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Sepsis is one of major reasons of cardiorenal syndrome type 5 (CRS-5), resulting in irreversible tissue damage and organ dysfunction. Macrophage has been demonstrated to play key role in the pathophysiology of sepsis, highlighting the need to identify therapeutic targets for modulating macrophage phenotype in sepsis. In this study, a rapid-releasing hydrogen sulfide (H2S) donor NaSH, and a slow-releasing H2S compound S-propargyl-cysteine (SPRC) which is derived from garlic, have been studied for the immune-regulatory effects on macrophages. The NaSH and SPRC showed the potential to protect the heart and kidney from tissue injury induced by LPS. The immunohistochemistry of F4/80+ revealed that the infiltration of macrophages in the heart and kidney tissues of LPS-treated mice was reduced by NaSH and SPRC. In addition, in the LPS-triggered inflammatory cascade of RAW264.7 macrophage cells, NaSH and SPRC exhibited significantly inhibitory effects on the secretion of inflammatory cytokines, production of reactive oxygen species (ROS), and regulation of the macrophage phenotype from M1-like to M2-like. Moreover, autophagy, a crucial process involved in the elimination of impaired proteins and organelles during oxidative stress and immune response, was induced by NaSH and SPRC in the presence of LPS stimulation. Consequently, there was an increase in the number of mitochondria and an improvement in mitochondrial membrane potential. This process was mainly mediated by PINK1/Parkin pathway mediated mitophagy. These results demonstrated that the immunoregulatory effects of H2S donors were through the PINK1/Parkin-mediated mitophagy pathway. Overall, our study provided a new therapeutic direction in LPS-induced cardiorenal injury. [ABSTRACT FROM AUTHOR]

[Display omitted] Metal-organic frameworks (MOFs) are prospective photocatalysts for removing pollutants. However, the large size of MOFs results in unsatisfactory photocatalytic performance, thus restricting their further usage. Herein, ultrasmall Ti MOF (NH 2 -MIL-125(Ti)) nanodots (diameter: < 10 nm) were prepared on carbon fiber (CF) (diameter: ∼7 μm) based MoS 2 (thickness: ∼20 nm, length: ∼200 nm) via a facile method and used as an efficient and reusable photocatalyst. The weaved CF/MoS 2 /NH 2 -MIL-125(Ti) cloth (0.15 g, 4 × 4 cm2) shows good reusability with an easy reusing process. Compared with large size NH 2 -MIL-125(Ti) based sample, our well-prepared NH 2 -MIL-125(Ti) nanodots based sample shows the improved surface area (290.1 m2 g−1) and it can generate more reactive oxygen species (ROS), which enhance removal performance (81.1% levofloxacin (LVFX), 67.9% acid orange 7 (AO7), 94.3% methylene blue (MB) and 100% Cr(Ⅵ)) in 120 min. Additionally, the recycling test for 4 cycles indicates high stability. This work highlights the function of easy-recyclable NH 2 -MIL-125(Ti) nanodots-based heterojunctions in wastewater purification. [ABSTRACT FROM AUTHOR]

Aims Endothelial progenitor cell (EPC) dysfunction underlies a critical risk factor in diabetic vascular complications due to function defect in restoring endothelium injury. Crocetin has attracted increasing attention in several vascular-related diseases. In present study, we aimed to explore the role of crocetin in diabetic EPC dysfunction. Main methods EPCs were isolated from bone marrow in diabetic mice and identified using the fluorescence staining and flow cytometry. After exposure to various doses of crocetin, cell viability was detected by MTT assy. Then, colony formation, lactate dehydrogenase (LDH) release, cell apoptosis and caspase-3 activity were assessed. The underlying mechanism was also investigated by western blotting. Key findings EPCs from diabetic mice exhibited dysfunction under hyperglycemia condition. Interestingly, crocetin treatment alleviated the impairment in diabetic EPC proliferation and colony formation. Simultaneously, the increases in LDH release, cell apoptosis and caspase-3 activity were also restrained following crocetin stimulation. Additionally, EPC migration response to SDF-1 was also impaired under diabetic condition, which was partly restored by crocetin. Mechanism analysis manifested that administration with crocetin repaired the damage in the activation of PI3K/AKT-eNOS pathway and NO production, but attenuated ROS elevation in diabetic EPCs. Importantly, preconditioning with antagonist of LY294002 (for PI3K/AKT) or N G -monomethyl- l -arginine (for eNOS) antagonized the beneficial effect of crocetin on diabetic EPC dysfunction. Significance These data corroborated that crocetin could restore the dysfunction of diabetic EPCs by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways. Therefore, this research supports a potential promising therapeutic aspect for diabetic patients. [ABSTRACT FROM AUTHOR]

The presence of too many reactive oxygen species (ROS) will damage cells. To eliminate ROS, a nanocomposite film containing diselenide bonds is fabricated via the layer‐by‐layer assembly method, using adamantane‐terminated diselenide block copolymer micelles and β‐cyclodextrin‐modified nanoparticles as building blocks. This film possesses potential stability under the normal physiological condition and can eliminate different kinds of ROS. [ABSTRACT FROM AUTHOR]

A novel tellurium-containing polymer micelle system is reported to be responsive to 100 μM H2O2 and can undergo a series of morphological changes. The polymer micelles also respond to 2 Gy gamma radiation, which is the exact dosage a patient receives per day for clinical radiation therapy. [ABSTRACT FROM AUTHOR]

Background: Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and low-concentration RSL3 and attempted to rise the sensitivity of NSCLC cells on RSL3. Methods: CCK-8 assay was employed to detect the change of cell viability. Microscopy and flowcytometry were applied to identify lipid peroxidation, cell death and reactive oxygen species (ROS) level respectively. The molecular mechanism was inspected with western blot and RT-qPCR. A xenograft mice model was adopted to investigate the effect of NTP and RSL3. Results: We found the synergism of NTP and low-concentration RSL3 triggered severe mitochondria damage, more cell death and rapid ferroptosis occurrence in vitro and in vivo. NTP and RSL3 synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, we revealed mitochondrial ROS was the main executor for ferroptosis induced by the combined treatment. Conclusion: Our research shows NTP treatment promoted the toxic effect of RSL3 by inducing more ferroptosis rapidly and provided possibility of RSL3 clinical application. DeK3en8zu4Ed_UHNNMi2cX Video Abstract [ABSTRACT FROM AUTHOR]

A lipidated polysaccharide, HDPS-2II, was isolated from the dried larva of Holotrichia diomphalia , which is used in traditional Chinese medicine. The molecular weight of HDPS-2II was 5.9 kDa, which contained a polysaccharide backbone of →4)-β-Man p -(1 → 4,6)-β-Man p -(1 → [6)-α-Glc p -(1] n → 6)-α-Glc p → with the side chain α-Glc p -(6 → 1)-α-Glc p -(6 → linked to the C-4 of β-1,4,6-Man p and four types of lipid chains including 4-(4-methyl-2-(methylamino)pentanamido)pentanoic acid, 5-(3-(tert-butyl)phenoxy)hexan-2-ol, N-(3-methyl-5-oxopentan-2-yl)palmitamide, and N-(5-amino-3-methyl-5-oxopentan-2-yl)stearamide. The lipid chains were linked to C-1 of terminal α-1,6-Glc p in carbohydrate chain through diacyl-glycerol. HDPS-2II exhibited DNA protective effects and antioxidative activity on H 2 O 2 - or adriamycin (ADM)-induced Chinese hamster lung cells. Furthermore, HDPS-2II significantly ameliorated chromosome aberrations and the accumulation of reactive oxygen species (ROS), reduced γ-H2AX signaling and the expressions of NADPH oxidase (NOX)2, NOX4, P22phox, and P47phox in ADM-induced cardiomyocytes. Mechanistically, HDPS-2II suppressed ADM-induced up-regulation of NOX2 and NOX4 in cardiomyocytes, but not in NOX2 or NOX4 knocked-down cardiomyocytes, indicating that HDPS-2II could relieve intracellular DNA damage by regulating NOX2/NOX4 signaling. These findings demonstrate that HDPS-2II is a new potential DNA protective agent. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is a multiple-function biopolymer that is widely used in food, cosmetic, and biomedical fields. In group C streptococci, the major workhorse of HA production in industry, the HA biosynthetic pathway has been proposed, while how HA synthesis is regulated is unclear. In this study, we identified twenty-five putative transcriptional repressors in S. zooepidemicus and studied whether they regulate HA synthesis or not. The individual gene deletion strain was firstly constructed, and the phenotypic changes of the corresponding deletion strains in stress tolerance and HA production were detected. The hrcA deletion strain is more sensitive to high temperature, and the rex deletion strain is more resistant to the oxidative stress. Three transcriptional repressor deletions resulted significantly decreased transcriptional levels of hasA, among which the scrR deletion strain shows most dramatical decrease in HA production. The regulatory mechanism of how ScrR affects the production of HA was further explored by transcriptional expression analysis of scrA and scrB, two direct target genes of ScrR regulon. Our results indicates that the deficiency of ScrR results in the unbalanced expression of scrA and scrB, which might also partly account for the decreasing production of HA. In agreement with the speculation, overexpression of scrB in ΔscrR genetic background results in 80% improvement in HA production. Taken together, the systemic genetic study of transcriptional repressors expands our understanding for the physiological regulation process of S. zooepidemicus and should help in the development of high-performance industrial strains for the efficient production of HA. Key points: • Twenty-two transcriptional repressor genes in S. zooepidemicus were deleted individually, and the phenotypes of corresponding mutants on a variety of conditions were characterized. • HrcA deficiency showed inferior cell tolerance to high temperature, and Rex deficiency showed superior cell tolerance to reactive oxygen stress, and four repressors deficiency showed inferior hyaluronic acid synthesis, among which the transcriptional levels of hasA of three mutants decreased significantly. • Optimizing sucrose metabolic flux can enhance hyaluronic acid synthesis significantly. [ABSTRACT FROM AUTHOR]

Allelopathy is mediated by plant-derived secondary metabolites (allelochemicals) which are released by donor plants and affect the growth and development of receptor plants. The plant root is the first organ which senses soil allelochemicals this results in the production of a shorter primary root. However, the mechanisms underlying this process remain elusive. Here, we report that a model allelochemical benzoic acid (BA) inhibited primary root elongation of Arabidopsis seedlings by reducing the sizes of both the meristem and elongation zones, and that auxin signaling affected this process. An increase in auxin level in the root tips was associated with increased expression of auxin biosynthesis genes and auxin polar transporter AUX1 and PIN2 genes under BA stress. Mutant analyses demonstrated that AUX1 and PIN2 rather than PIN1 were required for the inhibition of primary root elongation during BA exposure. Furthermore, BA stimulated ethylene evolution, whereas blocking BA-induced ethylene signaling with an ethylene biosynthesis inhibitor (Co2+), an ethylene perception antagonist (1-methylcyclopropene) or ethylene signaling mutant lines etr1-3 and ein3eil1 compromised BA-mediated inhibition of root elongation and up-regulation of auxin biosynthesis-related genes together with AUX1 and PIN2, indicating that ethylene signal was involved in auxin-mediated inhibition of primary root elongation during BA stress. Further analysis revealed that the BA-induced reactive oxygen species (ROS) burst contributed to BA-mediated root growth inhibition without affecting auxin and ethylene signals. Taken together, our results reveal that the allelochemical BA inhibits root elongation by increasing auxin accumulation via stimulation of auxin biosynthesis and AUX1 / PIN2 -mediated auxin transport via stimulation of ethylene production and an auxin/ethylene-independent ROS burst. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) with exogenous protoporphyrin IX (PpIX) or endogenous PpIX derived from 5-aminolevulinic acid (ALA) has been carried out to produce apoptotic effects on macrophages, indicating a potential treatment methodology for atherosclerosis. Our previous studies have found that mitochondria damage by reactive oxygen species (ROS) plays a major role in the SDT-induced apoptosis. This study aimed at investigating the potential involvement of the mitochondrial 18 kDa translocator protein (TSPO) and ROS in the pro-apoptotic effects of SDT on THP-1 macrophages. THP-1 macrophages were divided into control and SDT groups, and went through pretreatment of the specific TSPO ligand PK11195 and ROS scavengers N-Acetyl Cysteine (NAC), then compared with groups without pretreatment. Application of PK11195 reduced intracellular accumulation of endogenous PpIX. PK11195 and NAC reduced the generation of intracellular ROS and oxidation of cardiolipin induced by SDT, respectively. PK11195 and NAC also reduced SDT-induced mitochondrial membrane potential (ΔΨm) loss, the translocation of cytochrome c and cell apoptosis. PpIX accumulation, ROS generation and cell apoptosis were also attenuated by siTSPO. Our findings indicate the pivotal role of TSPO and ROS in SDT-induced cardiolipin oxidation, ΔΨm collapse, cytochrome c translocation and apoptosis in THP-1 macrophages. [ABSTRACT FROM AUTHOR]

Peach fruit deteriorates and senesces quickly during storage at ambient temperature. Research confirms that melatonin (MT) is involved in plant senescence. However, little information is available on the effects of MT on postharvest senescence. In this study, two cultivars of peach fruit ‘Shahong’ and ‘Qinmi’ were treated with MT at 0.1 mmol L −1 and then stored at ambient temperature (25–28 °C)for 7 days. The results showed that MT treatment effectively slowed process of senescence in both peach cultivars, as indicated by reduced weight loss, decay incidence and respiration rate as well as maintained firmness, total soluble solids and ascorbic acid contents. MT treatment significantly enhanced the activities of superoxide dismutase, catalase, peroxidase and ascorbate peroxidase in both cultivars, but decreased the activity of lipoxygenase, levels of superoxide anion and hydrogen peroxide, and malondialdehyde content. These results indicate that the activation of antioxidant enzymes to scavenge superoxide anion and hydrogen peroxide by MT treatment was associated with the maintenance of membrane integrity, which might be a part of the mechanism implicated in delay of senescence in peach fruit. [ABSTRACT FROM AUTHOR]

The construction of advanced systems that can accurately detect neuron-specific enolase (NSE) is critical to the rapid diagnosis of small cell lung cancer (SCLC). Herein, a luminol-based electrochemiluminescence (ECL) biosensor enhanced by reactive oxygen species (ROS) is proposed to perform the ultrasensitive detection of NSE. D-Fe 2 O 3 @Pt, synthesized as a signal indicator, was combined with luminol to significantly shorten its electron transfer pathway. Its peroxidase activity catalyzed the decomposition of H 2 O 2 to generate a large amount of •OH, thus considerably increasing the ECL signal of the luminol–H 2 O 2 system. CePO 4 /CeO 2 heterostructures with improved surface-active areas were then employed as sensing substrates. The platform enabled the accelerated generation of O 2 •− through enriched Ce4+/Ce3+ redox pairs, thereby amplifying the strength of the response of the foundation. Through integrated dual ROS amplification, the proposed sandwich ECL immunosensor configuration achieved sensitive detection in the detection range of 76 fg/mL – 100 ng/mL, with a detection limit of 72.4 fg/mL. Furthermore, the sensor exhibited high selectivity for the determination of NSE in human serum. Overall, this study serves as an important reference for integrating ROS and enzymatic strategies in ECL research to achieve accurate, sensitive, and highly selective detection of a target. [ABSTRACT FROM AUTHOR]

We report the preparation of selenium-containing platinum-based anticancer drug EG-Se/Pt. EG-Se/Pt was obtained from the coordination of selenium-containing molecules (EG-Se) with cisplatin (CDDP). The structure of EG-Se/Pt was characterized by 1H and 77Se NMR spectroscopy, XPS, ESI-MS, and MALDI-TOF. In aqueous solution, EG-Se/Pt self-assembles to form spherical aggregates. EG-Se/Pt shows enhanced stability against dilution and high salt concentration compared with EG-Se. EG-Se/Pt induces cell apoptosis via reactive oxygen species (ROS), which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays. More importantly, EG-Se/Pt effectively inhibits tumor growth in vivo in tumor-bearing mice. It is anticipated that tuning the ROS level through the assembly of selenium-containing molecules can be a general method to realize anticancer selectivity. [ABSTRACT FROM AUTHOR]

Biocompatible nitrogen-doped hydrazide-conjugated carbon dots (NHCDs) as an anodic luminophores with low excitation potential were equipped with an efficient multiple signal-amplification strategy for electrochemiluminescence (ECL) trace bioanalysis. To promote the ECL emission of NHCDs-H 2 O 2 system, gold nanoparticles (Au NPs) functionalized tin oxide nanocrystals (Au@SnO 2 NCs) were adopted to anchor large amount of NHCDs, the formed NHCDs-Au@SnO 2 NCs could conjugate with detection antibody as the signal label. Moreover, 3,4,9,10-perylenetetracarboxylic acid (PTCA) molecules were immobilized on the flower-like microsphere (PTCA@ZnCo 2 O 4 /ZnO) nanocomposites to fabricate as an electro-active sensing substrate to incubate the capture antibody, which could efficiently accelerate the generation of reactive oxygen species (OH · /O 2 ·- ) through electrocatalytic excitation and co-reaction acceleration. Integrating with the sandwich-type sensing model, an ECL immunosensor was established to detect biomarkers of squamous cell carcinomas named cytokeratin 19 fragments (cyfra21–1). Combining with the synergistic signal-amplification induced by the Au@SnO 2 NCs, PTCA, and ZnCo 2 O 4 /ZnO nanocomposites, the developed immunosensor performed detection range from 0.09 pg/mL to 100 ng/mL with a detection limit of 34.38 fg/mL. The results showcased the great potential of this sensing strategy for real sample analysis of biomarker with reliable stability, selectivity and repeatability. • Flower-like PTCA-modified ZnCo 2 O 4 /ZnO was synthesized by hydrothermal method. • PTCA-modified ZnCo 2 O 4 /ZnO was demonstrated that can efficiently achieve electrocatalytic excitation and catalyze the ROSs production to amplify the ECL signal. • Au@SnO 2 NCs was utilized to construct highly efficient catalytic nanocarriers. • Signal multiple-amplification strategy was built to improve sensitivity. • The established immunosensor exhibited low detection limit of 34.38 fg·mL-1 for CYFRA21-1. [ABSTRACT FROM AUTHOR]

Highlights: [•] Up-regulation of miR-34a inhibits cell viability. [•] Suppression of miR-34a enhances cell viability. [•] NOX2 is a target of miR-34a in A172 cells. [•] MiR-34a serves as a tumor suppressor in human glioma. [Copyright &y& Elsevier]

ABSTRACT Coconut sap is consumed as a juice or used as raw material for fermentation to produce beverages with various health benefits. To understand the underlying mechanisms of the health benefits of coconut sap, we investigated the in vitro reactive oxygen species scavenging activities and DNA protecting effects of fresh and naturally fermented coconut sap using a flow-injection chemiluminescence method. The results show that the fresh sap scavenges superoxide anion, hydroxyl radical and hydrogen peroxide better than the naturally fermented sap; in contrast, the fermented sap shows a more powerful ability to prevent damage to DNA than the fresh sap. The naturally fermented sap had a higher polyphenol level but a lower ascorbic acid content than fresh sap, suggesting that fermentation is beneficial for improving the polyphenol content of coconut sap. PRACTICAL APPLICATION Reactive oxygen species (ROS) are reported to be related to many diseases, such as cancer and Alzheimer's disease. Antioxidants are vital substances that possess the ability to protect the body from damage caused by ROS. There is an increasing interest in natural antioxidants, e.g., polyphenols, present in medicinal and dietary plants, which might help prevent oxidative damage. Coconut sap is obtained by tapping the unopened spadix of the coconut palm, and also used as the resource of sugar and alcoholic beverages by local people. Our experimental results testify that the coconut sap has powerful ROS scavenging activity and can be potentially used as the ingredients of functional food. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Owing to the limitations in the current therapeutic strategies for treating HCC, development of novel chemotherapeutic drugs is urgently needed. In the present study, we found that QQM, a newly-synthesized quinolinylmethyl substituted ethylenediamine compound, exhibited anti-HCC effects both in vitro and in vivo. QQM inhibited HCC cell growth and induced G0/G1-phase cell cycle arrest and apoptosis in a dose-dependent manner. Our results showed that QQM acted by significantly increasing intracellular reactive oxygen species in HCC cells, which led to cell apoptosis and growth inhibition. Furthermore, QQM treatment resulted in an accumulation of reactive nitric oxide (NO) in HCC cells, and introduction of a NO scavenger, carboxy-PTIO, largely attenuated QQM-induced cytotoxicity. Finally, we found that QQM inhibited growth and induced apoptosis of HCC xenograft tumors in vivo. Taken together, our results indicated that QQM exerted anti-HCC effects by inducing reactive oxygen species and NO accumulation in HCC cells. Thus, QQM exhibits the qualities of a novel, promising anti-tumor candidate for the treatment of HCC. Image 1 [ABSTRACT FROM AUTHOR]

Development of a simple, cost-effective and sensitive biosensing strategy is highly desirable to advance the applications in Alzheimer's disease diagnosis. In this paper, we present a simple, label-free and signal-on electrochemiluminescence (ECL) aptasensor for the detection of amyloid-beta (Aβ) peptide using luminol as ECL emitter and in-situ generated reactive oxygen species (ROS) as coreactant via catalytic reaction between Cu2+-Aβ and the dissolved O 2 in the presence of ascorbic acid (AA). Aβ 16 , the binding site of Cu2+ in the monomeric full-length Aβ, was used as a model in present study. As a result, this signal-on ECL aptasensor has exhibited favorable analytical performance for Aβ 16 monomer with a linear range of 1.0 × 10-13 mol/L-1.0 × 10-8 mol/L and a limit of detection of 3.5 × 10-14 mol/L (S/N=3). Furthermore, the proposed biosensor was also able to detect the full length Aβ 40 not only in the phosphate buffer saline (PBS) solution but also in human serum. The presented biosensor represents a promising, simple, turn-on and label-free diagnostic tool for blood analysis. • A simple, label-free and signal-on ECL aptasensor for the detection of Aβ peptide was development. • The aptasensor can monitor the aggregation process of Aβ 16 monomer accelerated by Cu2+. • The proposed biosensor was able to detect the full length Aβ 40 not only in the PBS solution but also in human serum. [ABSTRACT FROM AUTHOR]