Critical-size bone defects necessitate bone void fillers that should be integrated well and be easily vascularized. One viable option is to use a biocompatible synthetic polymer and sonocoat it with zinc oxide (ZnO) nanoparticles (NPs). However, the ideal NP concentration and size must be assessed because a high dose of ZnO NPs may be toxic. Electrospun PDLLA/PLGA scaffolds were produced with different concentrations (0.5 or 1.0 s of sonocoating) and sizes of ZnO NPs (25 nm and 70 nm). They were characterized by SEM, EDX, ICP-OES, and the water contact angle. Vascularization and integration into the surrounding tissue were assessed with the CAM assay in the living chicken embryo. SEM, EDX, and ICP-OES confirmed the presence of ZnO NPs on polymer fibers. Sonocoated ZnO NPs lowered the WCA compared with the control. Smaller NPs were more pro-angiogenic exhibiting a higher vessel density than the larger NPs. At a lower concentration, less but larger vessels were visible in an environment with a lower cell density. Hence, the favored combination of smaller ZnO NPs at a lower concentration sonocoated on PDLLA/PLGA electrospun meshes leads to an advanced state of tissue integration and vascularization, providing a valuable synthetic bone graft to be used in clinics in the future.

Atherosclerosis is a complex condition that involves the accumulation of lipids and subsequent plaque formation in the arterial intima. There are various stimuli, cellular receptors, and pathways involved in this process, but oxidative modifications of low-density lipoprotein (ox-LDL) are particularly important in the onset and progression of atherosclerosis. Ox-LDLs promote foam-cell formation, activate proinflammatory pathways, and induce smooth-muscle-cell migration, apoptosis, and cell death. One of the major receptors for ox-LDL is LOX-1, which is upregulated in several cardiovascular diseases, including atherosclerosis. LOX-1 activation in endothelial cells promotes endothelial dysfunction and induces pro-atherogenic signaling, leading to plaque formation. The binding of ox-LDLs to LOX-1 increases the generation of reactive oxygen species (ROS), which can induce LOX-1 expression and oxidize LDLs, contributing to ox-LDL generation and further upregulating LOX-1 expression. This creates a vicious circle that is amplified in pathological conditions characterized by high plasma levels of LDLs. Although LOX-1 has harmful effects, the clinical significance of inhibiting this protein remains unclear. Further studies both in vitro and in vivo are needed to determine whether LOX-1 inhibition could be a potential therapeutic target to counteract the atherosclerotic process.

The organophosphate insecticide chlorpyrifos (CPF), an acetylcholinesterase inhibitor, has raised serious concerns about human safety. Apart from inducing synaptic acetylcholine accumulation, CPF could also act at nicotinic acetylcholine receptors, like the α7-isoform (α7-nAChR), which could potentially be harmful to developing brains. Our aims were to use molecular docking to assess the binding interactions between CPF and α7-nAChR through, to test the neurocytotoxic and oxidative effects of very low concentrations of CPF on SH-SY5Y cells, and to hypothesize about the potential mediation of α7-nAChR. Docking analysis showed a significant binding affinity of CPH for the E fragment of the α7-nAChR (ΔGibbs: -5.63 to -6.85 Kcal/mol). According to the MTT- and Trypan Blue-based viability assays, commercial CPF showed concentration- and time-dependent neurotoxic effects at a concentration range (2.5-20 µM), ten-folds lower than those reported to have crucial effects for sheer CPF. A rise of the production of radical oxygen species (ROS) was seen at even lower concentrations (1-2.5 µM) of CPF after 24h. Notably, our docking analysis supports the antagonistic actions of CPF on α7-nAChR that were recently published. In conclusion, while α7-nAChR is responsible for neuronal survival and neurodevelopmental processes, its activity may also mediate the neurotoxicity of CPF.

Gestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring).
Gestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10-E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment.
The HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring.
Gestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring.

Despite decades of intense research, the precise etiology of Alzheimer\'s disease (AD) remains unclear. In this hypothesis, we present a new perspective on this matter by identifying carnitine palmitoyl transferase-2 (CPT2) as a central target in AD. CPT2 is an enzyme situated within the inner mitochondrial membrane, playing a crucial role in beta-oxidation of fatty acids. It exhibits high sensitivity to hydrogen peroxide. This sensitivity holds relevance for the etiology of AD, as all major risk factors for the disease share a commonality in producing an excess of hydrogen peroxide right at this very mitochondrial membrane. We will explain the high sensitivity of CPT2 to hydrogen peroxide and elucidate how the resulting inhibition of CPT2 can lead to the characteristic phenotype of AD, thus clarifying its central role in the disease\'s etiology. This insight holds promise for the development of therapies for AD which can be implemented immediately.

Gold nanoparticles, such as nanorods (AuNRs), present exceptionally high absorption cross sections that can be tuned to the near-infrared (NIR), the optimal window for light penetration in biological tissues. This makes them valuable photosensitizers for the treatment of cancer using photothermal therapy, where absorbed light energy is converted into heat. In addition, there is a strong interest in using hot electron carriers generated in AuNRs by NIR irradiation to produce cytotoxic radical oxygen species in order to enhance the efficiency of the phototherapy. Here, we show that hybrid nanoparticles composed of AuNRs with TiO2 deposited at their extremities are efficient sensitizers to produce hydroxyl radical species under NIR irradiation. We attribute this phenomenon to the transfer of hot electrons generated from the plasmon excitation in AuNR to the TiO2 tips, followed by reduction of dioxygen. We then functionalize these hybrid AuNR/TiO2 nanoparticles with block poly(ethylene glycol)-phosphonate polymer ligands to stabilize them in a physiological medium. We finally demonstrate that the photodynamic effect induces cell death upon irradiation with a greater efficiency than the photothermal effect alone.

Background: The incidence of glycolipid metabolic diseases is extremely high worldwide, which greatly hinders people\'s life expectancy and patients\' quality of life. Oxidative stress (OS) aggravates the development of diseases in glycolipid metabolism. Radical oxygen species (ROS) is a key factor in the signal transduction of OS, which can regulate cell apoptosis and contribute to inflammation. Currently, chemotherapies are the main method to treat disorders of glycolipid metabolism, but this can lead to drug resistance and damage to normal organs. Botanical drugs are an important source of new drugs. They are widely found in nature with availability, high practicality, and low cost. There is increasing evidence that herbal medicine has definite therapeutic effects on glycolipid metabolic diseases. Objective: This study aims to provide a valuable method for the treatment of glycolipid metabolic diseases with botanical drugs from the perspective of ROS regulation by botanical drugs and to further promote the development of effective drugs for the clinical treatment of glycolipid metabolic diseases. Methods: Using herb*, plant medicine, Chinese herbal medicine, phytochemicals, natural medicine, phytomedicine, plant extract, botanical drug, ROS, oxygen free radicals, oxygen radical, oxidizing agent, glucose and lipid metabolism, saccharometabolism, glycometabolism, lipid metabolism, blood glucose, lipoprotein, triglyceride, fatty liver, atherosclerosis, obesity, diabetes, dysglycemia, NAFLD, and DM as keywords or subject terms, relevant literature was retrieved from Web of Science and PubMed databases from 2013 to 2022 and was summarized. Results: Botanical drugs can regulate ROS by regulating mitochondrial function, endoplasmic reticulum, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), erythroid 2-related factor 2 (Nrf-2), nuclear factor κB (NF-κB), and other signaling pathways to improve OS and treat glucolipid metabolic diseases. Conclusion: The regulation of ROS by botanical drugs is multi-mechanism and multifaceted. Both cell studies and animal experiments have demonstrated the effectiveness of botanical drugs in the treatment of glycolipid metabolic diseases by regulating ROS. However, studies on safety need to be further improved, and more studies are needed to support the clinical application of botanical drugs.

Photocatalytic biomass conversion into high-value chemicals and fuels is considered one of the hottest ongoing research and industrial topics toward sustainable development. In short, this process can cleave Cβ -O/Cα -Cβ bonds in lignin to aromatic platform chemicals, and further conversion of the polysaccharides to other platform chemicals and H2 . From the chemistry point of view, the optimization of the unique cooperative interplay of radical oxidation species (which are activated via molecular oxygen species, ROSs) and substrate-derived radical intermediates by appropriate control of their type and/or yield is key to the selective production of desired products. Technically, several challenges have been raised that face successful real-world applications. This review aims to discuss the recently reported mechanistic pathways toward selective biomass conversion through the optimization of ROSs behavior and materials/system design. On top of that, through a SWOT analysis, we critically discussed this technology from both chemistry and technological viewpoints to help the scientists and engineers bridge the gap between lab-scale and large-scale production.

Severe physical injuries and associated traumatic brain injury and/or hemorrhagic shock (HS) remain leading causes of death worldwide, aggravated by accompanying extensive inflammation. Retrospective clinical data indicated an association between mild hyperoxemia and improved survival and outcome. However, corresponding prospective clinical data, including long-term resuscutation, are scarce. Therefore, the present study explored the effect of mild hyperoxemia for 24 hours in a prospective randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma (ASDH) and HS. ASDH was induced by injecting 0.1 ml × kg-1 autologous blood into the subdural space and HS was triggered by passive removal of blood. After 2 hours, the animals received full resuscitation, including retransfusion of the shed blood and vasopressor support. During the first 24 hours, the animals underwent targeted hyperoxemia (PaO2 = 200 - 250 mmHg) or normoxemia (PaO2 = 80 - 120 mmHg) with a total observation period of 55 hours after the initiation of ASDH and HS. Survival, cardiocirculatory stability, and demand for vasopressor support were comparable between both groups. Likewise, humoral markers of brain injury and systemic inflammation were similar. Multimodal brain monitoring, including microdialysis and partial pressure of O2 in brain tissue, did not show significant differences either, despite a significantly better outcome regarding the modified Glasgow Coma Scale 24 hours after shock that favors hyperoxemia. In summary, the present study reports no deleterious and few beneficial effects of mild targeted hyperoxemia in a clinically relevant model of ASDH and HS with long-term resuscitation in otherwise healthy pigs. Further beneficial effects on neurological function were probably missed due to the high mortality in both experimental groups. The present study remains exploratory due to the unavailability of an a priori power calculation resulting from the lack of necessary data.

The cultivation of rice is widespread worldwide, but its growth and productivity are hampered by heavy metals stress. However, sodium nitroprusside (SNP), a nitric oxide donor, has been found to be effective for imparting heavy metals stress tolerance to plants. Therefore, the current study evaluated the role of exogenously applied SNP in improving plant growth and development under Hg, Cr, Cu, and Zn stress. For this purpose, heavy metals stress was induced via the application of 1 mM mercury (Hg), chromium (Cr), copper (Cu), and zinc (Zn). To reverse the toxic effects of heavy metals stress, 0.1 mM SNP was administrated via the root zone. The results revealed that the said heavy metals significantly reduced the chlorophyll contents (SPAD), chlorophyll a and b, and protein contents. However, SNP treatment significantly reduced the toxic effects of the said heavy metals on chlorophyll (SPAD), chlorophyll a and b, and protein contents. In addition, the results also revealed that heavy metals significantly increased the production of superoxide anion (SOA), hydrogen peroxide (H2O2), malondialdehyde (MDA), and electrolyte leakage (EL). However, SNP administration significantly reduced the production of SOA, H2O2, MDA, and EL in response to the said heavy metals. Furthermore, to cope with the said heavy metals stress, SNP administration significantly enhanced the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol peroxidase (PPO). Furthermore, in response to the said heavy metals, SNP application also upregulated the transcript accumulation of OsPCS1, OsPCS2, OsMTP1, OsMTP5, OsMT-I-1a, and OsMT-I-1b. Therefore, SNP can be used as a regulator to improve the heavy metals tolerance of rice in heavy-metals-affected areas.