Ferroelectric 2D SnS2 Analog Synaptic FET.

In this study, the development and characterization of 2D ferroelectric field-effect transistor (2D FeFET) devices are presented, utilizing nanoscale ferroelectric HfZrO2 (HZO) and 2D semiconductors. The fabricated device demonstrated multi-level data storage capabilities. It successfully emulated essential biological characteristics, including excitatory/inhibitory postsynaptic currents (EPSC/IPSC), Pair-Pulse Facilitation (PPF), and Spike-Timing Dependent Plasticity (STDP). Extensive endurance tests ensured robust stability (107 switching cycles, 105 s (extrapolated to 10 years)), excellent linearity, and high Gmax/Gmin ratio (>105), all of which are essential for realizing multi-level data states (>7-bit operation). Beyond mimicking synaptic functionalities, the device achieved a pattern recognition accuracy of ≈94% on the Modified National Institute of Standards and Technology (MNIST) handwritten dataset when incorporated into a neural network, demonstrating its potential as an effective component in neuromorphic systems. The successful implementation of the 2D FeFET device paves the way for the development of high-efficiency, ultralow-power neuromorphic hardware which is in sub-femtojoule (48 aJ/spike) and fast response (1 µs), which is 104 folds faster than human synapse (≈10 ms). The results of the research underline the potential of nanoscale ferroelectric and 2D materials in building the next generation of artificial intelligence technologies.

Implementation of a Patient Summary Web Application According to the International Patient Summary and Validation in Common Use Cases in Japan.

BACKGROUND: The application of standardized patient summaries would reduce the risk of information overload and related problems for physicians and nurses. Although the International Patient Summary (IPS) standard has been developed, disseminating its applications has challenges, including data conversion of existing systems and development of application matching with common use cases in Japan. This study aimed to develop a patient summary application that summarizes and visualizes patient information accumulated by existing systems. METHODS: We converted clinical data from the Standardized Structured Medical Information eXchange version 2 (SS-MIX2) storage at Tohoku University Hospital into the Health Level 7 Fast Healthcare Interoperability Resource (FHIR) repository. Subsequently, we implemented a patient summary web application concerning the IPS and evaluated 12 common use cases of the discharge summary. RESULTS: The FHIR resources of seven of the necessary IPS sections were successfully converted from existing SS-MIX2 data. In the main view of the application we developed, all the minimum necessary patient information was summarized and visualized. All types of mandatory or required sections in the IPS and all structured information items of the discharge summary were displayed. Of the discharge summary, 75% of sections and 61.7% of information items were completely displayed, matching 12 common use cases in Japan. CONCLUSIONS: We implemented a patient summary application that summarizes and visualizes patient information accumulated by existing systems and is evaluated in common use cases in Japan. Efficient sharing of the minimum necessary patient information for physicians is expected to reduce information overload, workload, and burnout.

The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma.

PURPOSE: Temozolomide resistance remains a major obstacle in the treatment of glioblastoma (GBM). The combination of temozolomide with another agent could offer an improved treatment option if it could overcome chemoresistance and prevent side effects. Here, we determined the critical drug that cause ferroptosis in GBM cells and elucidated the possible mechanism by which drug combination overcomes chemoresistance. EXPERIMENTAL DESIGN: Haloperidol/temozolomide synergism was assessed in GBM cell lines with different dopamine D2 receptor (DRD2) expression in vitro and in vivo. Inhibitors of ferroptosis, autophagy, endoplasmic reticulum (ER) stress and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) were used to validate the specific mechanisms by which haloperidol and temozolomide induce ferroptosis in GBM cells. RESULTS: In the present work, we demonstrate that the DRD2 level is increased by temozolomide in a time-dependent manner and is inversely correlated with temozolomide sensitivity in GBM. The DRD2 antagonist haloperidol, a butylbenzene antipsychotic, markedly induces ferroptosis and effectively enhances temozolomide efficacy in vivo and in vitro. Mechanistically, haloperidol suppressed the effect of temozolomide on cAMP by antagonizing DRD2 receptor activity, and the increases in cAMP/PKA triggered ER stress, which led to autophagy and ferroptosis. Furthermore, elevated autophagy mediates downregulation of FTH1 expression at the posttranslational level in an autophagy-dependent manner and ultimately leads to ferroptosis. CONCLUSIONS: Our results provide experimental evidence for repurposing haloperidol as an effective adjunct therapy to inhibit adaptive temozolomide resistance to enhance the efficacy of chemoradiotherapy in GBM, a strategy that may have broad prospects for clinical application.

Recent evaluation about inflammatory mechanisms in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is common chronic metabolic liver disorder which is associated with fat accumulation in the liver. It causes a wide range of pathological effects such as insulin resistance, obesity, hypertension, diabetes, non-alcoholic steatohepatitis (NASH) and cirrhosis, cardiovascular diseases. The molecular mechanisms that cause the initiation and progression of NAFLD remain fully unclear. Inflammation is regarded as a significant mechanism which could result in cell death and tissue injury. Accumulation of leukocytes and hepatic inflammation are important contributors in NAFLD. Excessive inflammatory response can deteriorate the tissue injury in NAFLD. Thus, inhibition of inflammation improves NAFLD by reducing intrahepatic fat content, increasing ß-oxidation of fatty acids, inducing hepato-protective autophagy, overexpressing peroxisome proliferator-activated receptor- γ (PPAR-γ), as well as attenuating hepatocyte apoptosis and increasing insulin sensitivity. Therefore, understanding the molecules and signaling pathways suggests us valuable information about NAFLD progression. This review aimed to evaluate the inflammation in NAFLD and the molecular mechanism on NAFLD.

RBBP4 regulates the expression of the Mre11-Rad50-NBS1 (MRN) complex and promotes DNA double-strand break repair to mediate glioblastoma chemoradiotherapy resistance.

For treatment of glioblastoma (GBM), temozolomide (TMZ) and radiotherapy (RT) exert antitumor effects by inducing DNA double-strand breaks (DSBs), mainly via futile DNA mismatch repair (MMR) and inducing apoptosis. Here, we provide evidence that RBBP4 modulates glioblastoma resistance to chemotherapy and radiotherapy by recruiting transcription factors and epigenetic regulators that bind to their promoters to regulate the expression of the Mre11-Rad50-NBS1(MRN) complex and the level of DNA-DSB repair, which are closely associated with recovery from TMZ- and radiotherapy-induced DNA damage in U87MG and LN229 glioblastoma cells, which have negative MGMT expression. Disruption of RBBP4 induced GBM cell DNA damage and apoptosis in response to TMZ and radiotherapy and enhanced radiotherapy and chemotherapy sensitivity by the independent pathway of MGMT. These results displayed a possible chemo-radioresistant mechanism in MGMT negative GBM. In addition, the RBBP4-MRN complex regulation axis may provide an interesting target for developing therapy-sensitizing strategies for GBM.

Oxymatrine ameliorates myocardial injury by inhibiting oxidative stress and apoptosis via the Nrf2/HO-1 and JAK/STAT pathways in type 2 diabetic rats.

The necessity of increasing the efficiency of organ preservation has encouraged researchers to explore the mechanisms underlying diabetes-related myocardial injuries. This study intended to evaluate the protective effects of oxymatrine (OMT) in myocardial injury caused by type 2 diabetes mellitus. A model of diabetic rats was established to simulate type 2 diabetes mellitus using an intraperitoneal injection of a single dose of 65 mg/kg streptozotocin with a high-fat and high-cholesterol diet, and diabetic rats were subsequently treated with OMT (60, 120 mg/kg) by gavage for 8 weeks. Thereafter, diabetic rats demonstrated notable decreases in left ventricular systolic pressure (LVSP), ±dp/dtmax, and in the activities of glutathione peroxidase, superoxide dismutase, and catalase. Moreover, we found notable increases in left ventricular end-diastolic pressure, fasting blood glucose, and malondialdehyde, as well as changes in cell apoptosis and decreased expression levels of Nrf2, HO-1, tyrosine protein kinase JAK (JAK), and signal transducer and transcription activator (STAT). Treatment with OMT alleviated all of the measured parameters. Collectively, these findings suggest that activation of the Nrf2/HO-1 and inhibition of the JAK/STAT signaling are involved in mediating the cardioprotective effects of OMT and also highlight the benefits of OMT in ameliorating myocardial injury in diabetic rats.

SMARCC2 mediates the regulation of DKK1 by the transcription factor EGR1 through chromatin remodeling to reduce the proliferative capacity of glioblastoma.

Switch/sucrose-nonfermenting (SWI/SNF) complexes play a key role in chromatin remodeling. Recent studies have found that SMARCC2, as the core subunit of the fundamental module of the complex, plays a key role in its early assembly. In this study, we found a unique function of SMARCC2 in inhibiting the progression of glioblastoma by targeting the DKK1 signaling axis. Low expression of SMARCC2 is found in malignant glioblastoma (GBM) compared with low-grade gliomas. SMARCC2 knockout promoted the proliferation of glioblastoma cells, while its overexpression showed the opposite effect. Mechanistically, SMARCC2 negatively regulates transcription by dynamically regulating the chromatin structure and closing the promoter region of the target gene DKK1, which can be bound by the transcription factor EGR1. DKK1 knockdown significantly reduced the proliferation of glioblastoma cell lines by inhibiting the PI3K-AKT pathway. We also studied the functions of the SWIRM and SANT domains of SMARCC2 and found that the SWIRM domain plays a more important role in the complete chromatin remodeling function of SMARCC2. In addition, in vivo studies confirmed that overexpression of SMARCC2 could significantly inhibit the size of intracranial gliomas in situ in nude mice. Overall, this study shows that SMARCC2, as a tumor suppressor, inhibits the proliferation of glioblastoma by targeting the transcription of the oncogene DKK1 through chromatin remodeling, indicating that SMARCC2 is a potentially attractive therapeutic target in glioblastoma.

Microglial infiltration mediates cognitive dysfunction in rat models of hypothalamic obesity via a hypothalamic-hippocampal circuit involving the lateral hypothalamic area.

This study aimed to explore the mechanism underlying cognitive dysfunction mediated by the lateral hypothalamic area (LHA) in a hypothalamic-hippocampal circuit in rats with lesion-induced hypothalamic obesity (HO). The HO model was established by electrically lesioning the hypothalamic nuclei. The open field (OP) test, Morris water maze (MWM), novel object recognition (NOR), and novel object location memory (NLM) tests were used to evaluate changes in cognition due to alterations in the hypothalamic-hippocampal circuit. Western blotting, immunohistochemical staining, and cholera toxin subunit B conjugated with Alexa Fluor 488 (CTB488) reverse tracer technology were used to determine synaptophysin (SYN), postsynaptic density protein 95 (PSD95), ionized calcium binding adaptor molecule 1 (Iba1), neuronal nuclear protein (NeuN), and Caspase3 expression levels and the hypothalamic-hippocampal circuit. In HO rats, severe obesity was associated with cognitive dysfunction after the lesion of the hypothalamus. Furthermore, neuronal apoptosis and activated microglia in the downstream of the lesion area (the LHA) induced microglial infiltration into the intact hippocampus via the LHA-hippocampal circuit, and the synapses engulfment in the hippocampus may be the underlying mechanism by which the remodeled microglial mediates memory impairments in HO rats. The HO rats exhibited microglial infiltration and synapse loss into the hippocampus from the lesioned LHA via the hypothalamic-hippocampal circuit. The underlying mechanisms of memory function may be related to the circuit.

Research progress in endothelial cell injury and repair.

Endothelial cells, which are important metabolic and endocrine cells, play an important role in regulating vascular function. The occurrence and development of various cardiovascular and cerebrovascular diseases are associated with endothelial dysfunction. However, the underlying mechanism of vascular endothelial injury is not fully understood. It has been reported that the mechanism of endothelial injury mainly involves inflammation and oxidative stress. Moreover, endothelial progenitor cells are regarded as important contributors in repairing damaged endothelium. Multiple interventions (including chemical drugs and traditional Chinese medicines) exert endothelial protection by decreasing the release of inducing factors, suppressing inflammation and oxidative stress, and preventing endothelial cell senescence.

Evaluating Craniovertebral Stability in Chiari Malformation Coexisting with Type II Basilar Invagination: An Observational Study Based on Kinematic Computed Tomography and Its Clinical Application.

BACKGROUND: Treatment of Chiari malformation (CM) is controversial, especially when it coexists with "stable" or Type II basilar invagination (CM + II-BI). Precise evaluation of craniovertebral junction (CVJ) stability is crucial in such patients; however, this has never been validated. This study aimed to dynamically evaluate atlanto-condyle and atlantoaxial stability by kinematic computed tomography (CT) and report its surgical treatment. METHODS: The study recruited 101 patients (control, CM, and CM + II-BI groups: 48, 34, and 19 patients, respectively). During kinematic CT, the CVJ stability-related parameters were measured and compared between the 3 groups. The surgical strategy for treating CM + II-BI was based on these results. Preoperative and postoperative images were acquired, and functional scores were used to assess the outcome. RESULTS: Among the 3 groups, the length of the clivus and the height of the condyle were the shortest in the CM + II-BI group, which was accompanied by the greatest rotation of the atlas and atlanto-condyle facet movement on cervical flexion and extension. Moreover, in such patients, increased Chamberlain's baseline violation indicated the aggregate invagination of the odontoid in the flexed position, and asymmetric displacement of atlantoaxial facets was observed. Seventeen CM + II-BI patients underwent surgical treatment with atlantoaxial distraction and occipitocervical fusion. The syringomyelia width and tonsillar herniation decreased significantly, and functional scores indicated symptom relief and good outcomes. CONCLUSIONS: CVJ instability, especially the ultramovement of atlanto-condyle facets, commonly exists in II-BI as evaluated using kinematic CT. The surgical strategy of atlantoaxial distraction and occipitocervical fusion should be considered to treat such patients.

A Novel Detection Scheme in Image Domain for Multichannel Circular SAR Ground-Moving-Target Indication.

Circular synthetic aperture radar (CSAR), which can observe the region of interest for a long time and from multiple angles, offers the opportunity for moving-target detection (MTD). However, traditional MTD methods cannot effectively solve the problem of high probability of false alarm (PFA) caused by strong clutter. To mitigate this, a novel, three-step scheme combining clutter background extraction, multichannel clutter suppression, and the degree of linear consistency of radial velocity interferometric phase (DLRVP) test is proposed. In the first step, the spatial similarity of the scatterers and the correlation between sub-aperture images are fused to extract the strong clutter mask prior to clutter suppression. In the second step, using the data remaining after elimination of the background clutter in Step 1, an amplitude-based detector with higher processing gain is utilized to detect potential moving targets. In the third step, a novel test model based on DLRVP is proposed to further reduce the PFA caused by isolated strong scatterers. After the above processing, almost all false alarms are excluded. Measured data verified that the PFA of the proposed method is only 20% that of the comparison method, with improved detection of slow and weakly moving targets and with better robustness.

A necroptosis-related lncRNA signature was identified to predict the prognosis and immune microenvironment of IDH-wild-type GBM.

Introduction: Necroptosis-related genes are essential for the advancement of IDH-wild-type GBM. However, the putative effects of necroptosis-related lncRNAs (nrlncRNAs) in IDH-wild-type GBM remain unknown. Methods: By using the TCGA and GTEx databases, a nrlncRNA prognostic signature was created using LASSO Cox regression. The median risk score was used to categorize the patients into low and high-risk groups. To confirm the validity, univariate, multivariate Cox regression and ROC curves were used. Furthermore, by enrichment analysis, immune correlation analysis, and drug sensitivity analysis, the targeted lncRNAs were selected for further verification. As the highest upregulated expression in tumor than peritumor specimens, RP11-131L12.4 was selected for phenotype and functional experiments in primary GBM cells. Results: Six lncRNAs were proved to be closely related to necroptosis in IDH-1-wild-type GBM, which were used to create a new signature. For 1-, 2-, and 3-year OS, the AUCs were 0.709, 0.645 and 0.694, respectively. Patients in the low-risk group had a better prognosis, stronger immune function activity, and more immune cell infiltration. In contrast, enrichment analysis revealed that the malignant phenotype was more prevalent in the high-risk group. In vitro experiments indicated that RP11-131L12.4 increased the tumor proliferation, migration and invasion, but decreased the necroptosis. Moreover, this nrlncRNA was also proved to be negatively associated with patient prognosis. Conclusion: The signature of nrlncRNAs may aid in the formulation of tailored and precise treatment for individuals with IDH-wild-type GBM. RP11-131L12.4 may play indispensable role in necroptosis suppression.

SMARCC2 combined with c­Myc inhibits the migration and invasion of glioma cells via modulation of the Wnt/ß­catenin signaling pathway.

Glioma is the most common type of central nervous system tumor. SWItch/sucrose non­fermentable (SWI/SNF) is a tumor suppressor that serves an important role in epithelial­mesenchymal transition (EMT). The present study aimed to identify key molecules involved in the EMT process. SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) is mutated in and its expression is low in multiple types of cancer. SMARCC2 is the core subunit of the chromatin­remodeling complex, SWI/SNF. Relative mRNA SMARCC2 expression levels in human glioma tissue were analyzed via reverse transcription­quantitative PCR, whereas the protein expression levels were determined via immunohistochemistry staining. SMARCC2 expression was knocked down in glioma cells using small interfering RNA (si) and overexpressed by infection with adenovirus vectors carrying SMARCC2 cDNA. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. Subsequently, immunofluorescence and western blotting were performed to analyze the expression levels of the oncogene c­Myc, which is associated with SMARCC2. SMARCC2 combines with C­MYC to downregulate its expression. Consistent with the results of the bioinformatics analysis, which revealed that the upregulated expression levels of SMARCC2 were associated with a more favorable prognosis in patients with glioma, the mRNA and protein expression levels of SMARCC2 were significantly upregulated in low­grade glioma tissues compared with high­grade glioma tissues. The results of the wound healing assay demonstrated that cell migration was significantly increased in the siSMARCC2­1/3 groups compared with the negative control (NC) group. By contrast, the migratory ability of cells was significantly reduced following transduction with adenovirus overexpressing SMARCC2, which upregulated the expression of SMARCC2, compared with the lentiviral vector­non­specific control (LVS­NC) group. The Transwell assay results further showed that SMARCC2 overexpression significantly inhibited the migratory and invasive abilities of U87MG and LN229 cells compared with the LVS­NC group. Co­immunoprecipitation assays were subsequently conducted to validate the binding of SMARCC2 and c­Myc; the results demonstrated that the expression of c­Myc was downregulated in adenovirus­transfected cells compared with LVS­NC­transfected cells. The results of the western blotting experiments demonstrated that the expression levels of N­cadherin, vimentin, snail family transcriptional repressor 1 and ß­catenin were notably downregulated, whereas the expression levels of T­cadherin were markedly upregulated in cell lines stably overexpressing SMARCC2 compared with the LVS­NC group. In conclusion, the results of the present study suggested that SMARCC2 may inhibit Wnt/ß­catenin signaling by regulating c­Myc expression in glioma. SMARCC2 regulates the EMT status of the glioblastoma cell line by mediating the expression of the oncogene C­MYC to inhibit its migration and invasion ability. Thus, SMARCC2 may function as a tumor suppressor or oncogene by regulating associated oncogenes or tumor suppressor genes.

Development of an application concerning fast healthcare interoperability resources based on standardized structured medical information exchange version 2 data.

BACKGROUND AND OBJECTIVE: A mobile application for personal health records (PHR) would allow patients to access their clinical data easily. When PHR connects with multiple electronic health records (EHRs), doctors and patients can exchange large quantities of patient data from the EHR (e.g., medication list, diagnoses, allergies, and laboratory data). Furthermore, personal daily records can also be retrieved from PHR (e.g., blood pressure, pulse, dietary habits, and exercise). However, no standard interoperability between EHRs and PHR has been established. This study aims to convert clinical data in EHRs into the Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) data format while developing a PHR application to present the FHIR data. METHODS: In Japan, Standardized Structured Medical Information eXchange version 2 (SS-MIX2) is typically utilized as a health information exchange to preserve and elicit clinical data from EHRs. We converted clinical data in the SS-MIX2 storage at Tohoku University Hospital into the FHIR repository server using the R4 standard. Additionally, we used the Swift programming language to build a PHR application. RESULTS: We converted patients' basic information, disease names, diagnostic reports, prescriptions, and injection data from the SS-MIX2 to the FHIR server. Besides, we launched a PHR application that could retrieve data from the FHIR server to display patients' clinical information. CONCLUSIONS: Our work demonstrated the conversion of SS-MIX2 data into the FHIR and presented them with our PHR application. This mechanism may be useful to accelerate the sharing of clinical information among doctors and patients.

Utility of CT Perfusion Imaging in Patients With Vertebral Artery Stenosis Treated With Balloon Expandable Stent.

Objective: To investigate the clinical value of CT perfusion (CTP) imaging in vertebral artery stenosis stenting, so as to provide the basis for preoperative and postoperative evaluation. Ninety-seven patients with vertebral artery stenosis were accepted for endovascular stenting between Jan 2016 and Jan 2020. CT angiography, Digital Subtraction Angiography, and CTP were performed pre-operation and post-operation. The cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transmit time (MTT) between the health and affected sides were analyzed statistically, and the imaging results pre- and post-operation were evaluated. The stenosis was relieved by endovascular stents in all 97 patients without serious complications. The abnormal perfusion was observed in 66 patients (68%). The differences in CBF and MTT between the diseased side and healthy side were statistically significant (P < 0.05). Compared with the preoperative imaging, the postoperative CTP was improved in 59 patients (89%). The differences in CBF and MTT between pre-operation and post-operation were statistically significant (P < 0.05). But there was no significant difference in CBV. CTP can sensitively reflect the perfusion of brain, and can also be used for preoperative and postoperative evaluation of vertebral artery stenting. It may be helpful as an adequate indicator of vertebral artery stenosis stent surgery.

Extended GLRT Detection of Moving Targets for Multichannel SAR Based on Generalized Steering Vector.

A generalized likelihood ratio test (GLRT) with the constant false alarm rate (CFAR) property was recently developed for adaptive detection of moving targets in focusing synthetic aperture radar (SAR) images. However, in the multichannel SAR-ground moving-target indication (SAR-GMTI) system, image defocus is inevitable, which will remarkably degrade the performance of the GLRT detector, especially for the lower radar cross-section (RCS) and slower radial velocity moving targets. To address this issue, based on the generalized steering vector (GSV), an extended GLRT detector is proposed and its performance is evaluated by the optimum likelihood ratio test (LRT) in the Neyman-Pearson (NP) criterion. The joint data vector formulated by the current cell and its adjacent cells is used to obtain the GSV, and then the extended GLRT is derived, which coherently integrates signal and accomplishes moving-target detection and parameter estimation. Theoretical analysis and simulated SAR data demonstrate the effectiveness and robustness of the proposed detector in the defocusing SAR images.

A Coherence Improvement Method Based on Sub-Aperture InSAR for Human Activity Detection.

Human activity detection plays an important role in social security monitoring. Since human activity is very weak, it is necessary to employ the repeat-pass Interferometric Synthetic Aperture Radar (InSAR) technique to detect the potential activity between two data acquisitions; a high level of coherence is required for detection. With the object of detecting human activity of interest, this paper presents a coherence improvement approach based on sub-aperture InSAR for human activity detection. Different sub-apertures contain different scattering information of the target, as they represent the backscatter of the target from a different range of angles. Integrating corresponding sub-aperture interferometric results can improve the coherence between two complex images compared to the entire synthetic aperture, as well as removing a little disturbance in some circumstances. To validate the method presented in this paper, the actual airborne Ka-band frequency modulated continuous wave (FMCW) InSAR data acquired by the Aerospace Information Research Institute, Chinese Academy of Sciences (AIRCAS) are utilized. The experimental results demonstrate that the proposed method can effectively improve the coherence between two complex SAR images and can validly detect human activity of interest.