition. Targeting ferroptosis or DHODH has emerged as a novel therapeutic avenue for treating patients with CRC exhibiting resistance to 5-FU therapies. Display omitted
•The susceptibility of 5-FU-resistant CRC to ferroptosis is attributed to the combination of lipid accumulation and mitochondrial DHODH deficiency.•Cytosolic DHODH, like its mitochondrial counterpart, catalyzes dihydroorotate and is involved in pyrimidine biosynthesis.•Ferroptosis and DHODH could be therapeutic targets for 5-FU-resistant CRC patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Soybean agglutinin (SBA) is a primary antinutritional factor in soybeans that can inhibit the growth of humans and mammals, disrupt the intestinal environment, and cause pathological changes. ...Therefore, detecting and monitoring SBA in foods is essential for safeguarding human health. In this paper, M13 phage-displayed nanobodies against SBA were isolated from a naive nanobody library. An M13 phage-displayed nanobody-based competitive enzyme-linked immunosorbent assay (P-cELISA) was then established for SBA analysis using biotinylated anti-M13 phage antibody (biotin-anti-M13) and streptavidin poly-HRP conjugate (SA-poly-HRP). The biotin-anti-M13@SA-poly-HRP probe can easily amplify the detection signal without the chemical modifications of phage-displayed nanobodies. The established P-cELISA presented a linear detection range of 0.56–250.23 ng/mL and a limit of detection (LOD) of 0.20 ng/mL, which was 12.6-fold more sensitive than the traditional phage-ELISA. Moreover, the developed method showed good specificity for SBA and acceptable recoveries (78.21–121.11%) in spiked wheat flour, albumen powder, and whole milk powder. This study proposes that P-cELISA based on biotin-anti-M13@SA-poly-HRP may provide a convenient and effective strategy for the sensitive detection of SBA.
We report on the construction of PdAg/reduced graphene oxide (rGO)-based electrochemical H2O2 sensors by exploiting the high surface area and fast electron transfer rate of rGO, as well as the high ...electrocatalytic activity of palladium-silver nanoparticles. The nanocomposites were prepared via a one-step reduction method and characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), Fourier transform spectroscopy (FTIR), and X-ray diffraction (XRD) techniques. The performance of the sensors was evaluated by cyclic voltammetry and chronoamperometry methods. The SEM images showed that the constructed nanocomposites had three-dimensional structure (3D), which both provided large specific surface area for the electrochemical reactions and enhanced the transports of the analyte on the sensors surface. The PdAg/rGO sensors had a high sensitivity of 247.6 ± 2.7 μA·mM−1·cm−2 and the 3D structure of rGO along with the high electrocatalytic activity of PdAg nanoparticles allowed the detection of H2O2 in a wide concentration range from 0.05 mM to 28 mM. To evaluate the selectivity of the sensors, the analytical response toward the exposure of H2O2, ascorbic acid, uric acid, and glucose were measured. The practical applicability of PdAg/rGO-based sensor design was studied in human serum.
Ovarian epithelial cancer is a gynecological tumor with a high risk of recurrence and death. In the clinical diagnosis of ovarian epithelial cancer, CA125 has become an important indicator of disease ...burden. To account for patient recurrence and death, a proper method is needed to integrate information from biomarkers and recurrence simultaneously. In the past 10 years, many methods have been proposed for joint modeling of longitudinal biomarkers and survival data, but few of them are applicable to longitudinal data and disease processes, including recurrence and death. In this article, we proposed a new joint frailty model based on functional principal component analysis for dynamic prediction of survival probabilities on the total time scale, which took recurrent history and longitudinal data into account simultaneously. The estimation of the joint frailty model is achieved by maximizing the penalized log‐likelihood function. The simulation results demonstrated the advantages of our method in both discrimination and accuracy under different scenarios. To indicate the method's practicality, it is applied to an actual dataset of patients with ovarian epithelial cancer to predict survival dynamically using longitudinal data of biomarker CA125 and recurrent history data.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cysteine (Cys) plays a significant role in the stability and antioxidant capacity of peptide. This study was to prepare Cys-rich collagen peptide and evaluate its preventive effect on microparticle ...(MPs)-induced HK-2 cell damage. The results showed that the Cys-rich peptides (AMP-C) were successfully prepared from collagen hydrolysate by plastein reaction in the presence of exogenous Cys. The scavenging activities of 2,2-Diphenyl-1-picrylhydrazyl and hydroxyl radical of AMP-C were significantly higher than those of original peptides without Cys. The fraction with molecular weight <3 kDa (AMP-CA) significantly improved MPs-induced damage and apoptosis of HK-2 cells. Compared with the same fractions lacking Cys (AMP-A), AMP-CA showed better performance in reducing reactive oxygen species and increasing the total superoxide dismutase and glutathione peroxidase levels, which may be related to its down-regulation of Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, AMP-CA showed strong effects on inhibiting interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, kidney injury molecule-1, and nuclear factor kappa-B levels. Finally, 330 Cys-containing peptides were isolated from AMP-CA, among which Leucine-Glycine-Asparagine-Glycine-Cysteine-Proline (LGNGCP) showed the lowest binding energy with Keap1 protein. In conclusion, the Cys-rich collagen peptide with higher antioxidant activity was successfully prepared by plastein reaction, which alleviated the HK-2 cells damage induced by MPs through antioxidant and anti-inflammatory. Our findings suggested that Cys-rich collagen peptide might be used as a functional food to mitigate health hazards associated with MPs accumulation.
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•The cysteine-rich peptides (AMP-C) were prepared from skin collagen hydrolysates by plastein reaction.•The fraction with Mw < 3 kDa (AMP-CA) in AMP-C exhibited the excellent antioxidant properties and stability.•AMP-CA prevented microplastic-induced HK-2 cells damage through antioxidant and anti-inflammatory effects.•Peptide LGNGCP with high affinity to Keap1 were identified from AMP-CA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The dual activation mechanism of molecular oxygen (O
2
) and water (H
2
O) in the local structure of catalysts has not been elucidated yet. Herein, we report a strategy for manufacturing fully ...exposed Ag
4
sites in nano silver/graphdiyne (Ag/GDY) composites for activating O
2
and H
2
O. The synthesized nano Ag was uniformly anchored on the surface of GDY without any surfactant added, with an average particle size of 2.5 nm. The unique sp-hybrid C and triangular pore structure of GDY not only regulate the stable geometric structure of nano Ag, but also enhance the adsorption ability of Ag
4
sites for O
2
and H
2
O molecules in nano Ag/GDY. Electron spin resonance spectroscopy and density functional theory calculation results proved that O
2
is more favorable to synergistically promote the activation of H
2
O to generate reactive ·O
2
−
and ·OH radicals on the nano Ag/GDY surfaces, leading to outstanding antibacterial activity. This work provides a simple strategy for the preparation of stable nano Ag and proposes to improve the catalytic oxidation activity by adjusting the local electronic structure of catalysts to activate O
2
and H
2
O.
This work revealed the dual activation mechanism of O
2
and H
2
O on nano Ag/GDY and the excellent antibacterial efficiency.
