SPFS: SNR peak-based frequency selection method to alleviate resolution degradation in MPI real-time imaging.

OBJECTIVE: The primary objective of this study is to address the reconstruction time challenge in Magnetic Particle Imaging (MPI) by introducing a novel approach named SNR-Peak-Based Frequency Selection (SPFS). The focus is on improving spatial resolution without compromising reconstruction speed, thereby enhancing the clinical potential of MPI for real-time imaging. APPROACH: To overcome the trade-off between reconstruction time and spatial resolution in MPI, the researchers propose SPFS as an innovative frequency selection method. Unlike conventional SNR-based selection, SPFS prioritizes frequencies with Signal-to-Noise Ratio (SNR) peaks that capture crucial system matrix information. This adaptability to varying quantities of selected frequencies enhances versatility in the reconstruction process. The study compares the spatial resolution of MPI reconstruction using both SNR-based and SPFS frequency selection methods, utilizing simulated and real device data. MAIN RESULTS: The research findings demonstrate that the SPFS approach substantially improves image resolution in Magnetic Particle Imaging, especially when dealing with a limited number of frequency components. By focusing on SNR peaks associated with critical system matrix information, SPFS mitigates the spatial resolution degradation observed in conventional SNR-based selection methods. The study validates the effectiveness of SPFS through the assessment of MPI reconstruction spatial resolution using both simulated and real device data, highlighting its potential to address a critical limitation in the field. SIGNIFICANCE: The introduction of SNR-Peak-Based Frequency Selection (SPFS) represents a significant breakthrough in MPI technology. The method not only accelerates reconstruction time but also enhances spatial resolution, thus expanding the clinical potential of MPI for various applications. The improved real-time imaging capabilities of MPI, facilitated by SPFS, hold promise for advancements in drug delivery, plaque assessment, tumor treatment, cerebral perfusion evaluation, immunotherapy guidance, and in vivo cell tracking.

Glutathione Depletion-Induced ROS/NO Generation for Cascade Breast Cancer Therapy and Enhanced Anti-Tumor Immune Response.

Introduction: As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@Cu2O@L-Arg (BCL) co-assembly of cuprous oxide (Cu2O) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy. Methods: Cu2O particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions. In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated. Results: Cu2O was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration. Discussion: BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.

Chalcogen Atom-Modulated Croconaine for Efficient NIR-II Photothermal Theranostics.

Organic dye-based agents with near-infrared (NIR)-II absorption have great potential for cancer theranostics because of the deeper tissue penetration and good biocompatibility. However, proper design is required to develop NIR-II-absorbing dyes with good optical properties. We proposed to construct chalcogen atom-modulated croconaine for NIR-II light-triggered photothermal theranostics. By introducing different chalcogen atoms (O, S, Se, or Te) into the structure of croconaine, the light absorption of croconaine can be precisely regulated from the NIR-I to the NIR-II range due to the heavy-atom effect. Especially, Te-substituted croconaine (CRTe) and its nanoformulations exhibit superior NIR-II responsiveness, a high photothermal conversion efficiency (70.6%), and good photostability. With their favorable tumor accumulation, CRTe-NPs from tumor regions can be visualized by NIR-II optoacoustic systems with high resolution and high contrast; meanwhile, their superior photothermal performance also contributes to efficient cell killing and tumor elimination upon 1064 nm laser irradiation. Therefore, this work provides an efficient strategy for the molecular design of NIR-II organic photothermal agents.

Kinematic analysis in post-stroke patients with moderate to severe upper limb paresis and non-disabled controls.

BACKGROUND: Kinematic analysis has been recommended to quantify the upper limb motor function after stroke. However, previous studies have rarely reported the kinematic data of the post-stroke patients with moderate to severe upper limb paresis due to the poor accomplishment of the complex tasks. METHODS: 27 post-stroke individuals and 20 non-disabled people participated in the study. The trunk and upper limb movements during the Hand-to-mouth task were captured by the motion capture system and upper extremity kinematic analysis software automatically. The subgroup analysis within stroke group were conducted layering by the Fugl-Meyer Assessment for Upper Extremity scores (severe: 16-31; moderate: 32-50). FINDINGS: The paretic upper limbs in the stroke group tended to use more trunk and shoulder compensatory strategies to offset the impact of spasticity and weakness compared with non-disabled controls. The less-affected limbs in the stroke group also showed abnormal kinematic data. There were significant differences between the kinematic metrics of severe and moderate subgroups. INTERPRETATION: The Hand-to-mouth task is a good and feasible option for kinematic analysis of these patients. It is essential to layer the severity of the paresis and put more emphasis on trunk movements in the future kinematic studies.

Association Between Serum 25-Hydroxyvitamin D and Trichomonas vaginalis Infection Among American Adults: NHANES 2013-2016.

BACKGROUND: Previous studies have suggested that vitamin D may possess anti-infection properties, but the relationship between vitamin D and Trichomonas vaginalis infection remains unexplored. METHODS: Using data from the National Health and Nutrition Examination Survey between 2013 and 2016, we conducted multivariate regression analyses and subgroup analyses to investigate the association between 25-hydroxyvitamin D (25[OH]D) levels and T. vaginalis infection, ensuring the robustness of our results. RESULTS: The final sample included data from 4318 individuals aged 20 to 59 years, among which 92 were diagnosed with T. vaginalis infection. For every 10 nmol/L increase in serum 25(OH)D level, there was a 22% reduction in the likelihood of T. vaginalis infection incidence (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69-0.90). Similarly, higher concentration tertiles demonstrated relatively lower infection ratios compared with the tertile with the lowest 25(OH)D concentration (aOR, 0.54 [95% CI, 0.30-0.95; P = 0.030] for T2; aOR, 0.23 [95% CI, 0.09-0.61; P < 0.001] for T3). CONCLUSIONS: Our cross-sectional study indicates a negative association between 25(OH)D levels and the prevalence of T. vaginalis infection. However, further high-quality evidence is needed to establish a causal relationship between 25(OH)D levels and T. vaginalis infection, as well as to evaluate the potential role of vitamin D supplementation in preventing T. vaginalis infection.

A KDELR-mediated ER-retrieval system modulates mitochondrial functions via the unfolded protein response in fission yeast.

KDELR (Erd2 [ER retention defective 2] in yeasts) is a receptor protein that retrieves endoplasmic reticulum (ER)-resident proteins from the Golgi apparatus. However, the role of the KDELR-mediated ER-retrieval system in regulating cellular homeostasis remains elusive. Here, we show that the absence of Erd2 triggers the unfolded protein response (UPR) and enhances mitochondrial respiration and reactive oxygen species in an UPR-dependent manner in the fission yeast Schizosaccharomyces pombe. Moreover, we perform transcriptomic analysis and find that the expression of genes related to mitochondrial respiration and the tricarboxylic acid cycle is upregulated in a UPR-dependent manner in cells lacking Erd2. The increased mitochondrial respiration and reactive oxygen species production is required for cell survival in the absence of Erd2. Therefore, our findings reveal a novel role of the KDELR-Erd2-mediated ER-retrieval system in modulating mitochondrial functions and highlight its importance for cellular homeostasis in the fission yeast.

Summary of biological research on hepatoblastoma: a scoping review.

Background: Hepatoblastoma is the most prevalent primary hepatic malignancy in children, comprising 80% of pediatric hepatic malignancies and 1% of all pediatric malignancies. However, traditional treatments have proven inadequate in effectively curing hepatoblastoma, leading to a poor prognosis. Methods: A literature search was conducted on multiple electronic databases (PubMed and Google Scholar). A total of 86 articles were eligible for inclusion in this review. Result: This review aims to consolidate recent developments in hepatoblastoma research, focusing on the latest advances in cancer-associated genomics, epigenetic studies, transcriptional programs and molecular subtypes. We also discuss the current treatment approaches and forthcoming strategies to address cancer-associated biological challenges. Conclusion: To provide a comprehensive summary of the molecular mechanisms associated with hepatoblastoma occurrence, this review highlights three key aspects: genomics, epigenetics, and transcriptomics. Our review aims to facilitate the exploration of novel molecular mechanisms and the development of innovative clinical treatment strategies for hepatoblastoma.

Self-Supplied Reactive Oxygen Species-Responsive Mitoxantrone Polyprodrug for Chemosensitization-Enhanced Chemotherapy under Moderate Hyperthermia.

Currently, the secondary development and modification of clinical drugs has become one of the research priorities. Researchers have developed a variety of TME-responsive nanomedicine carriers to solve certain clinical problems. Unfortunately, endogenous stimuli such as reactive oxygen species (ROS), as an important prerequisite for effective therapeutic efficacy, are not enough to achieve the expected drug release process, therefore, it is difficult to achieve a continuous and efficient treatment process. Herein, a self-supply ROS-responsive cascade polyprodrug (PMTO) is designed. The encapsulation of the chemotherapy drug mitoxantrone (MTO) in a polymer backbone could effectively reduce systemic toxicity when transported in vivo. After PMTO is degraded by endogenous ROS of the TME, another part of the polyprodrug backbone becomes cinnamaldehyde (CA), which can further enhance intracellular ROS, thereby achieving a sustained drug release process. Meanwhile, due to the disruption of the intracellular redox environment, the efficacy of chemotherapy drugs is enhanced. Finally, the anticancer treatment efficacy is further enhanced due to the mild hyperthermia effect of PMTO. In conclusion, the designed PMTO demonstrates remarkable antitumor efficacy, effectively addressing the limitations associated with MTO.

Combination of time domain-system matrix and x-space methods to reconstruct magnetic particle images with isotropic resolution.

Objective. Imaging of superparamagnetic iron oxide nanoparticles based on their non-linear response to alternating magnetic fields shows promise for imaging cells and vasculature in healthy and diseased tissue. Such imaging can be achieved through x-space reconstruction typically along a unidirectional Cartesian trajectory, which rapidly convolutes the particle distribution with a 'anisotropic blurring' point spread function (PSF), leading to images with anisotropic resolution.Approach. Here we propose combining the time domine-system matrix and x-space reconstruction methods into a forward model, where the output of the forward model is the PSF-blurred x-space reconstructed image. We then treat the blur as an inverse problem solved by Kaczmarz iteration.Main results. After we have proposed the method optimization, the normal resolution of simulation and device images has been increased from 3.5 mm and 5.25 mm to 1.5 mm and 3.25 mm, which has reached the level in the tangential resolution. Quantitative indicators of image quality such as PSNR and SSIM have also been greatly improved.Significance. Simulation and imaging of real phantoms indicate that our approach provides better isotropic resolution and image quality than the x-space method alone or other methods for removing PSF blur. Using our proposed method to optimize the image quality of x-space reconstructed images using unidirectional Cartesian trajectories, it will promote the clinical application of MPI in the future.

Spider-Silk-Inspired Tough, Self-Healing, and Melt-Spinnable Ionogels.

As stretchable conductive materials, ionogels have gained increasing attention. However, it still remains crucial to integrate multiple functions including mechanically robust, room temperature self-healing capacity, facile processing, and recyclability into an ionogel-based device with high potential for applications such as soft robots, electronic skins, and wearable electronics. Herein, inspired by the structure of spider silk, a multilevel hydrogen bonding strategy to effectively produce multi-functional ionogels is proposed with a combination of the desirable properties. The ionogels are synthesized based on N-isopropylacrylamide (NIPAM), N, N-dimethylacrylamide (DMA), and ionic liquids (ILs) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMI][TFSI]). The synergistic hydrogen bonding interactions between PNIPAM chains, PDMA chains, and ILs endow the ionogels with improved mechanical strength along with fast self-healing ability at ambient conditions. Furthermore, the synthesized ionogels show great capability for the continuous fabrication of the ionogel-based fibers using the melt-spinning process. The ionogel fibers exhibit spider-silk-like features with hysteresis behavior, indicating their excellent energy dissipation performance. Moreover, an interwoven network of ionogel fibers with strain and thermal sensing performance can accurately sense the location of objects. In addition, the ionogels show great recyclability and processability into different shapes using 3D printing. This work provides a new strategy to design superior ionogels for diverse applications.

Selexipag for the Treatment of Pediatric Pulmonary Hypertension: A Systematic Review.

PURPOSE: To systematically evaluate the safety, dosing regimen, and efficacy of selexipag for pediatric patients with pulmonary hypertension (PH). METHODS: A literature search of the electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar was performed from inception through February 28, 2023. Two reviewers independently searched and evaluated the quality of the studies and pooled data when appropriate. Full-text articles of studies of children diagnosed with PH and treated with selexipag were eligible. Pediatric patients with PH were classified into 2 groups: the add-on therapy group, in which selexipag was used as a third therapy in addition to the baseline treatment, and the transition therapy group, in which patients were switched from parenteral prostacyclin analogs to selexipag. FINDINGS: Fourteen studies involving 58 pediatric patients with PH were included. All studies were either case reports or case series. Overall, 30 and 28 patients were in the add-on and transition therapy groups, respectively. In both groups, selexipag was initially administered as 50-200 µg twice daily and titrated to a tolerated dosage of 200-1,600 µg twice daily. Prostacyclin analogs were simultaneously weaned for patients in the transition group. In the add-on therapy group, 16 patients (80.0%) were at low risk of the World Health Organization functional class (WHO FC I/II), 12 (76.9%) were at low risk of the 6-minute walk distance (6MWD; >350 m), and 21 (95.5%) were at low risk of the pulmonary vascular resistance index (PVRi; <20 WU/m2). Furthermore, N-terminal pro-brain natriuretic peptide and mean pulmonary arterial pressure were significantly improved. More than 70% of patients experienced common tolerable side effects, such as headache, nausea, and diarrhea. In the transition therapy group, 5 patients (55.6%) were at low risk according to WHO FC I/II, 6 (66.7%) were at low risk according to 6MWD, and 14 (87.5) were at low risk according to PVRi; however, selexipag had no significant effect on their hemodynamic parameters. Additionally, more than 80% of patients experienced no side effects. IMPLICATIONS: Selexipag as add-on therapy or for transition from prostacyclin analogs may have a favorable safety profile and potential efficacy for pediatric patients with PH. Further high-quality evidence of the efficacy and safety of selexipag for the treatment of pediatric PH is warranted.

Continuous Melt Spinning of Adaptable Covalently Cross-Linked Self-Healing Ionogel Fibers for Multi-Functional Ionotronics.

Stretchable conductive fibers play key roles in electronic textiles, which have substantial improvements in terms of flexibility, breathability, and comfort. Compared to most existing electron-conductive fibers, ion-conductive fibers are usually soft, stretchable, and transparent, leading to increasing attention. However, the integration of desirable functions including high transparency, stretchability, conductivity, solvent resistance, self-healing ability, processability, and recyclability remains a challenge to be addressed. Herein, a new molecular strategy based on dynamic covalent cross-linking networks is developed to enable continuous melt spinning of the ionogel fiber with the aforementioned properties. As a proof of concept, adaptable covalently cross-linked ionogel fibers based on dimethylglyoximeurethane (DOU) groups (DOU-IG fiber) are prepared. The resultant DOU-IG fiber exhibited high transparency (>93%), tensile strength (0.76 MPa), stretchability (784%), and solvent resistance. Owing to the dynamic of DOU groups, the DOU-IG fiber shows high healing performance using near-infrared light. Taking advantage of DOU-IG fibers, multifunctional ionotronics with the integration of several desirable functionalities including sensor, triboelectric nanogenerator, and electroluminescent display are fabricated and used for motion monitoring, energy harvesting, and human-machine interaction. It is believed that these DOU-IG fibers are promising for fabricating the next generation of electronic textiles and other wearable electronics.

Tumor-immune microenvironment and NRF2 associate with clinical efficacy of PD-1 blockade combined with chemotherapy in lung squamous cell carcinoma.

The RATIONALE-307 study (ClinicalTrials.gov: NCT03594747) demonstrates prolonged progression-free survival (PFS) with first-line tislelizumab plus chemotherapy versus chemotherapy in advanced lung squamous cell carcinoma (LUSC; N = 360). Here we describe an immune-related gene expression signature (GES), composed of genes involved in both innate and adaptive immunity, that appears to differentiate tislelizumab plus chemotherapy PFS benefit versus chemotherapy. In contrast, a tislelizumab plus chemotherapy PFS benefit is observed regardless of programmed death ligand 1 (PD-L1) expression or tumor mutational burden (TMB). Genetic analysis reveals that NRF2 pathway activation is enriched in PD-L1positive and TMBhigh patients. NRF2 pathway activation is negatively associated with PFS, which affects efficacy outcomes associated with PD-L1 and TMB status, impairing their predictive potential. Mechanistic studies demonstrate that NRF2 directly mediates PD-L1 constitutive expression independent of adaptive PD-L1 regulation in LUSC. In summary, the GES is an immune signature that might identify LUSC patients likely to benefit from first-line tislelizumab plus chemotherapy.

Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial.

INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.

Prevalence of dry eye during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: During the COVID-19 pandemic, many people devoted longer time to screen viewing due to the need for study, work, and online social activities, instead of outdoor activities, which may have led to an increase in dry eye symptoms. This study aimed to evaluate the prevalence of dry eye during the COVID-19 pandemic. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were searched from January 1, 2020 to October 20, 2022. Cross-sectional surveys on dry eye prevalence conducted after January 1, 2020 were included. Two review authors independently performed data extraction and assessed study quality. The random-effects model was used to analyze the prevalence of dry eye, and the odds ratio was used to assess the strength of the association between variables. Subgroup analysis was performed to detect heterogeneity, the leave-one-out method for sensitivity analysis, and the Egger test for publication bias. RESULTS: A total of eleven studies with 15692 individuals met the eligibility criteria. The prevalence of dry eye during the COVID-19 pandemic was 61.0% (95%CI: 51.8%-70.2%) globally and 56.7% (95%CI: 45.3%-68.1%) in Asia. The prevalence of dry eye had significant differences in sex and visual display time, with higher prevalence among females and visual display time of more than 4 hours per day. Subgroup analysis was performed based on diagnostic tools, study population, and average age. A significant difference was found in diagnostic tools, but no significant change in heterogeneity (P<0.05). The leave-one-out method showed stable results, and the Egger test identified no significant publication bias. CONCLUSION: The prevalence of dry eye during the COVID-19 pandemic is significantly higher than before, and a higher prevalence is found among females and those having a visual display time of more than 4 hours per day.

DERnet: a deep neural network for end-to-end reconstruction in magnetic particle imaging.

Objective. Magnetic particle imaging (MPI) shows potential for contributing to biomedical research and clinical practice. However, MPI images are effectively affected by noise in the signal as its reconstruction is an ill-posed inverse problem. Thus, effective reconstruction method is required to reduce the impact of the noise while mapping signals to MPI images. Traditional methods rely on the hand-crafted data-consistency (DC) term and regularization term based on spatial priors to achieve noise-reducing and reconstruction. While these methods alleviate the ill-posedness and reduce noise effects, they may be difficult to fully capture spatial features.Approach. In this study, we propose a deep neural network for end-to-end reconstruction (DERnet) in MPI that emulates the DC term and regularization term using the feature mapping subnetwork and post-processing subnetwork, respectively, but in a data-driven manner. By doing so, DERnet can better capture signal and spatial features without relying on hand-crafted priors and strategies, thereby effectively reducing noise interference and achieving superior reconstruction quality.Main results. Our data-driven method outperforms the state-of-the-art algorithms with an improvement of 0.9-8.8 dB in terms of peak signal-to-noise ratio under various noise levels. The result demonstrates the advantages of our approach in suppressing noise interference. Furthermore, DERnet can be employed for measured data reconstruction with improved fidelity and reduced noise. In conclusion, our proposed method offers performance benefits in reducing noise interference and enhancing reconstruction quality by effectively capturing signal and spatial features.Significance. DERnet is a promising candidate method to improve MPI reconstruction performance and facilitate its more in-depth biomedical application.

SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.

BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear. METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting. RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more. CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. METHODS: RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. RESULTS: The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. CONCLUSION: We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

A juvenile mouse model of anti-N-methyl-D-aspartate receptor encephalitis by active immunization.

Introduction: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune encephalitis, and it is associated with psychosis, dyskinesia, and seizures. Anti-NMDAR encephalitis (NMDARE) in juveniles and adults presents different clinical charactreistics. However, the pathogenesis of juvenile anti-NMDAR encephalitis remains unclear, partly because of a lack of suitable animal models. Methods: We developed a model of juvenile anti-NMDAR encephalitis using active immunization with an amino terminal domain peptide from the GluN1 subunit (GluN1356 - 385) against NMDARs in 3-week-old female C57BL/6J mice. Results: Immunofluorescence staining suggested that autoantibody levels in the hippocampus increased, and HEK-293T cells staining identified the target of the autoantibodies as GluN1, suggesting that GluN1-specific immunoglobulin G was successfully induced. Behavior assessment showed that the mice suffered significant cognition impairment and sociability reduction, which is similar to what is observed in patients affected by anti-NMDAR encephalitis. The mice also exhibited impaired long-term potentiation in hippocampal CA1. Pilocarpine-induced epilepsy was more severe and had a longer duration, while no spontaneous seizures were observed. Conclusion: The juvenile mouse model for anti-NMDAR encephalitis is of great importance to investigate the pathological mechanism and therapeutic strategies for the disease, and could accelerate the study of autoimmune encephalitis.