Low Oxygen Concentrations Research Articles

Evolving Tumor Characteristics and Smart Nanodrugs for Tumor Immunotherapy.

Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their "new faces"; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become "invisible", that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.

Pyrolysis of oil palm trunk biomass using a fixed bed reactor to produce raw material for bio-carbon black

The abundance of palm oil plantation waste in Indonesia can be utilized as a raw material for making carbon black, which currently relies on fossil fuel-based raw materials. Out of the five types of palm oil biomass waste, including empty fruit bunches (EFB), palm kernel shells (PKS), palm mesocarp fibers (PMF), oil palm fronds (OPF), and oil palm trunks (OPT), one will be chosen as the raw material for carbon black production. Palm oil biomass waste typically has a relatively high ash content. To reduce the ash content, the biomass must first undergo pyrolysis to transform it into pyrolysis oil. The higher the carbon content and the lower the oxygen content, the more the pyrolysis oil meets the criteria for replacing crude oil. Among the criteria mentioned, the lowest ash content is found in palm kernel shells (1.4%). The highest carbon content is in palm trunks (55.8%), while the lowest oxygen content is also in palm kernel shells (34.5%). Palm kernel shells are the best palm oil biomass that can be used as a raw material for carbon black. However, because palm kernel shells are commonly used as boiler fuel, the second choice is palm trunks due to their high carbon content. Pyrolysis experiments were conducted using palm trunk biomass to produce bio-oil, which would be further processed into carbon black. The palm trunks were divided into three parts: outer trunk, middle trunk, and core trunk. The biomass size was also varied, with sizes of 20 mesh and 40 mesh. The pyrolysis process used a fixed bed reactor with a heating rate of 3°C/minute, reaching a pyrolysis temperature of 600°C, and maintaining that temperature for 1.5 hours. The highest yield of bio-oil obtained was from the outer trunk with a biomass size of 40 mesh (36.8%). Similarly, for a size of 20 mesh, the highest yield was also from the outer trunk (35.7%).

IGF-1 infusion increases growth in fetal sheep when euinsulinemia is maintained.

Insulin-like growth factor 1 (IGF-1) is a critical fetal anabolic hormone. IGF-1 infusion to the normally growing sheep fetus increases the weight of some organs but does not consistently increase body weight. However, IGF-1 infusion profoundly decreases fetal plasma insulin concentrations, which may limit fetal growth potential. In this study, normally growing late-gestation fetal sheep received an intravenous infusion of either: IGF-1 (IGF), IGF-1 with insulin and dextrose to maintain fetal euinsulinemia and euglycemia (IGF+INS), or vehicle control (CON) for 1 week. The fetus underwent a metabolic study immediately prior to infusion start and after 1 week of the infusion to measure uterine and umbilical uptake rates of nutrients and oxygen. IGF+INS fetuses were 23% heavier than CON (P = 0.0081) and had heavier heart, liver, and adrenal glands than IGF and CON (P < 0.01). By design, final fetal insulin concentrations in IGF were 62% and 65% lower than IGF+INS and CON, respectively. Final glucose concentrations were similar in all groups. IGF+INS had lower final oxygen content than IGF and CON (P < 0.0001) and lower final amino acid concentrations than CON (P = 0.0002). Final umbilical oxygen uptake was higher in IGF+INS compared to IGF and CON (P < 0.05). Final umbilical uptake of several essential amino acids was higher in IGF+INS compared to CON (P < 0.05). In summary, maintaining euinsulinemia and euglycemia during fetal IGF-1 infusion is necessary to maximally support body growth. We speculate that IGF-1 and insulin stimulate placental nutrient transport to support fetal growth.

Impact of light on protective fractions of Cu in white wine: Influence of oxygen and bottle colour

Cu(II)-organic acid (fraction I) and Cu(I)-thiol (fraction II) complexes can suppress sulfhydryl off-aromas in wine. This study investigated the impact of light exposure on the protective fractions of Cu of bottled white wine. Fluorescent light-exposed Chardonnay with two initial concentrations of dissolved oxygen (0.5 and 10 mg/L) was stored in different coloured bottles and concentrations of Cu fractions and riboflavin, a photo-initiator at 370–440 nm, were measured during 110 days storage. Light-exposed wines with lower oxygen concentrations resulted in a 100-fold decrease in the Cu fraction I half-life, and a 60-fold decrease for Cu fractions I and II combined. The half-life for Cu fraction I decay during light exposure was extended 30-fold with the use of brown compared to flint glass. Light exposure can rapidly exhaust the protective Cu fractions in wine, and bottles with less light transmission below 440 nm can slow this loss.

The comprehensive evaluation of nitrate origin and transformation pathways in the oxic alluvial aquifer in Serbia.

Accurate pollution source identification is essential for establishing adequate water management strategies, particularly in groundwater with slow flow and prolonged recharge process allowing long-term pollution retention. An integrated study based on hydrogeochemical, dual isotopic (δ15NNO3 and δ18ONO3), and microbiological approaches (DN, IRB, and SRB BART tests) along with the statistical data processing was conducted to determine nitrate origin and fate in oxic alluvial groundwater source Ključ in Serbia. The findings from a comprehensive investigation, encompassing 20 groundwater sampling locations during the period 2010-2019, delineated three distinct zones - the hinterland (anthropogenic impact area-untreated sewage inflow), the middle zone (area of mixed influence from fertilizer application, accompanied by a mitigated anthropogenic impact), and the zone of riparian denitrification. Significant linear relationship between anthropogenic impact parameters (Na, Cl, B, NO3-, NH4+, and electrical conductivity) along with the isotopic signatures (δ15N-NO3- ranking from + 10.01 to + 11.18‰ and δ18O-NO3- ranking from + 1.15 to + 6.24‰) and grouped sampling objects by cluster analysis indicated that hinterland is burdened by the nitrates originating from anthropogenic impact. The cross-section of groundwater flow data, concurrent increase of NH4+, and pH levels, along with the highest values of δ15N-NO3- (+ 12.90‰) and δ18O-NO3- (+ 9.70‰), indicated area of fertilizers (urea) impact. BART test results, pH increase, and low oxygen concentration, along with the groundwater flow data in riparian zone, indicated the unfolding of denitrification process. Presented research emphasizes the importance, necessities, and advantages of simultaneous and complementary use of hydrogeochemical, microbiological, and isotopic data.

Influence of powder surface chemistry on the defect formation in AlSi10Mg alloy processed via laser powder bed fusion additive manufacturing

In laser powder bed fusion(LPBF) additive manufacturing(AM) of Al alloys, surface chemistry and dissolved gas composition(oxygen/oxides/hydroxides, hydrogen and moisture) of AM powders is a major influencing factor for porosity formation. Therefore, in the present investigation, this aspect is addressed using two sets of virgin AM AlSi10Mg powders, namely, Hi-Ox (2770 ppm oxygen) and Lo-Ox (660 ppm oxygen), to assess the printability under various processing parameters and defect formation in printed parts. Comprehensive and in-depth metallurgical analysis of both powders utilizing multiple characterisation techniques established the presence of various types of oxides/hydroxides with different complex chemistries on the powders’ surface. Enhanced spherical gas porosity and oxide inclusions were witnessed in Hi-Ox print coupons in contrast to the least defects in Lo-Ox coupons rationalized due to surface chemistry difference between the virgin powders. Consequently, the mechanical properties of the Hi-Ox print coupons, even with minimum defect density, are significantly inferior to Lo-Ox specimens. These observations suggest a competing influence of surface chemistry/dissolved gas composition and laser parameters for the processing of both powders. Overall, by correlating the microstructures with processing conditions and oxide concentration, defects morphology, the probable melt pool formation mechanism in LPBF of AlSi10Mg alloy (for high and low oxygen concentration) is elucidated.

Effects of hypoxia on copepod egg hatching success: An in situ study

Hypoxia is a global concern, affecting marine ecosystems. In this study, we investigated the effect of low Oxygen concentration on the egg hatching rate of Acartia erythraea in Gamak Bay, where hypoxia frequently occurs in summer. Three in situ experiments were conducted in June and August 2013 and July 2014. Environmental parameters, including the water temperature, salinity, dissolved Oxygen (DO) concentration, and pH, were measured during the experiments. Hypoxic conditions had a significant negative impact on the hatching rate of A. erythraea eggs; hatching rate was positively correlated with the DO concentration (r = 0.843, p < 0.01) and pH (r = 0.600, p < 0.01). These findings suggest that hypoxia has significant negative impacts on recruitment of planktonic A. erythraea, with potential implications for overall plankton and nekton dynamics.

Multi-physical effects induced by spatiotemporal corrosion of T91 cladding in oxygen-controlled LBE environment

T91, a pivotal candidate material for cladding in lead-based fast reactors (LFRs), demonstrates considerable potential for corrosion resistance in liquid lead-bismuth eutectic (LBE) corrosion experiments. However, the multi-physics characteristics of T91 cladding corrosion in its operational environment remain unclear, posing an obstacle to its practical application. This study focuses on the spatiotemporal corrosion of T91 cladding in multi-physics coupling scenarios by means of COMMA (Cladding/Oxidation corrosion Multi-physics Modeling and Analysis code), in which, modules of cladding oxidation, cladding oxide removal, heat transfer, mechanical deformation, and fission gas release are integrated and collaboratively solved. The corrosion patterns of T91 cladding with different oxygen concentrations and the underlying multi-physics behavior of the corrosion processes under operational conditions simulating are summarized. For the lower oxygen concentration of 1.8e-9 wt% in LFRs, the results indicate a 0.2 m axial zone with base material exposed to LBE reveals the presence of the oxidation protection failure. An exacerbation of cladding heat transfer degradation is observed after oxygen concentration reaching the oxygen-dominant region, due to the enhanced temperature positive feedback of oxidation corrosion. For the high oxygen concentration of 1.4e-6 wt%, an axial offset of 0.24 m for the location of the minimum gap size is observed. This study identifies a trend of the reduction thickness of cladding that first decreasing and then increasing with an elevated oxygen concentration, attributed to a transition in corrosion patterns. The temperature and mechanical analyses indicate that the optimal oxygen concentration for corrosion inhibition and fuel safety is located around the critical oxygen-dominant concentration.

Co-pyrolysis characteristic of sugarcane waste with polyethylene terephthalate: thermal decomposition, product distribution, synergistic effect, and kinetics analysis.

This work has focused on the co-pyrolysis of sugarcane waste (SW) with polyethylene terephthalate (PET) to gain insight on its thermal decomposition, product distribution, kinetics, and synergistic effect. SW and PET were blended at different ratios (100:0, 80:20, 60:40, 40:60, and 0:100), and the Coats-Redfern method was used to determine the kinetics parameters. To ascertain the synergistic effect between SW and PET, product yields and composition of chemicals were compared with the synergistic effect of the individual components of pyrolysis. The bio-oil yield was significant at 60% of PET, with a difference of 19.41 wt% compared to the theoretical value. The synergistic impact of SW:PET on ester formation and acid compound inhibition was the most dominant at the 60:40 ratio. The kinetics analysis revealed that the diffusion mechanism, power law, and order of reactions were the most probable reaction models that can explain the pyrolysis of SW, and PET, and their blends. The resultant co-pyrolysis oil contained slightly larger hydrogen and carbon contents with low oxygen, and sulphur, and nitrogen contents, which improved the quality of the bio-oil. The results of this work could be used as a guide in selecting proper reaction conditions with optimal synergy during the co-pyrolysis process.

Characterization of Pyrolytic Tars Derived from Different Biomasses

The pyrolysis of three different biomasses, rice husk (RH), zoita wood sawdust (ZW) and pine wood sawdust (PW), was studied at 500 °C in a multipurpose unit at the bench scale to determine the yields of the different products and the compositions and properties of the liquid products, with particular emphasis given to the alquitranous fractions (tars). It was possible to link the characteristics of the tars with the compositions of the raw biomasses and verify their potential in various applications. The analytical techniques employed in the characterization of biomasses included lignin, celulose and hemicellulose analysis, ultimate and proximate analysis and thermogravimetry–mass spectrometry analysis (TG-MS). Elemental analysis, gas chromatography–mass spectrometry (GC-MS), nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FTIR) and size exclusion chromatography (SEC) were used to characterize the tars. The tar yields were 1.8, 7.4 and 4.0 %wt. in the cases of RH, ZW and PW, respectively. The tars showed higher carbon content, between 60.3 and 62.2 %wt., and lower oxygen content, between 28.8 and 31.6 %wt., than the corresponding raw biomasses. The main components of the tars had aromatic bases, with phenols representing more than 50%. Tar RH included more guaiacols, while Tars ZW and PW included more phenols and alkylated phenols.

Seasonal ventilation controls nitrous oxide emission in the NW Iberian upwelling

Despite their small spatial extent, coastal upwelling systems are an important source of oceanic nitrous oxide (N2O) to the atmosphere. To date, hot-spot N2O emissions have been reported for low oxygen waters of the eastern boundary upwelling systems at their tropical latitudes, but there is a limited number of studies in their “oxygenated” temperate latitudes. This is the first study of the N2O cycle in the NW Iberian Upwelling system, where we investigated the seasonality of the N2O concentrations and their emissions to the atmosphere, along with the spatial differences in this coastal region in response to the upwelling. Monthly observations were collected from February 2017 to July 2018, in two hydrographic sections within the Ría of Vigo and Ría of A Coruña, two coastal embayments with contrasting response to the upwelling of the Eastern North Atlantic Central Water (ENACW) in the region. N2O concentrations ranged between 8.56 to 12.53 nmol kg−1 (94–121 % of saturation) in the shelf, and from 8.62 to 17.60 nmol kg−1 (94–203 % of saturation) inside the rías, with the highest N2O concentration at the bottom, which increase as the upwelling progress from April to October. The air-sea fluxes of N2O varied between −1.6 to 3.26 µmol m−2 d−1 in the shelf and −1.53 to 7.00 µmol m−2 d−1 inside the rías. Local differences on the ventilation and remineralization pattern drives the seasonality of N2O and differences between Ria of Vigo and Ria of A Coruña, being the higher values of N2O concentrations and air-sea fluxes registered in the inner Ria of Vigo. Our study reports the N2O emissions of an upwelling system in a temperate latitude, where the upwelling waters are central waters relatively well ventilated in terms of oxygen content, behaving as a moderate low net source of N2O to the atmosphere compared to tropical upwelling latitudes, characterised by a lower oxygen content.

Culture of Human Embryos at High and Low Oxygen Levels.

One of the parameters potentially affecting the in vitro growth of preimplantation embryos is the oxygen concentration in the culture environment. An increased oxygen concentration causes the generation of ROS which in turn can cause damage to the cells and seriously disrupt the embryonic development. Previous studies have assessed oxygen concentrations in the fallopian tubes of several mammals of between 5 and 8%, while the oxygen levels in the uterus were found to be even lower; similar measurements have been confirmed in humans. In addition, studies in mammalian embryos showed that low oxygen concentrations improve embryo development. Multiple studies on the effect of the oxygen concentration on human embryos have been conducted so far with diverse methodologies and objectives. Data from these have been included in three meta-analyses. All meta-analyses indicate the potential benefit in favor of a low oxygen concentration, though data are considered to be of a low methodological quality and further studies are considered necessary. However, based on the existing evidence, it is suggested that a low oxygen concentration should be adopted in the routine of the IVF laboratory, especially in the case of blastocyst culture.

Functional single-cell analyses of mesenchymal stromal cell proliferation and differentiation using ALDH-activity and mitochondrial ROS content

BaskgroundPrevious research has unveiled a stem cell-like transcriptome enrichment in the aldehyde dehydrogenase-expressing (ALDHhigh) mesenchymal stromal cell (MStroC) fraction. However, considering the heterogeneity of MStroCs, with only a fraction of them presenting bona fide stem cells (MSCs), the actual potency of ALDH as an MSC-specific selection marker remains an issue. MethodsTo address this, the proliferative and differentiation potential of individual ALDHhigh and ALDHlow MStroCs incubated at low oxygen concentrations, estimated to mimic stem cell niches (0.1% O2), were assayed using single-cell clonal analysis, compared to standard conditions (20% O2). ResultsWe confirm that a high proliferative capacity and multi-potent MSCs are enriched in the ALDHhigh MStroC population, especially when cells are cultured at 0.1% O2. Measurements of reduced/oxidized glutathione and mitochondrial superoxide anions with MitoSoX (MSX) indicate that this advantage induced by low oxygen is related to a decrease in the oxidative and reactive oxygen species (ROS) levels in the stem cell metabolic setup. However, ALDH expression is neither specific nor exclusive to MSCs, as high proliferative capacity and multi-potent cells were also found in the ALDHlow fraction. Furthermore, single-cell assays performed after combined cell sorting based on ALDH and MSX showed that the MSXlow MStroC population is enriched in stem/progenitor cells in all conditions, irrespective of ALDH expression or culture oxygen concentration. Importantly, the ALDHhighMSXlow MStroC fraction exposed to 0.1% O2 was almost exclusively composed of genuine MSCs. In contrast, neither progenitors nor stem cells (with a complete absence of colony-forming ability) were detected in the MSXhigh fraction, which exclusively resides in the ALDHlow MStroC population. ConclusionOur study reveals that ALDH expression is not exclusively associated with MSCs. However, cell sorting using combined ALDH expression and ROS content can be utilized to exclude MStroCs lacking stem/progenitor cell properties.

3D Artificial Skin Platform for Investigating Pregnancy-Related Skin Pigmentation.

In this study, we created a 3D Artificial Skin Platform that can be used for the treatment of pigmentation by artificially realizing the skin of pregnant women. For the stable realization of 3D artificial skin, a bilayer hydrogel composed of collagen type I and fibrin was designed and applied to the study to reduce the tension-induced contraction of collagen type I, the extracellular matrix (ECM) of artificial skin, by dynamic culture. Oxygen concentration and 17β-Estradiol (E2) concentration, which are highly related to melanin production, were selected as parameters of the pregnancy environment and applied to cell culture. Oxygen concentration, which is locally reduced in the first trimester (2.5-3%), and E2, which is upregulated in the third trimester, were applied to the cell culture process. We analyzed whether the 3D artificial skin implemented in the 3D Artificial Skin Platform could better represent the tendency of melanin expression in pregnant women than cells cultured under the same conditions in 2D. The expression levels of melanin and melanin-related genes in the 2D cell culture did not show a significant trend that was similar to the melanin expression trend in pregnant women. However, the 3D artificial skin platform showed a significant trend towards a 2-6-fold increase in melanin expression in response to low oxygen concentrations (2.5%) and E2 concentrations (17 ng/mL), which was similar to the trend in pregnant women in vivo. These results suggest that 3D artificial skin cultured on the Artificial Skin Platform has the potential to be used as a substitute for human pregnant skin in various research fields related to the treatment of pigmentation.

Effects of Oxygen Content on Microstructure and Creep Property of Powder Metallurgy Superalloy

The effects of oxygen content on the microstructure and creep properties of the FGH96 superalloy were investigated. When oxygen content increased from 135 ppm to 341 ppm, the prior particle boundary (PPB) rose from degree 2 to degree 3, the size of the γ′ phase on PPB enlarged from 1.07 μm to 1.27 μm, and the MC carbide size grew from 77.4 nm to 104.0 nm. Meanwhile, the steady creep rate accelerated from 4.34 × 10−3 h−1 to 1.87 × 10−2 h−1, and the creep rupture life shortened from 176 h to 94 h, the creep rupture mode transferred from intergranular and transgranular mixed fracture to along PPB fracture. During creep, the micro-twin formation and gliding will be restrained by ∑3 boundaries. FGH96 superalloy with higher oxygen content contains less ∑3 boundaries, and its micro-twins cross-slipped instead of single-direction slip in lower oxygen content superalloy. Consequently, samples with a higher oxygen content crept faster and ruptured earlier.

Experimental study on combustion stability of a gas turbine model combustor under oxygen-lean conditions

Flue gas recirculation has emerged as a promising low-NOx emission technology in advanced gas turbines, while the slower oxidation rate induced by the low oxygen content could potentially cause combustion instability. We conducted an experimental investigation in a single-nozzle swirl combustor to examine the impact of oxygen content, inlet flow rate as well as temperature on combustion instability under oxygen-lean conditions. The results show that reducing oxygen content from 23.3% to 21% leads to reduced amplitudes of pressure pulsation and exothermic pulsation, indicating improved combustion stability. However, further reduction in oxygen content to 18.6% causes a decrease in the combustion reaction rate, resulting in an increase in the amplitude of pressure pulsation. As the oxygen content drops to below 18.6%, the exothermic intensity decreases, which results in a decrease in the amplitude of pressure pulsation. Besides, under oxygen-lean conditions, increasing the inlet temperature is conducive to reducing the amplitude of pressure pulsation and enhancing combustion stability. Additionally, as the incoming flow rate increases from 7.4 to 9.9 m/s, the refined fuel atomization and improved uniformity of oil-gas mixing contributed to decreased pressure pulsation amplitude. Nonetheless, when the incoming flow rate further increases to 12 m/s, the amplitude of exothermic and pressure pulsation increases.

Ferriphaselus amnicola strain GF-20, a new iron- and thiosulfate-oxidizing bacterium isolated from a hard rock aquifer.

Ferriphaselus amnicola GF-20 is the first Fe-oxidizing bacterium isolated from the continental subsurface. It was isolated from groundwater circulating at 20 m depth in the fractured-rock catchment observatory of Guidel-Ploemeur (France). Strain GF-20 is a neutrophilic, iron- and thiosulfate-oxidizer and grows autotrophically. The strain shows a preference for low oxygen concentrations, which suggests an adaptation to the limiting oxygen conditions of the subsurface. It produces extracellular stalks and dreads when grown with Fe(II) but does not secrete any structure when grown with thiosulfate. Phylogenetic analyses and genome comparisons revealed that strain GF-20 is affiliated with the species F. amnicola and is strikingly similar to F. amnicola strain OYT1, which was isolated from a groundwater seep in Japan. Based on the phenotypic and phylogenetic characteristics, we propose that GF-20 represents a new strain within the species F. amnicola.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18–24 months in very low birthweight infants?

BackgroundImmediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85–95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3–0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence.MethodsAn international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks’ gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months’ and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity).DiscussionThe use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18–24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.Trial registrationThe trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

What is the Initiating Reaction for the Lipid Radical Chain Reaction System That Can Induce Ferroptotic Cell Death at the Lower Oxygen Content?

The neural cell death in cerebral infarction is suggested to be ferroptosis-like cell death, involving the participation of 15-lipoxygenase (15-LOx). Ferroptosis is induced by lipid radical species generated through the one-electron reduction of lipid hydroperoxides, and it has been shown to propagate intracellularly and intercellularly. At lower oxygen concentration, it appeared that both regiospecificity and stereospecificity of conjugated diene moiety in lipoxygenase-catalysed lipid hydroperoxidation are drastically lost. As a result, in the reaction with linoleic acid, the linoleate 9-peroxyl radical-ferrous lipoxygenase complex dissolves into the linoleate 9-peroxyl radical and ferrous 15-lipoxygenase. Subsequently, the ferrous 15-lipoxygenase then undergoes one-electron reduction of 13-hydroperoxy octadecadienoic acid, generating an alkoxyl radical (pseudoperoxidase reaction). A part of the produced lipid alkoxyl radicals undergoes cleavage of C-C bonds, liberating small molecular hydrocarbon radicals. Particularly, in ω-3 polyunsaturated fatty acids, which are abundant in the vascular and nervous systems, the liberation of small molecular hydrocarbon radicals was more pronounced compared to ω-6 polyunsaturated fatty acids. The involvement of these small molecular hydrocarbon radicals in the propagation of membrane lipid damage is suggested.

Experimental and reactive molecular dynamics simulation of municipal sludge extract pyrolysis

The sludge extract obtained from degradation solvent extraction exhibits high carbon content, low oxygen content, and ash-free characteristics, making it an ideal fuel due to its excellent performance. In this study, the pyrolysis process of the extract was systematically studied by combining GC-MS experiment with ReaxFF molecular dynamics simulation. The comparison between GC-MS experimental results and ReaxFF-MD simulation shows a high degree of similarity, thus confirming the accuracy of the simulation. This study identified 2000 K as the turning temperature between initial pyrolysis and secondary pyrolysis. In the temperature range of 1200–2000 K, the extract mainly undergoes primary pyrolysis, while in the temperature range of 2000–3000 K, the secondary reaction is remarkable, which is characterized by the further decomposition of tar free radicals and the condensation reaction involving tar free radicals or char. The analysis of typical gas content shows that H2, CO, NH3 and HCN are by-products of the secondary reaction of tar, and there are a lot of reducing gases at high temperature, such as H2, CO and CH4. Finally, the migration patterns of carbon, hydrogen, oxygen and nitrogen are discussed. It is worth noting that hydrogen and nitrogen mainly migrate to the pyrolysis gas phase. This not only laid a foundation for the separation of nitrogen and hydrogen in the future, but also triggered thinking about the potential of “low-carbon emission resource” in future research work. When compared to raw municipal sludge, the initial pyrolysis temperature of municipal sludge extract is much lower, and its pyrolysis process becomes faster. The advantages of reactive gas components indicate that it is more reactive. This variance results in a distinct product distribution and pyrolysis mechanism.