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Purpose: The aim of this investigation was to assess alterations of pulmonary oxygen uptake ( V ˙ O 2 ) and muscle deoxygenation on-kinetics during heavy-intensity cycling in youth cyclists over a period of 15 months. Methods: Eleven cyclists (initial age, 14.3 [1.6] y; peak V ˙ O 2 , 62.2 [4.5] mL·min−1·kg−1) visited the laboratory twice on 3 occasions within 15 months. Participants performed an incremental ramp exercise test and a constant workrate test within the heavy-intensity domain during the first visit and second visit, respectively. Subsequently, parameter estimates of the V ˙ O 2 and muscle deoxygenation on-kinetics were determined with mono-exponential models. Results: The V ˙ O 2 phase II time constant decreased from occasion 1 (34 [4] s) to occasion 2 (30 [4] s, P =.005) and 3 (28 [4] s, P =.010). However, no significant alteration was observed between occasions 2 and 3 (P =.565). The V ˙ O 2 slow component amplitude either expressed in absolute values (ie, L·min−1) or relative to end exercise V ˙ O 2 (ie, %) showed no significant changes throughout the study (P =.972 and.996). Furthermore, the muscle deoxygenation on-kinetic mean response time showed no significant changes throughout the study (18 [8], 18 [3], and 16 [5] s for occasions 1, 2, and 3, respectively; P =.279). Conclusion: These results indicate proportional enhancements of local muscle oxygen distribution and utilization, which both contributed to the speeding of the V ˙ O 2 on-kinetics herein. [ABSTRACT FROM AUTHOR]

Thermal driven desorption of surface impurities is probed based on coupled Monte Carlo–heat flow–molecular dynamics simulations. Such adsorbates can lead to plasma formation during the operation of high-power microwave systems with various negative outcomes and so need to be curtailed. Our study attempts to obtain temperature thresholds for desorbing different surface contaminants such as C2, O2, CO, and CO2. The results show that carbon-based adsorbates on copper (chosen as an example anode material) could be ejected at a relatively modest surface temperature of 650 K. On the other hand, reactive species such as oxygen are very stable due to their large cohesive energies. Our calculations further suggest the benefit of using a platinum coating layer, as the noble metal is robust with strong resistance to oxidation. [ABSTRACT FROM AUTHOR]

Electron transfer plays a crucial role in living systems, including the generation of reactive oxygen species (ROS). Oxygen acts as the terminal electron acceptor in the respiratory chains of aerobic organisms as well as in some photoinduced processes followed by the formation of ROS. This is why the participation of exogenous antioxidants in electron transfer processes in living systems is of particular interest. In the present study, using chemically induced dynamic nuclear polarization (CIDNP) and dissociative electron attachment (DEA) techniques, we have elucidated the affinity of solvated and free electrons to glycyrrhetinic acid (GA)—the aglicon of glycyrrhizin (the main active component of Licorice root). CIDNP is a powerful instrument to study the mechanisms of electron transfer reactions in solution, but the DEA technique shows its effectiveness in gas phase processes. For CIDNP experiments, the photoionization of the dianion of 5-sulfosalicylic acid (HSSA2−) was used as a model reaction of solvated electron generation. DEA experiments testify that GA molecules are even better electron acceptors than molecular oxygen, at least under gas-phase conditions. In addition, the effect of the solvent on the energetics of the reactants is discussed. [ABSTRACT FROM AUTHOR]

Despite the abundance of research investigating the efficacy of caffeine supplementation on exercise performance, the physiological and biochemical responses to caffeine supplementation during intermittent activities are less evident. This study investigated the acute effects of caffeine supplementation on measures of exercise performance, ratings of perceived exertion, and biomarkers of oxidative stress induced by an acute bout of sprint interval training. In a randomized crossover design, 12 healthy males (age: 26 ± 4 years, height: 177.5 ± 6 cm, body mass: 80.7 ± 7.6 kg) ingested 6 mg/kg of caffeine or placebo 60 min prior to performing sprint interval training (12 × 6 s "all-out sprints" interspersed by 60 s of rest). Performance scores and ratings of perceived exertion were assessed after every sprint. Blood samples were collected before supplementation, prior to and following each sprint, and 5 and 60 min after the last sprint. Caffeine had no effect on any performance measures, ratings of perceived exertion, or biomarkers of oxidative stress (p >.05). In conclusion, caffeine supplementation does not improve performance or decrease oxidative stress after an acute bout of sprint interval training. [ABSTRACT FROM AUTHOR]

In photodynamic therapy (PDT) treatment, heavy-atom-free photosensitizers (PSs) are a great source of singlet oxygen photosensitizer. Reactive oxygen species (ROS) are produced by an energy transfer from the lowest energy triplet excited state to the molecular oxygen of cancer cells. To clarify the photophysical characteristics in the excited states of a few experimentally identified thionated (>C=S) molecules and their oxygenated congeners (>C=O), a quantum chemical study is conducted. This study illustrates the properties of the excited states in oxygen congeners that render them unsuitable for PDT treatment. Concurrently, a hierarchy is presented based on the utility of the lowest-energy triplet excitons of thionated compounds. Their non-radiative decay rates are calculated for reverse-ISC and inter-system crossover (ISC) processes. In addition, the vibronic importance of C=O and C=S bonds is clarified by the computation of the Huang–Rhys factor, effective vibrational mode, and reorganization energy inside the Marcus–Levich–Jörtner system. ROS generation in thionated PSs exceeds their oxygen congeners as kf ≪ kISC, where radiative decay rate is designated as kf. As a result, the current work offers a calculated strategy for analyzing the effectiveness of thionated photosensitizers in PDT. [ABSTRACT FROM AUTHOR]

Purpose: We examined the effects of increasing hypoxia severity on oxygenation kinetics in the vastus lateralis muscle during repeated treadmill sprints, using statistical parametric mapping (SPM). Methods: Ten physically active males completed 8 sprints of 5 seconds each (recovery = 25 s) on a motorized sprint treadmill in normoxia (sea level; inspired oxygen fraction = 0.21), moderate hypoxia (inspired oxygen fraction = 0.17), and severe hypoxia (SH; inspired oxygen fraction = 0.13). Continuous assessment of tissue saturation index (TSI) in the vastus lateralis muscle was conducted using near-infrared spectroscopy. Subsequently, TSI data were averaged for the sprint–recovery cycle of all sprints and compared between conditions. Results: The SPM analysis revealed no discernible difference in TSI signal amplitude between conditions during the actual 5-second sprint phase. However, during the latter portion of the 25-second recovery phase, TSI values were lower in SH compared with both sea level (from 22 to 30 s; P =.003) and moderate hypoxia (from 16 to 30 s; P =.001). The mean distance covered at sea level (22.9 [1.0] m) was greater than for both moderate hypoxia (22.5 [1.2] m; P =.045) and SH (22.3 [1.4] m; P =.043). Conclusions: The application of SPM demonstrated that only SH reduced muscle oxygenation levels during the late portion of the passive (recovery) phase and not the active (sprint) phase during repeated treadmill sprints. These findings underscore the usefulness of SPM for assessing muscle oxygenation differences due to hypoxic exposure and the importance of the duration of the between-sprints recovery period. [ABSTRACT FROM AUTHOR]

Purpose: An inspiratory muscle warm-up (IMW) improves inspiratory muscle function, but the effects of high-intensity exercise are inconsistent. We aimed to determine the effects of high-intensity IMW on high-intensity exercise performance and muscle oxygenation. Methods: Ten healthy men (maximal oxygen uptake [ V ˙ O 2 max ] 52.2 [5.0] mL·kg–1·min–1) performed constant-load exercise to exhaustion on a cycle ergometer at V ˙ O 2 max under 2 IMW conditions: a placebo condition (PLA) and a high-intensity IMW condition (HIGH). The inspiratory loads were set at 15% and 80% of maximal inspiratory pressure, respectively. Maximal inspiratory pressure was measured before and after IMW. Oxyhemoglobin was measured in the vastus lateralis by near-infrared spectroscopy during exercise. Rating of perceived exertion (RPE) for a leg was measured after 1 and 2 minutes of exercise. Results: Exercise tolerance was significantly higher under HIGH than PLA (228 [49] s vs 218 [49] s, P =.003). Maximal inspiratory pressure was significantly increased by IMW under HIGH (from 125 [20] to 136 [25] cm H2O, P =.031). Oxyhemoglobin was significantly higher under HIGH than PLA at 80% of the total duration of exercise (P =.048). RPE for the leg was significantly lower under HIGH than PLA after 2 minutes of exercise (P =.019). Conclusions: Given that oxyhemoglobin is an index of local oxygen supply, the results of this study suggest that high-intensity IMW increases the oxygen supply to active limbs. It may also reflect a reduction in RPE in the leg. In addition, high-intensity IMW may improve exercise performance. [ABSTRACT FROM AUTHOR]

Understanding the ignition and dynamic processes for the combustion of hydrate is crucial for efficient energy utilization. Through reactive force field molecular dynamics simulations, we studied the high-temperature decomposition and combustion processes of methane hydrates in a pure oxygen environment. We found that at an ignition temperature of 2800 K, hydrates decomposed from the interface to the interior, but the layer-by-layer manner was no longer strictly satisfied. At the beginning of combustion, water molecules reacted first to generate OH•, followed by methane oxidation. The combustion pathway of methane is C H 4 → CH 3 • → C H 3 O • → C H 2 O → H C • O → HCO O • → CO (C O 2 ). During the combustion process, a liquid water layer was formed between melted methane and oxygen, which hindered the reaction's progress. When there is no heat resistance, oxygen will transform into radicals such as OH• and O•, which have faster diffusion rates, allowing oxygen to conveniently cross the mass transfer barrier of the liquid water layer and participate in the combustion process. Increasing the amount of OH• may cause a surge in the reaction. On the other hand, when significant heat resistance exists, OH• is difficult to react with low-temperature hydrate components, but it can transform into O• to trigger the oxidation of methane. The H• generated has a sufficient lifetime to contact high-temperature oxygen molecules, converting oxygen into radicals that easily cross the water layer to achieve mass transfer. Therefore, finding ways to convert oxygen into various radicals is the key to solving the incomplete combustion of hydrates. Finally, the reaction pathways and microscopic reaction mechanisms of each species are proposed. [ABSTRACT FROM AUTHOR]

Photoredox properties of several earth-abundant light-harvesting transition metal complexes in combination with cobalt-based proton reduction catalysts have been investigated computationally to assess the fundamental viability of different photocatalytic systems of current experimental interest. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations using several GGA (BP86, BLYP), hybrid-GGA (B3LYP, B3LYP*), hybrid meta-GGA (M06, TPSSh), and range-separated hybrid (ωB97X, CAM-B3LYP) functionals were used to calculate relevant ground and excited state reduction potentials for photosensitizers, catalysts, and sacrificial electron donors. Linear energy correction factors for the DFT/TD-DFT results that provide the best agreement with available experimental reference results were determined in order to provide more accurate predictions. Among the selection of functionals, the B3LYP* and TPSSh sets of correction parameters were determined to give the best redox potentials and excited states energies, ΔEexc, with errors of ∼0.2 eV. Linear corrections for both reduction and oxidation processes significantly improve the predictions for all the redox pairs. In particular, for TPSSh and B3LYP*, the calculated errors decrease by more than 0.5 V against experimental values for catalyst reduction potentials, photosensitizer oxidation potentials, and electron donor oxidation potentials. Energy-corrected TPSSh results were finally used to predict the energetics of complete photocatalytic cycles for the light-driven activation of selected proton reduction cobalt catalysts. These predictions demonstrate the broader usefulness of the adopted approach to systematically predict full photocycle behavior for first-row transition metal photosensitizer–catalyst combinations more broadly. [ABSTRACT FROM AUTHOR]

The barrierless exothermic reactions between atomic oxygen and the cyano radical, O(3P) + CN(X2 Σ + ) → CO(X1Σ+) + N(2D)/N(4S), play a significant role in combustion, astrochemistry, and hypersonic environments. In this work, their dynamics and kinetics are investigated using both wave packet (WP) and quasi-classical trajectory (QCT) methods on recently developed potential energy surfaces of the 12A′, 12A,″ and 14A″ states. The product state distributions in the doublet pathway obtained with the WP method for a few partial waves show extensive internal excitation in the CO product. This observation, combined with highly oscillatory reaction probabilities, signals a complex-forming mechanism. The statistical nature of the reaction is confirmed by comparing the WP results with those from phase space theory. The calculated rate coefficients using the WP (with a J-shifting approximation) and QCT methods exhibit agreement with each other near room temperature, 1.77 × 10−10 and 1.31 × 10−10 cm3 molecule−1 s−1, but both are higher than the existing experimental results. The contribution of the quartet pathway is small at room temperature due to a small entrance channel bottleneck. The QCT rate coefficients are further compared with experimental results above 3000 K, and the agreement is excellent. [ABSTRACT FROM AUTHOR]

We report state-of-the-art first-principles molecular dynamics results on the heterogeneous chemical uptake of NO2, a major anthropogenic pollutant, on the dry and wet hydroxylated surface of α-quartz, which is a significant component of silica-based catalysts and atmospheric dust aerosols. Our investigation spotlights an unexpected chemical pathway by which NO2 (i) can be adsorbed as HONO by deprotonation of interfacial silanols (i.e., –Si–OH group) on silica, (ii) can be barrierless converted to nitric acid, and (iii) can finally dissociated to surface bounded NO and hydroxyl gas phase radicals. This chemical pathway does not invoke any previously experimentally postulated NO2 dimerization, dimerization that is less likely to occur at low NO2 concentrations. Moreover, water significantly catalyzes the HONO formation and the dissociation of nitric acid into surface-bounded NO and OH radicals, while visible light adsorption can further promote these chemical transformations. This work highlights how water-restricted solvation regimes on common mineral substrates are likely to be a source of reactive oxygen species, and it offers a theoretical framework for further and desirable experimental efforts, aiming to better constrain trace gases/mineral interactions at different relative humidity conditions. [ABSTRACT FROM AUTHOR]

We report the experimental measurements of the decay rate of polar cesium nD5/2 − 6S1/2 Rydberg-ground molecules with a large principal quantum number range of 35 ≤ n ≤ 40. Rydberg molecules are prepared employing the method of two-photon photoassociation and the molecular (atomic) ions, due to autoionization (blackbody photoionization), are detected with a microchannel plate detector. The decay rate Γ of the vibrational ground state of the deep and shadow bound molecules for triplet (TΣ) and mixed singlet-triplet (S,TΣ) are measured by fitting the molecular population with the exponential function. Comparing with the parent atom, the decay rate of the polar Rydberg-ground molecule shows an obvious increase with a magnitude of a few μs. The possible dissociation mechanism of polar Rydberg-ground molecules including a collisional decay, blackbody induced decay, and coupling of adjacent Rydberg states and tunneling decay are discussed in detail. The theoretical model is induced to simulate the measurements, showing agreement. [ABSTRACT FROM AUTHOR]

Resting metabolic rate (RMR) is an important component of total daily energy expenditure; however, it is currently not understood how it varies across a typical competitive match week in professional soccer players. For the first time, we aimed to assess RMR throughout an in-season competitive week in professional soccer players. Additionally, we aimed to assess energy and carbohydrate intake across the same week. Twenty-four professional soccer players from an English Premier League club (age: 18 ± 1.6 years) completed the study. RMR was assessed each morning of a typical competitive match week (match day [MD] −3, −2, −1, +1, +2, and + 3), and dietary intake (including MD) was assessed daily via the remote food photography method and 24-hr recall. Daily training load was quantified using Global Positioning System, daily muscle soreness ratings were recorded, and body composition was assessed via dual-energy X-ray absorptiometry. There was a significant (p =.0004) increase in mean RMR of ∼261 kcal/day on MD + 1, compared with MD − 1. Additionally, volume of oxygen consumed significantly increased at MD + 1 (p =.0002) versus MD − 1. There were no significant differences in daily energy or carbohydrate intake across the competitive week (p >.05), with inadequate carbohydrate intakes on MD − 1 (∼3.9 g/kg body mass), MD (∼4.2 g/kg body mass), and MD + 1 (∼3.6 g/kg body mass) in relation to current recommendations. We report, for the first time, that RMR is significantly increased following a competitive match in professional soccer players. In addition, we confirm previous findings to reinforce that players exhibit inadequate nutrition periodization practices, which may impair physical performance and recovery. [ABSTRACT FROM AUTHOR]

Surface property modification of catalyst support is a straightforward approach to optimize the performance of supported noble metal catalysts. In particular, oxygen vacancies and hydroxyl groups play significant roles in promoting noble metal dispersion on catalysts as well as catalytic stability. In this study, we developed a nanoflower-like TiO2-supported Pd catalyst that has a higher concentration of oxygen vacancies and surface hydroxyl groups compared to that of commercial anatase and P25 support. Notably, due to the distinctive structure of the nanoflower-like TiO2, our catalyst exhibited improved dispersion and stabilization of Pd species and the formation of abundant reactive oxygen species, thereby facilitating the activation of CO and O2 molecules. As a result, the catalyst showed remarkable efficiency in catalyzing the low-temperature CO oxidation reaction with a complete CO conversion at 80 °C and stability for over 100 h. [ABSTRACT FROM AUTHOR]

Atmospheric pressure plasmas generated from a helium gas with admixtures of water vapor have numerous applications in biomedicine. It is important that the chemistry of such plasmas can be tightly controlled so that they may be tailored for their intended use. In this study, computational modeling is used to vary the pulse repetition frequency of a nanosecond-pulsed, pin-to-pin He + 0.25% H 2 O discharge in the range of 1–100 kHz to determine the influence of the pulse repetition frequency on the resulting densities of reactive oxygen species and the rates of dominant reaction pathways involving them. The plasma is simulated using the 0D plasma-chemical kinetics model GlobalKin. The pulse shape is kept constant. The afterglow duration is, therefore, dependent on the repetition frequency. Analysis of the bulk plasma chemistry after the plasma has reached equilibrium shows that the peak electron density is only weakly dependent on the pulse repetition frequency. Increasing the pulse repetition frequency is shown to increase the density of H, O, and OH radicals, while the relationship between the repetition frequency and the densities of species with longer lifetimes, namely, H 2 O 2 and O 3 , is found to be more complex. These are formed throughout the afterglow, and their density depends on the availability of reactant species, the afterglow duration, and the background gas temperature. This work concludes that the pulse repetition frequency is not a simple control parameter, especially for species that are predominantly produced in the afterglow. Detailed modeling is required for accurate control of species densities using the pulse repetition frequency. [ABSTRACT FROM AUTHOR]

Herein, we describe the synthesis and characterization of a series of thiosemicarbazone platinacycles. Their activity towards HCT116 and A2780 cancer cell lines as well as normal fibroblasts was explored and conclusions about the influence of their structures were drawn based on the results. Ligands L1–3, tetranuclear compounds [Pt(L1–3)]4, [Pt(L1–3)(PPh3)], and [Pt(L1–L3)2{Ph2P(CH2)4PPh2}], and phosphine derivatives, were deemed unpromising owing to their lack of activity. However, mono-coordinated diphosphine complexes [Pt(L1–L3)(Ph2PCH2PPh2 -P)] showed high selectivity and low IC50 values, and their antiproliferative activity was further studied. The three studied derivatives 3a, 3b and 3c showed a fast internalization of HCT116 colorectal cancer cells with similar IC50 values, which induced a depolarization of mitochondrial membrane potential, with the subsequent triggering of apoptosis and autophagy in the case of 3c. In the case of compounds 3a and 3b, cell death mechanisms (extrinsic and intrinsic apoptosis, respectively) were triggered via the induction of reactive oxygen species (ROS). The three compounds were not toxic to a chicken embryo in vivo (after 48 h), and, importantly, showed an anti-angiogenic potential after exposure to the IC50 of compounds 3a, 3b and 3c. [ABSTRACT FROM AUTHOR]

Low-temperature plasma (LTP) jets are Food and Drug Administration (FDA)-approved medical devices to remove cancerous tissue and aid in wound healing. However, reports on their reaction with proteins are conflicting, ranging from fragmentation, oxidation, aggregation, or a combination thereof. In this study we bridge the gap between plasma-treatment of short peptides to proteins at physiologically relevant concentrations. The LTP in this study is based on a helium dielectric barrier discharge that forms a plasma-jet, which is directed at the solution without direct contact with the plasma, and results in the formation of reactive oxygen species (ROS) OH• and O2•− in solution. The longer the solution is treated, the more solution-phase ROS form. Treating peptide- and protein-containing solutions leads to extensive oxidation. The ROS led to the same oxidative modifications for peptide M with increasing chain length (9, 18, 37, 76 amino acids), which could be identified with high-resolution mass spectrometry. Oxidized species M + x O led to conformational changes such as compaction and elongation, while the unmodified peptide M remained unaltered, as found by ion mobility spectrometry and size exclusion chromatography. For proteins at high concentration, insoluble aggregates formed and could be identified by UV/V is light scattering and atomic force microscopy. The formation of aggregates is dependent on the amino acid chain length, the peptide concentration, and the time for aggregate formation. These findings highlight the importance of both peptide chain length and concentration in determining the fate of peptides following the exposure to LTP, while also offering valuable insights for the field of plasma medicine. [ABSTRACT FROM AUTHOR]

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]

Background: High levels of the polyunsaturated fatty acid arachidonic acid (AA) within the ovarian carcinoma (OC) microenvironment correlate with reduced relapse-free survival. Furthermore, OC progression is tied to compromised immunosurveillance, partially attributed to the impairment of natural killer (NK) cells. However, potential connections between AA and NK cell dysfunction in OC have not been studied. Methods: We employed a combination of phosphoproteomics, transcriptional profiling and biological assays to investigate AA's impact on NK cell functions. Results: AA (i) disrupts interleukin-2/15-mediated expression of pro-inflammatory genes by inhibiting STAT1-dependent signaling, (ii) hampers signaling by cytotoxicity receptors through disruption of their surface expression, (iii) diminishes phosphorylation of NKG2D-induced protein kinases, including ERK1/2, LYN, MSK1/2 and STAT1, and (iv) alters reactive oxygen species production by transcriptionally upregulating detoxification. These modifications lead to a cessation of NK cell proliferation and a reduction in cytotoxicity. Conclusion: Our findings highlight significant AA-induced alterations in the signaling network that regulates NK cell activity. As low expression of several NK cell receptors correlates with shorter OC patient survival, these findings suggest a functional linkage between AA, NK cell dysfunction and OC progression. Plain English summary: High levels of the fatty acid arachidonic acid (AA) in the ovarian cancer environment are associated with shorter survival. Ovarian cancer progression is linked to weakened immune defenses, partly due to malfunctioning natural killer (NK) cells. We used various scientific methods to study how AA affects NK cell function. Our results show that AA significantly changes the signaling processes that control NK cell activity. Specifically, AA (i) disrupts the expression of pro-inflammatory genes, (ii) impairs the function of receptors that activate killing mechanisms by preventing them from appearing on the cell surface, (iii) reduces the activity of intracellular signaling proteins that are activated by these receptors and (iv) changes the production of reactive oxygen species. These changes stop NK cells from multiplying and reduce their ability to kill cancer cells, suggesting that AA contributes to NK cell dysfunction and cancer progression. [ABSTRACT FROM AUTHOR]

Natural photolysis was the primary pathway for the transformation of pharmaceutical contaminants in surface water, whereas it could be easily influenced by dissolved organic matter (DOM). This study examined the complex effects of DOM on clofibric acid (CA) photodegradation in urban, town, and rural waters. Our results indicated rural water was the most conducive to CA photolysis followed by town water, then urban water. Quenching experiments revealed humic acid (HA) influenced the direct photolysis of CA mainly through two physical ways: internal filtering and active site competition. Reactive oxygen species were identified to be the main reason for CA photodegradation with fulvic acid (FA) or tyrosine (Tyr) involved, including hydroxyl radicals (OH•), singlet oxygen (1O2), and excited triplet DOM (3DOM*). We found that hydroxyl radical oxidation, C-O bond breaking, dechlorination, and rechlorination occurred in CA photolysis. Comparative eco-toxicity results showed that the toxicity of products during the CA natural photodegradation process with DOM involved was higher than CA itself, especially in urban waters. This finding emphasized the potential ecological risk of direct CA discharges in natural water and the need to develop risk management strategies that were critical to the health and sustainability of ecosystems. [ABSTRACT FROM AUTHOR]

Organic luminophores have been widely utilized in cells and in vivo fluorescence imaging but face extreme challenges, including a low signal-to-noise ratio (SNR) and even false signals, due to non-negligible background signals derived from real-time excitation lasers. To overcome these challenges, in the last decade, functionalized organic long-persistent luminophores have gained much attention. Such luminophores could not only overcome the biological toxicity of inorganic long-persistent luminescent materials (metabolic toxicity and leakage risk of inorganic heavy metals), but also continue to emit long-persistent luminescence after removing the excitation source, thus effectively improving imaging quality. More importantly, organic long-persistent luminophores have good structure tailorability for the construction of activable probes, which is favorable for biosensing. Recently, the development of reactive oxygen species (ROS)-mediated long-persistent (ROSLP) luminophores (especially organic small-molecule ROSLP luminophores) is still in the rising stage. Notably, ROSLP luminophores for in vivo imaging have experienced from two-component separated nano-systems to integrated uni-luminophores, which obtained gradually better designability and biocompatibility. In this review, we summarize the progress and challenges of organic long-persistent luminophores, focusing on their development history, long-persistent luminescence working mechanisms, and biomedical applications. We hope that these insights will help scientists further develop functionalized organic long-persistent luminophores for the biomedical field. [ABSTRACT FROM AUTHOR]

Despite notable advancements in cancer therapy, it remains a formidable global health challenge. The emergence of combinational treatments, particularly the integration of chemotherapy with photodynamic therapy (chemo-PDT), offers a glimmer of hope. This study introduces the development of zinc-coordinated quercetin-based self-assembled nanoparticles (ZnQ NPs) for advanced dual-mode cancer therapy. These cutting-edge ZnQ nanoparticles were synthesized in a rapid 15-minute single-step process, in stark contrast to the conventional hours or days required. Using Density Functional Theory (DFT) calculations, the optimal binding configurations of ZnQ NPs were precisely determined and further supported by band gap calculations between frontier molecular orbitals. Quercetin, a potent anticancer flavonoid, was used for the first time both as an active drug and as an organic ligand, resulting in pH-responsive nanoparticles with exceptional water dispersibility, stability, and biocompatibility. Additionally, these novel nanoparticles (NPs) were able to load chlorin e6 (Ce6), a photosensitizer known for its high singlet oxygen production, due to hydrophobic interactions within the pores. The ZnQ@Ce6 nanocomposite demonstrated remarkable Ce6 loading (19.03%) and significantly enhanced therapeutic effects, achieving a 77% cell inhibition rate under specific light conditions. This dual-functional platform, enhancing the solubility and bioavailability of Ce6 while harnessing the anticancer properties of quercetin, underscores the potential of ZnQ NPs in clinical nanomedicine, promising improved cancer treatment outcomes. [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]

Amyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer's disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described. Many cell death pathways can be activated in connection with Aβ action, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, alterations in mitophagy, autophagy, and endo/lysosomal functions. In this study, we used a model of differentiated SH-SY5Y cells and applied two different Aβ42 preparations for 2 and 4 days. Although we found no difference in the shape and size of Aβ species prepared by two different methods (NaOH or NH4OH for Aβ solubilization), we observed strong differences in their effects. Treatment of cells with NaOH-Aβ42 mainly resulted in damage of mitochondrial function and increased production of reactive oxygen species, whereas application of NH4OH-Aβ42 induced necroptosis and first steps of apoptosis, but also caused an increase in protective Hsp27. Moreover, the two Aβ42 preparations differed in the mechanism of interaction with the cells, with the effect of NaOH-Aβ42 being dependent on monosialotetrahexosylganglioside (GM1) content, whereas the effect of NH4OH-Aβ42 was independent of GM1. This suggests that, although both preparations were similar in size, minor differences in secondary/tertiary structure are likely to strongly influence the resulting processes. Our work reveals, at least in part, one of the possible causes of the inconsistency in the data observed in different studies on Aβ-toxicity pathways. [ABSTRACT FROM AUTHOR]

Oxygen (O2) electroreduction offers a green approach for singlet oxygen (1O2) synthesis in wastewater contaminants detoxification. However, traditional single O2 activation on single‐metal catalytic sites seriously suffers from the kinetically‐unfavorable desorption of adsorbed superoxide species (•O2−*/•OOH*). Here, we demonstrate a novel dual O2 coactivation pathway on shortened Fe1−OV−Ti sites for superior 1O2 electrosynthesis through a rapid disproportionate process between surface‐confined •O2−*/•OOH*. Theoretical calculations combined with in situ electrochemical spectroscopies demonstrated that the shortened distance between Fe single atom and adjacent unsaturated Ti atom facilitates the direct recombination of surface‐confined Fe−•OOH and Ti−•OO− to yield 1O2, bypassing the formidable •O2−*/•OOH* desorption process. Impressively, Fe1−OV−Ti could realize an excellent 1O2 electrosynthesis rate of 54.5 μmol L−1 min−1 with an outstanding 1O2 selectivity of 97.6 % under neutral condition, surpassing that of Fe1−O−Ti (27.1 μmol L−1 min−1, 91.7 %). Using tetracycline (TC) as a model pollutant, the resulting Fe1−OV−Ti electrode achieved nearly 100 % degradation in 120 min at −0.6 V, meanwhile preventing the generation of toxic intermediates. This study provides a new 1O2 electrosynthesis strategy by controlling the distance of adjacent catalytic sites for the coactivation of dual molecular oxygen. [ABSTRACT FROM AUTHOR]

Near‐infrared photosensitizers are valuable tools to improve treatment depth in photodynamic therapy (PDT). However, their low singlet oxygen (1O2) generation ability, indicated by low 1O2 quantum yield, presents a formidable challenge for PDT. To overcome this challenge, the heptamethine cyanine was decorated with biocompatible S (Scy7) and Se (Secy7) atom. We observe that Secy7 exhibits a redshift in the main absorption to ~840 nm and an ultra‐efficient 1O2 generation capacity. The emergence of a strong intramolecular charge transfer effect between the Se atom and polymethine chain considerably narrows the energy gap (0.51 eV), and the heavy atom effect of Se strengthens spin–orbit coupling (1.44 cm−1), both of which greatly improved the high triplet state yield (61 %), a state that determines the energy transfer to O2. Therefore, Secy7 demonstrated excellent 1O2 generation capacity, which is ~24.5‐fold that of indocyanine green, ~8.2‐fold that of IR780, and ~1.3‐fold that of methylene blue under low‐power‐density 850 nm irradiation (5 mW cm−2). Secy7 exhibits considerable phototoxicity toward cancer cells buried under 12 mm of tissue. Nanoparticles formed by encapsulating Secy7 within amphiphilic polymers and lecithin, demonstrated promising antitumor and anti‐pulmonary metastatic effects, exhibiting remarkable potential for advancing PDT in deep tissues. [ABSTRACT FROM AUTHOR]

Oxygen (O2) electroreduction offers a green approach for singlet oxygen (1O2) synthesis in wastewater contaminants detoxification. However, traditional single O2 activation on single‐metal catalytic sites seriously suffers from the kinetically‐unfavorable desorption of adsorbed superoxide species (•O2−*/•OOH*). Here, we demonstrate a novel dual O2 coactivation pathway on shortened Fe1−OV−Ti sites for superior 1O2 electrosynthesis through a rapid disproportionate process between surface‐confined •O2−*/•OOH*. Theoretical calculations combined with in situ electrochemical spectroscopies demonstrated that the shortened distance between Fe single atom and adjacent unsaturated Ti atom facilitates the direct recombination of surface‐confined Fe−•OOH and Ti−•OO− to yield 1O2, bypassing the formidable •O2−*/•OOH* desorption process. Impressively, Fe1−OV−Ti could realize an excellent 1O2 electrosynthesis rate of 54.5 μmol L−1 min−1 with an outstanding 1O2 selectivity of 97.6 % under neutral condition, surpassing that of Fe1−O−Ti (27.1 μmol L−1 min−1, 91.7 %). Using tetracycline (TC) as a model pollutant, the resulting Fe1−OV−Ti electrode achieved nearly 100 % degradation in 120 min at −0.6 V, meanwhile preventing the generation of toxic intermediates. This study provides a new 1O2 electrosynthesis strategy by controlling the distance of adjacent catalytic sites for the coactivation of dual molecular oxygen. [ABSTRACT FROM AUTHOR]

Near‐infrared photosensitizers are valuable tools to improve treatment depth in photodynamic therapy (PDT). However, their low singlet oxygen (1O2) generation ability, indicated by low 1O2 quantum yield, presents a formidable challenge for PDT. To overcome this challenge, the heptamethine cyanine was decorated with biocompatible S (Scy7) and Se (Secy7) atom. We observe that Secy7 exhibits a redshift in the main absorption to ~840 nm and an ultra‐efficient 1O2 generation capacity. The emergence of a strong intramolecular charge transfer effect between the Se atom and polymethine chain considerably narrows the energy gap (0.51 eV), and the heavy atom effect of Se strengthens spin–orbit coupling (1.44 cm−1), both of which greatly improved the high triplet state yield (61 %), a state that determines the energy transfer to O2. Therefore, Secy7 demonstrated excellent 1O2 generation capacity, which is ~24.5‐fold that of indocyanine green, ~8.2‐fold that of IR780, and ~1.3‐fold that of methylene blue under low‐power‐density 850 nm irradiation (5 mW cm−2). Secy7 exhibits considerable phototoxicity toward cancer cells buried under 12 mm of tissue. Nanoparticles formed by encapsulating Secy7 within amphiphilic polymers and lecithin, demonstrated promising antitumor and anti‐pulmonary metastatic effects, exhibiting remarkable potential for advancing PDT in deep tissues. [ABSTRACT FROM AUTHOR]

Background: Psychological anxiety and depression, as well as memory impairment, are frequently linked to inflammation. Clove essential oil (CEO) administration and hydrogen (H2) inhalation have been proven to have anti-inflammatory and alleviating effects on related psychological disorders in the past. The current study investigated the potential to improve anxiety-like behaviors and cognitive function by a combination of CEO and H2 treatment. Methods: The mice were administered lipopolysaccharide (LPS) to induce inflammation and oxidative stress response and cause psychological disorders. Using this animal model, we conducted experiments to test whether essential oil and H2 inhalation could improve the psychological damage in behavior caused by LPS. Subsequently, elevated plus maze (EPM), forced swimming test (FST), and passive avoidance (PA) test were performed for evaluation of mice anxiety, depression, and response to electric shock, respectively. Furthermore, the biochemical analysis was used to examine the expression levels of inflammatory and oxidative stress markers. Results: Our results showed that CEO administration and H2 inhalation alone or in combination positively improved inflammation-induced anxiety, depression, and cognitive memory deficits in the mice. In the single treatment groups, CEO demonstrated better results than H2 inhalation in the elevated plus maze, forced swimming, and passive avoidance tests, while combined treatment with both provided a further improved enhancement effect. Biochemical analysis of the cerebral cortex revealed that CEO and H2 therapy reversed the LPS-induced inflammation and oxidative stress response. Conclusions: Our results suggest that a combination of CEO and H2 has the potential to treat psychological disorders or neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: The intestinal epithelial barrier is the first line of defense against pathogens and noxious substances entering the body from the outside world. Through proliferation and differentiation, intestinal stem cells play vital roles in tissue regeneration, repair, and the maintenance of intestinal homeostasis. Inflammatory bowel disease (IBD) is caused by the disruption of intestinal homeostasis through the invasion of toxic compounds and pathogenic microorganisms. Hylotelephium erythrostictum (Miq.) H. Ohba (H. erythrostictum) is a plant with diverse pharmacological properties, including antioxidant, anti-inflammatory, antidiabetic, and antirheumatic properties. However, the roles of H. erythrostictum and its bioactive compounds in the treatment of intestinal injury are unknown. Methods: We examined the protective effects of H. erythrostictum water extract (HEWE) and H. erythrostictum butanol extract (HEBE) on Drosophila intestinal injury caused by dextran sodium sulfate (DSS) or Erwinia carotovoracarotovora 15 (Ecc15). Results: Our findings demonstrated that both HEWE and HEBE significantly prolonged the lifespan of flies fed toxic compounds, reduced cell mortality, and maintained intestinal integrity and gut acid‒base homeostasis. Furthermore, both HEWE and HEBE eliminated DSS-induced ROS accumulation, alleviated the increases in antimicrobial peptides(AMPs) and intestinal lipid droplets caused by Ecc15 infection, and prevented excessive ISC proliferation and differentiation by inhibiting the JNK, EGFR, and JAK/STAT pathways. In addition, they reversed the significant changes in the proportions of the gut microbiota induced by DSS. The bioactive compounds contained in H. erythrostictum extracts have sufficient potential for use as natural therapeutic agents for the treatment of IBD in humans. Conclusion: Our results suggest that HEWE and HEBE are highly effective in reducing intestinal inflammation and thus have the potential to be viable therapeutic agents for the treatment of gut inflammation. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses, with neutrophil extracellular traps (NETs) playing a significant role. NETs are recognized by autoantibodies in SLE patients, exacerbating pathology. Both excessive NET formation and impaired degradation contribute to SLE pathophysiology. Objective: To investigate the immunomodulatory effects of Dexamethasone-primed Wharton's jelly (WJ) derived MSCs CM (DW) and IFN-γ-primed WJ-MSCs-CM (IW) on NETosis and associated protein markers in SLE patients' LPS or ribonucleoprotein immune complexes (RNP ICs) induced neutrophils and in pristane induced lupus (PIL) model. And to elucidate the mechanism involved therein. Methods: We investigated the immunomodulatory effects of DW and IW on NETosis in SLE. Utilizing ex vivo and in vivo models, we assessed the impact of preconditioned media on NET formation and associated protein markers neutrophil elastase (NE), citrullinated histone (citH3), myeloperoxidase (MPO), cytoplasmic and mitochondrial ROS production. We also examined the involvement of key immunomodulatory factors present in DW and IW, including prostaglandin E2 (PGE2), indoleamine 2,3-dioxygenase (IDO), and transforming growth factor-beta (TGF-β). Results: Preconditioned media effectively suppressed NETosis and reduced ROS generation in SLE neutrophils, indicating their immunomodulatory potential. Inhibition studies implicated IDO and PGE2 in mediating this effect. Combined treatment with DW or IW together with hydroxychloroquine (HCQ) demonstrated superior efficacy over HCQ alone, a standard SLE medication. In PIL mouse model, DW and IW treatments reduced NETosis, ROS generation, as evidenced by decreased NET-associated protein expression in vital organs. Conclusion: Our study highlights the multifaceted impact of IW and DW on NETosis, ROS dynamics, and lupus severity in SLE. These findings underscore the potential of preconditioned media for the development of targeted, personalized approaches for SLE treatment. [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]

This study investigates novel zinc and indium phthalocyanines with Schiff base and sulphur moieties, focusing on their potential for cancer therapy and antimicrobial applications. It explores the effectiveness of photochemical and sono-photochemical methods to enhance singlet oxygen production, which is crucial for photodynamic therapy. The synthesized complexes in this study demonstrated high singlet oxygen quantum yields, with D3 (ZnPc) and D4 (InPc) showing ΦΔPDT values of 0.71 and 0.75, and ΦΔSPDT values of 0.91 and 0.94, respectively. Furthermore, the evaluation for biological properties revealed that both D3 and D4 exhibit significant antidiabetic properties, DPPH radical scavenging activity, DNA cleavage, antimicrobial activity, biofilm inhibition, and microbial cell viability impacts, both with and without photodynamic therapy. Notably, D3 and D4 achieved antimicrobial cell viability inhibition rates of 84.67 ± 4.67% and 98.32 ± 5.96%, respectively, showcasing their effectiveness in photodynamic antimicrobial therapy. Overall, the study highlights the potential of these phthalocyanine complexes as advanced photosensitizers, with strong singlet oxygen generation and promising biological activities, paving the way for future therapeutic applications. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment. [ABSTRACT FROM AUTHOR]

In this study, water-soluble polysaccharides purified from burdock root were used to intervene in carbon tetrachloride (CCl4)-induced acute liver injury (ALI) of BRL3A hepatocytes and rats. Our results indicated that CCl4 significantly inhibited hepatocyte viability and upregulated the expression of reactive oxygen species (ROS), malondialdehyde (MDA), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and the pro-apoptotic protein Bax. However, Arctium lappa L. root polysaccharides (ALP) could effectively ameliorate liver function and histopathology, oxidative stress, and inflammatory markers. In addition, ALP reduced the expression of apoptotic markers and promoted the proliferation of damaged hepatocytes. In conclusion, ALP possesses a hepatoprotective effect mediated by attenuating oxidative damage, inflammation and apoptosis in ALI. [ABSTRACT FROM AUTHOR]

Background: Chronic infection by Helicobacter pylori strains expressing cytotoxin-associated gene A (CagA) are the strongest risk factor for gastric cancer. CagA can be classified into East Asian-type and Western-type (CagAE and CagAW), with CagAE being more closely associated with gastric cancer. This study aimed to investigate the impact of CagAE on intracellular signaling pathways to explain its high oncogenicity. Results: Mutant H. pylori strains expressing either CagAE or CagAW were generated by transforming CagAE/W-expression plasmid into CagA-deleted G27 strain (G27ΔCagA). In human gastric epithelial cells (GES-1) infection, CagAE induced more severe cytopathic changes, including higher interleukin-8 (IL-8) secretion, reduced cell viability, more pronounced "hummingbird phenotype" alterations, and increased cell migration and invasion compared to CagAW. Transcriptome analysis revealed that CagAE had a stronger effect on the up-regulation of key intracellular processes, including tumor necrosis factor-ɑ (TNF-ɑ) signal pathway via nuclear factor kappa-B (NF-κB), inflammatory response, interferon-γ (IFN-γ) response, hypoxia, ultraviolet (UV) response, and Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) signaling. A significant upregulation of hypoxia-related genes was a notable feature of CagAE. GES-1 cells infected with CagAE exhibited more severe intracellular hypoxia and higher levels of reactive oxygen species (ROS) than those infected with CagAW. Inhibition of hypoxia-inducible factor-1α (HIF-1α), which blocks hypoxia signaling, mitigated CagAE-induced cell migration, emphasizing the role of hypoxia in mediating CagAE effects. Conclusions: The study provides transcriptome evidence of CagA-associated intracellular regulation during H. pylori infection, demonstrating that CagAE exerts stronger effects on intracellular signaling than CagAW. These findings offer insights into the heightened carcinogenic potential of CagAE in H. pylori-induced gastric cancer. [ABSTRACT FROM AUTHOR]

Noise‐induced hearing loss (NIHL), a prevalent sensory disability affecting a majority of the global population, is dominantly induced by mitochondrial dysfunction and oxidative stress, but no effective therapeutic strategy is available. Herein, the potential of a 2D catalytic niobium carbide (Nb2C) MXenzyme is investigated as a nanomedicine for treating NIHL by scavenging reactive oxygen species (ROS). The findings reveal that 2D Nb2C MXenzyme effectively eliminates free radicals, resulting in a substantial reduction of ROS in House Ear Institute‐Organ of Corti 1 (HEI‐OC1) cells treated with hydrogen peroxide (H2O2). Additionally, the 2D Nb2C MXenzyme demonstrates significant protection on hair cells by preventing cytotoxicity and apoptosis induced by H2O2. In vivo experiments further support the efficacy of the 2D Nb2C MXenzyme in restoring hearing impairment caused by extensive noise exposure. Specifically, it restores the raised amplitude of Wave I in auditory brainstem response (ABR) records and promotes the recovery of damaged ribbon synapses in inner hair cells. Notably, the therapeutic effect of the 2D Nb2C MXenzyme is attributed to its ability to suppress cochlear oxidative stress evidenced by immunohistochemical analysis. This research provides a new approach for treating hearing loss‐related ear diseases by utilizing catalytic biomaterials and nanomedicine with enzyme‐mimicking properties. [ABSTRACT FROM AUTHOR]

The heterogeneity and immunosuppression microenvironment of ovarian cancer seriously restrict the efficiency of monomodal treatment. Emerging multimodal therapy strategies based on sonodynamic therapy with enhanced antitumor effects have attracted intensive attention in the quest to combat cancer. However, exploring highly efficient sonosensitizers integrating chemodynamic/sonodynamic/immunotherapies with reversing immunosuppressive tumor microenvironment (TME) capacity is urgently desired but remains challenging. Here, a facile strategy is designed to synthesize immunomodulating sonocatalytic nanoagents (IrT‐SCN) with dual‐functional Ir‐N centers and narrow bandgap for reversing immunosuppression and potentiating ovarian cancer immunotherapy. IrT‐SCN with dual‐functional centers Ir‐N2 and Ir‐N4 and conjugated networks show a reduced bandgap, moderate interaction with H2O2, and efficient production of reactive oxygen species (ROS). Such ROS capabilities include: 1) utilizing H2O2 in TME to catalytically generate potent O2, as well as abundant superoxide anion (•O2−) and singlet oxygen (1O2) radicals; 2) external ultrasound (US) irradiation can also boost the production of 1O2 simultaneously; 3) M1 polarization of tumor‐associated macrophages and enhanced immune effect can promote the outcome of cancer treatment. This finding provides proof‐of‐concept evidence for the future development of immunomodulating sonocatalytic nanoagents for oncological treatments and other ROS‐related biomedical fields. [ABSTRACT FROM AUTHOR]

Singlet oxygen (1O2) has attracted great attention owing to its superior comprehensive oxidizing performance and extensive application in dealing with ever‐growing environmental pollution. However, the efficient catalytic generation of 1O2 is very challenging due to the low catalytic activity of most catalysts and the generation of oxygen‐containing radicals in the catalytic reaction. Herein, C‐doped Co nanoparticles (CoNPs) supported on porous carbon (C─Co/C) as highly reactive and selective 1O2‐producing catalysts are demonstrated for efficient catalytic oxidation of recalcitrant organics via activation of peroxymonosulfate (PMS). The doped C 2p orbitals can accept Co 3d electrons, thereby weakening the Co─O bonding between Co and PMS or other oxygen‐containing intermediates such as *SO4, *OH, *OOH, and *O. The adsorption and cleavage energy of PMS on Co nanoparticle is reduced from 8.09 to 4.64 eV by C doping. The energy barrier of the *OOH to 1O2 step is also lowered significantly, thereby kinetically improving the activity for the generation of 1O2. The C─Co/C catalysts promotes the efficient and 100% selective generation of 1O2 with high modified kinetic model (K) values of 457.0 and 94.5 µmol s−1 g−1 for rhodamine (RhB) and 2,4‐dichlorophenol (2,4‐DCP), respectively. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) presents a promising approach for combating periodontitis, an infectious disease triggered by bacteria. However, the hypoxic environment within periodontal pockets poses challenges for PDT efficacy. In this study, novel purine‐based C^N ligands are utilized to develop Ir(III) complexes with enhanced reactive oxygen species (ROS) generation capacity for periodontitis treatment. The type I/II PDT performance of Ir(III) is greatly enhanced by the purine ligands, which leads to potent bactericidal and biofilm elimination efficacy. In a rat model of periodontitis, local application of these purine‐based Ir(III) complexes effectively achieves antibacterial and anti‐inflammatory effects while promoting tissue repair under clinical luminaire exposure. This PDT strategy utilizing purine‐based Ir(III) complexes circumvents the need for antibiotics and surgical intervention, emerging as a promising, non‐invasive approach for managing periodontitis. [ABSTRACT FROM AUTHOR]

Ferroptosis and cuproptosis are emerging modes of programmed cell death and have been increasingly used to eliminate tumor cells. However, converting ferroptosis/cuproptosis into effective treatments is challenging because of the inherent antioxidant and plasma membrane repair systems and inefficient copper ion delivery. Herein, an engineered doping method is developed to encapsulate ZnO2 with Cu2+‐doped ZIF‐8 and modify the surface by transferrin (Tf). In the resulting ZnO2@Cu/ZIF‐8‐Tf nanosystem, Tf specifically binds to transferrin receptors for targeting and aggregation. In the tumor microenvironment, Cu2+/Fe3+ is released from the nanosystem and reacted with glutathione (GSH) to produce Cu+/Fe2+. Excessive accumulation of Cu+ interfered with the tricarboxylic acid cycle and induced coproptosis. Furthermore, the additional Fe2+ caused iron overload and enhanced ferroptosis. ZnO2 supplied hydrogen peroxide to mediate the overproduction of reactive oxygen species (ROS). Moreover, the depletion of GSH deactivated glutathione peroxidase 4 (GPX4) and inhibited the system Xc−‐GSH‐GPX4 pathway, and the amplified ROS triggered lipid peroxidation and reprogrammed lipid metabolism, causing malfunctioning of both antioxidant and membrane repair systems. In summary, the ferroptosis/cuproptosis pathways are activated at multiple levels in the ZnO2@Cu/ZIF‐8‐Tf nanosystem, which ensures its outstanding antitumor effect. [ABSTRACT FROM AUTHOR]

Immunotherapy, one of the most promising antitumor strategies, is used to treat prostate cancer (PCa). However, owing to the immunosuppressive tumor microenvironment (TME), the therapeutic effect of the antitumor immune response is greatly weakened. Therefore, there is an urgent need to explore new methods to enhance antitumor immune responses. In this study, a single‐atom nanozyme platform (Cu SA‐DOX@COD) that can trigger pyroptosis is developed to activate antitumor immune responses via a gasdermin E (GSDME)‐dependent pathway. It triggered pyroptosis by catalyzing the production of reactive oxygen species (ROS) and depleting reduced glutathione through intrinsic multi‐enzyme simulated activities and providing an oxygen source for cholesterol (CHOL) oxidation. Meanwhile, the loaded CHOL oxidase not only reduces the CHOL content of tumor cells to increase cell membrane permeability and inhibit tumor cell proliferation and invasion but also oxidizes CHOL and increases the level of H2O2 in tumor cells to enhance pyroptosis. In addition, the loaded doxorubicin activated caspase‐3 to cleave GSDME and further augment pyroptosis. Consequently, Cu SA‐DOX@COD enhances tumor cell immunocompetence and reshapes the immunosuppressive TME by triggering pyroptosis caused by a ROS storm, chemotherapy, and depleting CHOL, thereby activating systemic antitumor immunity to treat PCa. [ABSTRACT FROM AUTHOR]

The presence of bacterial persisters is a key factor contributing to chronic infection. However, no effective treatment methods are currently available. Thus, a platform is developed, called reactive oxygen species (ROS) bomb, based on microenvironment‐adaptive hydrogel microspheres, to oxidize the cell membranes of persisters in chronic periprosthetic joint infection (PJI). Fenton reagent hydroxy iron oxide (FeOOH) and a glucose oxidase (GOx)/calcium phosphate (CaP) acid‐responsive shell are sequentially induced on the surface of mesoporous polydopamine (PDA) nanoparticles by the PDA‐mediated ion precipitation and interfacial adhesion, followed by the coloaded with glucose into microfluidic hyaluronic acid hydrogel microspheres. Hydroxyl radicals are explosively generated through GOx‐mediated glucose oxidase, H2O2 production, and its Fenton‐like reactions with FeOOH, which also benefit from the weakly acidic microenvironment around persisters, result in the destruction of bacterial cell membrane, and subsequent overflow of cellular contents such as dsDNA, proteins, and K+. The bactericidal rates of methicillin‐resistant Staphylococcus aureus and Staphylococcus epidermidis persisters are up to 99.14% and 98.96%, and the bacterial loads in lesion location are significantly decreased after ROS bombs treated, effectively alleviated the inflammation and bone resorption damage. This work provides a new strategy toward persisters clearance and shows great application potential in other chronic infection‐related diseases. [ABSTRACT FROM AUTHOR]

Photo‐activated therapeutic strategies have great potential for preventing bacterial infections, especially infections associated with drug‐resistant bacteria, owing to their minimal tendency to induce drug resistance. A single course of light‐based therapeutics may lack the desired efficacy. The use of a high‐power excitation source or high doses of photo‐activated agents may cause excessive damage to normal tissues. Herein, a multimodal antibacterial platform that combines photodynamic and photothermal therapies has been developed. The fluoro‐substituted coumarin compound (TCF) and Prussian blue nanocubes (PB NCs) are integrated into the bacterial cellulose (BC) to form a versatile wound dressing (BC‐TCF‐PB). Fluoro‐substitution in TCF is found to enhance its production of 1O2 by boosting the intersystem crossing. Furthermore, the generated 1O2 can react with the thiocarbonyl group in TCF to form a highly emissive product. In situ self‐reporting fluorescence of TCF allows for the visualization of 1O2 generation, and assessment of the bacterial eradication. In addition, the BC‐TCF‐PB platform exhibits synergistic antibacterial effects on the methicillin‐resistant Staphylococcus aureus (MRSA), and provides an effective solution for infection control and wound healing. Thus, the BC‐TCF‐PB dressing, with self‐reporting of the reactive biocide generation in situ, has offered valuable insights into effective wound management. [ABSTRACT FROM AUTHOR]

Pathological scars (PS) are involved in the excessive response of inflammation and overactivation of myofibroblasts. Herein, a novel microneedle (MN) patch based on the adipose‐derived stem cell concentrated conditioned medium (ADSCC‐CM) cross‐linked keratin hydrogel is developed to load triamcinolone acetonide (TA), thereby achieving the dual‐drug delivery of ADSCC‐CM and TA to simultaneously reduce the inflammation and guide myofibroblast behaviors. Results not only confirm the ability of ADSCC‐CM to drive the formation of keratin‐based hydrogel, but also verify the dual‐drug release capacities of the hydrogel‐developed MNs (TA@AC‐MN). Using human hyperplastic scar fibroblast (HSF), the combination of ADSCC‐CM and TA demonstrates a pronounced synergistic effect in mitigating the detrimental effects of the inflammatory microenvironment on HSFs, including suppressing the production of reactive oxygen species and attenuating the expression of inflammatory factors. Compared with the clinically used TA, TA@AC‐MN promotes scar biomimetic repair (i.e., optimizing the proportion of collagen and increasing the tissue tensile strength). This study demonstrates that TA@AC‐MN has the capacity to provide a self‐managing and minimally invasive therapeutic strategy for PS. [ABSTRACT FROM AUTHOR]

The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action. Synthetic indole derivative kills gram-positive bacteria by quenching the respiratory metabolism pathway. [ABSTRACT FROM AUTHOR]

Dementia encompasses a spectrum of neurodegenerative disorders significantly impacting global health, with environmental factors increasingly recognized as crucial in their etiology. Among these, ozone, has been identified as a potential exacerbator of neurodegenerative processes, particularly in Alzheimer's disease (AD). Ozone exposure induces the production of reactive oxygen species (ROS), which penetrate the BBB, leading to oxidative damage in neuronal cells. This oxidative stress is closely linked with mitochondrial dysfunction and lipid peroxidation, processes that are foundational to the pathology observed in dementia, such as neuronal death and protein aggregation. Furthermore, ozone triggers chronic neuroinflammation, exacerbating these neurodegenerative processes and perpetuating a cycle of CNS damage. Recent studies highlight the role of peripheral biomarkers like High Mobility Group Box 1 (HMGB1) and Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in mediating ozone's effects. Disruption of these and other identified proteins by ozone exposure impairs microglial function and response to amyloid plaques, suggesting a novel pathway through which ozone may influence AD pathology via immune dysregulation. This review discusses the concept of a bidirectional lung-brain axis, illustrating that systemic responses to air pollutants like ozone may reflect and contribute to neurodegenerative processes in the CNS. By delineating these mechanisms, we emphasize the critical need for integrating environmental health management into strategies for the prevention and treatment of dementia. [ABSTRACT FROM AUTHOR]

Background: Sperm capacitation is a prerequisite for natural or in vitro fertilization. After capacitation, sperm become hyperactivated and undergo an acrosome reaction, which helps them penetrate the oocyte. Cordycepin, a bioactive compound first isolated from Cordyceps militaris, is an adenosine analog with numerous physiological activities. However, its effects on sperm capacitation remain unclear. This study aims to elucidate the effects and mechanisms of cordycepin on human sperm capacitation. Methods: During in vitro capacitation culture, healthy human sperm were treated with cordycepin (20, 100, 500 µM). Sperm motility and hyperactivation were detected using a computer-assisted sperm analyzer. Sperm acrosome reaction was measured using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin. Sperm protein kinase A (PKA) activity was analyzed using an ELISA kit. The levels of sperm protein tyrosine phosphorylation were detected by western blotting. Sperm DNA damage was detected by a sperm chromatin dispersion assay. Reactive oxygen species (ROS) were measured using the fluorescence probe 2′,7′-dichlorodihydrofluorescein diacetate. The expression and localization of adenosine receptors were analyzed by western blotting and immunofluorescence. The specific inhibitors of adenosine receptors were used to confirm their effects on cordycepin-induced sperm capacitation. Finally, molecular docking was performed to analyze the interaction between cordycepin and adenosine receptors. Results: Cordycepin improved hyperactivated sperm motility, acrosome reaction, PKA activity, and protein tyrosine phosphorylation during capacitation while having no obvious effects on sperm ROS or DNA damage. Four adenosine receptor subtypes were expressed in human sperm, but their localizations differed. Inhibition of adenosine receptors significantly decreased cordycepin-induced sperm hyperactivation and the acrosome reaction. Molecular docking showed that cordycepin can bind to the four subtypes of adenosine receptors. Conclusion: Cordycepin may promote human sperm capacitation through adenosine receptor-mediated signaling pathways. These findings may be useful for assisted reproductive technology and animal breeding. [ABSTRACT FROM AUTHOR]