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Studying specific subpopulations of cancer-derived extracellular vesicles (EVs) could help reveal their role in cancer progression. In cancer, an increase in reactive oxygen species (ROS) happens which results in lipid peroxidation with a major product of 4-hydroxynonenal (HNE). Adduction by HNE causes alteration to the structure of proteins, leading to loss of function. Blebbing of EVs carrying these HNE-adducted proteins as a cargo or carrying HNE-adducted on EV membrane are methods for clearing these molecules by the cells. We have referred to these EVs as Redox EVs. Here, we utilize a surface tension-mediated extraction process, termed exclusion-based sample preparation (ESP), for the rapid and efficient isolation of intact Redox EVs, from a mixed population of EVs derived from human glioblastoma cell line LN18. After optimizing different parameters, two populations of EVs were analyzed, those isolated from the sample (Redox EVs) and those remaining in the original sample (Remaining EVs). Electron microscopic imaging was used to confirm the presence of HNE adducts on the outer leaflet of Redox EVs. Moreover, the population of HNE-adducted Redox EVs shows significantly different characteristics to those of Remaining EVs including smaller size EVs and a more negative zeta potential EVs. We further treated glioblastoma cells (LN18), radiation-resistant glioblastoma cells (RR-LN18), and normal human astrocytes (NHA) with both Remaining and Redox EV populations. Our results indicate that Redox EVs promote the growth of glioblastoma cells, likely through the production of H2O2, and cause injury to normal astrocytes. In contrast, Remaining EVs have minimal impact on the viability of both glioblastoma cells and NHA cells. Thus, isolating a subpopulation of EVs employing ESP-based immunoaffinity could pave the way for a deeper mechanistic understanding of how subtypes of EVs, such as those containing HNE-adducted proteins, induce biological changes in the cells that take up these EVs. [ABSTRACT FROM AUTHOR]

The high catalytic activity of Cu-based nanozymes mainly depends on the efficient Fenton-like reaction of Cu+/ H2O2, but Cu+ cannot exist stably. Trying to find a material that can stably support Cu+ while promoting the electron cycle of Cu2+/Cu+ still faces serious challenges. C60 is expected to be an ideal candidate to solve this problem due to its unique structure and rich physicochemical properties. Here, we designed and synthesized a C60-doped Cu+-based nanozyme (termed as C60-Cu-Bpy) by loading high catalytic active site Cu+ onto C60 and coordinating with 2,2′-bipyridine (Bpy). The single crystal diffraction analysis and a series of auxiliary characterization technologies were used to demonstrate the successful preparation of C60-Cu-Bpy. Significantly, the C60-Cu-Bpy exhibited superior peroxidase-like activity during the catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). Then, the catalytic mechanism of C60-Cu-Bpy as peroxidase was elucidated in detail, mainly benefiting from the dual function of C60. On the one hand, C60 acted as a carrier to directly support Cu+, which has the ability to efficiently decompose H2O2 to produce reactive oxygen species. The other was that C60 acted as an electron buffer, contributing to promoting the Cu2+/Cu+ cycle to facilitate the reaction. Furthermore, a colorimetric sensor for the quantitative analysis of bleomycin was established based on the principle of bleomycin specific inhibition of C60-Cu-Bpy peroxidase-like activity, with satisfactory results in practical samples. This study provides a new strategy for the direct synthesis of Cu+-based nanozymes with high catalytic performance. Schematic illustration of the preparation of C60-Cu-Bpy (a) and the colorimetric detection of bleomycin based on specific inhibition of C60-Cu-Bpy peroxidase-like activity (b) [ABSTRACT FROM AUTHOR]

Gold nanoclusters (Au NCs) exhibit broad fluorescent spectra from visible to near-infrared regions and good enzyme-mimicking catalytic activities. Combined with excellent stability and exceptional biocompatibility, the Au NCs have been widely exploited in biomedicine such as biocatalysis and bioimaging. Especially, the long fluorescence lifetime and large Stokes shift attribute Au NCs to good probes for fluorescence sensing and biological detection. In this review, we systematically summarized the molecular structure and fluorescence properties of Au NCs and highlighted the advances in fluorescence sensing and biological detection. The Au NCs display high sensitivity and specificity in detecting iodine ions, metal ions, and reactive oxygen species, as well as certain diseases based on the fluorescence activities of Au NCs. We also proposed several points to improve the practicability and accelerate the clinical translation of the Au NCs. [ABSTRACT FROM AUTHOR]

Although traditional Fe-based nanozymes have shown great potential, generally only a small proportion of the Fe atoms on the catalyst's surface are used. Herein, we synthesized single-atom Fe on N-doped graphene nanosheets (Fe-CNG) with high atom utilization efficiency and a unique coordination structure. Active oxygen species including superoxide radicals (O2•−) and singlet oxygen (1O2) were efficiently generated from the interaction of the Fe-CNG with dissolved oxygen in acidic conditions. The Fe-CNG nanozymes were found to display enhanced oxidase-like and laccase-like activity, with Vmax of 2.07 × 10−7 M∙S−1 and 4.54 × 10−8 M∙S−1 and Km of 0.324 mM and 0.082 mM, respectively, which is mainly due to Fe active centers coordinating with O and N atoms simultaneously. The oxidase-like performance of the Fe-CNG can be effectively inhibited by ascorbic acid (AA) or hydroquinone (HQ), which can directly obstruct the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). Therefore, a direct and sensitive colorimetric method for the detection of AA and HQ activity was established, which exhibited good linear detection and limit of detection (LOD) of 0.048 μM and 0.025 μM, respectively. Moreover, a colorimetric method based on the Fe-CNG catalyst was fabricated for detecting the concentration of AA in vitamin C. Therefore, this work offers a new method for preparing a single-atom catalyst (SAC) nanozyme and a promising strategy for detecting AA and HQ. [ABSTRACT FROM AUTHOR]

Biothiols, characterized by their unique sulfhydryl (-SH) groups, possess excellent antioxidant properties, effectively neutralizing the damage to cellular structures caused by reactive oxygen species (ROS) in living organisms. Additionally, lysosomes play a crucial role in decomposing damaged biomolecules through the action of their internal enzymes, regulating the cellular redox state, and mitigating oxidative stress. To facilitate rapid monitoring of intracellular biothiols, particularly within lysosomes, we constructed a lysosome-targeted biothiol fluorescent probe, PHL-DNP, in this study. PHL-DNP exhibited excellent photophysical properties in an aqueous test system, including strong fluorescence enhancement response, excellent selectivity, and low detection limits (Cys 16.5 nM, Hcy 16.8 nM, GSH 21.3 nM, Cap 26.6 nM). These attributes enabled easy and efficient qualification of Cys on test strips and accurate determination of the effective content of captopril tablets. Notably, PHL-DNP demonstrated low cytotoxicity and precise lysosomal targeting. Through bioimaging, PHL-DNP not only monitored changes in biothiol levels under oxidative stress but also assessed biothiols in complex biological systems such as live HeLa cells, zebrafish, tumor tissue sections, and radish roots. This provides a promising tool for quantitative analysis of biothiols, disease marker detection, and drug testing. [ABSTRACT FROM AUTHOR]

In this work, ZnO, CuO, and CuO-ZnO nanomaterials have been synthesized via green and facile route using Argyreia nervosa leaf extract. The structural, morphological, optical, chemical, and textural characteristics of as-synthesized nanostructures were investigated using different techniques including X-ray diffraction (XRD); field emission scanning electron microscopy (FE-SEM); transmission electron microscopy (TEM);UV–visible diffuse reflectance spectroscopy (DRS), Fourier transform infrared spectroscopy (FTIR); Brunauer, Emmett and Teller (BET)/Barrett-Joyner-Halenda (BJH); and energy dispersive spectroscopy (EDS). Results obtained from the characterization study showed that the ZnO, CuO, and CuO-ZnO were successfully synthesized using the leaf extract of A. nervosa. The results exhibited the homogeneously growth of CuO particles on the surface of ZnO particles in a spherical-like shapes. The photocatalytic degradation efficiency of the synthesized nanostructures was investigated adopting Rhodamine B dye as an aqueous polluted model. The results have shown that the CuO-ZnO (10%) nanocomposite was the most efficient photocatalyst compared to other samples. The factors affecting the photodegradation process such as the effect of irradiation time (0–180 min), photocatalyst dose (0.4–1.4 g/L), initial RhB concentration (5–20 ppm), and the solution pH (3–11) were tested. The maximum photocatalytic degradation efficiency achieved was 90.25%. Additionally, reuse experiments proved that the CuO-ZnO (10%) photocatalyst retained 72.8% of its initial efficiency after recycling for five cycles. Finally, the results revealed that the most reactive oxygen species (ROS) responsible for the degradation of RhB are hydroxyl radicals (•OH). [ABSTRACT FROM AUTHOR]

In this pilot study, we assessed the role of autophagy in Crohn's Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management. [ABSTRACT FROM AUTHOR]

Although there have been remarkable advances in the treatment of hepatocellular carcinoma (HCC), the prognosis remains poor in those with advanced stage and more effective therapeutic options are urgently needed. Lenvatinib (Len), a multiple receptor tyrosine kinase inhibitor, is an emerging molecular targeted agent for HCC, whose immunomodulatory activities have been investigated. However, Len utilization is limited because of its low metabolic stability, poor bioavailability and dose-dependent toxicity, rendering its direct use insufficient for immune modulation. Stimuli-responsive nanoparticles, which are drug-targeted delivery platforms for on-demand drug release, facilitate deeper and uniform tumour penetration, providing alternative solutions to overcome current limitations. Ultrasound (US) exhibits superior tissue penetration abilities and can produce reactive oxygen species (ROS) at the tumour site to treat deeper tumours. In addition, US serves as an excellent and selective drug delivery mediator for tumour treatment. Herein, we designed US-triggered lenvatinib nanoparticles (Len-RNPs) for selective drug delivery that utilize US-triggered ROS to induce in situ oxidation reactions, resulting in nanoparticle disintegration. Len-RNPs mitigate the toxicity of Len and effectively trigger robust systemic anti-tumour immune responses in a H22 tumour model, resulting in a tumour suppression rate of 95.7%, with 60% of mice being cured. Our study elucidates a novel and precise strategy of combining Len and US therapy for enhanced HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) serves as a vital component in the chemotherapeutic approach to treat esophageal squamous cell carcinoma (ESCC). However, prolonged CDDP application frequently culminates in resistance, compromising therapeutic outcomes. Through genome-wide CRISPR library screening, our study elucidates the mechanisms underlying this resistance, pinpointing CYFIP2 as a pivotal mediator. Notably, the involvement CYFIP2 is characterized by pronounced autophagic activity and the modulation of multiple cellular pathways. Empirical validation was achieved by treating ESCC cell lines with CDDP, which resulted in an upsurge of CYFIP2 expression. The functional impact of CYFIP2 was further delineated through knockdown experiments, where a marked suppression in cell proliferation was observed, alongside a discernible decline in reactive oxygen species levels. This was complemented by a suite of assays and microscopic techniques, including GFP-LC3, mRFP-GFP-LC3, electron microscopy and western blot, which collectively affirmed the inhibitory effect of CYFIP2 knockdown on autophagic processes, particularly impeding autophagosome formation and their subsequent fusion with lysosomes. In vivo studies have also confirmed that CYFIP2 knockdown limits tumor progression and increases CDDP efficacy. Conclusively, our findings introduce CYFIP2 as a novel contributor to CDDP resistance in ESCC, underscoring its potential as a therapeutic target. This revelation not only deepens our understanding of resistance mechanisms but also paves the way for novel oncotherapeutic strategies, promising enhanced treatment efficacy against ESCC. [ABSTRACT FROM AUTHOR]

The roles of plant-specific transcription factor family YABBY may vary among different members. OsYABBY6 is a rice YABBY gene, whose function is not well elucidated so far. In this paper, we show that OsYABBY6 is a nucleus-localized protein with transcriptional activation activity. OsYABBY6 is predominantly expressed in the palea and lemma, as well as in the sheath, culm and node. OsYABBY6 RNA interference (RNAi) plants exhibited altered plant height and larger grain size. Under cold treatment, OsYABBY6 overexpression (OE) plants had up-regulated expression of cold responsive genes, and accumulated less reactive oxygen species but more proline compared to wild type, resulting in improved cold tolerance. On the other hand, RNAi plants showed enhanced drought tolerance compared to the wild type by slower water loss, less reactive oxygen species but more proline and soluble sugar accumulation. In addition, endogenous abscisic acid (ABA) level was reduced in OsYABBY6 RNAi plants, and RNAi and OE plants were more and less sensitive to ABA treatment, respectively. Accordingly, we deduce that OsYABBY6 positively regulates cold response but negatively regulates drought response through different pathways. Our study reveals the crucial roles of OsYABBY6 in plant architecture and grain development, as well as in abiotic stress response, providing new insights into the functions of YABBYs in rice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent type of dementia. Its causes are not fully understood, but it is now known that factors like mitochondrial dysfunction, oxidative stress, and compromised ion channels contribute to its onset and progression. Flickering light therapy has shown promise in AD treatment, though its mechanisms remain unclear. In this study, we used a rat model of streptozotocin (STZ)-induced AD to evaluate the effects of 40 Hz flickering light therapy. Rats received intracerebroventricular (ICV) STZ injections, and 7 days after, they were exposed to 40 Hz flickering light for 15 min daily over seven days. Cognitive and memory functions were assessed using Morris water maze, novel object recognition, and passive avoidance tests. STZ-induced AD rats exhibited cognitive decline, elevated reactive oxygen species, amyloid beta accumulation, decreased serotonin and dopamine levels, and impaired mitochondrial function. However, light therapy prevented these effects, preserving cognitive function and synaptic plasticity. Additionally, flickering light restored mitochondrial metabolites and normalized ATP-insensitive mitochondrial calcium-sensitive potassium (mitoBKCa) channel activity, which was otherwise downregulated in AD rats. Our findings suggest that 40 Hz flickering light therapy could be a promising treatment for neurodegenerative disorders like AD by preserving synaptic and mitochondrial function. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy characterized by dysregulated cellular metabolism leading to aberrant glucose metabolism, fatty acid accumulation, and excessive reactive oxygen species production. ccRCC cells exhibit an augmented oxidative stress response. Complex interactions between iron metabolism and lipid homeostasis in ccRCC cells require a counteracting response that enables ferroptosis evasion and survival maintenance. Additionally, abnormal GA-binding protein transcription factor subunit alpha (GABPA) expression is associated with ccRCC occurrence and development, but its impact on ferroptosis-related molecular mechanisms remains unclear. Herein, we examined the impact of the GABPA–ACSL4 pathway on ferroptosis in ccRCC through bioinformatics analysis, as well as in vitro and in vivo experiments. In contrast to that in adjacent normal tissues, GABPA expression was significantly downregulated in ccRCC tissues, and this downregulation was linked to poor overall survival. Increased GABPA expression suppressed ccRCC cell proliferation, migration, and invasion. Moreover, GABPA overexpression increased the susceptibility of ccRCC cells to ferroptosis. Additionally, GABPA directly bound to the promoter region of ACSL4, promoting ferroptosis. Thus, inducing the GABPA–ACSL4 pathway activates ferroptosis, inhibits proliferation or metastasis, and exerts anticancer activity in ccRCC. These findings have important implications for regulating ccRCC occurrence and development. [ABSTRACT FROM AUTHOR]

Compounds that can induce oxidative stress in cancer cells while remaining nontoxic to healthy cells are extremely promising for potential anticancer drugs. 2,2′:6′,2′′-terpyridine-metal complexes possess these properties. The high level of activity (IC50 = 0.605 µM) of 2,2′:6′,2′′-terpyridine-metal complexes on lung, breast, pancreatic, and glioblastoma multiforme cancer lines and their selectivity (SI > 41.32) on human normal fibroblasts were confirmed and presented in this paper. The mechanism of action of these compounds is associated with the generation of reactive oxygen species, which affects several cellular pathways and signals. The results demonstrate that 2,2′:6′,2′′-terpyridine-metal complexes affect cell cycle inhibition in the G0/G1 phase as well as the activation of apoptosis and autophagy cell death. These results were confirmed in several independent studies, including experiments measuring the fluorescence levels of reactive oxygen species, flow cytometry, and gene and protein analysis. [ABSTRACT FROM AUTHOR]

Photoaging damages the skin layers. The tumor necrosis factor-alpha (TNF-α) plays a crucial role in the central mechanism of photoaging. TNF-α production leads to direct damage to skin cells and facilitates the degradation of vital extracellular matrix (ECM) proteins. TNF-α stimulates matrix metalloproteinase-1 (MMP-1) activation This accelerates the loss of skin elasticity and wrinkle formation. Thus, preventing photoaging and delaying the skin aging process are important research objectives, and the development of new anti-aging substances that target the TNF-α and MMP-1 pathways is promising. In this context, the efficacies of four extracts derived from two types of Cephalotaxus harringtonia (CH) buds (CH-10Y-buds, CH-200Y-buds) and leaves (CH-10Y-leaves, CH-200Y-leaves) were investigated, exhibiting a significant reduction in reactive oxygen species (ROS). Among the four extracts, CH-10Y-buds was the most effective in reducing ROS and exhibited the highest amounts of harringtonine and homoharringtonine. The activities of harringtonine, homoharringtonine, and ginkgetin were evaluated; harringtonine exhibited a high efficacy in inhibiting TNF-α-induced inflammatory responses and MMP-1 activation, thereby reducing collagen degradation. These findings suggest that CH-10Y-buds and their components herringtonin are promising candidates for preventing damage caused by photoaging. Our results can facilitate the development of new methods for maintaining skin health and inhibiting the skin aging process. Further research is necessary to comprehensively evaluate the potential efficacy of these candidate substances and investigate their applicability to actual skin. Such studies will aid in the development of more effective anti-aging strategies in the future. [ABSTRACT FROM AUTHOR]

Tomato is the second most valuable vegetable crop, and its susceptibility to tropospheric ozone (O3) varies on the cultivar. Eight tomato cultivars with documented O3 sensitivity were reevaluated using ethylenediurea (400 ppm EDU) to determine the effectiveness of EDU in assessing O3 sensitivity under heavily O3-polluted tropical conditions. EDU helped in amending the growth, photosynthetic pigments, photosynthetic rate, stomatal conductance, and yield characteristics in the tomato cultivars. EDU reduced the lipid peroxidation and reactive oxygen species content, while enzymatic and non-enzymatic antioxidant responses differed across cultivars. The cultivar Superbug and Sel-7 (O3 susceptible) performed better by employing more biomass and yield and exhibiting more potent antioxidative defense machinery mainly non-enzymatic antioxidants after EDU treatment. The higher value of total antioxidative potential (TAP) in O3 susceptible cultivars suggested the adaptive resilience through EDU application against O3 stress. EDU application greatly enhanced the photosynthetic rate in O3 susceptible cultivars by increasing the stomatal conductance. Hence, both biophysical and biochemical responses were involved in protection against O3 provided by EDU. Kashi chayan and VRT02 (O3 tolerant) cultivars showed least response to EDU, due to their efficient inherent mechanisms in alleviating O3 stress. Thus, EDU may be used as an efficient biomonitoring tool against O3-sensitive cultivars. [ABSTRACT FROM AUTHOR]

Heavy metals (HMs) contamination has gained much attention due to its high degree of toxicity for living organisms. Therefore, different techniques are underway to eradicate HMs from the environment. Among the biological techniques, phytoremediation is a suitable method, but owing to the slow rate and chance of HMs penetration into the food chain, alternative techniques are needed to reduce their phytotoxicity, and biochar is one of them. Due to the diverse characteristics, biochar immobilizes HMs in the soil by improving soil pH, ion exchange, electrostatic interactions, complexation, precipitation, surface adsorption, and microbial activation. Thereby, amendment of biochar in the HMs-contaminated soils reduces HMs toxicity to plants and limits their penetration into the food chain. In contrast, some biochars have also been studied to induce metal availability in soils and subsequently its uptake by plants. This dual role of biochar depends on the feedstock of biochar, incineration temperature, and the rate of application. Moreover, biochar treatments enhance plant growth under HMs stress by improving nutrient availability, water retention capacity, scavenging of reactive oxygen species, and photosynthetic efficiency. Owing to the beneficial characteristics of biochar in HMs-contaminated sites, the number of publications has tremendously increased. Additionally, the plant species and the types of HMs that have been tested frequently under biochar treatments in these articles have been studied. Overall, the current study would help in understanding the mechanisms of how biochar influences phytoremediation of HMs and improves plant growth in HMs-polluted soils and the current scenario of the available literature. [ABSTRACT FROM AUTHOR]

The anti-Acanthamoeba properties of riboflavin and its enhanced amoebicidal effects when combined with ultraviolet A (UVA) radiation were investigated in vitro. The viability of cultured Acanthamoeba castellanii was assessed by adding varying concentrations (0 ~ 0.2% w/v) of riboflavin to the culture medium or after combined riboflavin and UVA treatment (30 min, 3 mW/cm2) over 1, 3, 5, and 7 days. Intracellular reactive oxygen species (ROS) levels were measured following a 30-minute exposure to riboflavin. Additionally, the cysticidal effects of riboflavin, UVA, and their combination were evaluated. Gene transcription in Acanthamoeba was analyzed using RNA-seq. Riboflavin demonstrated dose-dependent toxicity on Acanthamoeba, accompanied by an increase in intracellular ROS. Exposure to 0.2% riboflavin reduced Acanthamoeba viability by over 50% within one day. UVA treatment alone also reduced viability by over 50%. Combined treatment with 0.2% riboflavin decreased trophozoite survival by more than 80%, and approximately 60% of cysts were killed when 0.1% riboflavin was combined with UVA. RNA-seq analysis indicated significant changes in gene expression after exposure to riboflavin, UVA, and their combination, particularly affecting oxidoreductase activity, cystathionine β synthase, and serine-threonine kinase activity. These findings indicate that riboflavin exhibits dose-dependent toxicity in Acanthamoeba, primarily through increased ROS generation. Combining riboflavin and UVA did not fully eradicate trophozoites and cysts of Acanthamoeba, but was able to partially inactivate them. [ABSTRACT FROM AUTHOR]

Background: Breast cancer, a major health concern globally, often faces challenges in the non-invasive elimination of cancer cells. This has prompted researchers to explore alternative strategies, such as photothermal therapy (PTT), which takes advantage of the location of breast cancer lesions. Additionally, the tumor microenvironment with high hydrogen peroxide (H2O2) provides a key prerequisite for treating tumors with nanozymes, especially those with peroxidase (POD)-like activity. However, the overexpression of TrxR1, which maintains redox homeostasis in tumor cells, limits reactive oxygen species (ROS)-based cytotoxic therapy. This study aims to present molybdenum selenide nano urchins (MoSe2 NUs) with excellent photothermal conversion efficiency, POD-like activity and selective inhibition of TrxR1 to achieve photothermal enhanced nanocatalytic therapy for combating breast cancer. Methods: The characterization of MoSe2 NUs synthesized by the hydrothermal method was identified by TEM, XRD, Zeta potential and DLS. Whether MoSe2 NUs in conjunction with NIR possessed POD-like activities or not was identified via a TMB colorimetric method. The photothermal characteristics of MoSe2 NUs excited by near-infrared were recorded by an infrared thermal imaging camera. The antitumor effect of MoSe2 NUs was detected by cell death staining, apoptosis assay and animal experiments. TrxR1 and apoptosis-related protein expression were identified by Western blot and Immunohistochemistry. Results: MoSe2 NUs possessed excellent photothermal conversion efficiency, peroxidase (POD)-like activity, and selective inhibition of TrxR1. Furthermore, the photothermal effect of MoSe2 NUs can enhance their POD-like activity, allowing for accurate cancer treatment under near-infrared (NIR) light. MoSe2 NUs plus NIR and MoSe2 NUs alone exhibited in vivo tumor inhibition rates of 69.7% and 35.1%, respectively. Mechanistically, NIR-regulated MoSe2 NUs induced potent apoptosis of cancer cells by downregulating the TrxR1 and elevating intracellular ROS, thereby leading to caspase-3 cleavage. Conclusions: This study demonstrated that MoSe2 NUs under NIR irradiation can precisely and efficiently treat breast cancer and have great potential for clinical application. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) is susceptible to various abiotic stresses, such as salt, cold, and drought. Therefore, there is an urgent need to explore the relevant genes that enhance tolerance to these stresses. In this study, we identified a gene, OsNCED4 (9-cis-epoxycarotenoid dioxygenase 4), which regulates tolerance to multiple abiotic stresses. OsNCED4 encodes a chloroplast-localized abscisic acid (ABA) biosynthetic enzyme. The expression of OsNCED4 gene was significantly induced by 150 mM NaCl and cold stress. Disruption of OsNCED4 by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9-mediated mutagenesis resulted in significant sensitivity to NaCl and cold stress. The salt and cold sensitivity of osnced4 mutant was due to the reduction of ABA content and the excessive accumulation of reactive oxygen species (ROS) under stress. Moreover, OsNCED4 also regulates drought stress tolerance of rice seedlings. Taken together, these results indicate that OsNCED4 is a new regulator for multiple abiotic stress tolerance in rice, and provided a potential target gene for enhancing multiple stress tolerance in the future. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii's extensive antibiotic resistance makes its infections difficult to treat, so effective strategies to fight this bacterium are urgently needed. This study aims to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) mediated by Rutin-Gal(III) complex and Quercetin against A. baumannii. Absorbance spectra, fluorescence spectra, and minimum inhibitory concentration (MIC) of Rutin-Gal(III) complex and Quercetin were determined. The intracellular reactive oxygen species (ROS), extracellular polymeric substances (EPS), cell membrane permeability, expression of ompA and blaOXA−23, anti-biofilm activity, and anti-metabolic activity of Rutin-Gal(III) complex- and Quercetin-mediated aPDT were measured. Rutin-Gal(III) complex and Quercetin revealed absorption peaks in the visible spectra. Quercetin and Rutin-Gal(III) complex displayed fluorescence peaks at 524 nm and 540 nm, respectively. MIC values for the Rutin-Gal(III) complex and Quercetin were 64 µg/mL and 256 µg/mL, respectively. Quercetin- and Rutin-Gal(III) complex-mediated aPDT significantly reduced the colony forming units/mL (58.4% and 67.5%), EPS synthesis (47.4% and 56.5%), metabolic activity (30.5% and 36.3%), ompA (5.5- and 10.5-fold), and blaOXA−23 (4.1-fold and 7.8-fold) genes expression (respectively; all P < 0.05). Quercetin- and Rutin-Gal(III) complex-mediated aPDT enhanced notable biofilm degradation (36.2% and 40.6%), ROS production (2.55- and 2.90-folds), and membrane permeability (10.8– and 9.6-folds) (respectively; all P < 0.05). The findings indicate that Rutin-Gal(III) complex- and Quercetin-mediated aPDT exhibits antibacterial properties and could serve as a valuable adjunctive strategy to conventional antibiotic treatments for A. baumannii infections. One limitation of this study is that it was conducted solely on the standard strain; testing on clinical isolates would allow for more reliable interpretation of the results. [ABSTRACT FROM AUTHOR]

Background: The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD. Methods: This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6 months (short-term study) for the primary endpoints and extended to 2 years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8–7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury. Results: Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6 months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1 year, or p = 0.0186, vs. 2 years) and urinary excretion of 8-hydroxy-2′-deoxyguanosine (p = 0.0481, baseline vs. 6 months). Conclusion: This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD. [ABSTRACT FROM AUTHOR]

A novel fluorescent sensor based on silver nanoparticle-carbon dot composites (Ag@CDs) has been developed for the rapid and quantitative detection of aquatic bacteria. The sensor operates on the principle of plasmon-enhanced resonance energy transfer, where the fluorescence of CDs is quenched by Ag nanoparticles and restored upon bacterial interaction due to the generation of reactive oxygen species. The Ag@CDs exhibit a linear response to bacterial concentration over the range 7 × 104 ~ 4 × 107 CFU·mL−1, with a low detection limit of 4 × 104 CFU·mL−1. The fluorescence recovery is rapid, reaching maximum intensity within 5 min. The method demonstrates high selectivity, with minimal interference from common ions and compounds found in municipal and industrial wastewater. The Ag@CDs-based 96-well plate assay for quantitative measurement of bacteria was developed. The assay's performance was further validated through the analysis of real water samples, showing a recovery of 94.0 ~ 102% for domestic wastewater and 97.6 ~ 106% for industrial wastewater. Also, Ag@CDs-based test strips assay for semi-quantitation were developed for rapid in-field aquatic bacteria detection. Ag@CDs can be conveniently integrated into 96-well plates and test strips, providing rapid on-site aquatic bacteria testing. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been emerged as a promising modality for cancer treatment. However, the development of drug delivery system enabling continuous release of photosensitizers (PSs) for long-term PDT treatment still remains challenges. Herein, a H2O2-responsive injectable hydrogel, covalently crosslinked by N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA) with PVA containing polythiophene quaternary ammonium salt (PT2) polymer dots (PDots) as a photosensitizer was fabricated. Under the stimulation of H2O2, the obtained injectable hydrogel gradually degrades and releases PDots. In vitro experiments suggested that the released PDots could realize efficient tumor cells inhibition through its robust singlet oxygen generation capability upon 577 nm laser irradiation. In vivo studies demonstrated a sustained retention of PDots for at least 7 days following single-dose administration, facilitating efficient tumor inhibition with light treatments for 3 times without apparent biotoxicity. This work presents an innovative polymer dots-based composite local drug delivery system for long-term PDT in cancer treatment. [ABSTRACT FROM AUTHOR]

Highlights: Cynarin decreases neuroinflammation levels and attenuates microglial pyroptosis. Cynarin hinders the formation of NLRP3 inflammasome through Nrf2-dependent expression. Cynarin-treated mice showed lower levels of reactive oxygen species (ROS) and cell death, as well as reduced neurohistological damage, and improved hindlimb locomotor function compared to untreated mice. Background: Spinal cord injury (SCI) elicits excess neuroinflammation and resident microglial pyroptosis, leading further terrible neurological collapse and locomotor dysfunction. However, the current clinical therapy is useless and a feasible treatment is urgent to be explored. Cynarin is a natural component in artichoke playing anti-inflammatory and anti-aging roles in hepatoprotection and cardioprotection, but it is unclear that the pharmacologic action and underlying mechanism of Cynarin in neuropathy. Methods: Using the SCI mouse model and the BV2 cell line, we here investigated whether Cynarin reduces neuroinflammation and pyroptosis to promote neurological recovery after SCI. Results: Our results showed that treatment with Cynarin reduces the level of neuroinflammation and microglial pyroptosis. Moreover, the mice treated with Cynarin exhibited lower level of reactive oxygen species (ROS) and cell death, less damage of neurohistology and better locomotor improvement of hindlimbs than the untreated mice and the nuclear factor erythroid 2-related factor 2 (Nrf2)-inhibited mice. Mechanically, Cynarin inhibited the assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by Nrf2-dependent expression to attenuate microglial pyroptosis and neuroinflammation. Conclusions: To sum up, the current study suggested that administration of Cynarin is a promising compound for anti-neuroinflammation and anti-pyroptosis after SCI. It may be an efficient Nrf2 activator and a NLRP3 inhibitor for microglia in neuropathies. [ABSTRACT FROM AUTHOR]

Licochalcone A (Lico A), a naturally bioactive flavonoid, has shown antitumor activity in several types of cancers. However, few studies have focused on its effect on acute myeloid leukemia (AML). Cell viability and colony formation potential were detected by CCK-8 assay and colony formation assay, respectively. Cell cycle distribution and apoptosis were assessed by flow cytometry. Ferroptosis was assessed by measuring reactive oxygen species (ROS), lipid ROS, malondialdehyde (MDA), and glutathione (GSH). Protein expression levels were determined by immunoblotting and immunohistochemistry (IHC), and mRNA expression was detected by real-time qPCR. The m6A modification of MDM2 mRNA was verified by methylated RNA immunoprecipitation (MeRIP) assay, and the interaction of IGF2BP3 and MDM2 mRNA was analyzed by RIP assay. Actinomycin D was used to evaluate mRNA stability. The efficacy of Lico A in vivo was examined by a murine xenograft model. Lico A suppressed cell proliferation and induced ferroptosis in MOLM-13 and U-937 in vitro, and slowed the growth of xenograft tumors in vivo. IGF2BP3 was highly expressed in human AML specimens and cells, and Lico A suppressed IGF2BP3 expression in AML cells. Lico A exerted the anti-proliferative and pro-ferroptosis effects by downregulating IGF2BP3. Moreover, IGF2BP3 enhanced the stability and expression of MDM2 mRNA through an m6A-dependent manner. Downregulation of IGF2BP3 impeded AML cell proliferation and enhanced ferroptosis via repressing MDM2. Furthermore, Lico A could affect the MDM2/p53 pathway by downregulating IGF2BP3 expression. Lico A exerts the anti-proliferative and pro-ferroptosis activity in AML cells by affecting the IGF2BP3/MDM2/p53 pathway, providing new evidence for Lico A as a promising agent for the treatment of AML. [ABSTRACT FROM AUTHOR]

In the region of slightly acidic pH (рН 5.7), the manganese cluster in oxygen-evolving complex of photosystem II (PSII) is more resistant to exogenous reductants. The effect of such pH on the heat inactivation efficiency of the electron transport chain (O2 evolution and 2,6-dichlorophenolindophenol reduction) in PSII membranes and thylakoid membranes was investigated. Under thylakoid membranes illumination accompanied by lumen acidification, their resistance to heat inactivation increases. In the presence of protonophores, the rate of heat inactivation increases, which seems to be associated not with the protonophore mechanism, but with structural and/or functional changes in membranes. In PSII membrane preparations, the efficiency of the oxygen evolution inhibition at pH 5.7 is also lower than at pH 6.5. The role of reactive oxygen species in thermal inactivation of photosynthetic membranes was investigated using a lipophilic cyclic hydroxylamine ESR spin probe. [ABSTRACT FROM AUTHOR]

Fumarylacetoacetate hydrolase (FAH) catalyzes the final step of the tyrosine degradation pathway. In this study, we isolated and characterized two homologous BnaFAH genes in Brassica napus L. variant Westar, and then used CRISPR/Cas9-mediated targeted mutagenesis to generate a series of transgene-free mutant lines either with single or double-null bnafah alleles. Among these mutant lines, the aacc (bnafah) double-null mutant line, rather than the aaCC (bnaa06fah) mutant line, exhibited programmed cell death (PCD) under short days (SD). Histochemical staining and content measurement confirmed that the accumulation of reactive oxygen species (ROS) in bnafah was significantly higher than that in bnaa06fah. To further elucidate the mechanism of PCD, we performed transcriptomic analyses of bnaa06fah and bnafah at different SD stages. A heatmap cluster of differentially expressed genes (DEGs) revealed that PCD may be related to various redox regulatory genes involved in antioxidant activity, ROS-responsive regulation and calcium signaling. Combined with the results of previous studies, our work revealed that the expression levels of BnaC04CAT2, BnaA09/C09SAL1, BnaA08/C08ACO2, BnaA07/C06ERO1, BnaA08ACA1, BnaC04BIK1, BnaA09CRK36 and BnaA03CPK4 were significantly different and that these genes might be candidate hub genes for PCD. Together, our results underscore the ability of different PCD phenotypes to alter BnaFAH orthologs through gene editing and further elucidated the molecular mechanisms of oxidative stress-induced PCD in plants. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a major disease characterized by early albuminuria and heightened risk of renal deterioration. Increased reactive oxygen species (ROS) production, especially in glomeruli, plays an important role in the progression of DKD. ROS also cause activation of Apoptosis signal-regulating kinase 1 (ASK-1), which is implicated in various organ injuries. However, the detailed mechanisms remain unclear. This study investigates ASK-1 activation in advanced DKD and its underlying mechanisms using GS442172, an ASK-1 inhibitor. In the DKD mouse model, activation of ASK-1 was observed. Although inhibition of ASK-1 activation improved hyperpermeability in glomerular endothelial cells. ASK-1 inhibition significantly reduced glomerular injury and albuminuria, while also attenuating tubular damage and interstitial fibrosis. RNA-seq analysis revealed an aging phenotype associated with ASK-1 activation in DKD. In vitro experiments demonstrated ASK-1 activation-induced cellular senescence in tubular cells via redox signaling. These results suggested that the critical role of ASK-1 activation in DKD pathogenesis, implicating glomerular injury, tubular damage, and cellular senescence. ASK-1 inhibitors are promising therapeutic strategies to mitigate the progression of DKD. [ABSTRACT FROM AUTHOR]

Low temperatures are a key factor affecting the growth, development, and geographical distribution of prickly ash. This study investigated the impact of ecological and geographical factors on the freezing tolerance of prickly ash germplasm. Thirty-seven germplasm samples from 18 different origins were collected, and their freezing tolerance was comprehensively evaluated. The correlation between freezing tolerance and the ecological and geographical factors of their origins was also analyzed. Significant differences in freezing tolerance were observed among germplasm from different origins. The semi-lethal temperature of the germplasm ranged from − 12.37 to 1.08 °C. As temperatures decreased, the relative conductivity (REC) and catalase (CAT) activity of the germplasm gradually increased, while soluble sugar (SS), soluble protein (SP), free proline (Pro), and Peroxidase (POD) activities decreased and then increased. Superoxide dismutase (SOD) activity initially increased and then decreased. A comprehensive evaluation of freezing tolerance was conducted using a logistic equation, membership function, and cluster analysis. Germplasm from Tongchuan and Hancheng (Shaanxi Province, China), Asakura (Japan), and Yuncheng (Shanxi Province, China) exhibited the highest freezing tolerance, whereas those from Rongchang (Chongqing Municipality, China), Qujing (Yunnan Province, China), and Honghe (Yunnan Province, China) had the lowest. The correlation analysis revealed a significant positive correlation between freezing tolerance and latitude, and a significant negative correlation with the temperature of origin. Germplasm from higher latitudes showed higher SS content, SOD and CAT activities, stronger antioxidant enzyme activity, and better freezing tolerance compared to those from lower latitudes. REC was lower in germplasm originating from low-temperature areas than in those from high-temperature areas. Additionally, SP, Pro content, SOD, and POD activities were higher, indicating effective scavenging of active oxygen free radicals. No significant correlation was found between altitude and longitude of origin and freezing tolerance. However, at similar latitudes, prickly ash from higher altitudes displayed higher antioxidant enzyme activity and stronger freezing tolerance compared to those from lower altitudes. These findings provide a scientific basis for breeding prickly ash cultivars suited to different ecological regions. [ABSTRACT FROM AUTHOR]

In order to meet growing consumer demands in terms of naturalness, the pharmaceutical, food, and cosmetic industries are looking for active molecules of plant origin. In this context, hairy roots are considered a promising biotechnological system for the sustainable production of compounds of interest. Poplars (genus Populus, family Salicaceae) are trees of ecological interest in temperate alluvial forests and are also cultivated for their industrial timber. Poplar trees also produce specialized metabolites with a wide range of bioactive properties. The present study aimed to assess the hybrid poplar hairy root extracts for antimicrobial and antibiofilm activities against four main life-threatening strains of Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Ethyl acetate extracts from two hairy root lines (HP15-3 and HP A4-12) showed significant antibacterial properties as confirmed by disc diffusion assay. Antibiofilm activities were found to be dose dependent with significant biofilm inhibition (75–95%) recorded at 1000 µg.mL−1 in all the bacterial strains tested. Dose-dependent enhancement in the release of exopolysaccharides was observed in response to treatment with extracts, possibly because of stress and bacterial cell death. Fluorescence microscopy confirmed loss of cell viability of treated bacterial cells concomitant with increased production of reactive oxygen species compared to the untreated control. Overall, this study demonstrates for the first time a high potential of poplar hairy root extracts as a natural and safe platform to produce antimicrobial agents in pharmaceutical, food, industrial water management, or cosmetic industries. [ABSTRACT FROM AUTHOR]

Phyllosphere-associated microorganisms must deal with various abiotic stresses such as high-low temperature, low nutrients, and ultraviolet (UV) radiation. These collective actions may trigger the generation of reactive oxygen species (ROS) and causes cellular damage. Cellular defense mechanisms such as morphological changes (size or appearance), production of photo-protectant compounds, and enhancement of antioxidant activities, all of which may contribute to the suppression of ROS and significantly increase survival rates under UV radiation. In this study, five UVB-resistant plant growth-promoting methylotrophs (Methylorubrum thiocyanatum (SD2), Rhodococcus kroppenstedtii (UK3), Methylorubrum populi (KD5), and Methylobacterium brachiatum (KD1 and SD3)) were investigated as adaptive strategies against UVB radiation. Exposure to UVB radiation revealed that methylotrophs changed their morphology to club or dumbbell shapes, and formed biofilm-like structures. Furthermore, Fourier transform-infrared spectroscopy (FTIR) and Gas chromatography-mass spectroscopy (GC–MS) analyses of the methanol-based intracellular extracts of methylotrophs revealed the presence of carotenoids, flavonoids, fatty acids, and antioxidants. Additionally, methylotrophs showed enhanced antioxidant activities such as superoxide dismutase, peroxidase, phenylalanine ammonia-lyase, and proline content with increased UVB exposure (1 -4 h). These findings demonstrate the ability and various adaptation strategies of methylotrophs to survive UVB exposure. These adaptive strategies may be one reason for the promotion of plant growth by methylotrophs under UVB radiation. [ABSTRACT FROM AUTHOR]

Domestic and industrial effluents contain substantial amounts of micropollutants, such as pharmaceuticals, which may influence the balance of the phytoplankton community. A mesocosm approach was used to determine the effects of different fluoxetine concentrations (20 ng L−1, 20 µg L−1, and 20 mg L−1) on phytoplankton community structure, biochemical composition, antioxidant response, and primary productivity. The total cell density of the phytoplankton community was in the order of control > 20 µg > 20 ng > 20 mg by the 21st day of the experiment. On day 21, the phytoplankton community had chlorophyll a content in the order of 20 mg > 20 µg > 20 ng > control, but these changes were not significant (p > 0.05). Beta diversity results revealed that fluoxetine significantly affected the community structure and dynamics of exposed phytoplankton. Reactive oxygen species, malondialdehyde and peroxidase levels were significantly altered by changes in fluoxetine concentrations. Protein content increased at 20 µg L−1 and decreased at 20 ng L−1 and 20 mg L−1 by day 21 of the experiment. These results suggest that, even in the ng L−1 range, fluoxetine could contribute to the reshaping of phytoplankton community structure and dynamics in aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which activated CD4+ T cells participate in the disease process by inducing inflammation. We aimed to investigate the role of Toll-like receptor 2 (TLR2) on CD4+ T cells in RA patients, and to elucidate the underlying mechanisms by which TLR2 contributes to the pathogenesis of RA. Methods: Serum samples were collected from RA patients and healthy controls. Soluble TLR2 levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to assess the TLR2 expression level, activation status, cytokine production, reactive oxygen species (ROS) levels, and glucose uptake capacity of CD4+ T cells. Quantitative polymerase chain reaction (qPCR) was used to measure the expression of enzymes associated with glucose and lipid metabolism. The concentration of lactic acid in the culture supernatant was determined using a dedicated detection kit. Results: RA patients had higher levels of TLR2 in their serum, which positively correlated with C-reactive protein and rheumatoid factor. The expression level of TLR2 in CD4+ T cells of RA patients was increased, and TLR2+ cells showed higher activation levels than TLR2- cells. Activation of TLR2 in CD4+ T cells of RA patients promoted their activation, TNF-α secretion, and increased production of ROS. Furthermore, TLR2 activation led to changes in enzymes related to glucose metabolism, causing a shift in glucose metabolism towards the pentose phosphate pathway. Blocking oxidative phosphorylation and the pentose phosphate pathway had varying effects on CD4+ T cell function. Conclusion: TLR2 reprograms the glucose metabolism of CD4+ T cells in RA patients, contributing to the development of RA through ROS-mediated cell hyperactivation and TNF-α secretion. Key Points • TLR2 is upregulated in CD4+T cells of RA patients and correlates with disease severity markers such as CRP and RF. • Activation of TLR2 in CD4+T cells promotes cell activation, TNF-α secretion, and increased ROS production, contributing to the pathogenesis of RA. • TLR2 activates glucose metabolism in CD4+T cells, shifting towards the pentose phosphate pathway, which may be a novel therapeutic target for RA treatment. • Blocking glucose metabolism and ROS production can reduce CD4 + T cell hyperactivation and TNF-α secretion, indicating potential therapeutic strategies for RA management. [ABSTRACT FROM AUTHOR]

An important area of focus for developing antioxidant collagen hydrolysates (peptides) involves enhancing the antioxidant properties of collagen hydrolysates. In this study, fish scale collagen hydrolysate (FH) was used as the raw material for plastein reaction. Various enzymes, including papain, alcalase, flavourzyme, and the combination of alcalase and flavourzyme, were employed for this purpose. The plastein reaction significantly improved the thermal stability, chemical antioxidant activity, and capacity to scavenge cellular reactive oxygen species of FH. Notably, the plastein reaction catalyzed by alcalase exhibited the most significant improvement, increasing the hydroxyl radical scavenging rate from 72.3 to 93.4% and restoring the viability of the oxidative stress-induced HepG2 cell model from 50.8 ± 1.7 to 74.9 ± 1.7%. During the plastein reaction, condensation and hydrolysis reactions occurred simultaneously, with condensation being the dominant process. These reactions, along with physical aggregation, facilitated the formation of larger yet more concentrated collagen peptide aggregates, leading to increased exposure of hydrophobic groups. This enhanced the uptake of collagen hydrolysates by the cells and contributed to the enhancement of their antioxidant properties. Thus, the plastein reaction is an effective method for enhancing the antioxidant properties of collagen hydrolysates, with its simplicity of operation and promising application potential. [ABSTRACT FROM AUTHOR]

Key message: CRISPR/Cas9-mediated knockout of SlWOX4 gene in tomato enhances tolerance to drought stress. Drought stress is one of the major abiotic factors that seriously affects plant growth and crop yield. WUSCHEL-related homeobox (WOX) transcription factors are involved in plant growth, development and stress response. However, little is known about the role of WOX genes in drought tolerance in tomato. Here, SlWOX4, a member of the WOX family in tomato, was functionally characterized in mediating drought tolerance. SlWOX4 was homologous to Nicotiana tabacum NtWOX4 with a conserved HD domain, and was localized in the nucleus. SlWOX4 was significantly down-regulated by drought and abscisic acid (ABA) treatments. The loss-of-function mutations of SlWOX4 produced using the CRISPR–Cas9 system in tomato improved drought tolerance by reducing water loss rate and enhancing stomatal closure. In addition, the wox4 lines exhibited reduced accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), increased antioxidant enzyme activity, proline contents and ABA contents under drought stress. Moreover, gene editing of SlWOX4 in tomato enhanced drought tolerance by regulating the expression of genes encoding antioxidants and ABA signaling molecules. In summary, SlWOX4 gene might negatively regulate drought stress tolerance in tomato and has great potential as a drought-resistant crop-breeding target genes. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a debilitating and the second most common neurodegenerative disorder with a high prevalence. PD has a multifaceted etiology characterized by an altered redox state and an excessive inflammatory response. Extensive research has consistently demonstrated the role of the nuclear factor E2-related factor (Nrf2) and inflammasomes, notably NLRP3 in neurodegenerative diseases. In this study, our focus was on exploring the potential neuroprotective properties of carveol in Parkinson's disease. Our findings suggest that carveol may exhibit these effects through Nrf2 and by suppressing pyroptosis. Male albino mice were treated with carveol, and the animal PD model was induced through a single intranigral dose of 2 µg/2µl lipopolysaccharide (LPS). To further demonstrate the essential role of the Nrf2 pathway, we utilized all-trans retinoic acid (ATRA) to inhibit the Nrf2. Our finding showed the induction of pyroptosis as evidenced by increased levels of NLRP3 and other inflammatory mediators, including IL-1β, iNOS, p-NFKB, and apoptotic cell death indicated by positive fluoro Jade B (FJB) staining. Moreover, increased levels of lipid peroxides and reactive oxygen species indicated a significant rise in oxidative stress due to LPS. The administration of carveol mitigates oxidative stress and suppresses inflammatory pathways through the augmentation of intrinsic antioxidant defenses, primarily via the activation of the Nrf2. Conversely, ATRA reversed carveol protective effects by increasing FJB-positive cells, inflammatory and oxidative biomarkers. Taken together, our findings suggest that carveol mitigated LPS-induced Parkinson-like symptoms, partially through the activation of the Nrf2 and downregulation of pyroptosis notably NLRP3. [ABSTRACT FROM AUTHOR]

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits. [ABSTRACT FROM AUTHOR]

Candida parapsilosis was introduced as the second most responsible for nail involvement. The colonization of biotic and abiotic surfaces by Candida spp. can result in the formation of biofilms, which possess a high level of resistance to typical antifungal agents. Since Candida spp. can produce biofilm mass on the surface of the nails, dermatologists should consider appropriate antifungals to eliminate both the planktonic and biofilm cells. The aim of this research was to determine the antifungal efficacy of itraconazole against C. parapsilosis sensu lato biofilm formations, in addition to its static effects. Ten C. parapsilosis sensu lato isolates were enrolled in this study. The use of itraconazole results in the accumulation of reactive oxygen species (ROS) during treatment. In order to verify the correlation between ROS and itraconazole-induced cell death, the viability of cells was analyzed by administering the ROS scavenger Ascorbic acid. The apoptotic features of itraconazole were analyzed using the Annexin V-FITC method. Based on current data, it was found that the generation of intracellular stresses by itraconazole is not observed in cells upon ROS inhibition, emphasizing the importance of intracellular ROS in the apoptotic mechanism of itraconazole. Targeting the oxidative defense system is a powerful point to use ROS-inducing antifungals as a superior choice for more effective therapies in case of recalcitrant onychomycosis. [ABSTRACT FROM AUTHOR]

Pearl millet (Pennisetum glaucum (L.) R. Br.), a vital C4 Panicoid millet crop, predominantly thrives in rainfed regions subject to various abiotic stresses, notably drought and cold stress, limiting its growth potential and yield. As climate change exacerbates water scarcity, understanding methods to mitigate drought's adverse effects becomes crucial. However, particular bacteria flourishing in the rhizosphere, demonstrating resilience to drought and skilled at nurturing plant health, are recognized for their ability to enhance growth under various abiotic stresses. The current study demonstrated the varying effects of Pseudomonas putida MTCC5279 (RA) on mitigating drought stress under low-temperature field conditions for the pearl millet genotypes PRLT2/89–33 (drought-tolerant) and H77/833–2 (drought-resistant). Plants of both genotypes are grown till panicle emergence and subjected to drought stress at the start of January where temperature also drops in field conditions. The compound effect of drought with low temperature severely affects the inflorescence of both the genotypes but RA-inoculated PRLT2/89–33 plants have better performance than their respective control and drought plants as well compared to H77/833–2 genotypes. Abiotic stresses markedly influenced growth metrics, osmolyte buildup, MDA levels, and the capability to scavenge reactive oxygen species (ROS), all of which saw positive modulation following the application of RA in PRLT2/89–33. To our knowledge, this study represents the first comprehensive examination of P. putida-mediated plant growth enhancement in pearl millet under the combined effects of abiotic stresses. [ABSTRACT FROM AUTHOR]

Faster ripening and senescence of banana fruit is closely associated with higher ethylene production and oxidative damages. Present study evaluated the mechanism of sodium nitroprusside (as a nitric oxide donor) on delayed ripening and senescence in banana as well as mitigating the oxidative damage. Nitric oxide (NO) was applied to fruit by vacuum infiltration (1 mM) and stored for 8 days at 25 °C with 65–70% relative humidity. Fruit quality, electrolytic leakage, phenolic content, reactive oxygen species production and scavenging activity were investigated. The results showed that NO treated fruit retained higher phenolics, antioxidant capacity (radical scavenging activity), and reduced electrolytic leakage, malondialdehyde (MDA) content and free radical production (H2O2 and O2−) than control on the last day. The inhibitory effect of NO on ripening was observed with delayed chlorophyll loss as well as reduced ethylene and CO2 production rate in banana during storage. Therefore, vacuum infiltrated NO could be a possible postharvest treatment for mitigating the oxidative damages and preserving banana fruit up to 8 days at ambient condition. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) and ferroptosis therapy have received extensive attention in breast cancer treatment. PDT induced apoptosis of tumor cells by producing a large amount of reactive oxygen species (ROS) under laser irradiation. Differently, ferroptosis therapy exerts its antitumor effect by inducing excessive accumulation of lipid peroxides on tumor cell membranes. Based on that, ROS produced by PDT may promote ferroptosis in tumor cells, and ferroptosis therapy is expected eliminate apoptosis-resistant tumor cells. Therefore, a synergistic ferroptosis-photodynamic therapy will be more effective and more potential in breast cancer treatment. Considering PDT has the characteristic of producing ROS, and neutrophil has a natural tendency to ROS, a neutrophil-mimetic hybrid liposome (CR-NML) was designed for co-delivery of the photosensitizer Ce6 and the ferroptosis inducer RSL3. CR-NML targeted tumor through the ROS tendency of neutrophil and the enhanced permeability and retention (EPR) effect of liposome, then induced both apoptosis and ferroptosis in tumor cells, which increased ROS level and finally realized ROS cascade amplification. The synergistic ferroptosis-photodynamic therapy demonstrated significant therapeutic efficacy in 4T1 tumor bearing mice, which provided a promising strategy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The rapid quantification of hydroxyl radical (·OH) in real samples is a great challenge due to its highly reactive nature and the potential interferences from other coexisting reactive oxygen species (ROS). Herein, a chemiluminescence (CL) probe (ox-CDs) was rationally developed for the detection of ·OH through controlled oxidation treatment of original CDs (o-CDs) with H2O2. Post-oxidation of CDs can reduce the surface defects or functional groups on the CDs, exposing reactive sites capable of effectively reacting with ·OH. The chemical energy generated from redox reaction between ·OH and the ox-CDs can be efficiently utilized to generate strong and selective CL responses to ·OH without interferences from other ROS. Thus, a highly selective and sensitive CL method with a linear range from 0.01 to 150 μM and a detection limit of 3 nM was developed, which was successfully applied for monitoring the ·OH production from cigarette and mosquito coil smoke. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease characterized by the hyperproliferation of keratinocytes and an overactive autoimmune response. Photodynamic therapy (PDT) has been established as a promising intervention for alleviating psoriasis. However, the current transdermal delivery of photosensitizers is inefficient and imprecise. In this study, we developed a foamed microemulsion nanodroplets system containing chlorin e6 (Ce6 FM), exhibiting precise epidermal targeting and retention, which targeted the aberrantly proliferating epidermal cells at psoriatic skin lesions and avoided the damage to the normal cutaneous cells. Upon application in a psoriatic mouse model, Ce6 FM efficiently induced keratinocyte apoptosis by generating reactive oxygen species under laser. Furthermore, Ce6 FM-based PDT activated the cyclooxygenase-2-induced immunosuppressive pathway in keratinocytes, resulting in the amelioration of the autoimmune microenvironment in psoriatic skin. Additionally, Ce6 FM-based PDT did not induce skin damage or atrophy associated with non-targeted halometasone treatment. Overall, Ce6 FM-based PDT holds promise as an effective, safe and compliant strategy for psoriasis treatment. [ABSTRACT FROM AUTHOR]

The excessive reactive oxygen species (ROS) accumulation and overactivated osteoclastogenesis in subchondral bone has proved to be a major cause of osteoarthritis (OA). Scavenging of ROS microenvironment to inhibit the osteoclastogenesis is highly valued in the therapeutic process of osteoarthritis. Despite the excellent ability of polyphenolic colloidal to scavenge reactive oxygen species and its affinity for macrophages, the preparation of polyphenolic colloidal nanoparticles is limited by the complex intermolecular forces between phenol molecules and the lack of understanding of polymerization/sol-gel chemistry. Herein, our work introduces a novel poly-tannin-phenylboronic colloidal nanoparticle (PTA) exclusively linked by ROS-responsive bondings. Nanocolloidal PTA has a uniform particle size, is easy and scalable to synthesize, has excellent scavenging of ROS, and can be slowly degraded. For in vitro experiments, we demonstrated that, PTA could eliminate ROS within RAW264.7 cells and impede osteoclastogenesis and bone resorption. RNA sequencing results of PTA-treated RAW264.7 cells further reveal the promotion of antioxidant activity and inhibition of osteoclastogenesis. For in vivo experiments, PTA could eliminate the ROS environment and reduce the number of osteoclasts in the subchondral bone, thereby alleviating the damage of subchondral bone and symptoms of osteoarthritis. Our research, by delving into the formation of polyphenol colloidal nanoparticles and validating their role in ROS scavenging to inhibit osteoclastogenesis in subchondral bone, may open new avenues for OA treatment in the future. [ABSTRACT FROM AUTHOR]

Heterogeneous Fenton-like reaction shows great potential for eliminating organic substances (e.g. emerging organic contaminants (EOCs)) in water, which has been widely explored in recent decades. However, the catalytic mechanisms reported in current studies are extremely complicated because multiple mechanisms coexist and contribute to the removal efficiencies. Most importantly, heterogeneous systems show selective oxidation properties, which are crucial for improving the efficiencies in the catalytic elimination of organic substances. Thus, this critical review summarizes and compares the diverse existing mechanisms (non-radical and radical pathways) in heterogeneous catalytic processes based on recent studies. The typical oxidation mechanisms during selective advanced oxidation of EOCs were systematically discussed based on the following sections, including the selective adsorption and generation of reactive oxygen species (ROS) in photo/electron-Fenton and Fenton-like systems. Moreover, the non-radical pathways are discussed in depth by the singlet oxygen, high-valent metal-oxo, electron transfer process, etc. Moreover, the direct oxidative transfer process for the removal of EOCs was introduced in recent studies. Finally, the cost, feasibility as well as the sustainability of heterogeneous Fenton-like catalysts are summarized. This review offers useful guidance for developing suitable strategies to develop materials for decomposing the organic substrates. [ABSTRACT FROM AUTHOR]

Plasma activated water (PAW) has been prepared using atmospheric pressure air dielectric barrier discharge with the bubbling method. This study aims to elucidate the crucial role of gas-liquid interface in determining the physicochemical properties and biological reactivity of PAW, as well as describe the process of mass transfer for reactive oxygen and nitrogen species (RONS) during the PAW generation. Gas-liquid interfacial area is regulated by varying the airflow rate. When the airflow rate increases from 0.5 to 16.0 SLM, the concentrations of , , and activated oxygen in PAW increase significantly, and the water-activated time for complete E. coli inactivation can be shortened from more than 320 s to 40 s. The numerical simulation result shows that when the airflow rate increases from 0.5 to 16.0 SLM, the gas-liquid interfacial area increases from 0.014 to 0.3 m2/600 mL. The analysis shows that the dependence of the chemical reactivity and the biological reactivity on the interface area is mainly attributed to the change of the mass flux with the interface area. [ABSTRACT FROM AUTHOR]

Accumulation studies confirmed that oxidative stress caused by ischemia after myocardial infarction (MI) is an important cause of ventricular remodeling. Exosome secretion through hypoxic pretreatment adipose-derived mesenchymal stem cells (ADSCs) ameliorates myocardial damaging post-MI. However, if ADSCs exosome can improve the microenvironment and ameliorate cardiac damage post-MI still unknown. Next-generation sequencing (NGS) was used to study abnormally expressed circRNAs in hypoxic pretreatment ADSC exosomes (HExos) and untreated ADSC exosomes (Exos). Bioinformatics and luciferase reporting were used to elucidate interaction correlation related to circRNA, mRNA, and miRNA. HL-1 cells were used to analyze the reactive oxygen species (ROS) and apoptosis under hypoxic conditions using immunofluorescence and flow cytometry. An MI mouse model was constructed and the therapeutic effect of Exos was determined using immunohistochemistry, immunofluorescence, and ELISA. The results showed that HExos had a more pronounced treatment effect than ADSC Exos on cardiac damage amelioration after MI. NGS showed that circ-Stt3b plays a role in HExo-mediated cardiac damage repair after MI. Overexpression of circ-Stt3b decreased apoptosis, ROS level, and inflammatory factor expression in HL-1 cells under hypoxic conditions. Bioinformatics and luciferase reporting data validated miR-15a-5p and GPX4 as downstream circ-Stt3b targets. GPX4 downregulation or miR-15a-5p overexpression reversed protective effect regarding circ-Stt3b upon HL-1 cells after exposure to a hypoxic microenvironment. Overexpression of circ-Stt3b increased the treatment effect of ASDSC Exos on cardiac damage amelioration after MI. Taken together, the study results demonstrated that Exos from hypoxic pretreatment ADSCs ameliorate cardiac damage post-MI through circ-Stt3b/miR-15a-5p/GPX4 signaling activation and decreased ferroptosis. [ABSTRACT FROM AUTHOR]

The environmental threat posed by industrial dyes necessitates the development of efficient photocatalytic systems for their degradation. This study focuses on the Ce-doped Zn:Zr system as an innovative solution for visible-light-driven photocatalytic degradation of textile dyes offering significant environmental and industrial benefits. The Ce-doping effect on the photocatalytic efficiency of the Zn:Zr system was investigated. Both undoped and Ce-doped Zn:Zr systems exhibited hexagonal nanostructures with high atomic percentages of Zn, while Ce was incorporated at lower percentages. X-ray diffraction confirmed the unaltered hexagonal ZnO, tetragonal, and monoclinic ZrO2 crystal structures in the systems. The peak broadening in the Ce-doped samples indicates successful doping. Even the tiniest alteration in band gap resulted in a dramatic increase in methylene blue dye degradation up to 98.4%, significant at p < 0.05. This enhanced efficiency is attributed to the heterogeneous pairing mechanism which improves charge carrier separation with superoxide anions and singlet oxygen identified as the primary reactive species. The findings demonstrate the applicability of band gap engineering in organic pollutant degradation and highlight the potential of Ce-doped Zn:Zr systems as a cost-effective and energy-efficient solution for industrial wastewater management. [ABSTRACT FROM AUTHOR]

Biogenic metallic nanoparticles (NPs) have garnered significant attention in recent years due to their unique properties and various applications in different fields. NPs, including gold, silver, zinc oxide, copper, titanium, and magnesium oxide NPs, have attracted considerable interest. Green synthesis approaches, utilizing natural products, offer advantages such as sustainability and environmental friendliness. The theranostics applications of these NPs hold immense significance in the fields of medicine and diagnostics. The review explores intricate cellular uptake pathways, internalization dynamics, reactive oxygen species generation, and ensuing inflammatory responses, shedding light on the intricate mechanisms governing their behaviour at a molecular level. Intriguingly, biogenic metallic NPs exhibit a wide array of applications in medicine, including but not limited to anti-inflammatory, anticancer, anti-diabetic, anti-plasmodial, antiviral properties and radical scavenging efficacy. Their potential in personalized medicine stands out, with a focus on tailoring treatments to individual patients based on these NPs' unique attributes and targeted delivery capabilities. The article culminates in emphasizing the role of biogenic metallic NPs in shaping the landscape of personalized medicine. Harnessing their unique properties for tailored therapeutics, diagnostics and targeted interventions, these NPs pave the way for a paradigm shift in healthcare, promising enhanced efficacy and reduced adverse effects. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a persistent interstitial lung condition for which effective treatment options are currently lacking. Zerumbone (zerum), a humulane sesquiterpenoid extracted from Zingiber zerumbet Smith, has been documented in previous studies to possess various pharmacological benefits. The aim of this study was to observe and investigate the therapeutic effects and mechanisms of zerum on pulmonary fibrosis. We utilized a transforming growth factor (TGF)-β1-induced human lung fibroblast (MRC-5) activation model and a bleomycin-induced pulmonary fibrosis mouse model. Cell counting kit 8 (CCK8) and cell migration assays were performed to assess the effects of zerum on MRC-5 cells. Masson's trichrome, Hematoxylin and Eosin (HE), and Sirius Red staining were conducted for pathological evaluation of lung tissue. Western blot experiments were conducted to measure the protein expression levels of Collagen I, α-SMA, Nrf2, and SIRT1. Immunofluorescence and immunohistochemistry assays were used to detect the expression of reactive oxygen species (ROS), Nrf2, and α-SMA. ELISA was employed to measure the levels of MDA, SOD, and GSH-Px. Our findings from in vitro and in vivo studies demonstrated that zerum significantly inhibited the migration ability of TGF-β1-induced MRC-5 cells, reduced ROS production in TGF-β1-induced MRC-5 cells and pulmonary fibrosis mice, and decreased the expression of Collagen I and α-SMA proteins. Additionally, zerum activated the SIRT1/Nrf2 signaling pathway in TGF-β1-induced MRC-5 cells and pulmonary fibrosis mice. Knockdown of SIRT1 abolished the anti-fibrotic effects of zerum. These results suggest that zerum inhibits TGF-β1 and BLM-induced cell and mouse pulmonary fibrosis by activating the SIRT1/Nrf2 pathway. [ABSTRACT FROM AUTHOR]