Modulation Of Resistance Research Articles

Magnetic-Field Response and Giant Electric-Field Modulation of Cu2S.

Cu2S likely plays an important role in the sharp resistivity transition of LK-99. Nevertheless, this immediately arouses an intriguing question of whether the extraordinary room-temperature colossal magnetoresistance in the initial reports, which has been less focused, originates from Cu2S as well. To resolve this issue, we have systematically investigated the electrical transport and magnetotransport properties of near-stoichiometric Cu2S pellets and thin films. Neither Cu2S nor LK-99 containing Cu2S in this study was found to exhibit the remarkable magnetoresistance effect implied by Lee et al. This implies that Cu2S could not account for all of the intriguing transport properties of the initially reported LK-99, and the initially reported LK-99 samples might contain magnetic impurities. Moreover, based on the crystal-structure-sensitive electrical properties of Cu2S, we have constructed a piezoelectric-strain-controlled device and obtained a giant and reversible resistance modulation of 2 orders of magnitude at room temperature, yielding a huge gauge factor of 160,000.

Disease-Associated Streptococcus pneumoniae Genetic Variation.

Streptococcus pneumoniae is an opportunistic pathogen that causes substantial illness and death among children worldwide. The genetic backgrounds of pneumococci that cause infection versus asymptomatic carriage vary substantially. To determine the evolutionary mechanisms of opportunistic pathogenicity, we conducted a genomic surveillance study in China. We collected 783 S. pneumoniae isolates from infected and asymptomatic children. By using a 2-stage genomewide association study process, we compared genomic differences between infection and carriage isolates to address genomic variation associated with pathogenicity. We identified 8 consensus k-mers associated with adherence, antimicrobial resistance, and immune modulation, which were unevenly distributed in the infection isolates. Classification accuracy of the best k-mer predictor for S. pneumoniae infection was good, giving a simple target for predicting pathogenic isolates. Our findings suggest that S. pneumoniae pathogenicity is complex and multifactorial, and we provide genetic evidence for precise targeted interventions.

Drug Resistance Modulation of Dairy MRSA through Berberine, Artesunate and Quercetin in Combination with β-Lactams

Drug Resistance Modulation of Dairy MRSA through Berberine, Artesunate and Quercetin in Combination with β-Lactams

GaN/rGO nanocomposite gas sensor for enhanced NH3 sensing performances at room temperature

In this work, we developed a high-performance NH3 sensor based on GaN/rGO nanocomposites via a low-cost solvothermal method and subsequent nitridation process. The morphological, structural, and chemical compositions were investigated to demonstrate that GaN and rGO were coupled together by interfacial modulation, and the GaN/rGO heterostructure chemical bonds are successfully formed. Gas-sensing performance test results show that the fabricated GaN/rGO (2.2 wt%) NH3 sensor exhibited a high response value (92%), fast response time (11 s), and low limit of detection (500 ppb) at room temperature. In addition, reproducibility, humidity, and long-term stability tests of the GaN/rGO sensor were also conducted in this work. The enhancement sensing mechanisms are attributed to the large specific surface area, the excellent conductivity of rGO, and resistance modulation effect of the heterojunction potential. Hence, the GaN/rGO gas sensor can be regarded as a promising sensing solution for atmospheric and exhaled NH3 detection at room temperature.

Differences in heart rate responses to upright posture are associated with variations in the high-frequency power of heart rate variability.

High resting heart rate is a cardiovascular risk factor, but limited data exist on the underlying hemodynamics and reproducibility of supine-to-upright increase in heart rate. We recorded noninvasive hemodynamics in 574 volunteers [age, 44.9 yr; body mass index (BMI), 26.4 kg/m2; 49% male] during passive head-up tilt (HUT) using whole body impedance cardiography and radial artery tonometry. Heart rate regulation was evaluated using heart rate variability (HRV) analyses. Comparisons were made between quartiles of supine-to-upright heart rate changes, in which heart rate at rest ranged 62.6-64.8 beats/min (P = 0.285). The average upright increases in heart rate in the quartiles 1-4 were 4.7, 9.9, 13.5, and 21.0 beats/min, respectively (P < 0.0001). No differences were observed in the low-frequency power of HRV, whether in the supine or upright position, or in the high-frequency power of HRV in the supine position. Upright high-frequency power of HRV was highest in quartile 1 with lowest upright heart rate and lowest in quartile 4 with highest upright heart rate. Mean systolic blood pressure before and during HUT (126 vs. 108 mmHg) and the increase in systemic vascular resistance during HUT (650 vs. 173 dyn·s/cm5/m2) were highest in quartile 1 and lowest in quartile 4. The increases in heart rate during HUT on three separate occasions several weeks apart were highly reproducible (r = 0.682) among 215 participants. To conclude, supine-to-upright increase in heart rate is a reproducible phenotype with underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. As heart rate at rest influences prognosis, future research should elucidate the prognostic significance of these phenotypic differences.NEW & NOTEWORTHY Subjects with similar supine heart rates are characterized by variable increases in heart rate during upright posture. Individual heart rate increases in response to upright posture are highly reproducible as hemodynamic phenotypes and present underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. These results indicate that resting heart rate obtained in the supine position alone is not an optimal means of classifying people into groups with differences in cardiovascular function.

Emerging roles of lysosome homeostasis (repair, lysophagy and biogenesis) in cancer progression and therapy

In the era of personalized therapy, precise targeting of subcellular organelles holds great promise for cancer modality. Taking into consideration that lysosome represents the intersection site in numerous endosomal trafficking pathways and their modulation in cancer growth, progression, and resistance against cancer therapies, the lysosome is proposed as an attractive therapeutic target for cancer treatment. Based on the recent advances, the current review provides a comprehensive understanding of molecular mechanisms of lysosome homeostasis under 3R responses: Repair, Removal (lysophagy) and Regeneration of lysosomes. These arms of 3R responses have distinct role in lysosome homeostasis although their interdependency along with switching between the pathways still remain elusive. Recent advances underpinning the crucial role of (1) ESCRT complex dependent/independent repair of lysosome, (2) various Galectins-based sensing and ubiquitination in lysophagy and (3) TFEB/TFE proteins in lysosome regeneration/biogenesis of lysosome are outlined. Later, we also emphasised how these recent advancements may aid in development of phytochemicals and pharmacological agents for targeting lysosomes for efficient cancer therapy. Some of these lysosome targeting agents, which are now at various stages of clinical trials and patents, are also highlighted in this review.

Antibacterial, Resistance Modulation, Anti-Biofilm Formation, and Efflux Pump Inhibition Properties of Loeseneriella africana (Willd.) N. Halle (Celastraceae) Stem Extract and Its Constituents.

This study investigated the antibacterial, resistance modulation, biofilm inhibition, and efflux pump inhibition potentials of Loeseneriella africana stem extract and its constituents. The antimicrobial activity was investigated by the high-throughput spot culture growth inhibition (HT-SPOTi) and broth microdilution assays. The resistance modulation activity was investigated using the anti-biofilm formation and efflux pump inhibition assays. Purification of the extract was carried out by chromatographic methods, and the isolated compounds were characterized based on nuclear magnetic resonance, Fourier transform infrared and mass spectrometry spectral data and comparison with published literature. The whole extract, methanol, ethyl acetate, and pet-ether fractions of L. africana all showed antibacterial activity against the test bacteria with MICs ranging from 62.5 to 500.0 µg/mL The whole extract demonstrated resistance modulation effect through strong biofilm inhibition and efflux pump inhibition activities against S. aureus ATCC 25923, E. coli ATCC 25922 and P. aeruginosa ATCC 27853. Chromatographic fractionation of the ethyl acetate fraction resulted in the isolation of a triterpenoid (4S,4αS,6αR,6βS,8αS,12αS,12βR,14αS,14βR)-4,4α,6β,8α,11,11,12β,14α-Octamethyloctadecahydropicene-1,3(2H,4H)-dione) and a phytosterol (β-sitosterol). These compounds showed antibacterial activity against susceptible bacteria at a MIC range of 31-125 µg/mL and potentiated the antibacterial activity of amoxicillin (at ¼ MIC of compounds) against E. coli and P. aeruginosa with modulation factors of 32 and 10, respectively. These compounds also demonstrated good anti-biofilm formation effect at a concentration range of 3-100 µg/mL, and bacterial efflux pump inhibition activity at ½ MIC and ¼ MIC against E. coli and P. aeruginosa. Loeseneriella africana stem bark extracts and constituents elicit considerable antibacterial, resistance modulation, and biofilm and efflux pump inhibition activities. The results justify the indigenous uses of L. africana for managing microbial infections.

The role of circRNAs in regulation of drug resistance in ovarian cancer.

Ovarian cancer is one of the female reproductive system tumors. Chemotherapy is used for advanced ovarian cancer patients; however, drug resistance is a pivotal cause of chemotherapeutic failure. Hence, it is critical to explore the molecular mechanisms of drug resistance of ovarian cancer cells and to ameliorate chemoresistance. Noncoding RNAs (ncRNAs) have been identified to critically participate in drug sensitivity in a variety of human cancers, including ovarian cancer. Among ncRNAs, circRNAs sponge miRNAs and prevent miRNAs from regulation of their target mRNAs. CircRNAs can interact with DNA or proteins to modulate gene expression. In this review, we briefly describe the biological functions of circRNAs in the development and progression of ovarian cancer. Moreover, we discuss the underneath regulatory molecular mechanisms of circRNAs on governing drug resistance in ovarian cancer. Furthermore, we mention the novel strategies to overcome drug resistance via targeting circRNAs in ovarian cancer. Due to that circRNAs play a key role in modulation of drug resistance in ovarian cancer, targeting circRNAs could be a novel approach for attenuation of chemoresistance in ovarian cancer.

Hydrogenation effect on 2D ZnO single crystal/ZnO–SnO2 two phase ceramics and its enhanced mechanism in H2 gas sensing

In this work, a 1D/2D two-phase structure of ZnO single-crystal nanosheets/ZnO–SnO2 nanorods was constructed, and the hydrogen gas sensing properties including selectivity have been enhanced by this low-cost way without noble metal doping. It was proved that hydrogenation effect on ZnO (0001) single crystal facets was the key to forming the low resistance surface in hydrogen gas, leading significantly enhancement in response and selectivity. The response (Ra/Rg) to 200 ppm hydrogen gas exceeded 400 at a low operating temperature of 150 °C, response/recovery time in 100 ppm H2 was only 30 s/8 s. The sensor also has good selectivity for hydrogen detection. The enhancement in gas sensing properties due to dual mechanism of the hydrogenated low-resistance surface and the resistance modulation of ZnO/SnO2 heterojunctions, which proposed in this paper.

Effect of calcination frequency on the thermoelectric properties of Ti doped CuCrO2 by solid state method

In this study, the influence of titanium oxide (TiO2) dopants and varying calcination processes on the thermoelectric properties of CuCrO2 was systematically explored. It was emphasized that these factors were not only affecting dislocation density but also exerting a profound influence on thermoelectric performance through the modulation of Seebeck coefficient and resistivity. The findings highlighted CrT-2, which incorporated TiO2 and underwent a two-time calcination process, as the top-performing sample in terms of power factor values, underscoring the significance of TiO2 as a dopant for enhancing thermoelectric efficiency. Conversely, Cr-4, exposed to four calcination cycles, exhibited slightly lower power factor values compared to Cr-2. Notably, CrT-4, despite containing the titanium dopant, showed the lowest power factor values, potentially due to intricate interactions between the dopant and the extended calcination process. These results underscore the intricate interplay between dopants, calcination processes, and thermoelectric performance in CuCrO2, necessitating precise optimization to achieve the desired material efficiency.

New insights into the interaction between m6A modification and lncRNA in cancer drug resistance.

Drug resistance is perhaps the greatest obstacle in improving outcomes for cancer patients, leading to recurrence, progression and metastasis of various cancers. Exploring the underlying mechanism worth further study. N6-methyladenosine (m6A) is the most common RNA modification found in eukaryotes, playing a vital role in RNA translation, transportation, stability, degradation, splicing and processing. Long noncoding RNA (lncRNA) refers to a group of transcripts that are longer than 200 nucleotides (nt) and typically lack the ability to code for proteins. LncRNA has been identified to play a significant role in regulating multiple aspects of tumour development and progression, including proliferation, metastasis, metabolism, and resistance to treatment. In recent years, a growing body of evidence has emerged, highlighting the crucial role of the interplay between m6A modification and lncRNA in determining the sensitivity of cancer cells to chemotherapeutic agents. In this review, we focus on the recent advancements in the interaction between m6A modification and lncRNA in the modulation of cancer drug resistance. Additionally, we aim to explore the underlying mechanisms involved in this process. The objective of this review is to provide valuable insights and suggest potential future directions for the reversal of chemoresistance in cancer.

Chalcogen-Varied Imidazolone Derivatives as Antibiotic Resistance Breakers in Staphylococcus aureus Strains.

In this study, a search for new therapeutic agents that may improve the antibacterial activity of conventional antibiotics and help to successfully overcome methicillin-resistant Staphylococcus aureus (MRSA) infections has been conducted. The purpose of this work was to extend the scope of our preliminary studies and to evaluate the adjuvant potency of new derivatives in a set of S. aureus clinical isolates. The study confirmed the high efficacy of piperazine derivatives of 5-arylideneimidazol-4-one (7-9) tested previously, and it enabled the authors to identify even more efficient modulators of bacterial resistance among new analogs. The greatest capacity to enhance oxacillin activity was determined for 1-benzhydrylpiperazine 5-spirofluorenehydantoin derivative (13) which, at concentrations as low as 0.0625 mM, restores the effectiveness of β-lactam antibiotics against MRSA strains. In silico studies showed that the probable mechanism of action of 13 is related to the binding of the molecule with the allosteric site of PBP2a. Interestingly, thiazole derivatives tested were shown to act as both oxacillin and erythromycin conjugators in S. aureus isolates, suggesting a complex mode of action (i.e., influence on the Msr(A) efflux pump). This high enhancer activity indicates the high potential of imidazolones to become commercially available antibiotic adjuvants.

PDP1 is a key metabolic gatekeeper and modulator of drug resistance in FLT3-ITD-positive acute myeloid leukemia

High metabolic flexibility is pivotal for the persistence and therapy resistance of acute myeloid leukemia (AML). In 20–30% of AML patients, activating mutations of FLT3, specifically FLT3-ITD, are key therapeutic targets. Here, we investigated the influence of FLT3-ITD on AML metabolism. Nuclear Magnetic Resonance (NMR) profiling showed enhanced reshuffling of pyruvate towards the tricarboxylic acid (TCA) cycle, suggesting an increased activity of the pyruvate dehydrogenase complex (PDC). Consistently, FLT3-ITD-positive cells expressed high levels of PDP1, an activator of the PDC. Combining endogenous tagging of PDP1 with genome-wide CRISPR screens revealed that FLT3-ITD induces PDP1 expression through the RAS signaling axis. PDP1 knockdown resulted in reduced cellular respiration thereby impairing the proliferation of only FLT3-ITD cells. These cells continued to depend on PDP1, even in hypoxic conditions, and unlike FLT3-ITD-negative cells, they exhibited a rapid, PDP1-dependent revival of their respiratory capacity during reoxygenation. Moreover, we show that PDP1 modifies the response to FLT3 inhibition. Upon incubation with the FLT3 tyrosine kinase inhibitor quizartinib (AC220), PDP1 persisted or was upregulated, resulting in a further shift of glucose/pyruvate metabolism towards the TCA cycle. Overexpression of PDP1 enhanced, while PDP1 depletion diminished AC220 resistance in cell lines and peripheral blasts from an AC220-resistant AML patient in vivo. In conclusion, FLT3-ITD assures the expression of PDP1, a pivotal metabolic regulator that enhances oxidative glucose metabolism and drug resistance. Hence, PDP1 emerges as a potentially targetable vulnerability in the management of AML.

Resistance Modulation of Individual and Polymicrobial Culture of S. aureus and E. coli through Nanoparticle-Coupled Antibiotics.

Polymicrobial mastitis is now becoming very common in dairy animals, resulting in exaggerated resistance to multiple antibiotics. The current study was executed to find drug responses in individual and mixed Culture of Staphylococcus aureus and Escherichia coli isolated from milk samples, as well as to evaluate the antibacterial potential of tungsten oxide nanoparticles. These isolates (alone and in mixed culture) were further processed for their responses to antibiotics using the disc diffusion method. On the other hand, tungsten oxide WO3 (W) nanoparticles coupled with antibiotics (ampicillin, A, and oxytetracycline, O) were prepared through the chemical method and characterized by X-ray diffraction, scanning electron microscopy (SEM), and UV-visible techniques. The preparations consisting of nanoparticles alone (W) and coupled with ampicillin (WA) and oxytetracycline (WO) were tested against individual and mixed Culture through the well diffusion and broth microdilution methods. The findings of the current study showed the highest resistance in E. coli was against penicillin (60%) and ampicillin (50%), while amikacin, erythromycin, ciprofloxacin, and oxytetracycline were the most effective antibiotics. S. aureus showed the highest resistance against penicillin (50%), oxytetracycline (40%), and ciprofloxacin (40%), while, except for ampicillin, the sensitive strains of S. aureus were in the range of 40-60% against the rest of antibiotics. The highest zones of inhibition (ZOI) against mixed Culture were shown by imipenem and ampicillin, whereas the highest percentage decrease in ZOI was noted in cases of ciprofloxacin (-240%) and gentamicin (-119.4%) in comparison to individual Culture of S. aureus and E. coli. It was noteworthy that the increase in ZOI was not more than 38% against mixed Culture as compared to the individual Culture. On the other hand, there was a significant reduction in the minimum inhibitory concentration (MIC) of nanoparticle-coupled antibiotics compared to nanoparticles alone for individual and mixed-culture bacteria, while MICs in the case of mixed Culture remained consistently high throughout the trial. This study therefore concluded that diverse drug resistance was present in both individual and mixed-culture bacteria, whereas the application of tungsten oxide nanoparticle-coupled antibiotics proved to be an effective candidate in reversing the drug resistance in bacterial strains.

Machine learning modeling of lung mechanics: Assessing the variability and propagation of uncertainty in respiratory-system compliance and airway resistance

Background and ObjectiveTraditional assessment of patient response in mechanical ventilation relies on respiratory-system compliance and airway resistance. Clinical evidence has shown high variability in these parameters, highlighting the difficulty of predicting them before the start of ventilation therapy. This motivates the creation of computational models that can connect structural and tissue features with lung mechanics. In this work, we leverage machine learning (ML) techniques to construct predictive lung function models informed by non-linear finite element simulations, and use them to investigate the propagation of uncertainty in the lung mechanical response. MethodsWe revisit a continuum poromechanical formulation of the lungs suitable for determining patient response. Based on this framework, we create high-fidelity finite element models of human lungs from medical images. We also develop a low-fidelity model based on an idealized sphere geometry. We then use these models to train and validate three ML architectures: single-fidelity and multi-fidelity Gaussian process regression, and artificial neural networks. We use the best predictive ML model to further study the sensitivity of lung response to variations in tissue structural parameters and boundary conditions via sensitivity analysis and forward uncertainty quantification. Codes are available for download at https://github.com/comp-medicine-uc/ML-lung-mechanics-UQ ResultsThe low-fidelity model delivers a lung response very close to that predicted by high-fidelity simulations and at a fraction of the computational time. Regarding the trained ML models, the multi-fidelity GP model consistently delivers better accuracy than the single-fidelity GP and neural network models in estimating respiratory-system compliance and resistance (R2∼0.99). In terms of computational efficiency, our ML model delivers a massive speed-up of ∼970,000× with respect to high-fidelity simulations. Regarding lung function, we observed an almost matched and non-linear behavior between specific structural parameters and chest wall stiffness with compliance. Also, we observed a strong modulation of airways resistance with tissue permeability. ConclusionsOur findings unveil the relevance of specific lung tissue parameters and boundary conditions in the respiratory-system response. Furthermore, we highlight the advantages of adopting a multi-fidelity ML approach that combines data from different levels to yield accurate and efficient estimates of clinical mechanical markers. We envision that the methods presented here can open the way to the development of predictive ML models of the lung response that can inform clinical decisions.

Resistive switching modulation by incorporating thermally enhanced layer in HfO2-based memristor.

Oxide-based memristors by incorporating thermally enhanced layer (TEL) have showed great potential in electronic devices for high-efficient and high-density neuromorphic computing owing to the improvement of multilevel resistive switching. However, research on the mechanism of resistive switching regulation is still lacking. In this work, based on the method of finite element numerical simulation analysis, a bilayer oxide-based memristor Pt/HfO2 (5 nm)/Ta2O5 (5 nm)/Pt with the Ta2O5 TEL was proposed. The oxygen vacancy concentrates distribution shows that the fracture of conductive filaments (CF) is at the interface where the local temperature is the highest during the reset process. The multilevel resistive switching properties were also obtained by applying different stop voltages. The fracture gap of CF can be enlarged with the increase of the stopping voltage, which is attributed to the heat-gathering ability of the TEL. Moreover, it was found that the fracture position of oxygen CF is dependent on the thickness of TEL, which exhibits a modulation of device RS performance. These results provide a theoretical guidance on the suitability of memristor devices for use in high-density memory and brain-actuated computer systems.

Sensitizing effect of montmorillonite on the gas sensing property of CuO particles to n-butanol

Individual montmorillonite (MMT) platelets as an electronic additive were inserted into CuO particle matrix to derive CuO-MMT nanocomposites via a 2-methylimidazole ligand-assisted hydrolysis method in combination with thermal decomposition. The analyses by XRD, FTIR, and XPS confirmed the presence of monoclinic copper oxide and aluminosilicate in the nanocomposites. MMT platelets were observed to be surrounded among quasi-spherical CuO particles closely, even generating some large-sized aggregates. While CuO particles had a decrease in surface area after the loading of MMT, their electrical resistance was modulated to gradually increase. The CuO-MMT(0.050) based sensor showed the highest response of ∼31 (Rg/Ra) to 200 ppm n-butanol at 260 °C. The limit of detection was estimated to be ∼0.75 ppm for CuO-MMT(0.050), which was lower than that of CuO (∼3.12 ppm). Additionally, the nanocomposite-base sensor was also relatively tolerant against humidity. The improved sensing property could be attributed to the resistance modulation, nanoscale junction, and interface oxygen vacancies upon the addition of MMT. This work suggests that aluminosilicate clays can serve as a promising additive with the ability to enhance the gas sensing property of p-type metal oxides.

Metal–insulator–superconductor transition in nickelate-based heterostructures driven by topotactic reduction

The discovery of superconductivity in doped infinite-layer nickelates has attracted great interest recently. Here, a metal–insulator–superconductor transition is demonstrated by engineering the process of topotactic reduction. By employing topotactic reduction, a superconducting Nd0.8Sr0.2NiO2 layer is obtained from high-quality Nd0.8Sr0.2NiO3, which is characterized by layer-by-layer growth and low room-temperature resistivity, rather than the low-quality Nd0.8Sr0.2NiO3 with mixed phases. Moreover, an insulating intermediate state is uncovered within the transition from metallic Nd0.8Sr0.2NiO3 to superconducting Nd0.8Sr0.2NiO2, corresponding to a non-monotonic modulation of resistivity driven by topotactic reduction. In the incompletely reduced Nd0.8Sr0.2NiO2+δ, residual oxygen atoms in the Nd/Sr plane disrupt the long-range order of the infinite-layer structure, resulting in suppressed superconductivity with a low transition temperature and non-zero residual resistivity. On the other hand, the superconductivity is optimized in the fully reduced sample, where a sign change in the Hall coefficient is always observed at low temperatures. Our study highlights the diverse electronic states achievable by controlling topotactic reduction, providing valuable insight into the understanding and manipulating of superconductivity in infinite-layer nickelates.

Substituents-triggered modulation of structure and alkali resistance in cyano-based disperse dyes

Alkali-resistant disperse dyes have garnered significant interest due to their numerous advantages in alkaline one-bath dyeing procedures. Herein, six cyano-based disperse dyes (D1–D6) with either 2-aminobenzothiazole or 2-amino-6-nitrobenzothiazole, as well as N-substituted anilines as coupling components, were designed and synthesized to investigate the effect of substituents and π-π conjugation of the alkali-resistant stability of dyes. High-performance liquid chromatography (HPLC) was used to monitor the dye hydrolysis behavior, indicating that dyes with strong intramolecular π-π conjugation and bulky benzyl substituents on the n-phenylamine substituent exhibited good alkaline resistance. The hydrolysis processes of cyano disperse dyes under alkaline conditions were consistent with SN2 Nucleophilic substitution, and followed first-order reaction kinetics. Furthermore, PET fabrics were dyed with D1–D3 under various alkaline conditions, proving that D2 and D3 possessed good dyeing performance even under a 5 g/L NaOH dye bath. Our study contributes valuable insights into the relationship between molecular structure and alkali resistance in cyanide disperse dyes, offering practical guidance for enhancing the performance of such dyes.

Adaptive responses of neuronal cells to chronic endoplasmic reticulum (ER) stress

Accumulation of misfolded proteins or perturbation of calcium homeostasis leads to endoplasmic reticulum (ER) stress and is linked to the pathogenesis of neurodegenerative diseases. Hence, understanding the ability of neuronal cells to cope with chronic ER stress is of fundamental interest. Interestingly, several brain areas uphold functions that enable them to resist challenges associated with neurodegeneration. Here, we established novel clonal mouse hippocampal (HT22) cell lines that are resistant to prolonged (chronic) ER stress induced by thapsigargin (TgR) or tunicamycin (TmR) as in vitro models to study the adaption to ER stress. Morphologically, we observed a significant increase in vesicular und autophagosomal structures in both resistant lines and ‘giant lysosomes’, especially striking in TgR cells. While autophagic activity increased under ER stress, lysosomal function appeared slightly impaired; in both cell lines, we observed enhanced ER-phagy. However, proteomic analyses revealed that various protein clusters and signaling pathways were differentially regulated in TgR versus TmR cells in response to chronic ER stress. Additionally, bioenergetic analyses in both resistant cell lines showed a shift toward aerobic glycolysis (‘Warburg effect’) and a defective complex I of the oxidative phosphorylation (OXPHOS) machinery. Furthermore, ER stress-resistant cells differentially activated the unfolded protein response (UPR) comprising IRE1α and ATF6 pathways. These findings display the wide portfolio of adaptive responses of neuronal cells to chronic ER stress. ER stress-resistant neuronal cells could be the basis to uncover molecular modulators of adaptation, resistance, and neuroprotection as potential pharmacological targets for preventing neurodegeneration.