Facilely Fabricated Single-Site Ptδ+-O(OH)x- Species Associated with Alkali on Zirconia Exhibiting Superior Catalytic Oxidation Reactivity.

Fabrication of robust isolated atom catalysts has been a research hotspot in the environment catalysis field for the removal of various contaminants, but there are still challenges in improving the reactivity and stability. Herein, through facile doping alkali metals in Pt catalyst on zirconia (Pt-Na/ZrO2), the atomically dispersed Ptδ+-O(OH)x- associated with alkali metal via oxygen bridge was successfully fabricated. This novel catalyst presented remarkably higher CO and hydrocarbon (HCs: C3H8, C7H8, C3H6, and CH4) oxidation activity than its counterpart (Pt/ZrO2). Systematically direct and solid evidence from experiments and density functional theory calculations demonstrated that the fabricated electron-rich Ptδ+-O(OH)x- related to Na species rather than the original Ptδ+-O(OH)x-, serving as the catalytically active species, can readily react with CO adsorbed on Ptδ+ to produce CO2 with significantly decreasing energy barrier in the rate-determining step from 1.97 to 0.93 eV. Additionally, owing to the strongly adsorbed and activated water by Na species, those fabricated single-site Ptδ+-O(OH)x- linked by Na species could be easily regenerated during the oxidation reaction, thus considerably boosting its oxidation reactivity and durability. Such facile construction of the alkali ion-linked active hydroxyl group was also realized by Li and K modification which could guide to the design of efficient catalysts for the removal of CO and HCs from industrial exhaust.

Biomechanical comparisons of F.E.R.I. techniques with different type of intramedullary screws fixation for Jones fractures.

Introduction: Jones fractures frequently fail to unite, and adequate fixation stability is crucial. This study aimed to elucidate the biomechanical stability of various intramedullary screw fixation constructs. Methods: Jones fracture model over the proximal 5th metatarsal of artificial bone was created in all specimens. Six groups were divided based on varied screw constructs with different screw lengths, either 30 or 40 mm, including cannulated screws-C30 and C40 groups, one high-resistance suture combined with intramedullary cannulated screws (F.E.R.I. technique)-CF30 and CF40 groups, and second-generation headless compression screws (SG-HCS) -HL30 and HL40 groups. Mechanical testing was conducted sequentially, and the maximal force (N) and stiffness (N/mm) of all constructs were recorded. Results: The maximal force (N) at 1.0 mm downward displacement in C30, C40, CF30, CF40, HL30, and HL40 groups were 0.56 ± 0.02, 0.49 ± 0.02, 0.65 ± 0.02, 0.49 ± 0.01, 0.68 ± 0.02, and 0.73 ± 0.02, respectively, and the stiffness (N/mm) in subgroups were 0.49 ± 0.01, 0.43 ± 0.01, 0.67 ± 0.01, 0.42 ± 0.01, 0.61 ± 0.01, and 0.58 ± 0.02, respectively. SG-HCS subgroups exhibited greater maximal force and stiffness than conventional cannulated screws. Screws of 30 mm in length demonstrated better stability than all 40 mm-length screws in each subgroup. In C30 fixation, the stiffness and maximum force endured increased by 1.16 and 1.12 times, respectively, compared with the C40 fixation method. There were no significant differences between CF30 and SG-HCS groups. Only the F.E.R.I technique combined with the 4.5 mm cannulated screw of 30 mm in length increased the biomechanical stability for Jones fractures. Discussion: These biomechanical findings help clinicians decide on better screw fixation options for greater stability in Jones fractures, especially when large-diameter screws are limited in use. However, this biomechanical testing of intramedullary screw fixation on Jones fracture model lacks clinical validation and no comparisons to extramedullary plate fixations. Moving forward, additional clinical and biomechanical research is necessary to validate our findings.

Multi-tracer PET correlation analysis reveals disease-specific patterns in Parkinson's disease and asymptomatic LRRK2 pathogenic variant carriers compared to healthy controls.

Several genetic pathogenic variants increase the risk of Parkinson's disease (PD) with pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene being among the most common. A joint pattern analysis based on multi-set canonical correlation analysis (MCCA) was utilized to extract PD and LRRK2 pathogenic variant-specific spatial patterns in relation to healthy controls (HCs) from multi-tracer Positron Emission Tomography (PET) data. Spatial patterns were extracted for individual subject cohorts, as well as for pooled subject cohorts, to explore whether complementary spatial patterns of dopaminergic denervation are different in the asymptomatic and symptomatic stages of PD. The MCCA results are also compared to the traditional univariate analysis, which serves as a reference. We identified PD-induced spatial distribution alterations common to DAT and VMAT2 in both asymptomatic LRRK2 pathogenic variant carriers and PD subjects. The inclusion of HCs in the analysis demonstrated that the dominant common PD-induced pattern is related to an overall dopaminergic terminal density denervation, followed by asymmetry and rostro-caudal gradient with deficits in the less affected side still being the best marker of disease progression. The analysis was able to capture a trend towards PD-related patterns in the LRRK2 pathogenic variant carrier cohort with increasing age in line with the known increased risk of this patient cohort to develop PD as they age. The advantage of this method thus resides in its ability to identify not only regional differences in tracer binding between groups, but also common disease-related alterations in the spatial distribution patterns of tracer binding, thus potentially capturing more complex aspects of disease induced alterations.

Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome.

BACKGROUND: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. METHODS: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). RESULTS: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. CONCLUSIONS: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.

Virtual plates: Getting the best out of high content screens.

High content screening (HCS) is becoming widely adopted as a high throughput screening modality, using hundred-of-thousands compounds library. The use of machine learning and artificial intelligence in image analysis is amplifying this trend. Another factor is the recognition that diverse cell phenotypes can be associated with changes in biological pathways relevant to disease processes. There are numerous challenges in HCS campaigns. These include limited ability to support replicates, low availability of precious and unique cells or reagents, high number of experimental batches, lengthy preparation of cells for imaging, image acquisition time (45-60 min per plate) and image processing time, deterioration of image quality with time post cell fixation and variability within wells and batches. To take advantage of the data in HCS, cell population based rather than well-based analyses are required. Historically, statistical analysis and hypothesis testing played only a limited role in non-high content high throughput campaigns. Thus, only a limited number of standard statistical criteria for hit selection in HCS have been developed so far. In addition to complex biological content in HCS campaigns, additional variability is impacted by cell and reagent handling and by instruments which may malfunction or perform unevenly. Together these can cause a significant number of wells or plates to fail. Here we describe an automated approach for hit analysis and detection in HCS. Our approach automates HCS hit detection using a methodology that is based on a documented statistical framework. We introduce the Virtual Plate concept in which selected wells from different plates are collated into a new, virtual plate. This allows the rescue and analysis of compound wells which have failed due to technical issues as well as to collect hit wells into one plate, allowing the user easier access to the hit data.

Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System.

Multiple sclerosis (MS) is an immune-mediated disease that is characterized by demyelination and inflammation in the central nervous system (CNS). Previous studies demonstrated that sphingosine-1-phosphate receptor (S1PR) modulators effectively inhibit S1PR1 in immune cell trafficking and reduce entry of pathogenic cells into the CNS. Studies have also implicated a nonimmune, inflammatory role of S1PR1 within the CNS in MS. In this study, we explored the expression of S1PR1 in the development and progression of demyelinating pathology of MS by quantitative assessment of S1PR1 expression using our S1PR1-specific radioligand, [3H]CS1P1, in the postmortem human CNS tissues including cortex, cerebellum, and spinal cord of MS cases and age- and sex-matched healthy cases. Immunohistochemistry with whole slide scanning for S1PR1 and various myelin proteins was also performed. Autoradiographic analysis using [3H]CS1P1 showed that the expression of S1PR1 was statistically significantly elevated in lesions compared to nonlesion regions in the MS cases, as well as normal healthy controls. The uptake of [3H]CS1P1 in the gray matter and nonlesion white matter did not significantly differ between healthy and MS CNS tissues. Saturation autoradiography analysis showed an increased binding affinity (Kd) of [3H]CS1P1 to S1PR1 in both gray matter and white matter of MS brains compared to healthy brains. Our blocking study using NIBR-0213, a S1PR1 antagonist, indicated [3H]CS1P1 is highly specific to S1PR1. Our findings demonstrated the activation of S1PR1 and an increased uptake of [3H]CS1P1 in the lesions of MS CNS. In summary, our quantitative autoradiography analysis using [3H]CS1P1 on human postmortem tissues shows the feasibility of novel imaging strategies for MS by targeting S1PR1.

P2X7 receptors and pannexin1 hemichannels shape presynaptic transmission.

Over the last decades, since the discovery of ATP as a transmitter, accumulating evidence has been reported about the role of this nucleotide and purinergic receptors, in particular P2X7 receptors, in the modulation of synaptic strength and plasticity. Purinergic signaling has emerged as a crucial player in orchestrating the molecular interaction between the components of the tripartite synapse, and much progress has been made in how this neuron-glia interaction impacts neuronal physiology under basal and pathological conditions. On the other hand, pannexin1 hemichannels, which are functionally linked to P2X7 receptors, have appeared more recently as important modulators of excitatory synaptic function and plasticity under diverse contexts. In this review, we will discuss the contribution of ATP, P2X7 receptors, and pannexin hemichannels to the modulation of presynaptic strength and its impact on motor function, sensory processing, synaptic plasticity, and neuroglial communication, with special focus on the P2X7 receptor/pannexin hemichannel interplay. We also address major hypotheses about the role of this interaction in physiological and pathological circumstances.

Random Telegraph Noise Degradation Caused by Hot Carrier Injection in a 0.8 µm-Pitch 8.3Mpixel Stacked CMOS Image Sensor.

In this work, the degradation of the random telegraph noise (RTN) and the threshold voltage (Vt) shift of an 8.3Mpixel stacked CMOS image sensor (CIS) under hot carrier injection (HCI) stress are investigated. We report for the first time the significant statistical differences between these two device aging phenomena. The Vt shift is relatively uniform among all the devices and gradually evolves over time. By contrast, the RTN degradation is evidently abrupt and random in nature and only happens to a small percentage of devices. The generation of new RTN traps by HCI during times of stress is demonstrated both statistically and on the individual device level. An improved method is developed to identify RTN devices with degenerate amplitude histograms.

Conversion of waste polystyrene into valuable aromatic hydrocarbons via microwave-assisted pyrolysis.

The prime objective of the current research work was to understand the role of microwave-assisted pyrolysis for the upgradation of expanded polystyrene (EPS) waste into valuable aromatic hydrocarbons. Ethyl acetate solvent was used to dissolve the EPS to enhance the homogeneous dispersion of EPS with susceptor particles. Biochar obtained from the pyrolysis was used as a susceptor. The design of experiments method was used to understand the role of microwave power (300 W, 450 W, and 600 W) and susceptor quantity (5 g, 10 g, and 15 g) in the pyrolysis process. The pyrolysis was conducted till the temperature reached up to 600 °C, and this temperature was achieved in the time interval of 14-38 min based on the experimental conditions. The obtained average heating rates varied in the range of 15 to 41 °C/min to attain the pyrolysis temperature. The EPS feed was converted into char (~ 2.5 wt.%), oil (51 to 60 wt.%), and gaseous (37 to 47 wt.%) products. The specific microwave energy (J/g) was calculated to know the energy requirement; it increased with an increase in susceptor quantity and microwave power, whereas specific microwave power (W/g) was a function of microwave power and increased from 15 to 30 W/g. The predicted values calculated using the model equations closely matched the actual values showing that the developed model equations via optimization had a good fit. The obtained pyrolysis oil physicochemical properties including viscosity (1 to 1.4 cP), density (990 to 1030 kg/m3), heating value (39 to 42 MJ/kg), and flash point (98 to 101 °C) were thoroughly analyzed. The pyrolysis oil was rich in aromatic hydrocarbons and it was predominantly composed of styrene, cyclopropyl methylbenzene, and alkylbenzene derivates.

Beyond current treatment of Fanconi Anemia: What do advances in cell and gene-based approaches offer?

Fanconi anemia (FA) is a rare inherited disorder that mainly affects the bone marrow. This condition causes decreased production of all types of blood cells. FA is caused by a defective repair of DNA interstrand crosslinks and to date, mutations in over 20 genes have been linked to the disease. Advances in science and molecular biology have provided new insight between FA gene mutations and the severity of clinical manifestations. Here, we will highlight the current and promising therapeutic options for this rare disease. The current standard treatment for FA patients is hematopoietic stem cell transplantation, a treatment associated to exposure to radiation or chemotherapy, immunological complications, plus opportunistic infections from prolonged immune incompetence or increased risk of morbidity. New arising treatments include gene addition therapy, genome editing using CRISPR-Cas9 nuclease, and hematopoietic stem cell generation from induced pluripotent stem cells. Finally, we will also discuss the revolutionary developments in mRNA therapeutics as an opportunity for this disease.

A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles.

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

Effect of Gupi Xiaoji Decoction on mitochondrial structure and function of human hepatoma cell line HepG2 / 中国药理学通报

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

Limiting medical certainties? Funding challenges for German and comparable public healthcare systems due to AI prediction and how to address them.

Current technological and medical advances lend substantial momentum to efforts to attain new medical certainties. Artificial Intelligence can enable unprecedented precision and capabilities in forecasting the health conditions of individuals. But, as we lay out, this novel access to medical information threatens to exacerbate adverse selection in the health insurance market. We conduct an interdisciplinary conceptual analysis to study how this risk might be averted, considering legal, ethical, and economic angles. We ask whether it is viable and effective to ban or limit AI and its medical use as well as to limit medical certainties and find that neither of these limitation-based approaches provides an entirely sufficient resolution. Hence, we argue that this challenge must not be neglected in future discussions regarding medical applications of AI forecasting, that it should be addressed on a structural level and we encourage further research on the topic.

High Throughput 3D Cell Migration Assay Using Micropillar/Microwell Chips.

The 3D cell migration assay was developed for the evaluation of drugs that inhibit cell migration using high throughput methods. Wound-healing assays have commonly been used for cell migration assays. However, these assays have limitations in mimicking the in vivo microenvironment of the tumor and measuring cell viability for evaluation of cell migration inhibition without cell toxicity. As an attempt to manage these limitations, cells were encapsulated with Matrigel on the surface of the pillar, and an analysis of the morphology of cells attached to the pillar through Matrigel was performed for the measurement of cell migration. The micropillar/microwell chips contained 532 pillars and wells, which measure the migration and viability of cells by analyzing the roundness and size of the cells, respectively. Cells seeded in Matrigel have a spherical form. Over time, cells migrate through the Matrigel and attach to the surface of the pillar. Cells that have migrated and adhered have a diffused shape that is different from the initial spherical shape. Based on our analysis of the roundness of the cells, we were able to distinguish between the diffuse and spherical shapes. Cells in Matrigel on the pillar that were treated with migration-inhibiting drugs did not move to the surface of the pillar and remained in spherical forms. During the conduct of experiments, 70 drugs were tested in single chips and migration-inhibiting drugs without cell toxicity were identified. Conventional migration assays were performed using transwell for verification of the four main migration-inhibiting drugs found on the chip.

Microbiome profiling of nasal extracellular vesicles in patients with allergic rhinitis.

Background: Nasal microbiota is crucial for the pathogenesis of allergic rhinitis (AR), which has been reported to be different from that of healthy individuals. However, no study has investigated the microbiota in nasal extracellular vesicles (EVs). We aimed to compare the microbiome composition and diversity in EVs between AR patients and healthy controls (HCs) and reveal the potential metabolic mechanisms in AR. Methods: Eosinophil counts and serum immunoglobulin E (IgE) levels were measured in patients with AR (n = 20) and HCs (n = 19). Nasal EVs were identified using transmission electron microscopy and flow cytometry. 16S rRNA sequencing was used to profile the microbial communities. Alpha and beta diversities were analyzed to determine microbial diversity. Taxonomic abundance was analyzed based on the linear discriminant analysis effect size (LEfSe). Microbial metabolic pathways were characterized using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUst2) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Eosinophils, total serum IgE, and IgE specific to Dermatophagoides were increased in patients with AR. Alpha diversity in nasal EVs from patients with AR was lower than that in HCs. Beta diversity showed microbiome differences between the AR and HCs groups. The microbial abundance was distinct between AR and HCs at different taxonomic levels. Significantly higher levels of the genera Acetobacter, Mycoplasma, Escherichia, and Halomonas were observed in AR patients than in HCs. Conversely, Zoogloea, Streptococcus, Burkholderia, and Pseudomonas were more abundant in the HCs group than in the AR group. Moreover, 35 microbial metabolic pathways recognized in AR patients and HCs, and 25 pathways were more abundant in the AR group. Conclusion: Patients with AR had distinct microbiota characteristics in nasal EVs compared to that in HCs. The metabolic mechanisms of the microbiota that regulate AR development were also different. These findings show that nasal fluid may reflect the specific pattern of microbiome EVs in patients with AR.

Essential and non-essential US workers' health behaviors during the COVID-19 pandemic.

We seek to quantify the relationship between health behaviors and work-related experiences during the COVID-19 pandemic by predicting health behaviors as a function of essential worker status, job loss, change in work hours, and COVID-19 experiences. We use multivariate models and survey data from 913 employed adults in a semi-rural mid-Atlantic US county, and test whether essential worker results vary by gender, parenthood, and/or university employment. Multivariate models indicate that essential workers used tobacco on more days (4.5; p <.01) and were less likely to sleep 8 h (odds ratio [OR] 0.6; p <.01) than non-essential workers. The risk of sleeping less than 8 h is concentrated among essential workers in the service industry (OR 0.5; p <.05) and non-parents (OR 0.5; p <.05). Feminine essential workers exercised on fewer days (-0.8; p <.05) than feminine non-essential workers. Workers with reduced work hours consumed more alcoholic drinks (0.3; p <.05), while workers with increased work hours consumed alcohol (0.3; p <.05) and exercised (0.6; p <.05) on more days. Essential worker status and changes in work hours are correlated with unhealthy behaviors during the COVID-19 pandemic.

The effect of drug loading and multiple administration on the protein corona formation and brain delivery property of PEG-PLA nanoparticles.

The presence of protein corona on the surface of nanoparticles modulates their physiological interactions such as cellular association and targeting property. It has been shown that α-mangostin (αM)-loaded poly(ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles (NP-αM) specifically increased low density lipoprotein receptor (LDLR) expression in microglia and improved clearance of amyloid beta (Aß) after multiple administration. However, how do the nanoparticles cross the blood‒brain barrier and access microglia remain unknown. Here, we studied the brain delivery property of PEG-PLA nanoparticles under different conditions, finding that the nanoparticles exhibited higher brain transport efficiency and microglia uptake efficiency after αM loading and multiple administration. To reveal the mechanism, we performed proteomic analysis to characterize the composition of protein corona formed under various conditions, finding that both drug loading and multiple dosing affect the composition of protein corona and subsequently influence the cellular uptake of nanoparticles in b.End3 and BV-2 cells. Complement proteins, immunoglobulins, RAB5A and CD36 were found to be enriched in the corona and associated with the process of nanoparticles uptake. Collectively, we bring a mechanistic understanding about the modulator role of protein corona on targeted drug delivery, and provide theoretical basis for engineering brain or microglia-specific targeted delivery system.

Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway.

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

circRNA Expression Pattern and circRNA-miRNA-mRNA Network in HCs, HSCs, and KCs of Murine Liver After Echinococcus multilocularis Infection.

Caused by Echinococcus multilocularis (E. multilocularis), alveolar echinococcosis is reported every year around the world and severely threatens the safety of human beings and animals. However, the molecular interaction relationships between host and E. multilocularis still remains unclear. With multiple functions, circRNA plays a crucial role in regulating the development of a parasitic disease. With that in mind, the main purpose of this study was to reveal the circRNA expression profiles and circRNA-miRNA-mRNA network relationships in hepatocytes (HCs), hepatic stellate cells (HSCs), and Kupffer cells (KCs) of murine liver after E. multilocularis infection. After sequencing, 6,290 circRNAs were identified from 12 hepatic cell samples. Based on the subsequent analysis, 426 and 372 circRNAs were significantly different in HC expression at 2 and 3 months after E. multilocularis infection, and similar results were also demonstrated in HSCs (426 and 372 circRNAs) and KCs (429 and 331 circRNAs), respectively. Eight candidate circRNAs were randomly selected to identify the accuracy of the sequencing results by using qRT-PCR. Additionally, three circRNAs-miRNA-mRNA networks in HCs, HSCs, and KCs were constructed. Taken together, our study provided a systematic presentation of circRNAs in murine liver cells after E. multilocularis infection, and these networks are essential for research in circRNAs associated with E. multilocularis infection.