Motor proteins, spermatogenesis and testis function.

The role of motor proteins in supporting intracellular transports of vesicles and organelles in mammalian cells has been known for decades. On the other hand, the function of motor proteins that support spermatogenesis is also well established since the deletion of motor protein genes leads to subfertility and/or infertility. Furthermore, mutations and genetic variations of motor protein genes affect fertility in men, but also a wide range of developmental defects in humans including multiple organs besides the testis. In this review, we seek to provide a summary of microtubule and actin-dependent motor proteins based on earlier and recent findings in the field. Since these two cytoskeletons are polarized structures, different motor proteins are being used to transport cargoes to different ends of these cytoskeletons. However, their involvement in germ cell transport across the blood-testis barrier (BTB) and the epithelium of the seminiferous tubules remains relatively unknown. It is based on recent findings in the field, we have provided a hypothetical model by which motor proteins are being used to support germ cell transport across the BTB and the seminiferous epithelium during the epithelial cycle of spermatogenesis. In our discussion, we have highlighted the areas of research that deserve attention to bridge the gap of research in relating the function of motor proteins to spermatogenesis.

A Review of Motor Brain-Computer Interfaces Using Intracranial Electroencephalography Based on Surface Electrodes and Depth Electrodes.

Brain-computer interfaces (BCIs) provide a communication interface between the brain and external devices and have the potential to restore communication and control in patients with neurological injury or disease. For the invasive BCIs, most studies recruited participants from hospitals requiring invasive device implantation. Three widely used clinical invasive devices that have the potential for BCIs applications include surface electrodes used in electrocorticography (ECoG) and depth electrodes used in Stereo-electroencephalography (SEEG) and deep brain stimulation (DBS). This review focused on BCIs research using surface (ECoG) and depth electrodes (including SEEG, and DBS electrodes) for movement decoding on human subjects. Unlike previous reviews, the findings presented here are from the perspective of the decoding target or task. In detail, five tasks will be considered, consisting of the kinematic decoding, kinetic decoding,identification of body parts, dexterous hand decoding, and motion intention decoding. The typical studies are surveyed and analyzed. The reviewed literature demonstrated a distributed motor-related network that spanned multiple brain regions. Comparison between surface and depth studies demonstrated that richer information can be obtained using surface electrodes. With regard to the decoding algorithms, deep learning exhibited superior performance using raw signals than traditional machine learning algorithms. Despite the promising achievement made by the open-loop BCIs, closed-loop BCIs with sensory feedback are still in their early stage, and the chronic implantation of both ECoG surface and depth electrodes has not been thoroughly evaluated.

Simulation and experimental study of gas-phase diffusion coefficient of selenium dioxide.

Improving the removal effect of selenium in wet flue gas desulfurization system is a key way to reduce the emission of selenium pollutants from coal-fired power plants. In order to clarify the removal mechanism of selenium pollutants in the desulfurization tower, it is necessary to obtain accurate selenium gas-phase diffusion coefficient. In this paper, molecular dynamics simulations were used to carry out theoretical calculations of gas-phase diffusion coefficients of SeO2 (the main form of selenium in coal combustion flue gas). The gas-phase diffusion coefficients of SeO2 in the range of 393 K-433 K were measured by a self-developed heavy metal gas diffusion coefficient testing device to verify the accuracy of the molecular dynamics calculations. Furthermore, the calculated gas-phase diffusion coefficients of SeO2 under typical binary and ternary components were obtained by correcting on the basis of Fuller's formula. Finally, a single-droplet absorption model for SeO2 was constructed and experiments were carried out to compare the effect of the gas-phase diffusion coefficient on the accuracy of the model calculations. The error of the model calculations was reduced from 8.09 % to 1.96 % after the correction. In this study, the gas-phase diffusion coefficient of SeO2 in the low-temperature range of coal-fired flue gas was obtained. This study can provide basic data for the development of selenium migration mechanism and control technology.

Plasma extracellular vesicles proteomics in meningioma patients.

Tumor derived Extracellular vesicles (EVs) in circulating system may contain tumor-specific markers, and EV detection in body fluids could become an important tool for early tumor diagnosis, prognosis assessment. Meningiomas are the most common benign intracranial tumors, few studies have revealed specific protein markers for meningiomas from patients' body fluids. In this study, using proximity labeling technology and non-tumor patient plasma as a control, we detected protein levels of EVs in plasma samples from meningioma patients before and after surgery. Through bioinformatics analysis, we discovered that the levels of EV count and protein count in meningioma patients were significantly higher than those in healthy controls, and were significantly decreased postoperatively. Among EV proteins in meningioma patients, the levels of MUC1, SIGLEC11, E-Cadherin, KIT, and TASCTD2 were found not only significantly elevated than those in healthy controls, but also significantly decreased after tumor resection. Moreover, using publicly available GEO databases, we verified that the mRNA level of MUC1, SIGLEC11, and CDH1 in meningiomas were significantly higher in comparison with normal dura mater tissues. Additionally, by analyzing human meningioma specimens collected in this study, we validated the protein levels of MUC1 and SIGLEC11 were significantly increased in WHO grade 2 meningiomas and were positively correlated with tumor proliferation levels. This study indicates that meningiomas secret EV proteins into circulating system, which may serve as specific markers for diagnosis, malignancy predicting and tumor recurrent assessment.

Speech decoding from stereo-electroencephalography (sEEG) signals using advanced deep learning methods.

Objective.Brain-computer interfaces (BCIs) are technologies that bypass damaged or disrupted neural pathways and directly decode brain signals to perform intended actions. BCIs for speech have the potential to restore communication by decoding the intended speech directly. Many studies have demonstrated promising results using invasive micro-electrode arrays and electrocorticography. However, the use of stereo-electroencephalography (sEEG) for speech decoding has not been fully recognized.Approach.In this research, recently released sEEG data were used to decode Dutch words spoken by epileptic participants. We decoded speech waveforms from sEEG data using advanced deep-learning methods. Three methods were implemented: a linear regression method, an recurrent neural network (RNN)-based sequence-to-sequence model (RNN), and a transformer model.Main results.Our RNN and transformer models outperformed the linear regression significantly, while no significant difference was found between the two deep-learning methods. Further investigation on individual electrodes showed that the same decoding result can be obtained using only a few of the electrodes.Significance.This study demonstrated that decoding speech from sEEG signals is possible, and the location of the electrodes is critical to the decoding performance.

PFOS-induced Sertoli cell injury through c-Jun N-terminal kinase (JNK) - a study by RNA-Seq.

Per- and polyfluoroalkyl substances (PFAS) are a family of "forever chemicals" including PFOS (perfluorooctane sulfonate). These toxic chemicals do not break down in the environment nor in our bodies. In the human body, PFOS and PFOA (perfluoroctanoic acid) have a half-life (T1/2) of about 4-5 years so low daily consumption of these chemicals can accumulate in the human body to a harmful level over a long period. Although the use of PFOS in consumer products was banned in the U.S. in 2022/2023, this forever chemical remains detectable in our tap water and food products. Every American tested has a high level of PFAS in their blood (https://cleanwater.org/pfas-forever-chemicals). In this report, we used a Sertoli cell blood-testis barrier (BTB) model with primary Sertoli cells cultured in vitro with an established functional tight junction (TJ)-permeability barrier that mimicked the BTB in vivo. Treatment of Sertoli cells with PFOS was found to perturb the TJ-barrier, which was the result of cytoskeletal disruption across the cell cytoplasm, disrupting actin and microtubule polymerization. These changes thus affected the proper localization of BTB-associated proteins at the BTB. Using RNA-Seq transcriptome profiling, bioinformatics analysis, and pertinent biochemical and cell biology techniques, it was discovered that PFOS-induced Sertoli cell toxicity through the c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase, SAPK) and its phosphorylated/active form p-JNK signaling pathway. More importantly, KB-R7943 mesylate (KB), a JNK/p-JNK activator, was capable of blocking PFOS-induced Sertoli cell injury, supporting the notion that PFOS-induced cell injury can possibly be therapeutically managed.

Preoperative diffusion tensor imaging: Fiber-trajectory-distribution-based tractography to identify facial nerve in vestibular schwannoma.

PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.

Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATAC-seq and scRNA-seq.

Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during meiosis, especially in prophase I, are limited. Here, we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes. This event, conserved in mice, involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset. Furthermore, we identified 282 transcriptional regulators (TRs) that underwent activation or deactivation subsequent to this process. Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes, while secreted ENHO signals may alter metabolic patterns in these cells. Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia (NOA). This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.

Wearable sensor devices can automatically identify the ON-OFF status of patients with Parkinson's disease through an interpretable machine learning model.

Introduction: Accurately and objectively quantifying the clinical features of Parkinson's disease (PD) is crucial for assisting in diagnosis and guiding the formulation of treatment plans. Therefore, based on the data on multi-site motor features, this study aimed to develop an interpretable machine learning (ML) model for classifying the "OFF" and "ON" status of patients with PD, as well as to explore the motor features that are most associated with changes in clinical symptoms. Methods: We employed a support vector machine with a recursive feature elimination (SVM-RFE) algorithm to select promising motion features. Subsequently, 12 ML models were constructed based on these features, and we identified the model with the best classification performance. Then, we used the SHapley Additive exPlanations (SHAP) and the Local Interpretable Model agnostic Explanations (LIME) methods to explain the model and rank the importance of those motor features. Results: A total of 96 patients were finally included in this study. The naive Bayes (NB) model had the highest classification performance (AUC = 0.956; sensitivity = 0.8947, 95% CI 0.6686-0.9870; accuracy = 0.8421, 95% CI 0.6875-0.9398). Based on the NB model, we analyzed the importance of eight motor features toward the classification results using the SHAP algorithm. The Gait: range of motion (RoM) Shank left (L) (degrees) [Mean] might be the most important motor feature for all classification horizons. Conclusion: The symptoms of PD could be objectively quantified. By utilizing suitable motor features to construct ML models, it became possible to intelligently identify whether patients with PD were in the "ON" or "OFF" status. The variations in these motor features were significantly correlated with improvement rates in patients' quality of life. In the future, they might act as objective digital biomarkers to elucidate the changes in symptoms observed in patients with PD and might be used to assist in the diagnosis and treatment of patients with PD.

Map-1a regulates Sertoli cell BTB dynamics through the cytoskeletal organization of microtubule and F-actin.

Microtubule-associated protein 1a (Map1a) is a microtubule (MT) regulatory protein that binds to the MT protofilaments in mammalian cells to promote MT stabilization. Maps work with MT cleavage proteins and other MT catastrophe-inducing proteins to confer MT dynamics to support changes in the Sertoli cell shape to sustain spermatogenesis. However, no functional studies are found in the literature to probe its role in spermatogenesis. Using an RNAi approach, coupled with the use of toxicant-induced testis (in vivo)- and Sertoli cell (in vitro)-injury models, RNA-Seq analysis, transcriptome profiling, and relevant bioinformatics analysis, immunofluorescence analysis, and pertinent biochemical assays for cytoskeletal organization, we have delineated the functional role of Map1a in Sertoli cells and testes. Map1a was shown to support MT structural organization, and its knockdown (KD) also perturbed the structural organization of actin, vimentin, and septin cytoskeletons as these cytoskeletons are intimately related, working in concert to support spermatogenesis. More importantly, cadmium-induced Sertoli cell injury that perturbed the MT structural organization across the cell cytoplasm was associated with disruptive changes in the distribution of Map1a and a surge in p-p38-MAPK (phosphorylated p38-mitogen-activated protein kinase) expression but not total p38-MAPK. These findings thus support the notion that p-p38-MAPK activation is involved in cadmium-induced Sertoli cell injury. This conclusion was supported by studies using doramapimod, a specific p38-MAPK phosphorylation (activation) inhibitor, which was capable of restoring the cadmium-induced disruptive structural organization of MTs across the Sertoli cell cytoplasm. In summary: this study provides mechanistic insights regarding restoration of toxicant-induced Sertoli cell and testis injury and male infertility.

A Fully Methylated Cyclic Ether Solvent Enables Graphite Anode Cycling at Low Temperatures.

Graphite anode suffers from great capacity loss and larger cell polarization under low-temperature conditions in lithium-ion batteries (LIBs), which are mainly caused by the high energy barrier for the Li+ desolvation process and sluggish Li+ transfer rate across the solid electrolyte interface (SEI). Regulating an electrolyte with an anion-dominated solvation structure could synchronously stabilize the interface and boost the reaction kinetics of the graphite anode. Herein, a highly ionic conductive electrolyte consisting of a fully methylated cyclic ether solvent of 2,2,4,4,5,5-hexamethyl-1,3-dioxolane (HMD) and fluoroethylene carbonate (FEC) cosolvent was designed. The high electron-donating effect and steric hindrance of -(CH3)2 in HMD endow the HMD-based electrolyte with high ionic conductivity but lower coordination numbers with Li+, and an anion-dominated solvation structure was formed. Such configuration can accelerate the desolvation process and induce the forming of a LiF-rich SEI film on the anode, avoiding the solvent coembedding into graphite and enhancing the ion migration rate under low temperatures. The assembled Li||graphite cell with the tame electrolyte outperformed the conventional carbonates-based cell, showing 93.8% capacity retention after 227 cycles for the DF-based cell compared to 64.7% after 150 cycles. It also exhibited a prolonged cycle life for 200 rounds with 81% capacity retention under -20 °C. Therefore, this work offers a valuable thought for solvent design and provides approaches to electrolyte design for low-temperature LIBs.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma.

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1ß (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1ß, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

The Planar Cell Polarity Protein Fat1 in Sertoli Cell Function.

Fat (FAT atypical cadherin) and Dchs (Dachsous cadherin-related protein) in adjacent Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interfaces create an important intercellular bridge whose adhesive function is in turn supported by Fjx1, a nonreceptor Ser/Thr protein kinase. This concept is derived from earlier studies of Drosophila, which has been confirmed in this and earlier reports as well. Herein, we use the approach of knockdown of Fat1 by RNAi using primary cultures of Sertoli cells that mimicked the blood-testis barrier (BTB) in vivo, and a series of coherent experiments including functional assays to monitor the Sertoli cell tight junction (TJ) permeability barrier and a functional in vitro TJ integrity assay to assess the role of Fat1 in the testis. It was shown that planar cell polarity (PCP) protein Fat1 affected Sertoli cell function through its modulation of actin and microtubule cytoskeletal function, altering their polymerization activity through the Fat1/Fjx1 complex. Furthermore, Fat1 is intimately associated with ß-catenin and α-N-catenin, as well as with Prickle 1 of the Vangl1/Prickle 1 complex, another PCP core protein to support intercellular interactions to confer PCP. In summary, these findings support the notion that the Fat:Dchs and the Vangl2:Fzd PCP intercellular bridges are tightly associated with basal ES/TJ structural proteins to stabilize PCP function at the Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interface to sustain spermatogenesis.

The Interplay Between Epilepsy and Parkinson's Disease: Gene Expression Profiling and Functional Analysis.

The results of many epidemiological studies suggest a bidirectional causality may exist between epilepsy and Parkinson's disease (PD). However, the underlying molecular landscape linking these two diseases remains largely unknown. This study aimed to explore this possible bidirectional causality by identifying differentially expressed genes (DEGs) in each disease as well as their intersection based on two respective disease-related datasets. We performed enrichment analyses and explored immune cell infiltration based on an intersection of the DEGs. Identifying a protein-protein interaction (PPI) network between epilepsy and PD, and this network was visualised using Cytoscape software to screen key modules and hub genes. Finally, exploring the diagnostic values of the identified hub genes. NetworkAnalyst 3.0 and Cytoscape software were also used to construct and visualise the transcription factor-micro-RNA regulatory and co-regulatory networks, the gene-microRNA interaction network, as well as gene-disease association. Based on the enrichment results, the intersection of the DEGs mainly revealed enrichment in immunity-, phosphorylation-, metabolism-, and inflammation-related pathways. The boxplots revealed similar trends in infiltration of many immune cells in epilepsy and Parkinson's disease, with greater infiltration in patients than in controls. A complex PPI network comprising 186 nodes and 512 edges were constructed. According to node connection degree, top 15 hub genes were considered the kernel targets of epilepsy and PD. The area under curve values of hub gene expression profiles confirmed their excellent diagnostic values. This study is the first to analyse the molecular landscape underlying the epidemiological link between epilepsy and Parkinson's disease. The two diseases are closely linked through immunity-, inflammation-, and metabolism-related pathways. This information was of great help in understanding the pathogenesis, diagnosis, and treatment of the diseases. The present results may provide guidance for further in-depth analysis about molecular mechanisms of epilepsy and PD and novel potential targets.

Therapeutic potential of ADSC-EV-derived lncRNA DLEU2: A novel molecular pathway in alleviating sepsis-induced lung injury via the miR-106a-5p/LXN axis.

This study investigates the molecular mechanisms by which extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSCs) promote M2 polarization of macrophages and thus reduce lung injury caused by sepsis. High-throughput sequencing was used to identify differentially expressed genes related to long non-coding RNA (lncRNA) in ADSC-derived EVs (ADSC-EVs) in sepsis lung tissue. Weighted gene co-expression network analysis (WGCNA) was employed to predict the downstream target genes of the lncRNA DLEU2. The RNAInter database predicted miRNAs that interact with DLEU2 and LXN. Functional and pathway enrichment analyses were performed using GO and KEGG analysis. A mouse model of sepsis was established, and treatment with a placebo or ADSC-EVs was administered, followed by RT-qPCR analysis. ADSC-EVs were isolated and identified. In vitro cell experiments were conducted using the mouse lung epithelial cell line MLE-12, mouse macrophage cell line RAW264.7, and mouse lung epithelial cell line (LEPC). ADSC-EVs were co-cultured with RAW264.7 and MLE-12/LEPC cells to study the regulatory mechanism of the lncRNA DLEU2. Cell viability, proliferation, and apoptosis of lung injury cells were assessed using CCK-8, EdU, and flow cytometry. ELISA was used to measure the levels of inflammatory cytokines in the sepsis mouse model, flow cytometry was performed to determine the number of M1 and M2 macrophages, lung tissue pathology was evaluated by H&E staining, and immunohistochemistry was conducted to examine the expression of proliferation- and apoptosis-related proteins. High-throughput sequencing and bioinformatics analysis revealed enrichment of the lncRNA DLEU2 in ADSC-EVs in sepsis lung tissue. Animal and in vitro cell experiments showed increased expression of the lncRNA DLEU2 in sepsis lung tissue after treatment with ADSC-EVs. Furthermore, ADSC-EVs were found to transfer the lncRNA DLEU2 to macrophages, promoting M2 polarization, reducing inflammation response in lung injury cells, and enhancing their viability, proliferation, and apoptosis inhibition. Further functional experiments indicated that lncRNA DLEU2 promotes M2 polarization of macrophages by regulating miR-106a-5p/LXN, thereby enhancing the viability and proliferation of lung injury cells and inhibiting apoptosis. Overexpression of miR-106a-5p could reverse the biological effects of ADSC-EVs-DLEU2 on MLE-12 and LEPC in vitro cell models. Lastly, in vivo animal experiments confirmed that ADSC-EVs-DLEU2 promotes high expression of LXN by inhibiting the expression of miR-106a-5p, further facilitating M2 macrophage polarization and reducing lung edema, thus alleviating sepsis-induced lung injury. lncRNA DLEU2 in ADSC-EVs may promote M2 polarization of macrophages and enhance the viability and proliferation of lung injury cells while inhibiting inflammation and apoptosis reactions, thus ameliorating sepsis-induced lung injury in a mechanism involving the regulation of the miR-106a-5p/LXN axis.

Induction of lung progenitor cell-like organoids by porcine pluripotent stem cells.

Organoids are in vitro 3D models that are generated using stem cells to study organ development and regeneration. Despite the extensive research on lung organoids, there is limited information on pig lung cell generation or development. Here, we identified five epithelial cell types along with their characteristic markers using scRNA-seq. Additionally, we found that NKX2.1 and FOXA2 acted as the crucial core transcription factors in porcine lung development. The presence of SOX9/SOX2 double-positive cells was identified as a key marker for lung progenitor cells. The Monocle algorithm was used to create a pseudo-temporal differentiation trajectory of epithelial cells, leading to the identification of signaling pathways related to porcine lung development. Moreover, we established the differentiation method from porcine pluripotent stem cells (pPSCs) to SOX17+ FOXA2+ definitive endoderm (DE) and NKX2.1+ FOXA2+ CDX2- anterior foregut endoderm (AFE). The AFE is further differentiated into lung organoids while closely monitoring the differentiation process. We showed that NKX2.1 overexpression facilitated the induction of lung organoids and supported subsequent lung differentiation and maturation. This model offers valuable insights into studying the interaction patterns between cells and the signaling pathways during the development of the porcine lung.

Internet hospital response to the COVID-19 pandemic in a tertiary hospital in China: Perspectives based on a mixed-methods.

Objective: This study aimed to summarize the characteristics of the Internet hospital services of the Seventh Affiliated Hospital of Sun Yat-sen University (SAHSYSU), describe diagnosis and treatment patterns in each department, determine SAHSYSU Internet hospital's role in pandemic control, and explore development strategies in non-pandemic situations. Methods: Mixed-methods was used in this study. Qualitative organizational behavior analysis was conducted on hospital meeting records and semi-structured interview records to determine the research analysis indicators. We quantitatively analyzed online consultation record data of SAHSYSU Internet hospital from January to December 2020, and conduct classification analysis on departmental case studies using K-means clustering algorithm. Results: 29,944 patient data items were retrieved. Internet hospital services synchronized with COVID-19 pandemic development in China and Guangdong province. The service volume peaked during the period of January to March, which coincided with the height of the pandemic. Out of the total visits, 58.90% were conducted during office hours while 41.10% were conducted during non-office hours. The majority of the patients came from Guangdong (19.67%) and Hubei (9.09%) provinces. The cluster analysis identified three clusters, each with different change rates and magnitudes of change for various departments. Conclusion: Internet hospitals complemented conventional medical services, providing crucial medical care during the COVID-19 pandemic. Internet hospitals are the future trend of medical services and should be improved based on each department's treatment characteristics.

ICBP90, an epigenetic regulator, induces DKK3 promoter methylation, promotes glioma progression, and reduces sensitivity to cis-platinum.

Glioma is the most common brain malignancy, characterized by high morbidity, high mortality, and treatment-resistance. Inverted CCAAT box Binding Protein of 90 kDa (ICBP90) has been reported to be involved in tumor progression and the maintenance of DNA methylation. Herein, we constructed ICBP90 over-expression and knockdown glioma cell lines, and found that ICBP90 knockdown inhibited glioma cell proliferation, migration, and invasion. ICBP90 silencing potentially enhanced cellular sensitivity to cis-platinum (DDP) and exacerbated DDP-induced pyroptosis, manifested by the elevated levels of gasdermin D-N-terminal and cleaved caspase 1; whereas, ICBP90 over-expression exhibited the opposite effects. Consistently, ICBP90 knockdown inhibited tumor growth in an in vivo mouse xenograft study using U251 cells stably expressing sh-ICBP90 and oe-ICBP90. Further experiments found that ICBP90 reduced the expression of Dickkopf 3 homolog (DKK3), a negative regulator of ß-catenin, by binding its promoter and inducing DNA methylation. ICBP90 knockdown prevented the nuclear translocation of ß-catenin and suppressed the expression of c-Myc and cyclin D1. Besides, DKK3 over-expression restored the effects of ICBP90 over-expression on cell proliferation, migration, invasion, and DDP sensitivity. Our findings suggest that ICBP90 inhibits the expression of DKK3 in glioma by maintaining DKK3 promoter methylation, thereby conducing to ICBP90-mediated carcinogenesis and drug insensitivity.

Channel Selection for Stereo- Electroencephalography (SEEG)-Based Invasive Brain-Computer Interfaces Using Deep Learning Methods.

Brain-computer interfaces (BCIs) can enable direct communication with assistive devices by recording and decoding signals from the brain. To achieve high performance, many electrodes will be used, such as the recently developed invasive BCIs with channel numbers up to hundreds or even thousands. For those high-throughput BCIs, channel selection is important to reduce signal redundancy and invasiveness while maintaining decoding performance. However, such endeavour is rarely reported for invasive BCIs, especially those using deep learning methods. Two deep learning-based methods, referred to as Gumbel and STG, were proposed in this paper. They were evaluated using the Stereo-electroencephalography (SEEG) signals, and compared with three other methods, including manual selection, mutual information-based method (MI), and all channels (all channels without selection). The task is to classify the SEEG signals into five movements using channels selected by each method. When 10 channels were selected, the mean classification accuracies using Gumbel, STG (referred to as STG-10), manual selection, and MI selection were 65%, 60%, 60%, and 47%, respectively, whilst the accuracy was 59% using all channels (no selection). In addition, an investigation of the selected channels showed that Gumbel and STG have successfully identified the pre-central and post-central areas, which are closely related to motor control. Both Gumbel and STG successfully selected the informative channels in SEEG recordings while maintaining decoding accuracy. This study enables future high-throughput BCIs using deep learning methods, to identify useful channels and reduce computing and wireless transmission pressure.