Relative Sensitivity Research Articles

Dual lanthanide Complexes-Loaded ratiometric nanothermometer for elucidating intracellular variations of temperature and calcium transport

Herein, we report a ratiometric nanothermometer to study the correlation of heat/temperature and intracellular calcium transport. Firstly, poly(methyl methacrylate)-based copolymeric nanoparticles (NPs) from nanoprecipitation encapsulates two lanthanide complexes (Eu(DNPD)3Phen and Sm(DBM)3Phen) to enhance fluorescence of lanthanide ions (Ln3+). NPs were thereafter coated with an amphiphilic block copolymer pluronic F-127 to prevent nonspecific interaction between NPs and proteins, which ensures internalization of the nanothermometer into living cells. The back energy transfer (BET) from the excited state of Ln3+ to the triplet energy levels of ligand endows the temperature dependence on ratiometric fluorescence of Eu3+ and Sm3+. This nanothermometer has excellent anti-interference ability, ensuring accurate cell temperature measurement within a range of 29.0–40.0℃. It exhibits a maximum relative thermal sensitivity of 1.9 % ℃-1 at 29.0℃ and a minimum temperature resolution of 0.1℃ at 39.0℃ in live HeLa cells. The nanothermometer was applied for studying temperature or heat induced intracellular Ca2+ transport. It illustrated that free cytoplasmic Ca2+ concentration ([Ca2+]i) increased only when the cell temperature reached a certain threshold under photothermal stimulation, and the rise of temperature corresponds to the increase of [Ca2+]i. Furthermore, Ca2+ burst induced Ca2+ transport from cytoplasm to endoplasmic reticulum, which promoted ATP hydrolysis along with the rise of intracellular temperature. 200 s stimulation with FCCP enhanced ca. 1.7℃ of intracellular temperature along with 2.2 folds increment of [Ca2+]i, as FCCP induces Ca2+ efflux from mitochondria by increasing proton concentration therein. These results indicate that a close relationship between intracellular temperature and Ca2+ transport, which is of great significance for further understanding the role of temperature in signaling pathways and neurotransmitter release events.

The estimation and translation uncertainties in applying NOAEL to clinical dose escalation.

The systemic exposure at the no-observed-adverse-effect-level (NOAEL) estimated from animals is an important criterion commonly applied to guard the safety of participants in clinical trials of investigational drugs. However, the discrepancy in toxicity profile between species is widely recognized. The objective of the work reported here was to assess, via simulation, the level of uncertainty in the NOAEL estimated from an animal species and the effectiveness of applying its associated exposure value to minimizing the toxicity risk to human. Simulations were conducted for dose escalation of an investigational new chemical entity with hypothetical exposure-response models for the dose-limiting toxicity under a variety of conditions, in terms of between-species relative sensitivity to the toxicity and the between-subject variability in the key parameters determining the sensitivity and pharmacokinetics. Results show a high uncertainty in the NOAEL estimation. Notably, even when the animal species and humans are assumed to have the same sensitivity, which may not be realistic, limiting clinical dose to the exposure at the NOAEL that has been identified in the animals carries a high risk of either causing toxicity or under-dosing, hence undermining the therapeutic potential of the drug candidate. These findings highlight the importance of understanding the mechanism of the toxicity profile and its cross-species translatability, as well as the importance of understanding the dose requirement for achieving adequate pharmacology.

Harnessing THz Technology: Biosensor for Highly Accurate Cervical Cancer Cell Detection via Refractive Index.

In order to rapidly identify various species of cancer cells in the tissues of person, a unique diamond shaped hollow-core photonic crystal fiber (PCF)-formed by optical waveform is developed and computationally studied. In this investigation, we found the most prevalent cancers, such as HeLa-derived cervical carcinoma. Since normal and cancer cells differ in their refractive indices (RIs), other significant optical properties can be assessed using this information. With the use of the finite element method, a computational tool for solving simultaneous equations, the defining characteristics the suggested cancer cell sensor are examined using COMSOL-Multiphysics software. Additionally, strict mesh parts are used to preserve the utmost level of modeling realism. At 2.4 THz, the PCF detector attains a Relative Sensitivity of around 97.51% and 96.29%, Confinement Loss of 6.1 × 10 -09db/m and 4.39 × 10-07db/m with respect to cervical carcinoma cell and cervical normal cell. The straightforward PCF structure provides a wide chance of application using the continuing fabrication technique, based on these conventional values of performance indices. This biosensor utilizes the distinctive refractive characteristics of cancer cells, providing a highly accurate and dependable approach for the early identification of cervical cancer. This has the potential to significantly transform the process of cervical cancer screening. The novel method boosts the ability to detect and identify certain conditions, leading to increased diagnostic capabilities for early treatment and better results for patients.

Simultaneous modulation of multicolor upconversion emission and thermal‐sensing performance of Ba5Zn4Y8O21 phosphors

AbstractIn this study, we report the modulation of the emission color and optical temperature‐sensing properties of Er3+ in Ba5Zn4Y8O21 crystals. Er3+ single‐doped Ba5Zn4Y8O21 phosphors showed green emission under 980 nm excitation. When codoping with Yb3+ ions, the red emission component from the Er3+ ions increased significantly, and the sample emission turned orange. Yb3+–Er3+ codoped Ba5Zn4Y8O21 samples exhibited bright red emission with a maximum IR/IG value of 89.30 when excited with a longer wavelength, 1550 nm. A broad range of emission colors could be modulated by adjusting the dopant concentration. The possible modulation mechanisms and upconversion processes were analyzed based on the luminescence decay curves and power‐dependent emission intensities. Furthermore, the optical temperature‐sensing properties of Ba5Zn4Y8O21:Er3+ and Ba5Zn4Y8O21:Er3+, Yb3+ phosphors with thermal coupled energy levels (TCELs) and nonthermal coupled energy levels (N‐TCELs) of Er3+ ions were investigated using fluorescence intensity ratio technique. Based on the TCELs (2H11/2/4S3/2), the Er3+ single‐doped and Yb3+–Er3+ codoped Ba5Zn4Y8O21 phosphors present the similar optical thermometry behaviors under 980 and 1550 nm excitation. The highest absolute (Sa) and relative sensitivity (Sr) are 3.95 × 10−3 K−1 at 573 K and 1.31% K−1 at 303 K, respectively. Based on N‐TCELs (4F9/2/2H11/2), the temperature‐sensing performance depends on the Yb3+ dopant and excitation wavelength. The highest values for Sa and Sr reached 5.46 K−1 at 303 K and 1.38% K−1 at 573 K for the Ba5Zn4Y8O21:Er3+, Yb3+ phosphor under 1550 nm excitation, respectively. In addition, the present phosphor exhibited high stability and repeatability over a wide temperature range. These results indicate that the multicolor modulation upconversion Ba5Zn4Y8O21‐based phosphor can be considered a potential reusable optical thermometer for noncontact temperature detection.

A new molecular method for fast differentiation of cockles Cerastoderma edule and Cerastoderma glaucum

AbstractCerastoderma edule and C. glaucum are two species of cockles that co-exist in European waters. They are morphologically similar but exhibit remarkable differences in biological, ecological, and genetic aspects, as well as in resistance to parasites (e.g., Martellia cochilia) and in disease incidence (e.g., disseminated neoplasia). Moreover, they differ in their economic significance; while C. edule represents a highly valuable marine resource, C. glaucum is only marginally fished. The aim of this work was to develop a simple and fast method that, for the first time, uses the sequence of a mitochondrial gene for the molecular differentiation of the two cockle species. A total of 304 partial sequences of the cytochrome c oxidase subunit I (COI) gene, retrieved from the Nucleotide database, were used to design two sets of species-specific primers to generate PCR products of different sizes (322 bp in C. glaucum and 247 bp in C. edule). The discriminatory ability of the PCR assay was tested in cockles from the Spanish, French, and Italian coasts with successful differentiation in all cases. This novel molecular identification method requires minimal technical equipment and can be carried out in one working day. For its simplicity, it can be very useful for conservation and sustainable management of the two cockle species, facilitating the assessment of distribution, abundance and relative sensitivity to viruses, parasites and diseases.

Is trust an essential therapeutic goal in working with childhood sexual abuse (CSA)? – a body of empirical research

ABSTRACT Impaired ability to develop trusting relationships, self-dysregulation, poor emotional regulation, poor self valuation, and relational sensitivity are key challenges for survivors of Childhood Sexual Abuse. These increase the risk of ruptures in the therapeutic relationship and dropouts. Nevertheless, there is little evidence of the role of therapeutic trust in CSA. We collectively present the findings of a 15-year research journey into CSA recovering. Central to recovering was the establishment and maintenance of trust. Trust was also key for client satisfaction and facilitating the recovering process. Trust mediated regulation of threat responses, facilitated empathy, and enabled accurate symbolisation and re-contextualisation of traumatic narratives. In an increasingly traumatogenic world, more clinicians will be called to respond to disclosures of abuse and maintain engagement. Given the lack of effective interventions for CSA/complex trauma, trust-based person-centred psychotherapies are a promising alternative for managing dropouts, supporting the therapeutic relationship, and facilitating change.

The Butterfly Effect: Multifaceted Consequences of Sensitizer Concentration Change in Phase Transition-based Luminescent Thermometer of LiYO2:Er3+,Yb3.

In response to the ongoing quest for new, highly sensitive upconverting luminescent thermometers, this article introduces, for the first time, upconverting luminescent thermometers based on thermally induced structured phase transitions. As demonstrated, the transition from the low-temperature monoclinic to the high-temperature tetragonal structures of LiYO2:Yb3+,Er3+ induces multifaceted modification in the spectroscopic properties of the examined material, influencing the spectral positions of luminescence bands, energy gap values between thermally coupled energy levels, and the red-to-green emission intensities ratio. Moreover, as illustrated, both the color of the emitted light and the phase transition temperature (from 265 K, for LiYO2:Er3+, 1%Yb3+, to 180 K, for 10%Yb3+), and consequently, the thermometric parameters of the luminescent thermometer can be modulated by the concentration of Yb3+ sensitizer ions. Establishing a correlation between the phase transition temperature and the mismatch of ion radii between the host material and dopant ions allows for smooth adjustment of the thermometric performance of such a thermometer following specific application requirements. Three different thermometric approaches were investigated using thermally coupled levels (SR = 1.8%/K at 180 K for 1%Yb3+), green to red emission intensities ratio (SR = 1.5%/K at 305 K for 2%Yb3+), and single band ratiometric approach (SR = 2.5%/K at 240 K for 10%Yb3+). The thermally induced structural phase transition in LiYO2:Er3+,Yb3+ has enabled the development of multiple upconverting luminescent thermometers. This innovative approach opens avenues for advancing the field of luminescence thermometry, offering enhanced relative thermal sensitivity and adaptability for various applications.

Effect of Human Head Shape on the Risk of Traumatic Brain Injury: A Gaussian Process Regression-based Machine Learning Approach.

Computational head injury models are promising tools for understanding and predicting traumatic brain injuries. However, most available head injury models are "average" models that employ a single set of head geometry (e.g., 50th-percentile U.S. male) without considering variability in these parameters across the human population. A significant variability of head shapes exists in U.S. Army soldiers, evident from the Anthropometric Survey of U.S. Army Personnel (ANSUR II). The objective of this study is to elucidate the effects of head shape on the predicted risk of traumatic brain injury from computational head injury models. Magnetic resonance imaging scans of 25 human subjects are collected. These images are registered to the standard MNI152 brain atlas, and the resulting transformation matrix components (called head shape parameters) are used to quantify head shapes of the subjects. A generative machine learning model is used to generate 25 additional head shape parameter datasets to augment our database. Head injury models are developed for these head shapes, and a rapid injurious head rotation event is simulated to obtain several brain injury predictor variables (BIPVs): Peak cumulative maximum principal strain (CMPS), average CMPS, and the volume fraction of brain exceeding an injurious CMPS threshold. A Gaussian process regression model is trained between head shape parameters and BIPVs, which is then used to study the relative sensitivity of the various BIPVs on individual head shape parameters. We distinguish head shape parameters into 2 types: Scaling components ${T_{xx}}$, ${T_{yy}}$, and ${T_{zz}}$ that capture the breadth, length, and height of the head, respectively, and shearing components (${T_{xy}},{T_{xz}},{T_{yx}},{T_{yz}},{T_{zx}}$, and ${T_{zy}}$) that capture the relative skewness of the head shape. An overall positive correlation is evident between scaling components and BIPVs. Notably, a very high, positive correlation is seen between the BIPVs and the head volume. As an example, a 57% increase in peak CMPS was noted between the smallest and the largest investigated head volume parameters. The variation in shearing components ${T_{xy}},{T_{xz}},{T_{yx}},{T_{yz}},{T_{zx}}$, and ${T_{zy}}$ on average does not cause notable changes in the BIPVs. From the Gaussian process regression model, all 3 BIPVs showed an increasing trend with each of the 3 scaling components, but the BIPVs are found to be most sensitive to the height dimension of the head. From the Sobol sensitivity analysis, the ${T_{zz}}$ scaling parameter contributes nearly 60% to the total variance in peak and average CMPS; ${T_{yy}}$ contributes approximately 20%, whereas ${T_{xx}}$ contributes less than 5%. The remaining contribution is from the 6 shearing components. Unlike peak and average CMPS, the VF-CMPS BIPV is associated with relatively evenly distributed Sobol indices across the 3 scaling parameters. Furthermore, the contribution of shearing components on the total variance in this case is negligible. Head shape has a considerable influence on the injury predictions of computational head injury models. Available "average" head injury models based on a 50th-percentile U.S. male are likely associated with considerable uncertainty. In general, larger head sizes correspond to greater BIPV magnitudes, which point to potentially a greater injury risk under rapid neck rotation for people with larger heads.

Broadleaf afforestation impacts on terrestrial hydrology insignificant compared to climate change in Great Britain

Abstract. Widespread afforestation has been proposed internationally to reduce atmospheric carbon dioxide; however, the specific hydrological consequences and benefits of such large-scale afforestation (e.g. natural flood management) are poorly understood. We use a high-resolution land surface model, the Joint UK Land Environment Simulator (JULES), with realistic potential afforestation scenarios to quantify possible hydrological change across Great Britain in both present and projected climate. We assess whether proposed afforestation produces significantly different regional responses across regions; whether hydrological fluxes, stores and events are significantly altered by afforestation relative to climate; and how future hydrological processes may be altered up to 2050. Additionally, this enables determination of the relative sensitivity of land surface process representation in JULES compared to climate changes. For these three aims we run simulations using (i) past climate with proposed land cover changes and known floods and drought events; (ii) past climate with independent changes in precipitation, temperature, and CO2; and (iii) a potential future climate (2020–2050). We find the proposed scale of afforestation is unlikely to significantly alter regional hydrology; however, it can noticeably decrease low flows whilst not reducing high flows. The afforestation levels minimally impact hydrological processes compared to changes in precipitation, temperature, and CO2. Warming average temperatures (+3 °C) decreases streamflow, while rising precipitation (130 %) and CO2 (600 ppm) increase streamflow. Changes in high flow are generated because of evaporative parameterizations, whereas low flows are controlled by runoff model parameterizations. In this study, land surface parameters within a land surface model do not substantially alter hydrological processes when compared to climate.

Intense NIR-II luminescence through stabilization of tetrahedral (Mn5+O4) lumophore in apatites with high external quantum efficiency

The discovery of highly efficient near-infrared (NIR) emitting phosphors is essential for multiple spectroscopic applications. Pentavalent-manganese (Mn5+) is a rarely-reported NIR-II activator due to the its instability in inorganic solids. In this study, Mn5+-activated apatite phosphors A5(B1-xMnxO4)3X (A = Sr, Ba; B = P, V; X = OH, F, Cl, Br) were reported. Benefiting from the discrete P/VO4 tetrahedron and stabilization effect of alkaline-earth cation, Mn5+ existed as MnO43− anion can be effectively incorporated into the A5(P/VO4)3X. A selection of 16 different apatites is conducted to test the structural and compositional effect on Mn5+ stabilization and luminescence. The structure-property relationship was discussed with a detailed analysis on Mn5+ Tanabe-Sugano diagram and Dq/B calculation. Particularly, the optimized Ba5(VO4)3Cl: 0.01Mn5+ (λex = 650 nm, λem = 1181 nm) reveals an exceptional external quantum efficiency of 61.1 % with vivid turquoise body color. The multiparametric thermometry by luminescence intensity ratio (LIR) and 1E lifetime were demonstrated with excellent linear regressions (R2 > 99.9 %) and high relative sensitivities of > 1.0% K−1 in the range of physiological temperatures. A NIR-II phosphor-converted light-emitting diode (pc-LED) is fabricated with a NIR output power of 30.18 mW at 60 mA driven current and photoelectric conversion efficiency of 6.63 %.

A novel TFET based nanogap high-sensitive biosensor by boosted reliability- new metric for sensitivity definition

This is a detailed report about the proposal of an efficient nanogap dielectrically modulated tunnel field-effect transistor (TFET) biodevice granting a high sensitivity in the detection of the targeted biomolecules while keeping high performance in the realistic situations with boosting the reliability. Two attractive approaches in the cases of the bandgap engineering and charge plasma concept have been suggested for the band energy correction increasing the sensing current and the sensitivity without occurrence possibility of fabrication process related issues as compared to common TFET and PNPN TFET biosensors. The streptavidin, biotin and APTES samples have been selected as typical biomolecules for the sensing performance comparison of the biosensors under the study. Also, the proposed biosensor showed performance superiority for other biomolecules. For the first time, a new metric for measuring sensitivity is proposed to combine both maximum current sensitivity and well-defined average sensitivity in a unique relation named effective sensitivity. This prevents the possible noise impact on the sensitivity of the biosensors since the TFET based biosensors suffer from the low detection current. Defining the effective sensitivity, the proposed biosensor has been evaluated in more realistic conditions including partial hybridization of biomolecules inside the nanogap, trap-assisted-tunneling (TAT) component, neutral/charged biomolecules and biomolecules accumulation in different orientations showing the performance superiority of the proposed biosensor.

Erbium-based hydrothermal YOF with stark sublevels for in vivo NIR II luminescence nanothermometer

Rare earth luminescent materials have attracted extensive attention in the biomedical field as noncontact temperature monitoring devices with microscopic resolution due to their properties in the visible and near-infrared regions. At the application level, it is required to have a certain temperature monitoring capability in the near-infrared region II window to enhance the tissue penetration depth. Here, two kinds of YOFs: Er[Formula: see text], Yb[Formula: see text] were prepared by co-precipitation and hydrothermal method, and the luminescence was enhanced by ion doping. An Er[Formula: see text]-based ratiometric nanothermometer of 4F[Formula: see text]I[Formula: see text] (672[Formula: see text]nm, upconversion luminescence) to 4I[Formula: see text]I[Formula: see text] (1580[Formula: see text]nm/1566[Formula: see text]nm, NIR II downshifting luminescence) were designed with the Stark energy level. When doped with 2% Zn[Formula: see text], the relative temperature sensitivity of YOF prepared by co-precipitation method was improved from 0.30% [Formula: see text] (30∘C) to 0.59% [Formula: see text] (30∘C), expanding its use as a temperature monitoring device possibility. The temperature sensitivity of YOF prepared by hydrothermal method was 1.01% [Formula: see text] (30∘C). Finally, the NIR II luminescence of the prepared nanothermometer was used as a control for temperature monitoring of heating sites in mice. The results showed that it can distinguish heating site from control site and no significant cytotoxicity or damage to the tissues was revealed, indicating its broad prospects in the biomedical field and other temperature monitoring scenarios in the future.

Core@shell strategies to enhance green upconversion emission of LaAlO3:ErIII, YbIII nanoparticles

Seeking enhanced luminescence in upconverter nanoparticles, LAO:ErIII0.01, YbIII0.01, LAO = LaAlO3, with an average diameter of 30–40 nm, was synthesized via a modified Pechini method. Two coating strategies were employed: the first with three layers of 1 % LAO, and the second with LAO:NdIIIx at% (x = 10 or 30) or LAO:NdIIIx at%, YbIIIy at% (x, y = 30, 2 or 30, 20). Characterization included FTIR, UV–Vis diffuse reflectance, TEM, XRD, and photoluminescence. In the first strategy, undoped phase coating maintained the LaAlO3 rhombohedral crystalline structure, enhancing ErIII core emission under 980 nm laser excitation. In the second case, the shell containing YbIII (3 or 20 at%) under laser at 808 nm, favored the increase in the relative emission intensity of the activator, exciting ErIII directly in the core or via the outer NdIII sensitizer. Kinetic measurements fixing excitation at 980 nm and emission at 542.5 nm resulted in ErIII excited state decay values between 56 and 68 μs. The doped shell favored increased excited state lifetimes, exhibiting concentration quenching in the 30 % YbIII condition. Both NdIII presence and its combination with YbIII enhanced green emission compared to the uncoated core. From thermometric studies, the successive depositions of inert layers of LAO contributed to the highest relative thermal sensitivity of 1.79 % K−1 at 305 K, among the systems studied. Therefore, the core@shell strategies were successful in intensifying ErIII emission, both in the green and red regions, and resulted in relevant figures of merit that qualify them for applications in nanothermometry in the biological window.

Yb3+ concentration influence on NIR and upconversion emission and temperature sensing properties of Er3+/Yb3+ co-doped Ta2O5 particles

We synthesized Er3+ and Yb3+ co-doped tantalum oxide (Ta2O5) spherical sub-micrometric particles by a facile method involving formation of tantalum glycolates after pouring in acetone. Then, we investigated how the annealing temperature and Yb3+ concentration (0–30 mol %) affect their structural and luminescence properties. Particle sizes ranged from 146 to 258 nm for the samples annealed at 800 °C. XRD analysis revealed the orthorhombic L-Ta2O5 crystalline structure. The different symmetry sites that the rare earth ions can occupy within the Ta2O5 structure led to intense and broad emission bands centered around 1530 nm. Up-conversion measurements and the calculated number of photons for intense green and red emissions obtained with 980 and 1550 nm excitations helped us to elucidate the mechanisms involved at both excitation wavelengths. We investigated how the 0.5 mol % Er3+/1.5 mol % Yb3+ co-doped Ta2O5 sample performs as a primary thermometer by using the Boltzmann distribution law to predict the absolute temperature from the ratio between the Er3+ 2H11/2 → 4I15/2 and 4S3/2 → 4I15/2 transitions. We obtained a maximum relative thermal sensitivity of 0.97 ± 0.04 % K−1 and a minimum δT of 2.41 K. The calculated repeatability was above 95%. These results show that promising nanothermometer based on Ta2O5 with controlled size and morphology can be designed.

How does vertical wind shear influence updraft characteristics and hydrometeor distributions in supercell thunderstorms?

Abstract Vertical wind shear is known to affect supercell thunderstorms by displacing updraft hydrometeor mass downshear, thereby facilitating the storms’ longevity. Shear also impacts the size of supercell updrafts, with stronger shear leading to wider, less dilute, and stronger updrafts with likely greater hydrometeor production. To more clearly define the role of shear across different vertical layers on hydrometeor concentrations and displacements relative to supercell updrafts, a suite of idealized numerical model simulations of supercells was conducted. Shear magnitudes were systematically varied across the 0–1 km, 1–6 km, and 6–12 km AGL layers while the thermodynamic environment was held fixed. Simulations show that as shear magnitude increases, especially from 1–6 km, updrafts become wider and less dilute with an increase in hydrometeor loading, along with an increase in the low-level precipitation area/rate and total precipitation accumulation. Even with greater updraft hydrometeor loading amid stronger shear, updrafts are more intense in stronger shear simulations due to larger thermal buoyancy owing to wider, less dilute updraft cores. Furthermore, downshear hydrometeor displacements are larger in environments with stronger 1–6 km shear. In contrast, there is relatively less sensitivity of hydrometeor concentrations and displacements to variations in either 0–1 km or 6–12 km shear. Results are consistent across free tropospheric relative humidity sensitivity simulations, which show an increase in updraft size and hydrometeor mass with increasing free tropospheric relative humidity owing to a reduction in entrainment-driven dilution for wider updrafts in moister environments.

Abstract PO3-24-05: Cysteine metabolism related ferroptosis sensitivity in trastuzumab resistant HER2 positive breast cancer

Abstract Background Trastuzumab has shown great effectiveness in HER2 positive breast cancer treatment, but about 50% patients would undergo resistance during or after treatment. Although previous research has suggested several potential reasons for trastuzumab resistance, the metabolic reprogramming during resistance formation remains largely unclear. Here we identified aberrant ferroptosis associated cysteine metabolism in trastuzumab resistant HER2 positive breast cancer, which might become a novel target for overcoming resistance. Methods Trastuzumab sensitive HER2 positive breast cancer cell SKBR3 and resistant JITM1 were obtained for transcriptomics, proteomics, metabolomics and epigenomics analysis. Gene silencing was mediated by siRNAs. CUT&Tag was applied to compare H3K4me3 and H3K27me3 binding regions. DNA methylation levels and different methylated regions were evaluated by WGBS-seq. CRISPRi with dCas9-DNMT3A was applied to regulate specific DNA methylation in CpG islands. Lipid ROS was measured by flow cytometry with BODIPY-C11. Results Joint analyses of transcriptomics and proteomics according to ferroptosis pathways revealed downregulated glutathione metabolism, glutamate transmembrane and homocysteine metabolism processes, as well as upregulated fatty acid metabolism and iron metabolism pathways in JIMT1. Metabolomics verified that JIMT1 increased cysteine metabolism and decreased glutathione metabolism. SLC7A11 expression and GSH/GSSG ratio were increased in JIMT1, while no difference was observed in free cysteine. JIMT1 featured significant higher UGC codon usage bias and increased cysteinyl-tRNA synthetase. The abundance of H3K4me3 other than H3K27me3 in SLC7A11 promoter region was found increased in JIMT1, and the 5-mC level of CpG islands in SLC7A11 promoter region was shown decreased. Using dCas9-DNMT3A, the methylation of SLC7A11 promoter was enhanced and SLC7A11 expression was reduced in JIMT1. Inhibition of SLC7A11 by siRNAs, CRISPRi or Erastin all indicated a higher ferroptosis sensitivity in JIMT1. Conclusion Trastuzumab resistant HER2 positive breast cancer features aberrant cysteine metabolism resulting from altered H3K4me3 modification and DNA methylation in SLC7A11 promoter region. This might provide novel targets for further anti-HER2 treatment. Citation Format: Yongmei Yin, Yijia Hua, Ningjun Duan, Chunxiao Sun, Fan Yang. Cysteine metabolism related ferroptosis sensitivity in trastuzumab resistant HER2 positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-24-05.

Acute toxicity testing of 6PPD-quinone on the estuarine-dependent sport fish, Sciaenops ocellatus.

Recently, large-scale fish kills in the Pacific Northwest were linked to tire wear particles (TWPs) left on roadways, with the lethality attributed to 6PPD-quinone. which has a median lethal concentration of <1 µg/L for selected salmonids. However, there remains a paucity of 6PPD-quinone toxicity values developed for estuarine fish species, which is particularly significant because estuaries receiving inflows from highly urbanized watersheds are especially vulnerable to TWP contamination. Therefore, the present study aimed to determine the toxicity of 6PPD-quinone to an economically and ecologically important estuarine-dependent fish-red drum (Sciaenops ocellatus). Here, we examined the relative sensitivities of three early life stages within red drum: embryonic, larval, and post-settlement for 24-72 hours, depending on the life stage. Exposure concentrations ranged from 10 μg/L to 500 μg/L. We also assessed the sub-lethal impacts of 6PPD-quinone exposure on development during embryonic and larval stages, including body and organ sizes. Our results indicate that red drum are not acutely sensitive to 6PPD-quinone at each early life stage tested. We also found that yolk-sac larvae did not exhibit sub-lethal morphological impacts in a dose-dependent manner, regardless of exposure during embryonic and larval stages. These data are the first to assess the impacts of 6PPD-quinone on estuarine-dependent non-model fishes.

Tunable Multicolor-Emission in Eu3+ and Tb3+ Codoped Cs2NaInCl6:Sb3+ Double Perovskite Nanocrystals and its Dual-Model Anti-Counterfeiting and Temperature-Sensing Applications

Lead-free metal halide double perovskites with non-toxicity and stable self-trapped excitons (STEs) have received considerable attention in the field of photoelectric applications. However, it is difficult to achieve independent control of its photoluminescence performance to meet the requirements of multi-band emission. Herein, a doping strategy was employed to introduce lanthanide ions (Ln3+) into Cs2NaInCl6:Sb3+ nanocrystals (NCs), enabling the multicolor emission modulation ranging from blue to red and even white light. Benefiting from the efficient energy transfer from Sb-related self-trapped excitons to Ln3+ ions, green and red emissions originate from the 5D0→7FJ (J=1, 2, 3, 4) transition of Eu3+ ions and 5D4-7FJ (J = 6, 5, 4, 3) transition of Tb3+ ions, respectively. According to the tunable polychromatic photoluminescence characteristics of doped NCs, the dual-mode fluorescent anti-counterfeiting applications were exhibited. Furthermore, the distinct temperature sensitivities exhibited by blue (453 nm) and red (617 nm) emission in Cs2NaInCl6:Sb3+/Eu3+ NCs provide the opportunity for the optical thermometry, which demonstrates the maximum absolute and relative sensitivity are 0.0018 and 0.43% K−1, respectively. These results indicate that the synthesized codoped NCs have the potential applications in multifunctional fields, such as optical thermometer, fluorescence anti-counterfeiting, and multicolor-LEDs.

Color tunability and temperature sensing capabilities in Dy3+/Sm3+ co-doped transparent oxyfluoride glass ceramics containing K3YF6 nanocrystals

This paper presents the preparation and characterization of transparent oxyfluoride glass ceramics (GCs) that contain nanocrystals of K3YF6 co-doped with Dy3+ and Sm3+. The study investigates the luminescence characteristics, the process of energy transfer (ET) and the behavior of the ratio-metric temperature sensing. The formation of well-defined nanocrystals of K3YF6 in the glass substrate was confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM). By varying Sm3+ concentration, a tunable emission ranging from pale yellow to orange-red was observed. Energy transfer from Dy3+ to Sm3+ ions was confirmed through fluorescence spectra and decay curves. Sample K3YF6, containing 0.5 mol%Dy3+/1.2 mol%Sm3+, showed an absolute sensitivity (Sa) of 0.635 % K−1 and relative sensitivity (Sr) of 0.401 % K−1. These findings underscore the promising applications of K3YF6: Dy3+, Sm3+ GCs in multicolor displays and high-performance temperature sensing devices.

Development of a Reduced Mechanism for Methane Combustion in OpenFOAM: A Computational Approach for Efficient and Accurate Simulations

The primary aim of this study is to develop a more efficient reaction mechanism for accurately simulating methane combustion, with a specific focus on ignition delay, laminar flame speed, and 2-D simulated flames, while also reducing computational time. Ten reduced reaction mechanisms for methane combustion were evaluated, with only one, "SK30," meeting the required accuracy standards. However, SK30 proved to be computationally intensive when simulating a 2-D premixed flame at a microscale. To address this challenge, a two-step reduction process was implemented. Firstly, an automated algorithm utilized direct relation graphs and sensitivity analysis with ignition delays as a reference to streamline the mechanism while maintaining accuracy. Subsequently, the second step involved identifying key reactions that had a more significant impact on flame speed than ignition delay through sensitivity analysis. Any missing reactions were then added judiciously, prioritizing the retrieval of the missing but important reactions to overall accuracy while minimizing computational cost. This process resulted in a novel mechanism comprising 25 species and 132 reactions for methane-air combustion. The validity of this mechanism was confirmed through comparison with a benchmark model, demonstrating satisfactory agreement in 1-D flame speed and 2-D premixed flame modeling. Most notably, the new mechanism substantially reduced processing time, achieving a 50% speedup compared to SK30.