Mechanism of extracellular electron transport and reactive oxygen mediated Sb(III) oxidation by Klebsiella aerogenes HC10.

Microbial oxidation and the mechanism of Sb(III) are key governing elements in biogeochemical cycling. A novel Sb oxidizing bacterium, Klebsiella aerogenes HC10, was attracted early and revealed that extracellular metabolites were the main fractions driving Sb oxidation. However, linkages between the extracellular metabolite driven Sb oxidation process and mechanism remain elusive. Here, model phenolic and quinone compounds, i.e., anthraquinone-2,6-disulfonate (AQDS) and hydroquinone (HYD), representing extracellular oxidants secreted by K. aerogenes HC10, were chosen to further study the Sb(III) oxidation mechanism. N2 purging and free radical quenching showed that oxygen-induced oxidation accounted for 36.78% of Sb(III) in the metabolite reaction system, while hydroxyl free radicals (·OH) accounted for 15.52%. ·OH and H2O2 are the main driving factors for Sb oxidation. Radical quenching, methanol purification and electron paramagnetic resonance (EPR) analysis revealed that ·OH, superoxide radical (O2•-) and semiquinone (SQ-•) were reactive intermediates of the phenolic induced oxidation process. Phenolic-induced ROS are one of the main oxidants in metabolites. Cyclic voltammetry (CV) showed that electron transfer of quinone also mediated Sb(III) oxidation. Part of Sb(V) was scavenged by the formation of the secondary Sb(V)-bearing mineral mopungite [NaSb(OH)6] in the incubation system. Our study demonstrates the microbial role of oxidation detoxification and mineralization of Sb and provides scientific references for the biochemical remediation of Sb-contaminated soil.

Oxygen atmosphere enhances ball milling remediation of petroleum-contaminated soil and reuse as adsorptive/catalytic materials for wastewater treatment.

Ball milling is an environmentally friendly technology for the remediation of petroleum-contaminated soil (PCS), but the cleanup of organic pollutants requires a long time, and the post-remediation soil needs an economically viable disposal/reuse strategy due to its vast volume. The present paper develops a ball milling process under oxygen atmosphere to enhance PCS remediation and reuse the obtained carbonized soil (BCS-O) as wastewater treatment materials. The total petroleum hydrocarbon removal rates by ball milling under vacuum, air, and oxygen atmospheres are 39.83%, 55.21%, and 93.84%, respectively. The Langmuir and pseudo second-order models satisfactorily describe the adsorption capacity and behavior of BCS-O for transition metals. The Cu2+, Ni2+, and Mn2+ adsorbed onto BCS-O were mainly bound to metal carbonates and metal oxides. Furthermore, BCS-O can effectively activate persulfate (PDS) oxidation to degrade aniline, while BCS-O loaded with transition metal (BCS-O-Me) shows better activation efficiency and reusability. BCS-O and BCS-O-Me activated PDS oxidation systems are dominated by 1O2 oxidation and electron transfer. The main active sites are oxygen-containing functional groups, vacancy defects, and graphitized carbon. The oxygen-containing functional groups and vacancy defects primarily activate PDS to generate 1O2 and attack aniline. Graphitized carbon promotes aniline degradation by accelerating electron transfer. The paper develops an innovative strategy to simultaneously realize efficient remediation of PCS and sequential reuse of the post-remediation soil.

Abiotic aerobic oxidation pathways of stibnite revealed by oxygen and sulfur isotope systematics of sulfate.

The environmental threat posed by stibnite is an important geoenvironmental issue of current concern. To better understand stibnite oxidation pathways, aerobic abiotic batch experiments were conducted in aqueous solution with varying δ18OH2O value at initial neutral pH for different lengths of time (15-300 days). The sulfate oxygen and sulfur isotope compositions as well as concentrations of sulfur and antimony species were determined. The sulfur isotope fractionation factor (Δ34SSO4-stibnite) values decreased from 0.8‰ to -2.1‰ during the first 90 days, and increased to 2.6‰ at the 180 days, indicating the dominated intermediate sulfur species such as S2O32-, S0, and H2S (g) involved in Sb2S3 oxidation processes. The incorporation of O into sulfate derived from O2 (∼100%) indicated that the dissociated O2 was only directly adsorbed on the stibnite-S sites in the initial stage (0-90 days). The proportion of O incorporation into sulfate from water (27%-52%) increased in the late stage (90-300 days), which suggested the oxidation mechanism changed to hydroxyl attack on stibnite-S sites promoted by nearby adsorbed O2 on stibnite-Sb sites. The exchange of oxygen between sulfite and water may also contributed to the increase of water derived O into SO42-. The new insight of stibnite oxidation pathway contributes to the understanding of sulfide oxidation mechanism and helps to interpret field data.

Creating Asymmetric Fe-N3C-N Sites in Single-Atom Catalysts Boosts Catalytic Performance for Oxygen Reduction Reaction.

Fine tuning of the metal site coordination environment of a single-atom catalyst (SAC) to boost its catalytic activity for oxygen reduction reaction (ORR) is of significance but challenging. Herein, we report a new SAC bearing Fe-N3C-N sites with asymmetric in-plane coordinated Fe-N3C and axial coordinated N atom for ORR, which was obtained by pyrolysis of an iron isoporphyrin on polyvinylimidazole (PVI) coated carbon black. The C@PVI-(NCTPP)Fe-800 catalyst exhibited significantly improved ORR activity (E1/2 = 0.89 V vs RHE) than the counterpart SAC with Fe-N4-N sites in 0.1 M KOH. Significantly, the Zn-air batteries equipped with the C@PVI-(NCTPP)Fe-800 catalyst demonstrated an open-circuit voltage (OCV) of 1.45 V and a peak power density (Pmax) of 130 mW/cm2, outperforming the commercial Pt/C catalyst (OCV = 1.42 V; Pmax = 119 mW/cm2). The density functional theory (DFT) calculations revealed that the d-band center of the asymmetric Fe-N3C-N structure shifted upward, which enhances its electron-donating ability, favors O2 adsorption, and supports O-O bond activation, thus leading to significantly promoted catalytic activity. This research presents an intriguing strategy for the designing of the active site architecture in metal SACs with a structure-function controlled approach, significantly enhancing their catalytic efficiency for the ORR and offering promising prospects in energy-conversion technologies.

The Effect of Co-Delivery of Oxygen and Anticancer Drugs on the Viability of Healthy and Cancer Cells under Normoxic and Hypoxic Conditions.

Hypoxia, cancer, tissue damage, and acidic pH conditions are interrelated, as chronic hypoxic conditions enhance the malignant phenotype of cancer cells, causing more aggressive tissue destruction, and hypoxic cells rely on anaerobic glycolysis, leading to the accumulation of lactic acid. Therefore, the administration of oxygen is necessary to support the functions of healthy cells until the formation of new blood vessels and to increase the oxygen supply to cancerous tissues to improve the efficacy of antitumor drugs on tumor cells. In addition to O2 supply, pH-dependent delivery of anticancer drugs is desired to target cancer cells and reduce drug side effects on healthy cells. However, the simultaneous delivery of O2 and pH-dependent anticancer drugs via nanomaterials and their effects on the viability of normal and cancer cells under hypoxic conditions have not been studied in sufficient numbers. This study describes the synthesis of a pH-responsive nanomaterial containing oxygen and anticancer drugs that exhibits sustained O2 release over a 14 d period under hypoxic conditions and pH-dependent sustained release of anticancer drugs over 30 d. The simultaneous administration of O2 and anticancer drugs results in higher cell survival of normal cells than that of cancer cells under hypoxic and normoxic conditions.

Selective CO2 Photoreduction into CH4 Triggered by the Synergy between Oxygen Vacancy and Ru Substitution under Near-Infrared Light Irradiation.

Near-infrared (NIR) light powdered CO2 photoreduction reaction is generally restricted to the separation efficiency of photogenerated carriers and the supply of active hydrogen (*H). Herein, the study reports a retrofitting hydrogenated MoO3-x (H-MoO3-x) nanosheet photocatalysts with Ru single atom substitution (Ru@H-MoO3-x) fabricated by one-step solvothermal method. Experiments together with theoretical calculations demonstrate that the synergistic effect of Ru substitution and oxygen vacancy can not only inhibit the recombination of photogenerated carriers, but also facilitate the CO2 adsorption/activation as well as the supply of *H. Compared with H-MoO3-x, the Ru@H-MoO3-x exhibit more favorable formation of *CHO in the process of *CO conversion due to the fast *H generation on electron-rich Ru sites and transfer to *CO intermediates, leading to the preferential photoreduction of CO2 to CH4 with high selectivity. The optimized Ru@H-MoO3-x exhibits a superior CO2 photoreduction activity with CH4 evolution rate of 111.6 and 39.0 µmol gcatalyst -1 under full spectrum and NIR light irradiation, respectively, which is 8.8 and 15.0 times much higher than that of H-MoO3-x. This work provides an in-depth understanding at the atomic level on the design of NIR responsive photocatalyst for achieving the goal of carbon neutrality.

Oxygen-Assisted Supercapacitive Swing Adsorption of Carbon Dioxide.

We report on the supercapacitive swing adsorption (SSA) of carbon dioxide at different voltage windows in the presence of oxygen using activated carbon electrodes, and deliquescent, aqueous electrolytes. The presence of O2 in the CO2/N2 gas mixture results in an up to 11 times higher CO2 adsorption capacity with 3M MgBr2 (at 0.6V) and up to 4-5 times higher adsorption capacity with 3M MgCl2 (at 1V). A tradeoff between high CO2 adsorption capacities and lower coulombic efficiencies was observed at voltages above 0.6V. The energetic and adsorptive performance of the electrodes in the presence of oxygen below 0.5V was similar to the performance with a CO2/N2 mixture without oxygen at 1V. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) of the electrodes demonstrate that the specific capacitance increases while the diffusion resistance decreases in the presence of oxygen. Oxygen concentrations ranging between 5-20% give similar energetic and adsorptive performance. The electrodes exhibit stable performance for up to 100 cycles of operation.

Interface States in Gate Stack of Carbon Nanotube Array Transistors.

A deep understanding of the interface states in metal-oxide-semiconductor (MOS) structures is the premise of improving the gate stack quality, which sets the foundation for building field-effect transistors (FETs) with high performance and high reliability. Although MOSFETs built on aligned semiconducting carbon nanotube (A-CNT) arrays have been considered ideal energy-efficient successors to commercial silicon (Si) transistors, research on the interface states of A-CNT MOS devices, let alone their optimization, is lacking. Here, we fabricate MOS capacitors based on an A-CNT array with a well-designed layout and accurately measure the capacitance-voltage and conductance-voltage (C-V and G-V) data. Then, the gate electrostatics and the physical origins of interface states are systematically analyzed and revealed. In particular, targeted improvement of gate dielectric growth in the A-CNT MOS device contributes to suppressing the interface state density (Dit) to 6.1 × 1011 cm-2 eV-1, which is a record for CNT- or low-dimensional semiconductors-based MOSFETs, boosting a record transconductance (gm) of 2.42 mS/µm and an on-off ratio of 105. Further decreasing Dit below 1 × 1011 cm-2 eV-1 is necessary for A-CNT MOSFETs to achieve the expected high energy efficiency.

Synergistic Assistance of Ir Clusters and NiCo2O4 Nanosheets Interfaces in Direct O-O Coupling for High-Efficiency Alkaline Oxygen Evolution.

Adopting noble metals on non-noble metals is an effective strategy to balance the cost and activity of electrocatalysts. Herein, a thorough analysis of the synergistic OER is conducted at the heterogeneous interface formed by Ir clusters and NiCo2O4 based on DFT calculations. Specifically, the electrons spontaneously bring an eg occupancy of interfacial Ir close to unity after the absorbed O, providing more transferable electrons for the conversion of the absorbed O-intermediates. Besides, the diffuse distribution of electrons in the Ir 5d orbital fills the antibonding orbital after O is absorbed, avoiding the desorption difficulties caused by the stronger Ir-O bonds. The electrons transfer from Ir to Co atoms at the heterogeneous interface and fill the Co 3d band near the Fermi level, stimulating the interfacial Co to participate in the direct O-O coupling (DOOC) pathway. Experimentally, the ultrathin-modulated NiCo2O4 nanosheets are used to support Ir clusters (Ircluster-E-NiCo2O4) by the electrodeposition method. The as-synthesized Ircluster-E-NiCo2O4 catalyst achieves a current density of 10 mA cm-2 at an ultralow overpotential of 238 mV and works steadily for 100 h under a high current of 100 mA cm-2, benefiting from the efficient DOOC pathway during the OER.

Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.

PURPOSE: To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). MATERIALS AND METHODS: Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. RESULTS: Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. CONCLUSIONS: Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

A standardized approach to evaluate effectiveness of aerobic exercise training interventions in cardiovascular disease at the individual level.

BACKGROUND: Reliable change indices can determine pre-post intervention changes at an individual level that are greater than chance or practice effect. We applied previously developed minimal meaningful change (MMCRCI) scores for oxygen uptake (V̇O2) values associated with estimated lactate threshold (θLT), respiratory compensation point (RCP), and peak oxygen uptake (V̇O2peak) to evaluate the effectiveness of exercise training in cardiovascular disease patients. METHODS: 303 patients (65 ± 11 yrs.; 27% female) that completed a symptom-limited cardiopulmonary exercise test (CPET) before and after 6-months of guideline-recommended exercise training were assessed to determine absolute and relative V̇O2 at θLT, RCP, and V̇O2peak. Using MMCRCI ∆V̇O2 scores of ±3.9 mL·kg-1·min-1, ±4.0 mL·kg-1·min-1, and ± 3.6 mL·kg-1·min-1 for θLT, RCP, and V̇O2peak, respectively, patients were classified as "positive" (ΔθLT, ΔRCP, and/or ΔV̇O2peak ≥ +MMCRCI), "non-" (between ±MMCRCI), or "negative" responders (≤ -MMCRCI). RESULTS: Mean RCP (n = 86) and V̇O2peak (n = 303) increased (p < 0.05) from 19.4 ± 3.6 mL·kg-1·min-1 and 18.0 ± 6.3 mL·kg-1·min-1 to 20.1 ± 3.8 mL·kg-1·min-1 and 19.2 ± 7.0 mL·kg-1·min-1 at exit, respectively, whereas θLT (n = 140) did not change (15.5 ± 3.4 mL·kg-1·min-1 versus 15.7 ± 3.8 mL·kg-1·min-1, p = 0.324). For changes in θLT, 6% were classified as "positive" responders, 90% as "non-responders", and 4% as "negative" responders. For RCP, 10% exhibited "positive" changes, 87% were "non-responders", and 2% were "negative" responders. For ΔV̇O2peak, 57 patients (19%) were classified as "positive" responders, 229 (76%) as "non-responders", and 17 (6%) as "negative" responders. CONCLUSION: Most patients that completed the exercise training program did not achieve reliable improvements greater than that of chance or practice at an individual level in θLT, RCP and V̇O2peak.

Impact of varying dissolved organic carbon load on sediment phosphorus release and its periodic mechanisms.

Phosphorus (P) release from sediment poses a severe challenge for eutrophication management in the aquatic environment. The dissolved organic carbon (DOC) concentrations in riverine ecosystems have shown an increasing trend due to intensified climate change and anthropogenic activities, while their impact on sediment P cycling remains unclear. To investigate the effects of different DOC loads on sediment P release and the underlying mechanisms, we conducted a two-month experiment in 15 plexiglass tanks, with five gradient-increasing target DOC concentrations set according to reality: control (S0), 5 mg/L (S5), 10 mg/L (S10), 15 mg/L (S15), and 20 mg/L (S20). The results demonstrated that: i) DOC enrichment promoted the sediment P mobilization and release, with the underlying mechanisms exhibited periodic characteristics. ii) reduced dissolved oxygen (DO) concentration and stimulated alkaline phosphatase activity (APA) were likely the primary and sustained facilitating mechanisms. While after the termination of DOC load, elevated pH level was also considered a contributing factor when chlorophyll a (Chl a) ranged between 5.9 µg/L and 7.7 µg/L iii) ultimate concentration of total P (TP) in the overlying water depended on DOC load. After DOC addition was terminated, decreased TP concentrations were observed when DOC concentration was in the range of 5-15 mg/L, which may be attributed to the direct uptake of P by phytoplankton counteracting the minor promotion of P release induced by anoxic conditions. However, when DOC concentrations exceeded 15-20 mg/L, there were notable increments in TP concentrations. Our findings provide further insight into the response mechanisms of sediment P release to the increasing organic C load in natural ecosystems. The impact of broader C forms or C loads on sediment P cycling needs to be fully elucidated and even quantified in future studies, especially through large-scale field investigations to further clarify the coupled roles between C and P.

Degree of PEGylatation of Lumbricus terrestris Hemoglobin Improves Microcirculatory Blood Flow but Increases the Rate of Auto-Oxidation.

INTRODUCTION: The demand for red blood cells (RBCs) is on the rise due to the increasing diagnosis of chronic diseases such as sickle cell anemia, malaria, and thalassemia. Despite many commercial attempts, there are no U.S. FDA-approved artificial RBCs for use in humans. Existing RBC substitutes have employed various strategies to transport oxygen, extend the circulation time, and reduce organ toxicity, but none have replicated the natural protective mechanisms of RBCs, which prevent hemoglobin (Hb) dimerization and heme iron oxidation. Lumbricus terrestris (earthworm) erythrocruorin (LtEc) is a naturally occurring extracellular hemoglobin (Hb) with promising attributes: large molecular diameter (30 nm), high molecular weight (3.6 MDa), low auto-oxidation rate, and limited nitric oxide-scavenging properties. These characteristics make LtEc an ideal candidate as an RBC substitute. However, LtEc has a significant drawback, its short circulatory half-life. To address this issue, we explored thiol-mediated surface PEGylation of LtEc (PEG-LtEc) at varying polyethylene glycol (PEG) surface coverages. Increasing PEG surface coverage beyond 40% destabilizes LtEc into smaller subunits that are 1/12th the size of LtEc. Therefore, we evaluated two PEG surface coverage options: PEG-LtEc-0.2 (20% PEGylation) and PEG-LtEc-1.0 (100% PEGylation). METHODS: We conducted experiments using golden Syrian hamsters with dorsal window chambers and catheters to assess the efficacy of these solutions. We measured microvascular parameters, organ function, cerebral blood flow, circulation time, mean arterial pressure, heart rate, and blood gases and performed histology to screen for toxicity. CONCLUSION: Our findings indicate that both PEG-LtEc molecules offer significant benefits in restoring microvascular parameters, organ function, cerebral blood flow, and circulation time compared to LtEc alone. Notably, PEG-LtEc-1.0 showed superior microvascular perfusion, although it exhibited a higher rate of auto-oxidation compared to PEG-LtEc-0.2. These results underscore the advantages of PEGylation in terms of tissue perfusion and organ health while highlighting its limitations.

Contribution of oxidation reactions to photo-induced damage to cellular DNA.

This review article is aimed at providing updated information on the contribution of immediate and delayed oxidative reactions to the photo-induced damage to cellular DNA/skin under exposure to UVB/UVA radiations and visible light. Low-intensity UVC and UVB radiations that operate predominantly through direct excitation of the nucleobases are very poor oxidizing agents giving rise to very low amounts of 8-oxo-7,8-dihydroguanine and DNA strand breaks with respect to the overwhelming bipyrimidine dimeric photoproducts. The importance of these two classes of oxidatively generated damage to DNA significantly increases together with a smaller contribution of oxidized pyrimidine bases upon UVA irradiation. This is rationalized in terms of sensitized photooxidation reactions predominantly mediated by singlet oxygen together with a small contribution of hydroxyl radical that appear to also be implicated in the photodynamic effects of the blue light component of visible light. Chemiexcitation-mediated formation of "dark" cyclobutane pyrimidine dimers in UVA-irradiated melanocytes is a recent major discovery that implicates in the initial stage, a delayed generation of reactive oxygen and nitrogen species giving rise to triplet excited carbonyl intermediate and possibly singlet oxygen. High-intensity UVC nanosecond laser radiation constitutes a suitable source of light to generate pyrimidine and purine radical cations in cellular DNA via efficient biphotonic ionization.

Improving the Oxygen Evolution Reaction Kinetics in Zn-Air Battery by Iodide Oxidation Reaction.

Zinc-air batteries (ZABs) have garnered considerable attention as a highly promising contender in the field of energy storage and conversion. Nevertheless, their performance is considerably impeded by the proliferation of dendrites on the Zinc anode and the slow kinetics of the redox reaction on the air cathode. Herein, taking Ag30%@LaCoO3 (Ag30%@LCO) heterojunction catalyst as the cathode, it is demonstrated that adding KI additives to the alkaline electrolyte can not only enhance the oxygen electrocatalytic reaction but also inhibit the formation of zinc anode dendrites, thereby achieving a comprehensive improvement in the performance of ZABs. Under the action of the KI additive, the optimized Ag30%@LCO catalyst shows a decreased overpotential from 460 to 220 mV at j = 10 mA cm-2, while the assembled ZAB shows reduced charging potential (1.8 V), and long cycle stability (180 h). Furthermore, the morphology characterization results indicate a reduction in dendrites on the Zn anode. Both experimental and calculated results indicate that the presence of I- as a reaction modifier alters the trajectory of the conventional oxygen evolution reaction, resulting in a more thermodynamically favorable pathway. The introduction of KI additives as electrolytes provides a straightforward approach to developing comprehensively improved ZABs.

Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome.

The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.

Hypoxia in uterine fibroids: role in pathobiology and therapeutic opportunities.

Uterine fibroids are the most common tumors in females affecting up to 70% of women world-wide, yet targeted therapeutic options are limited. Oxidative stress has recently surfaced as a key driver of fibroid pathogenesis and provides insights into hypoxia-induced cell transformation, extracellular matrix pathophysiology, hypoxic cell signaling cascades, and uterine biology. Hypoxia drives fibroid tumorigenesis through (1) promoting myometrial stem cell proliferation, (2) causing DNA damage propelling transformation of stem cells to tumor initiating cells, and (3) driving excess extracellular matrix (ECM) production. Common fibroid-associated DNA mutations include MED12 mutations, HMGA2 overexpression, and Fumarate hydratase loss of function. Evidence suggests an interaction between hypoxia signaling and these mutations. Fibroid development and growth are promoted by hypoxia-triggered cell signaling via various pathways including HIF-1, TGFß, and Wnt/ß-catenin. Fibroid-associated hypoxia persists due to antioxidant imbalance, ECM accumulation, and growth beyond adequate vascular supply. Current clinically available fibroid treatments do not take advantage of hypoxia-targeting therapies. Growing pre-clinical and clinical studies identify ROS inhibitors, anti-HIF-1 agents, Wnt/ß-catenin inhibition, and TGFß cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.

Exercise-Induced Oxygen Desaturation Increases Arterial Stiffness in Patients with COPD During the 6WMT.

Objective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD. Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO2) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO2 during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study. Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was -0.53 (-0.95 to -0.31) in non-EID group, -0.20 (-1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038). Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.

Andrographolide induces protective autophagy and targeting DJ-1 triggers reactive oxygen species-induced cell death in pancreatic cancer.

Background: Andrographolide (Andro), an extract of Andrographis paniculate (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear. Methods: The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through in vitro experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy. Results: Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both in vitro and in vivo. The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro. Conclusion: Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.

Role of oxidative stress in the concurrent development of osteoporosis and tendinopathy: Emerging challenges and prospects for treatment modalities.

Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.