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Background Mesenchymal stem cell (MSC) transplantation is a promising therapeutic approach for noise-induced hearing loss (NIHL). As the indispensable role of apoptosis in MSC transplantation was raised, the benefits of MSC-derived apoptotic vesicles (apoVs) in several disease models have been proved. However, whether apoVs benefit in NIHL have not been studied yet. Methods Female CBA/J mice and HEI-OC1 cells were used in this study. Flow cytometry, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were used to characterize apoVs. Proteomic analysis was used to identify function proteins in apoVs. Immunofluorescence was used to reveal distribution pattern. Auditory brainstem response (ABR) test was used to measure the effect of apoVs treatment. DCFH-DA staining and MitoSOX staining were used to indicate oxidative damage. Western-blot and qRT-PCR were used to study the signaling pathways. Results We found that apoVs can be endocytosed by hair cells through systemic administration. Importantly, apoVs administration effectively attenuated NIHL and reduced hair cell loss by resisting oxidative damage in vivo. Further, apoVs application activated forkhead box o3 (FOXO3a)—mitochondrial superoxide dismutase 2(SOD2) pathway, which may relate to signal transduction and activators of transcription 3 (STAT3) in apoVs. Conclusions These findings uncovered the role of apoVs in preventing NIHL and resisting oxidative damage, indicating that apoVs is a promising way for inner ear delivery and a prospective cell-free therapy for NIHL.

Purpose Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity. Methods In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy. Results MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function. Conclusion MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.

Accurate assessments of exposure to urban air pollution with higher traffic emissions and its health risks still face several challenges, such as intensive computation of air pollution modeling and the limited availability of personal activity data. The macroscopic health effects can be transmitted to the whole population for personal prevention via air quality health index (AQHI), but the possibility risk index of the specific allergic diseases is still lacking. This interdisciplinary study aims at evaluating the forecasted results of high-resolution air quality with updated traffic emissions and accessing the potential impacts of outdoor pollution on morbidity of rhinitis for urban residents. A high-resolution modelling system (1 km × 1 km) containing the online traffic emission model (VEIN), meteorological and air quality model (WRF-CHIMERE) and the health impact module was developed. A new health index of Potential Morbidity Risk Index (PMRI) was further established using higher resolution health risk coefficients of major air pollutants on allergic rhinitis, and different methods (with/without considering population distributions) targeting different user groups (residents, hospitals and health administrations) were calculated and analyzed. Operational forecasted results of hourly PMRI can be further combined with online map services to serve as an effective tool for patients with allergic rhinitis to arrange their daily activities so as to avoid acute exacerbation. The forecasted PMRIs accessible to the public will also be beneficial for the public health administrations in planning the medical resource and improving the outpatient efficiency.

Cisplatin-induced ototoxicity is one of the common side effects during its treatment and there are no effective measures to prevent it. Our study aimed to investigate the effect of ACSL4-catalyzed lipid peroxidation on cisplatin-induced hearing loss and its possible protective mechanisms. We used a variety of cisplatin ototoxicity models, including HEI-OC1 cell line, cochlear explants, and ET4 GFP+ zebrafish. After measuring the experimental concentrations of cisplatin by CCK8 assay and immunofluorescence, respectively, we examined the levels of lipid peroxidation by MDA content, 4-HNE content, and C11-BODIPY (581/591) probe. Then, we used two ferroptosis inhibitors, FER-1, and Vit-E to protect hair cells. We found that cisplatin significantly increased the levels of lipid peroxidation and that this process can be resisted by the ferroptosis inhibitors. Afterwards, we performed metabolomic assays on the cisplatin-treated hair cells. The metabolite levels were significantly altered in the experimental group compared to the control group, and the highest degree of change was observed in the glutathione metabolic pathway and the arachidonic acid metabolic pathway. Therefore, we screened the key enzymes on the arachidonic acid metabolic pathway in the hair cells after cisplatin treatment and found that ACSL4 had the greatest regulatory value. Further, we reduced the level of lipid peroxide in hair cells by specifically inhibiting the expression of ACSL4, which protected hair cells from cisplatin damage at source. In conclusion, the lipid peroxidation process regulated by ACSL4 may be an important factor contributing to the sensitivity of hair cells to cisplatin. Inhibition of ACSL4 expression may be an effective preventive measure against cisplatin ototoxicity.

This study analyses the main techniques for constructing a three-dimensional (3D) digital core, and summarizes the advantages and disadvantages of each reconstruction technique. The direction for the development of reconstruction technology for 3D digital cores is also proposed. The integration of multiscale, multicomponent, and nanoscale technology under different resolutions will play a significant role in future research efforts surrounding the physical properties of 3D digital cores. This study also introduces the main evaluation methods of digital cores, while analyzing and comparing the applicable scenarios of each method. The results of the pore statistics method, based on the seed filling algorithm, can be used as a new and effective evaluation method for the 3D reconstruction of digital cores.

Background The triglyceride glucose (TyG) index, which is a new surrogate indicator of insulin resistance (IR), is thought to be associated with many diseases, such as cardiovascular disease, but its relationship with cerebrovascular disease is still controversial. Methods The PubMed, EMBASE, Cochrane Library, Web of Science and Medline databases were searched until March 2022 to evaluate the association between the TyG index and cerebrovascular disease risk. A random‒effects model was used to calculate the effect estimates and 95% confidence intervals (CIs). Results A total of 19 cohort studies and 10 case‒control/cross‒sectional studies were included in our study, which included 11,944,688 participants. Compared with a low TyG index, a higher TyG index increased the risk of cerebrovascular disease (RR/HR = 1.22, 95% CI [1.14, 1.30], P <  0.001; OR = 1.15, 95% CI [1.07, 1.23], P <  0.001). Furthermore, the results of the dose-response analysis of the cohort study demonstrated that the risk of cerebrovascular disease increased by 1.19 times per 1 mg/dl increment of the TyG index (relative risk = 1.19, 95% CI [1.13,1.25], P <  0.001). Conclusion TyG index is related to cerebrovascular disease. More data and basic research are needed to confirm the association.

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

Background Over the past decades, extensive comparative mapping research has been performed in the plant family Solanaceae. The recent identification of a large set of single-copy conserved orthologous (COSII) markers has greatly accelerated comparative mapping studies among major solanaceous species including tomato, potato, eggplant, pepper and diploid Nicotiana species (as well as tetraploid tobacco). The large amount of comparative data now available for these species provides the opportunity to describe the overall patterns of chromosomal evolution in this important plant family. The results of this investigation are described herein. Results We combined data from multiple COSII studies, and other comparative mapping studies performed in tomato, potato, eggplant, pepper and diploid Nicotiana species, to deduce the features and outcomes of chromosomal evolution in the Solanaceae over the past 30 million years. This includes estimating the rates and timing of chromosomal changes (inversions and translocations) as well as deducing the age of ancestral progenitor species and predicting their genome configurations. Conclusions The Solanaceae has experienced chromosomal changes at a modest rate compared with other families and the rates are likely conserved across different lineages of the family. Chromosomal inversions occur at a consistently higher rate than do translocations. Further, we find evidences for non-random positioning of the chromosomal rearrangement breakpoints. This finding is consistent with the similar finding in mammals, where hot spots for chromosomal breakages have apparently played a significant role in shaping genome evolution. Finally, by utilizing multiple genome comparisons we were able to reconstruct the most likely genome configuration for a number of now-extinct progenitor species that gave rise to the extant solanaceous species used in this research. The results from this study provide the first broad overview of chromosomal evolution in the family Solanaceae, and one of the most detailed thus far for any family of plants.

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

Soil moisture is a key factor in the water and heat exchange and energy transformation of the ecological systems and is of critical importance to the accurate obtainment of the soil moisture content for supervising water resources and protecting regional and global eco environments. In this study, we selected the soil moisture monitoring networks of Naqu, Maqu, and Tianjun on the Qinghai–Tibetan Plateau as the research areas, and we established a database of surface microwave scattering with the AIEM (advanced integral equation model) and the mathematical expressions for the backscattering coefficient, soil moisture, and surface roughness of the VV and VH polarizations.We proposed the soil moisture retrieval models of empirical and machine learnings algorithms (backpropagation neural network (BPNN), support vector machine (SVM), K-nearest neighbors (KNN), and random forest (RF)) for the ascending and descending orbits using Sentinel-1 and measurement data, and we also validated the accuracies of the retrieval model in the research areas. According to the results, there is a substantial logarithmic correlation among the backscattering coefficient, soil moisture, and combined roughness. Generally, we can use empirical models to estimate the soil moisture content, with an R² of 0.609, RMSE of 0.08, and MAE of 0.064 for the ascending orbit model and an R² of 0.554, RMSE of 0.086, and MAE of 0.071 for the descending orbit model. The soil moisture contents are underestimated when the volumetric water content is high. The soil moisture retrieval accuracy is improved with machine learning algorithms compared to the empirical model, and the performance of the RF algorithm is superior to those of the other machine learning algorithms. The RF algorithm also achieved satisfactory performances for the Maqu and Tianjun networks. The accuracies of the inversion models for the ascending orbit in the three soil moisture monitoring networks were better than those for the descending orbit.