Occurrence, Sources, and Health Risks of Polycyclic Aromatic Hydrocarbons in Road Environments from Harbin, a Megacity of China.

To obtain a comprehensive understanding about that occurrence, sources, and effects on human health of polycyclic aromatic hydrocarbons (PAHs) in road environmental samples from Harbin, concentrations of 32 PAHs in road dust, green belt soil, and parking lot dust samples were quantified. The total PAH concentrations ranged from 0.95 to 40.7 µg/g and 0.39 to 43.9 µg/g in road dust and green belt soil, respectively, and were dominated by high molecular weight PAHs (HMW-PAHs). Despite the content of PAHs in arterial roads being higher, the composition profile of PAHs was hardly influenced by road types. For parking lot dust, the range of total PAH concentrations was 0.81-190 µg/g, and three-ring to five-ring PAHs produced the maximum contribution. Compared with surface parking lots (mean: 6.12 µg/g), higher total PAH concentrations were detected in underground parking lots (mean: 33.1 µg/g). The diagnostic ratios of PAHs showed that petroleum, petroleum combustion, and biomass/coal combustion were major sources of PAHs in the samples. Furthermore, according to the Incremental Lifetime Cancer Risk model, the cancer risks of three kinds of samples for adults and children were above the threshold (10-6). Overall, this study demonstrated that PAHs in the road environment of Harbin have a certain health impact on local citizens.

Modeling historical budget for ß-Hexachlorocyclohexane (HCH) in the Arctic Ocean: A contrast to α-HCH.

The historical annual loading to, removal from, and cumulative burden in the Arctic Ocean for ß-hexachlorocyclohexane (ß-HCH), an isomer comprising 5-12% of technical HCH, is investigated using a mass balance box model from 1945 to 2020. Over the 76 years, loading occurred predominantly through ocean currents and river inflow (83%) and only a small portion via atmospheric transport (16%). ß-HCH started to accumulate in the Arctic Ocean in the late 1940s, reached a peak of 810 t in 1986, and decreased to 87 t in 2020, when its concentrations in the Arctic water and air were ∼30 ng m-3 and ∼0.02 pg m-3, respectively. Even though ß-HCH and α-HCH (60-70% of technical HCH) are both the isomers of HCHs with almost identical temporal and spatial emission patterns, these two chemicals have shown different major pathways entering the Arctic. Different from α-HCH with the long-range atmospheric transport (LRAT) as its major transport pathway, ß-HCH reached the Arctic mainly through long-range oceanic transport (LROT). The much higher tendency of ß-HCH to partition into the water, mainly due to its much lower Henry's Law Constant than α-HCH, produced an exceptionally strong pathway divergence with ß-HCH favoring slow transport in water and α-HCH favoring rapid transport in air. The concentration and burden of ß-HCH in the Arctic Ocean are also predicted for the year 2050 when only 4.4-5.3 t will remain in the Arctic Ocean under the influence of climate change.

The AM-4 Family of Layered Titanosilicates: Single-Crystal-to-Single-Crystal Transformation, Synthesis and Ionic Conductivity.

Flexible crystal() structures, which exhibit() single-crystal()-to-single-crystal() (SCSC) transformations(), are attracting attention() in many applied aspects: magnetic() switches, catalysis, ferroelectrics and sorption. Acid treatment() for titanosilicate material() AM-4 and natural() compounds with the same structures led to SCSC transformation() by loss() Na+, Li+ and Zn2+ cations with large structural() changes (20% of the unit()-cell() volume()). The conservation() of crystallinity through complex() transformation() is possible due() to the formation() of a strong hydrogen bonding() system(). The mechanism() of transformation() has been characterized using single-crystal() X-ray() diffraction analysis(), powder() diffraction, Rietvield refinement, Raman spectroscopy and electron microscopy. The low migration() energy() of cations in the considered materials() is confirmed using bond()-valence and density() functional() theory() calculations, and the ion conductivity of the AM-4 family's materials() has been experimentally verified.

Steady-State Based Model of Airborne Particle/Gas and Settled Dust/Gas Partitioning for Semivolatile Organic Compounds in the Indoor Environment.

Indoor semivolatile organic compounds (SVOCs), present in the air, airborne particles, settled dust, and other indoor surfaces, can enter the human body through several pathways. Knowing the partitioning between gaseous and particulate phases is important in identifying specific pathway contributions and thereby accurately assessing human exposure. Numerous studies have developed equilibrium equations to predict airborne particle/gas (P/G) partitioning in air (KP) and dust/gas (D/G) partitioning in settled dust (KD). The assumption that P/G and D/G equilibria are instantaneous for airborne and settled dust phases, commonly adopted by current indoor fate models, is not likely valid for compounds with high octanol-air partition coefficients (KOA). Here, we develop steady-state based equations to predict KP and KD in the indoor environment. Results show that these equations perform well and are verified by worldwide monitoring data. It is suggested that instantaneous steady state could work for P/G and D/G partitioning of SVOCs in indoor environments, and the equilibrium is just a special case of the steady state when log KOA < 11.38 for P/G partitioning and log KOA < 10.38 for D/G partitioning. These newly developed equations and methods provide a tool for more accurate assessment for human exposure to SVOCs in the indoor environment.

Determination of 123 polycyclic aromatic hydrocarbons and their derivatives in atmospheric samples.

Polycyclic aromatic hydrocarbons (PAHs) are a class of toxic organic pollutants. Until now, they have been detected in many regions and various environmental matrix. However, not all PAHs are usually detected by researchers, and no methods is established to analyze systematically hundreds of PAHs. In this study, 123 PAHs were identified and quantified using gas chromatography-tandem triple-quadrupole mass spectrometry (GC-MS/MS), which were divided into 3 groups: 32 regular PAHs (R-PAHs), 50 methyl-PAHs (Me-PAHs), 30 Nitro-PAHs (N-PAHs) and 11 hydroxyl-PAHs (OH-PAHs). The developed method was applied to detect the target PAHs in 6 marine gaseous samples and 6 particulate samples collected on board the research vessel Snow Dragon. Limits of detection (LOD) and limits of quantification (LOQ) were determined from 0.009 to 2.50 and 0.03-8.33 pg/m3, respectively. Recoveries of the internal standards in atmosphere were from 88% to 112%, 70%-104%, and 72%-102% for R-PAHs、Me-PAHs、N-PAHs and OH-PAHs, respectively, which showed the reliability of the experimental method. The total concentrations of 123 PAHs in marine air and particle samples were from 1532 to 7877 and 206-1022 pg/m3, respectively.

In Situ Control of Thermal Activation Conditions by Color for Serpentines with a High Iron Content.

Serpentine heat treatment at temperatures of 650-750 °C yields magnesium-silicate reagent with high chemical activity. Precise and express control of roasting conditions in laboratory kilns and industrial aggregates is needed to derive thermally activated serpentines on a large scale. Color change in serpentines with a high iron content during roasting might be used to indicate the changes in chemical activity in the technological process. This study gives a scientific basis for the express control of roasting of such serpentines by comparing the colors of the obtained material and the reference sample. Serpentines with different chemical activity were studied by X-ray diffraction, Mössbauer spectroscopy, and optical spectroscopy. The color parameters were determined using RGB (red, green, blue), CIELAB (International Commission on Illumination 1976 L*a*b), and HSB (hue, brightness, saturation) color models. The color of heat-treated samples was found to be affected by changes in the crystallochemical characteristics of iron included in the structure of the serpentine minerals. The color characteristics given by the CIELAB model were in good coherence with the acid-neutralizing ability and optical spectra of heat-treated serpentines. Thus, in contrast to the long-term analysis by these methods, the control by color palette provides an express assessment of the quality of the resulting product.

Approach to Predicting the Size-Dependent Inhalation Intake of Particulate Novel Brominated Flame Retardants.

The risk of human exposure to particulate novel brominated flame retardants (NBFRs) in the atmosphere has received increasing attention from scientists and the public, but currently, there is no reliable approach to predict the intake of these compounds on the basis of their size distribution. Here, we develop a reliable approach to predict the size-dependent inhalation intake of particulate NBFRs, based on the gas/particle (G/P) partitioning behavior of the NBFRs. We analyzed the concentrations of eight NBFRs in 363 size-segregated particulate samples and 99 paired samples of gaseous and bulk particles. Using these data, we developed an equation to predict the G/P partitioning quotients of NBFRs in particles in different size ranges (KPi) based on particle size. This equation was then successfully applied to predict the size-dependent inhalation intake of particulate NBFRs in combination with an inhalation exposure model. This new approach provides the first demonstration of the effects of the temperature-dependent octanol-air partitioning coefficient (KOA) and total suspended particle concentration (TSP) on the intake of particulate NBFRs by inhalation. In an illustrative case where TSP = 100 µg m-3, inhalation intake of particulate NBFRs exceeded the intake of gaseous NBFRs when log KOA > 11.4.

Determination of Polycyclic Aromatic Hydrocarbons and Their Methylated Derivatives in Sewage Sludge from Northeastern China: Occurrence, Profiles and Toxicity Evaluation.

This paper assesses the occurrence, distribution, source, and toxicity of polycyclic aromatic hydrocarbons (PAHs), and their methylated form (Me-PAHs) in sewage sludge from 10 WWTPs in Northeastern China was noted. The concentrations of ∑PAHs, ∑Me-PAHs ranged from 567 to 5040 and 48.1 to 479 ng.g-1dw, which is greater than the safety limit for sludge in agriculture in China. High and low molecular weight 4 and 2-ring PAHs and Me-PAHs in sludge were prevalent. The flux of sludge PAHs and Me-PAHs released from ten WWTPs, in Heilongjiang province, was calculated to be over 100 kg/year. Principal component analysis (PCA), diagnostic ratios and positive matrix factorization (PMF) determined a similar mixed pyrogenic and petrogenic source of sewage sludge. The average values of Benzo[a]pyrene was below the safe value of 600 ng.g-1 dependent on an incremental lifetime cancer risk ILCR of 10-6. Sludge is an important source for the transfer of pollutants into the environment, such as PAHs and Me-PAHs. Consequently, greater consideration should be given to its widespread occurrence.

Occurrence, removal and mass balance of substituted diphenylamine antioxidants in wastewater treatment plants in Northeast China.

Substituted diphenylamine antioxidants (SDPAs) are additives used in various commodities and are commonly found in environmental samples. However, limited information was available on their fate and removal in wastewater treatment plants (WWTPs). This paper reports the results on the occurrence and removal efficiency of ten selected SDPAs in six WWTPs equipped with different treatment processes in Northeast China. Quite similar distributions of different SDPA congeners were shown in the studied WWTPs, with ditertoctyl-diphenylamine (C8/C8-DPA), tertbutyl-tertoctyl-diphenylamine (C4/C8-DPA), and tertoctyl-diphenylamine (C8-DPA) being always dominant in the influent, effluent, and sludge (total > 80%). A cyclic activated sludge system combined with a V-shape filter achieved the highest removal efficiencies of SDPAs among various treatment processes. Styrenated-diphenylamine1 (S-DPA1) (96 ± 10%), C8-DPA (95 ± 5.5%), and distyrenated-diphenylamine1 (DS-DPA1) (94 ± 9.3%) showed high and stable removal efficiencies, whereas C4/C8-DPA (85 ± 31%) and C8/C8-DPA (84 ± 62%) showed considerably varied removal efficiencies. Per-day discharges of SDPAs to the receiving environment through effluent and sludge were estimated as 828 ± 350 and 5578 ± 5196 mg, respectively. A median of 85% of the initial mass loadings of SDPAs was found in the sludge samples, suggesting that the observed removal of SDPAs in the WWTPs was caused by their sorption to the sludge, rather than biodegradation/transformation. This work provides an overall description of the occurrence, fate, and mass balance of SDPAs in WWTPs in Northeast China and highlights a new emission route to the environment via WWTPs.

Fate processes of Parabens, Triclocarban and Triclosan during wastewater treatment: assessment via field measurements and model simulations.

The high levels of parabens (including methyl-, ethyl- and propyl congeners), triclocarban (TCC) and triclosan (TCS) used every year in China might be a problem to the typical wastewater treatment plant (WWTP). This study addresses measurements of parabens, TCC and TCS Northern China WWTP and a modelling assessment on the occurrence, fate and removal pathways in WWTP. Per-capita emissions of the three parabens, TCC and TCS to the WWTP were estimated as 0.41, 0.11 and 0.07 mg/d. After the wastewater treatment processes, 94, 92 and 87% of parabens, TCC and TCS were removed. The major removal pathway of parabens was biodegradation while that of TCC and TCS were sorption to sludge. Computer simulations on the fate processes of parabens, TCC and TCS in the WWTP using the SimpleTreat 4.0 model suggested the model could generally reproduce the measurements with root mean squared errors (RMSEs) of less than 10 ng/L. However, the model underestimated the removal of TCC and TCS from water to sludge in the primary tank. These discrepancies were attributed to the uncertainty of the predicted organic carbon-water partition coefficients (Koc) to which the modelling results are highly sensitive. The model predictions using updated Koc became more accurate and RMSEs of TCC and TCS were reduced by 40 and 80%, respectively. The modelling assessment suggests that the SimpleTreat, as a generic model to simulate chemical fate processes in WWTPs, has the potential to be applied to other similar WWTPs in China for estimating environmental releases of parabens, TCC and TCS at a larger spatial scale.

Occurrence, Removal, and Mass Balance of Polycyclic Aromatic Hydrocarbons and Their Derivatives in Wastewater Treatment Plants in Northeast China.

Polycyclic aromatic hydrocarbons (PAHs), 33 methylated PAHs (Me-PAHs), and 14 nitrated PAHs (NPAHs) were measured in wastewater treatment plants (WWTPs) to study the removal efficiency of these compounds through the WWTPs, as well as their source appointment and potential risk in the effluent. The concentrations of ∑PAHs, ∑Me-PAHs, and ∑NPAHs were 2.01-8.91, 23.0-102, and 6.21-171 µg/L in the influent, and 0.17-1.37, 0.06-0.41 and 0.01-2.41 µg/L in the effluent, respectively. Simple Treat 4.0 and meta-regression methods were applied to calculate the removal efficiencies (REs) for the 63 PAHs and their derivatives in 10 WWTPs and the results were compared with the monitoring data. Overall, the ranges of REs were 55.3-95.4% predicated by the Simple Treat and 47.5-97.7% by the meta-regression. The results by diagnostic ratios and principal component analysis PCA showed that "mixed source" biomass, coal composition, and petroleum could be recognized to either petrogenic or pyrogenic sources. The risk assessment of the effluent was also evaluated, indicating that seven carcinogenic PAHs, Benzo[a]pyrene, Dibenz[a,h]anthracene, and Benzo(a)anthracene were major contributors to the toxics equivalency concentrations (TEQs) in the effluent of WWTPs, to which attention should be paid.

Treatment of particle/gas partitioning using level III fugacity models in a six-compartment system.

In this paper, two level III fugacity models are developed and applied using an environmental system containing six compartments, including air, aerosols, soil, water, suspended particulate matters (SPMs), and sediments, as a "unit world". The first model, assumes equilibrium between air and aerosols and between water and SPMs. These assumptions lead to a four-fugacity model. The second model removes these two assumptions leading to a six-fugacity model. The two models, compared using four PBDE congeners, BDE-28, -99, -153, and -209, with a steady flux of gaseous congeners entering the air, lead to the following conclusions. 1. When the octanol-air partition coefficient (KOA) is less than 1011.4, the two models produce similar results; when KOA > 1011.4, and especially when KOA > 1012.5, the model results diverge significantly. 2. Chemicals are in an imposed equilibrium in the four-fugacity model, but in a steady state and not necessary an equilibrium in the six-fugacity model, between air and aerosols. 3. The results from the six-fugacity model indicate an internally consistent system with chemicals in steady state in all six compartments, whereas the four-fugacity model presents an internally inconsistent system where chemicals are in equilibrium but not a steady state between air and aerosols. 4. Chemicals are mass balanced in air and aerosols predicted by the six-fugacity model but not by the four-fugacity model. If the mass balance in air and aerosols is achieved in the four-fugacity model, the condition of equilibrium between air and aerosols will be no longer valid.

Slopes and intercepts from log-log correlations of gas/particle quotient and octanol-air partition coefficient (vapor-pressure) for semi-volatile organic compounds: II. Theoretical predictions vs. monitoring.

The logarithm of gas/particle (G/P) partition quotient (logKP) has been found to have a linear relationship with logKOA (octanol-air partition coefficient) with slope mo and intercept bo and logPL (subcooled liquid vapor pressure) with slope mp and intercept bp. In the sister paper of the present work, analytical equations to predict the slope mo and intercept bo based on logKOA and predict the slope mp and intercept bp based on logPL are developed using steady state theory. In this work, the equations are evaluated using world-wide monitoring data (262 pairs for mo and bo values and 292 pairs for mp and bp values produced from more than 10,000 monitiring data worldwide) for selected seven groups of semi-volatile organic compounds (SVOCs), including polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo-p-dioxins and polychorinated dibenzofurans (PCDD/Fs), polyclorinated biphenyl (PCBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated naphthalenes (PCNs), organochlorinated pesticides (OCPs), novel brominated flame retardants (NBFRs), and other selected halogenated flame retardants. The slopes and intercepts predicted by the steady state equations reproduce the trends observed in monitoring regression results for the seven SVOC groups, with 44.4% of the variation of monitoring mo values accounted for by logKOA and 48.2% of the variation of monitoring mp values accounted for by logPL. Theoretically, the values of mo can be any value between 0 and 1 dependent on the values of KOA, and are not constrained to 1 as in equilibrium theory. Likewise, the values of mp can be any value between 0 and -1 dependent on the values of PL, and not constrained to -1 predicted by the equilibrium theory. The influence of sampling artifacts on the G/P partitioning of SVOCs has most likely been overemphasized by the equilibrium theory. Thus, the equilibrium approach should be abandoned in favor of the steady state approach for calculating the G/P partition quotients for SVOCs with high KOA values (>1011.38) or low PL values (<10-4.92).

New equation to predict size-resolved gas-particle partitioning quotients for polybrominated diphenyl ethers.

Gas/particle (G/P) partition quotients of semi-volatile organic compounds (SVOCs) for bulk air have been widely discussed in experimental and theoretical contexts, but research on size-resolved G/P partition quotients (KPi) are scarce and limited in scope. To investigate G/P partition behavior of polybrominated diphenyl ethers (PBDEs) for size-segregated particles in the atmosphere, 396 individual size-segregated particulate samples (36 batches × 11 size-ranges), and 108 pairs of concurrent gaseous and bulk particulate samples were collected in Harbin, China. A steady-state equation based on bulk particles is derived to determine G/P partition quotients of PBDEs for size-segregated particles, which depends on the organic matter contents of size-segregated particles (fOMi). This equation can well predict KPi with knowledge of bulk partition quotient (KPS), ambient temperature, and fOMi, the results of which match well with monitoring data in Harbin and other published data collected in Shanghai and Guangzhou of China and Thessaloniki of Greece, and remedies a defect of over-estimate KPi for high-brominated PBDEs by the previous equation. In particular, the new equation contributes to obtaining the PBDEs concentrations in all atmospheric phase from partial phase, then provides a credible path to evaluate healthy exposure dose from the airborne PBDEs, by co-utilization with exposure models.

Modeling gas/particle partitioning of polybrominated diphenyl ethers (PBDEs) in the atmosphere: A review.

Gas/particle (G/P) partitioning of semi-volatile organic compounds (SVOCs) such as polybrominated diphenyl ethers (PBDEs), is an important atmospheric process due to its significance in governing atmospheric fate, wet/dry deposition, and long-range atmospheric transport. In this article, eight models published to predict the G/P partitioning of PBDEs are reviewed. These eight models are used to calculate the G/P partitioning quotient and particulate phase fraction of selected PBDE congeners. A comparison of the predicted results from the eight models with monitoring data published by several research groups worldwide leads to the following conclusions: 1) when the values of the logarithm of the octanol-air partition coefficient (logKOA) fall below 11.4 (the first threshold value, logKOA1), all 8 models perform well in predicting the G/P partitioning of PBDEs in the atmosphere, and 2) when logKOA is >11.4, and especially above 12.5 (the second threshold value, logKOA2), the Li-Ma-Yang model, a steady-state model developed based on wet and dry deposition of the particles (Li et al., Atmos. Chem. Phys. 2015; 15:1669-1681), shows the best performance with highest conformity to the measurements for selected PBDEs (94.4 ± 1.6% data points within ±1 log unit). Overall, the Li-Ma-Yang model appears to capture the most important factors that affect the partitioning of PBDEs between gaseous and particular phases in the atmosphere.

CHK1/2 Inhibitor Prexasertib Suppresses NOTCH Signaling and Enhances Cytotoxicity of Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma.

Platinum-based chemoradiotherapy is a mainstay of organ-preserving therapy for patients with head and neck squamous cell carcinoma cancer (HNSCC). However, the disease eventually becomes resistant to treatment necessitating new therapies. Checkpoint kinase 1 and 2 (CHK1/2) are serine/threonine kinases that activate cell-cycle checkpoints and serve a critical role in the DNA-damage response (DDR). As resistance to cisplatin and radiation may involve a heightened DDR, we hypothesized that prexasertib, an inhibitor of CHK1/2, may enhance the cytotoxicity induced by cisplatin and irradiation in HNSCC. In this study, we found that combining prexasertib with cisplatin and radiation significantly decreased the in vitro survival fraction in HNSCC cell lines both with and without radiotherapy. Reduced survival was accompanied by inhibition of DNA repair checkpoint activation, which resulted in persistent DNA damage and increased apoptosis. In addition, NanoString analysis with the PanCancer Pathways Panel revealed that prexasertib downregulated NOTCH signaling target genes (NOTCH1, NOTCH2, and NOTCH3) and their associated ligands (JAG1, JAG2, SKP2, MAML2, and DLL1). Prexasertib also reduced NOTCH1, NOTCH3 and HES1 protein expression. Importantly, a significant tumor growth delay was observed in vivo in both human papillomavirus (HPV)-positive UM-SCC47 and HPV-negative UM-SCC1 cell line xenografts treated with prexasertib, cisplatin, and radiotherapy without increased toxicity as measured by mouse body weight. Taken together, prexasertib reduced NOTCH signaling and enhanced the in vitro and in vivo response of HNSCCs to cisplatin and radiation, suggesting combination therapy may increase clinical benefit. A clinical trial has recently completed accrual (NCT02555644).

Titanite-Containing Mineral Compositions and Their Chemical Treatment with Preparation of Functional Materials.

The waste of apatite-nepheline ore processing was chosen as the material of study for the present investigation. The chemical and phase compositions have been analyzed and the route of the new technology has been developed. Treatment of the waste with diluted hydrochloric acid enables to separate apatite, nepheline, titano-magnetite minerals from titanite (CaSiTiO5). The obtained titanite concentrate contains 30-32% of titanium dioxide. Interaction of titanite with hydrochloric acid under heating and stirring conditions results in calcium leaching. The titanite decomposition is accompanied by titanium and silica oxides precipitation. The resulting solid has been used as a precursor for the synthesis of functional materials. Mechanochemical activation of the precursor provides the structural and morphological disorder of the initial particles. Thermodynamic stability of activated particles is achieved by chemisorption or roasting.

Combined Targeting of Mutant p53 and Jumonji Family Histone Demethylase Augments Therapeutic Efficacy of Radiation in H3K27M DIPG.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor with a 5-year survival of <1%. Up to 80% of the DIPG tumors contain a specific K27M mutation in one of the two genes encoding histone H3 (H3K27M). Furthermore, p53 mutations found in >70-80% of H3K27M DIPG, and mutant p53 status is associated with a decreased response to radiation treatment and worse overall prognosis. Recent evidence indicates that H3K27M mutation disrupts tri-methylation at H3K27 leading to aberrant gene expression. Jumonji family histone demethylases collaborates with H3K27 mutation in DIPG by erasing H3K27 trimethylation and thus contributing to derepression of genes involved in tumorigenesis. Since the first line of treatment for pediatric DIPG is fractionated radiation, we investigated the effects of Jumonji demethylase inhibition with GSK-J4, and mutant p53 targeting/oxidative stress induction with APR-246, on radio-sensitization of human H3K27M DIPG cells. Both APR-246 and GSK-J4 displayed growth inhibitory effects as single agents in H3K27M DIPG cells. Furthermore, both of these agents elicited mild radiosensitizing effects in human DIPG cells (sensitizer enhancement ratios (SERs) of 1.12 and 1.35, respectively; p < 0.05). Strikingly, a combination of APR-246 and GSK-J4 displayed a significant enhancement of radiosensitization, with SER of 1.50 (p < 0.05) at sub-micro-molar concentrations of the drugs (0.5 µM). The molecular mechanism of the observed radiosensitization appears to involve DNA damage repair deficiency triggered by APR-246/GSK-J4, leading to the induction of apoptotic cell death. Thus, a therapeutic approach of combined targeting of mutant p53, oxidative stress induction, and Jumonji demethylase inhibition with radiation in DIPG warrants further investigation.

The Impact of DNA Repair Pathways in Cancer Biology and Therapy.

Genomic instability is one of the key hallmarks of cancer progression [1].[...].