Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that encodes numerous cellular homologs, including cyclin D, G protein-coupled protein, interleukin-6, and macrophage inflammatory proteins 1 and 2. KSHV vCyclin encoded by ORF72, is the homolog of cellular cyclinD2. KSHV vCyclin can regulate virus replication and cell proliferation by constitutively activating cellular cyclin-dependent kinase 6 (CDK6). However, the regulatory mechanism of KSHV vCyclin has not been fully elucidated. In the present study, we identified a host protein named protein arginine methyltransferase 5 (PRMT5) that interacts with KSHV vCyclin. We further demonstrated that PRMT5 is upregulated by latency-associated nuclear antigen (LANA) through transcriptional activation. Remarkably, knockdown or pharmaceutical inhibition (using EPZ015666) of PRMT5 inhibited the cell cycle progression and cell proliferation of KSHV latently infected tumor cells. Mechanistically, PRMT5 methylates vCyclin symmetrically at arginine 128 and stabilizes vCyclin in a methyltransferase activity-dependent manner. We also show that the methylation of vCyclin by PRMT5 positively regulates the phosphorylate retinoblastoma protein (pRB) pathway. Taken together, our findings reveal an important regulatory effect of PRMT5 on vCyclin that facilitates cell cycle progression and proliferation, which provides a potential therapeutic target for KSHV-associated malignancies.

Study on the mechanism of macrophages activated by phosphoesterified rehmanniae polysaccharide on human gastric cancer cells.

Gastric cancer(GC)is one of the most common gastrointestinal malignant tumors in the world, requiring the development of novel therapeutic agents with reduced toxicity. Rehmannia polysaccharide (RPS) possesses immunomodulatory and anti-tumor properties, yet its efficacy is suboptimal. To enhance its biological activity, we subjected RPS to molecular modifications, resulting in phosphorylated Rehmannia polysaccharides (P-RPS). Using the mixed phosphate method, we synthesized P-RPS and optimized the synthesis conditions through a combination of single-factor and response surface methodologies. In vitro studies on P-RPS's anti-tumor activity showed no direct influence on the viability of GC cells. However, P-RPS induced the transformation of PMA-activated THP-1 cells into the M1 phenotype. We collected conditioned medium (CM) of THP-1 cells to stimulate gastric cancer cells and CM-P-RPS significantly promoted apoptosis of gastric cancer cells and inhibited cell proliferation, and reduced cell migration. Mechanistically, CM-P-RPS inhibits the Wnt/ß-catenin signaling pathway through LGR6, leading to the suppression of tumor growth. Furthermore, P-RPS demonstrated a significant inhibitory effect on tumor growth in vivo, suggesting its potential as a promising therapeutic agent for GC treatment.

Constant-pH Simulations with the Polarizable Atomic Multipole AMOEBA Force Field.

Accurately predicting protein behavior across diverse pH environments remains a significant challenge in biomolecular simulations. Existing constant-pH molecular dynamics (CpHMD) algorithms are limited to fixed-charge force fields, hindering their application to biomolecular systems described by permanent atomic multipoles or induced dipoles. This work overcomes these limitations by introducing the first polarizable CpHMD algorithm in the context of the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) force field. Additionally, our implementation in the open-source Force Field X (FFX) software has the unique ability to handle titration state changes for crystalline systems including flexible support for all 230 space groups. The evaluation of constant-pH molecular dynamics (CpHMD) with the AMOEBA force field was performed on 11 crystalline peptide systems that span the titrating amino acids (Asp, Glu, His, Lys, and Cys). Titration states were correctly predicted for 15 out of the 16 amino acids present in the 11 systems, including for the coordination of Zn2+ by cysteines. The lone exception was for a HIS-ALA peptide where CpHMD predicted both neutral histidine tautomers to be equally populated, whereas the experimental model did not consider multiple conformers and diffraction data are unavailable for rerefinement. This work demonstrates the promise polarizable CpHMD simulations for pKa predictions, the study of biochemical mechanisms such as the catalytic triad of proteases, and for improved protein-ligand binding affinity accuracy in the context of pharmaceutical lead optimization.

RUNX3 inhibits KSHV lytic replication by binding to the viral genome and repressing transcription.

Kaposi's sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family, which can cause human malignancies including Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman's diseases. KSHV typically maintains a persistent latent infection within the host. However, after exposure to intracellular or extracellular stimuli, KSHV lytic replication can be reactivated. The reactivation process of KSHV triggers the innate immune response to limit viral replication. Here, we found that the transcriptional regulator RUNX3 is transcriptionally upregulated by the NF-κB signaling pathway in KSHV-infected SLK cells and B cells during KSHV reactivation. Notably, knockdown of RUNX3 significantly promotes viral lytic replication as well as the gene transcription of KSHV. Consistent with this finding, overexpression of RUNX3 impairs viral lytic replication. Mechanistically, RUNX3 binds to the KSHV genome and limits viral replication through transcriptional repression, which is related to its DNA- and ATP-binding ability. However, KSHV has also evolved corresponding strategies to antagonize this inhibition by using the viral protein RTA to target RUNX3 for ubiquitination and proteasomal degradation. Altogether, our study suggests that RUNX3, a novel host-restriction factor of KSHV that represses the transcription of viral genes, may serve as a potential target to restrict KSHV transmission and disease development.IMPORTANCEThe reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) from latent infection to lytic replication is important for persistent viral infection and tumorigenicity. However, reactivation is a complex event, and the regulatory mechanisms of this process are not fully elucidated. Our study revealed that the host RUNX3 is upregulated by the NF-κB signaling pathway during KSHV reactivation, which can repress the transcription of KSHV genes. At the late stage of lytic replication, KSHV utilizes a mechanism involving RTA to degrade RUNX3, thus evading host inhibition. This finding helps elucidate the regulatory mechanism of the KSHV life cycle and may provide new clues for the development of therapeutic strategies for KSHV-associated diseases.

[Recent progress in vestibular prosthesis].

Bilateral vestibulopathy（BVP） is one of the common diseases in the vestibular nervous system, with an incidence rate of about 4%-7% in the population, which can lead to a variety of body dysfunctions. At present, there are two main treatment methods for BVP. One is vestibular rehabilitation. However, only part of BVP patients can finally benefit from vestibular rehabilitation, and most patients will remain with permanent vestibular dysfunction. Benefiting from the maturity of cochlear implant technology, European and American countries took the lead in the development of vestibular prosthesis（VP） technology to restore the vestibular function in patients with BVP. This review will focus on the development history, principles, future applications and the related research progress of VP in China.

Unleashing the Potential of 1,3-Diketone Analogues as Selective LH2 Inhibitors.

Lysyl hydroxylase 2 (LH2) catalyzes the formation of highly stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), thus promoting lung cancer metastasis through its capacity to modulate specific types of collagen cross-links within the tumor stroma. Using 1 and 2 from our previous high-throughput screening (HTS) as lead probes, we prepared a series of 1,3-diketone analogues, 1-18, and identified 12 and 13 that inhibit LH2 with IC50's of approximately 300 and 500 nM, respectively. Compounds 12 and 13 demonstrate selectivity for LH2 over LH1 and LH3. Quantum mechanics/molecular mechanics (QM/MM) modeling indicates that the selectivity of 12 and 13 may stem from noncovalent interactions like hydrogen bonding between the morpholine/piperazine rings with the LH2-specific Arg661. Treatment of 344SQ WT cells with 13 resulted in a dose-dependent reduction in their migration potential, whereas the compound did not impede the migration of the same cell line with an LH2 knockout (LH2KO).

Impact of Learning Burnout on Mobile Phone Dependence Among Adolescents in Western China Under the "Double Reduction" Policy: The Mediating Role of Social Support.

Purpose: This paper investigated the prevalence of mobile phone dependence (MPD) and its associated with learning burnout under the "double reduction" policy among adolescents in Guizhou Province in western China. In addition, the influence of the mediating mechanism of social support on this relationship was investigated. Methods: The sample was collected from 16,216 adolescents in West China's Guizhou province, from December 2021 to January 2022 via multistage stratified random sampling. The Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) was used to assess the MPD, the Adolescent Student Burnout Scale (ASBI) was used to assess the learning burnout, and the Social Support Scale (SSS) was used to assess the social support. A hierarchical linear regression model was used to analyze the relationship between MPD, learning burnout, and social support. The mediating effect of social support between MPD and learning burnout was analyzed by structural equation model. Results: Prevalence of MPD was 26.4% among adolescents in Guizhou province in western China. After adjusting for confounding variables like demographics, multiple linear regression model has revealed that learning burnout positively predicted MPD and social support negatively predicted MPD. The structural equation model showed that 10.9% of the effect was explained by the mediating effect of social support. Conclusion: These findings could inform service delivery and policy formulation to reduce learning and avoid MPD in adolescents.

Development of AMOEBA Polarizable Force Field for Rare-Earth La3+ Interaction with Bioinspired Ligands.

Rare-earth metals (REMs) are crucial for many important industries, such as power generation and storage, in addition to cancer treatment and medical imaging. One promising new REM refinement approach involves mimicking the highly selective and efficient binding of REMs observed in relatively recently discovered proteins. However, realizing any such bioinspired approach requires an understanding of the biological recognition mechanisms. Here, we developed a new classical polarizable force field based on the AMOEBA framework for modeling a lanthanum ion (La3+) interacting with water, acetate, and acetamide, which have been found to coordinate the ion in proteins. The parameters were derived by comparing to high-level ab initio quantum mechanical (QM) calculations that include relativistic effects. The AMOEBA model, with advanced atomic multipoles and electronic polarization, is successful in capturing both the QM distance-dependent La3+-ligand interaction energies and experimental hydration free energy. A new scheme for pairwise polarization damping (POLPAIR) was developed to describe the polarization energy in La3+ interactions with both charged and neutral ligands. Simulations of La3+ in water showed water coordination numbers and ion-water distances consistent with previous experimental and theoretical findings. Water residence time analysis revealed both fast and slow kinetics in water exchange around the ion. This new model will allow investigation of fully solvated lanthanum ion-protein systems using GPU-accelerated dynamics simulations to gain insights on binding selectivity, which may be applied to the design of synthetic analogues.

Computational Investigation of a Series of Small Molecules as Potential Compounds for Lysyl Hydroxylase-2 (LH2) Inhibition.

The catalytic function of lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O2 tunnels, which aid in transporting one of the required cosubstrates into the active site. While LH2 can be a promising target to combat these diseases, efficacious inhibitors are still lacking. We have used computational simulations to investigate a series of 44 small molecules as lead compounds for LH2 inhibition. Tunneling analyses indicate the existence of several intramolecular tunnels. The lengths of the calculated O2-transporting tunnels in holoenzymes are relatively longer than those in the apoenzyme, suggesting that the ligands may affect the enzyme's structure and possibly block (at least partially) the tunnels. The sequence alignment analysis between LH enzymes from different organisms shows that all of the amino acid residues with the highest occurrence rate in the oxygen tunnels are conserved. Our results suggest that the enolate form of diketone compounds establishes stronger interactions with the Fe(II) in the active site. Branching the enolate compounds with functional groups such as phenyl and pyridinyl enhances the interaction with various residues around the active site. Our results provide information about possible leads for further LH2 inhibition design and development.

A novel risk score model based on fourteen chromatin regulators-based genes for predicting overall survival of patients with lower-grade gliomas.

Background: Low grade gliomas(LGGs) present vexatious management issues for neurosurgeons. Chromatin regulators (CRs) are emerging as a focus of tumor research due to their pivotal role in tumorigenesis and progression. Hence, the goal of the current work was to unveil the function and value of CRs in patients with LGGs. Methods: RNA-Sequencing and corresponding clinical data were extracted from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) database. A single-cell RNA-seq dataset was sourced from the Gene Expression Omnibus (GEO) database. Altogether 870 CRs were retrieved from the published articles in top academic journals. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were applied to construct the prognostic risk model. Patients were then assigned into high- and low-risk groups based on the median risk score. The Kaplan-Meier (K-M) survival curve and receiver operating characteristic curve (ROC) were performed to assess the prognostic value. Sequentially, functional enrichment, tumor immune microenvironment, tumor mutation burden, drug prediction, single cell analysis and so on were analyzed to further explore the value of CR-based signature. Finally, the expression of signature genes were validated by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR). Results: We successfully constructed and validated a 14 CRs-based model for predicting the prognosis of patients with LGGs. Moreover, we also found 14 CRs-based model was an independent prognostic factor. Functional analysis revealed that the differentially expressed genes were mainly enriched in tumor and immune related pathways. Subsequently, our research uncovered that LGGs patients with higher risk scores exhibited a higher TMB and were less likely to be responsive to immunotherapy. Meanwhile, the results of drug analysis offered several potential drug candidates. Furthermore, tSNE plots highlighting the magnitude of expression of the genes of interest in the cells from the scRNA-seq assay. Ultimately, transcription expression of six representative signature genes at the mRNA level was consistent with their protein expression changes. Conclusion: Our findings provided a reliable biomarker for predicting the prognosis, which is expected to offer new insight into LGGs management and would hopefully become a promising target for future research.

[Otitis media with antineutrophil cytoplasmic antibody-associated vasculitis].

Objective:To analyze clinical features, diagnosis and treatment of otitis media with antineutrophil cytoplasmic antibody（ANCA） -associated vasculitis（OMAAV）. Methods:This study reported three OMAAV patients and discussed the diagnosis and treatment of OMAAV combined with the recent literature. Results:Two males and one female were included. The age of these three patients ranged from 56 to 72 years. Their characteristics were as follows: ①tympanic membrane with granulation and bloody secretions in two patients; ②progressive bone-conducted hearing loss within a short period of time; ③facial palsy in two patients; ④the laboratory test of ANCA is positive; ⑤conventional treatment of otitis media is ineffective, while glucocorticoid combined with immunosuppressive therapy is effective. Conclusion:OMAAV is a rare disease and prone to misdiagnosis. Early diagnosis and treatment with corticosteroids and immunosuppressants are critical. Invasive tests and surgery during the active phase of OMAAV may aggravate symptoms and should be avoided.

[The working principle and prototype construction of the Chinese vestibular prosthesis].

Objective:To complete the working principle design and prototype construction of the Chinese multichannel vestibular prosthesis （CMVP） with independent intellectual property rights, and verify its working performance, so as to lay the foundation for the clinical promotion and application of CMVP. Methods:On the basis of previous research, the working principle of CMVP was constructed based on the information encoding principle of vestibular nervous system, and the circuit was designed according to the principle. Then, appropriate electronic components and software systems were selected to construct a CMVP prototype according to the design. Finally, the input and output characteristics of the CMVP prototype were verified through the performance test. Results:In the present study, a block diagram of the working principle of the CMVP was successfully designed and drawn, and the working principle was explained in detail according to the block diagram. Further, the circuit diagram of the CMVP was designed and drawn based on the working principle, then the selected electronic components and software systems were combined one by one to complete the construction of a prototype. Finally, the performance test for the prototype was completed, which showed that all stimulus electrodes of the prototype could output biphasic pulse current, and the frequency of biphasic pulse current was modulated by the spatial rotation data input sensed by a motion sensor. Conclusion:The working principle and circuit design of the CMVP are reasonable; the CMVP prototype in China has been successfully constructed; the spatial rotation motion sensing input and the modulated pulse current output are stable and reliable.

Inhibition of FAM83D displays antitumor effects in glioblastoma via down-regulation of the AKT/Wnt/ß-catenin pathway.

Up-regulation of family with sequence similarity 83 member D (FAM83D) has been acknowledged as a vital contributor for the carcinogenesis of numerous cancers. The relevance of FAM83D in glioblastoma (GBM), however, is not well understood. This current work aimed to determine the possible roles and mechanisms of FAM83D in GBM. By analyzing The Cancer Genome Atlas (TCGA) data, we found dramatic increases in FAM83D expression in GBM tissue. We also observed elevated levels of FAM83D in the clinical specimens of GBM. In vitro data showed that silencing FAM83D resulted in remarkable antitumor effects via inhibiting the proliferation, invasion and epithelial-mesenchymal transition of GBM cells. Moreover, the knockdown of FAM83D improved sensitivity to the chemotherapy drug temozolomide. In-depth mechanism research revealed that the silencing of FAM83D strikingly decreased the phosphorylation levels of AKT and glycogen synthase kinase-3ß, and prohibited activation of the Wnt/ß-catenin pathway. The suppression of AKT abolished FAM83D-mediated activation of the Wnt/ß-catenin pathway. The re-expression of ß-catenin reversed FAM83D-silencing-induced antitumor effects in GBM cells. In addition, GBM cells with FAM83D silencing exhibited reduced tumorigenic potential in vivo. Overall, the data from this work show that the inhibition of FAM83D displays antitumor effects in GBM via down-regulation of the AKT/Wnt/ß-catenin pathway and propose FAM83D as a new therapeutic target for GBM.

Long non-coding RNA AGAP2-AS1 promotes cell proliferation and invasion through regulating miR-193a-3p/LOXL4 axis in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy with highly mortality rate. Long non-coding RNA (lncRNA) AGAP2-AS1 is an identified oncogene in several types of cancers. However, the role of AGAP2-AS1 in LSCC remains unclear. The expression levels of AGAP2-AS1 in LSCC tissues and cell lines were measured using qRT-PCR. AGAP2-AS1 was knocked down in LSCC cells through transfection with siRNA-AGAP2-AS1. Cell proliferation and invasion were detected using MTT and transwell assays. Dual-luciferase reporter gene assay was performed to confirm the interaction with AGAP2-AS1 and downstream genes. Our results showed that AGAP2-AS1 expression was remarkably increased in human LSCC tissues and cell lines. Knockdown of AGAP2-AS1 significantly inhibited the proliferation and invasion of LSCC cells. In addition, AGAP2-AS1 sponged miR-193a-3p and regulated its expression in LSCC cells. Inhibition of miR-193a-3p reversed the effects of AGAP2-AS1 knockdown on LSCC cells. Furthermore, Lysyl oxidase-like 4 (LOXL4) was a target gene of miR-193a-3p and the role of miR-193a-3p was mediated by LOXL4. In conclusion, these findings suggest that knockdown of AGAP2-AS1 inhibited the proliferation and invasion of LSCC cells through regulating the miR-193a-3p/LOXL4 axis.

Hydrothermal Synthesis of Hierarchical SnO2 Nanostructures for Improved Formaldehyde Gas Sensing.

The indoor environment of buildings affects people's daily life. Indoor harmful gases include volatile organic gas and greenhouse gas. Therefore, the detection of harmful gas by gas sensors is a key method for developing green buildings. The reasonable design of SnO2-sensing materials with excellent structures is an ideal choice for gas sensors. In this study, three types of hierarchical SnO2 microspheres assembled with one-dimensional nanorods, including urchin-like microspheres (SN-1), flower-like microspheres (SN-2), and hydrangea-like microspheres (SN-3), are prepared by a simple hydrothermal method and further applied as gas-sensing materials for an indoor formaldehyde (HCHO) gas-sensing test. The SN-1 sample-based gas sensor demonstrates improved HCHO gas-sensing performance, especially demonstrating greater sensor responses and faster response/recovery speeds than SN-2- and SN-3-based gas sensors. The improved HCHO gas-sensing properties could be mainly attributed to the structural difference of smaller nanorods. These results further indicate the uniqueness of the structure of the SN-1 sample and its suitability as HCHO- sensing material.

Imaging sub-diffuse optical properties of cancerous and normal skin tissue using machine learning-aided spatial frequency domain imaging.

SIGNIFICANCE: Sub-diffuse optical properties may serve as useful cancer biomarkers, and wide-field heatmaps of these properties could aid physicians in identifying cancerous tissue. Sub-diffuse spatial frequency domain imaging (sd-SFDI) can reveal such wide-field maps, but the current time cost of experimentally validated methods for rendering these heatmaps precludes this technology from potential real-time applications. AIM: Our study renders heatmaps of sub-diffuse optical properties from experimental sd-SFDI images in real time and reports these properties for cancerous and normal skin tissue subtypes. APPROACH: A phase function sampling method was used to simulate sd-SFDI spectra over a wide range of optical properties. A machine learning model trained on these simulations and tested on tissue phantoms was used to render sub-diffuse optical property heatmaps from sd-SFDI images of cancerous and normal skin tissue. RESULTS: The model accurately rendered heatmaps from experimental sd-SFDI images in real time. In addition, heatmaps of a small number of tissue samples are presented to inform hypotheses on sub-diffuse optical property differences across skin tissue subtypes. CONCLUSION: These results bring the overall process of sd-SFDI a fundamental step closer to real-time speeds and set a foundation for future real-time medical applications of sd-SFDI such as image guided surgery.

Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264.7 Macrophages.

Macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in the immune system, performing pro-inflammatory and anti-inflammatory functions, respectively. Human THP-1 and mouse RAW264.7 cell line models have been widely used in various macrophage-associated studies, while the similarities and differences in protein expression profiles between the two macrophage models are still largely unclear. In this study, the protein expression profiles of M1 and M2 phenotypes from both THP-1 and RAW264.7 macrophages were systematically investigated using mass spectrometry-based proteomics. By quantitatively analyzing more than 5,000 proteins among different types of macrophages (M0, M1 and M2) from both cell lines, we identified a list of proteins that were uniquely up-regulated in each macrophage type and further confirmed 43 proteins that were commonly up-regulated in M1 macrophages of both cell lines. These results revealed considerable divergences of each polarization type between THP-1 and RAW264.7 macrophages. Moreover, the mRNA and protein expression of CMPK2, RSAD2, DDX58, and DHX58 were strongly up-regulated in M1 macrophages for both macrophage models. These data can serve as important resources for further studies of macrophage-associated diseases in experimental pathology using human and mouse cell line models.

[Outcome of otolith organ function after treatment of sudden sensorineural hearing loss].

Objective:This study aimed to assess the clinical practice value of ocular vestibular evoked myogenic potential（oVEMP） and cervical vestibular evoked myogenic potential（cVEMP） in monitoring the rehabilitation of vestibular function in patients with suddensen sorineural hearing loss（SSHL）. Method:Twenty-four patients with SSHL were retrospectively enrolled， showing no VEMP response on the affected side but exhibiting VEMP responses after therapies We analyzed the improvement and the restoration of hearing and the parameters of VEMP response. Result:After treatment, seven patients showed VEMP recovery, including three cases with both oVEMP and cVEMP recovery, three cases with oVEMP recovery, and one case with cVEMP recovery. Between VEMP recoved group and VEMP unrecoved group, before treatment, no significant difference was found in the thresholds of pure-tone audiometry（PTA）. However, after treatment, VEMP recoved group exhibited lower PTA thresholds and better PTA shift （P<0.01）. Multivariate analysis revealed that recovery of VEMP was the independent risk factor for the therapeutic effect of SSHL. Conclusion:The Combination of oVEMP and cVEMP is an objective tool for assessing vestibular otolithic end organ function during dynamic functional recovery in SSHL and the recovery of VEMP could predict the auditory improvement.

[Optimal design of neural modulation strategy of vestibular prosthesis].

Objective:To reveal the response characteristics of semicircular canal neurons（SCN） in the nonlinear perceptual interval, and to establish and screen out the precise SCN information coding model and function expression, which lays a foundation for the optimization and improvement of neuromodulation strategy of multichannel vestibular prosthesis. Method:The perceptual electrophysiological information data of the SCNs during the rotational stimulation was recorded in the nonlinear perceptual interval. The nonlinear least-squares algorithm was used to fit the electrophysiological information data to establish the linear-nonlinear models. The Akaike information criterion was used to calculate the goodness of fit of each model to determine the optimal expression function. Result:In the frequency experiment, the accurate information coding model of more than 85% of SCNs is a quadratic polynomial, and the frequency has no significant effect on the linear-nonlinear selection of the SCNs information coding model（P>0.05）. In the amplitude experiment, the accurate information coding model of more than 83.33% of SCNs is quadratic polynomial when the maximum angular velocity is>80 deg/s, and the amplitude has a significant effect on the linear-nonlinear selection of the SCNs information coding model（P=0.038）. Conclusion:The information coding models of SCN population in the nonlinear perceptual interval have two expressions, linear and nonlinear function, which is closely related to angular velocity. The quadratic polynomial function is more accurate and more advantageous and it can be used to design the precise neuromodulation strategy of multichannel vestibular prosthesis.

Self-assembled nucleo-tripeptide hydrogels provide local and sustained doxorubicin release.

Self-assembled nucleo-peptide hydrogels have a nanofibril structure composed of noncovalent molecular interactions between peptide groups as well as π-π stacking and Watson-Crick interactions via complementary nucleobases. These hydrogels have specific benefits for biomedical applications due to their DNA-like interactions in addition to the well-known advantages of peptide biomaterials: biocompatibility, extracellular matrix (ECM)-like structure, and bottom-up design. Inspired by the nucleobase stacking structure, we hypothesized that nucleo-peptides would be able to deliver the DNA-intercalating chemotherapeutic, doxorubicin (Dox) in a sustained manner when delivered locally to a solid tumor. Ade-FFF nucleo-peptide hydrogels were able to load a high concentration of Dox (1 mM) and demonstrated continuous release under in vitro degradation conditions. We adopted an in vivo tumor-bearing mouse model to evaluate the delivery of Dox by Ade-FFF hydrogels. We found that Dox-containing hydrogels reduced tumor growth and resulted in greater apoptosis-mediated cell death in the tumor as evidenced by caspase-3 expression. Pharmacokinetics and biodistribution studies also supported the observation that Dox delivery by an Ade-FFF hydrogel improves sustained delivery in the local tumor site. This study demonstrates the potential of self-assembled nucleo-peptides in biomedical applications by using their distinctive DNA-like structure.