Investigating the ID3/SLC22A4 as immune-related signatures in ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a fearful disease that can cause a variety of immune events. Nevertheless, precise immune-related mechanisms have yet to be systematically elucidated. This study aimed to identify immune-related signatures using machine learning and to validate them with animal experiments and single cell analysis. METHODS: In this study, we screened 24 differentially expressed genes (DEGs) while identifying immune-related signatures that may play a key role in IS development through a comprehensive strategy between least absolute shrinkage and selection operation (LASSO) regression, support vector machine (SVM) and immune-related genes. In addition, we explored immune infiltration using the CIBERSORT algorithm. Finally, we performed validation in mouse brain tissue and single cell analysis. RESULTS: We identified 24 DEGs for follow-up analysis. ID3 and SLC22A4 were finally identified as the better immune-related signatures through a comprehensive strategy among DEGs, LASSO, SVM and immune-related genes. RT-qPCR, western blot, and immunofluorescence revealed a significant decrease in ID3 and a significant increase in SLC22A4 in the middle cerebral artery occlusion group. Single cell analysis revealed that ID3 was mainly concentrated in endothelial_2 cells and SLC22A4 in astrocytes in the MCAO group. A CIBERSORT finds significantly altered levels of immune infiltration in IS patients. CONCLUSIONS: This study focused on immune-related signatures after stroke and ID3 and SLC22A4 may be new therapeutic targets to promote functional recovery after stroke. Furthermore, the association of ID3 and SLC22A4 with immune cells may be a new direction for post-stroke immunotherapy.

Comparing Outcomes of Single-Incision Laparoscopic Herniorrhaphy in Newborns and Infants.

BACKGROUND: As surgical techniques progress, laparoscopic herniorrhaphy is now performed more often in premature babies. The aim of this study was to analyze the outcomes of newborns and infants who underwent single-incision laparoscopic herniorrhaphy (SILH) at our center. METHODS: We retrospectively reviewed patients younger than 12 months old who received SILH at our department from 2016 to 2020. SILH involved a 5 mm 30-degree scope and 3 mm instruments with a 3-0 Silk purse-string intracorporeal suture for closure of the internal ring. At the time of surgery, Group 1 newborns, whose corrected age was 2 months and below, were compared to the Group 2 infants, whose age was above 2 months. We assessed the patients' characteristics, anesthesia, surgical data, and complications. RESULTS: A total of 197 patients were included (114 newborns in Group 1 and 83 infants in Group 2). The mean age and body weight in Group 1 were 1.2 months and 3.8 kg, respectively, whereas in Group 2, they were 3.2 months and 6.7 kg, respectively. There were no significant differences in operative time (Group 1 = 34.1 min vs. Group 2 = 32.3 min, p = 0.26), anesthetic time (Group 1 = 80.0 min vs. Group 2 = 76.3 min, p = 0.07), length of hospitalization (Group 1 = 2.3 days vs. Group 2 = 2.4 days, p = 0.88), postoperative complications including omphalitis (Group 1 = 5.3% vs. Group 2 = 1.2%, p = 0.13), wound infection (Group 1 = 0.9% vs. Group 2 = 1.2%, p = 0.81), and hydrocele (Group 1 = 0.35% vs. Group 2 = 8.4%, p = 0.14). No recurrence, testicular ascent or atrophy, or mortality was observed in either group during the 2-year follow-up period. CONCLUSIONS: Single-incision laparoscopic herniorrhaphy is a safe and effective operation for inguinal hernia repair in infants, even those with prematurity, lower body weight at the time of surgery, or cardiac and/or pulmonary comorbidities. Comparable results revealed no significant differences in perioperative complications despite younger ages and lower body weights.

Severe burn injury from the common Asian practice of heat application in patients with diabetic neuropathy.

This was the first study to analyse patients who sustained severe self-induced burns from this common Asian practice. There is a need to raise public awareness and physician attention about the consequences of preventable burn injuries and the importance of first aid in patients with diabetic neuropathy. Retrospective data on 16 consecutive patients who had diabetes and neuropathy admitted to the plastic surgery ward at the Tri-Service General Hospital from January 1, 2015, to February 2, 2021 with burn injuries because of heat applications were collected and analysed for this study. Age, gender, season, first aid adequacy, comorbidity, interventions, total body surface area (TBSA), degree of burn, aetiology, length of stay (LOS), and status at discharge were reviewed. The mean age of the 16 patients was 65.13 years. The most common burn aetiology was contact (50%), followed by scald (37.5%) and radiation burns (12.5%). TBSA burn averaged ± standard deviation 1.54 ± 1.22. Seven patients (44%) had wound infections, and three patients underwent amputations. The average LOS was 28.2 days. Asian practice of heat application is the common aetiology of severe and preventable burn injuries. Education about neuropathy and the consequences of a burn injury should be provided to patients with diabetes.

Focused ultrasound enhanced molecular imaging and gene therapy for multifusion reporter gene in glioma-bearing rat model.

The ability to monitor the responses of and inhibit the growth of brain tumors during gene therapy has been severely limited due to the blood-brain barrier (BBB). A previous study has demonstrated the feasibility of noninvasive in vivo imaging with 123I-2'-fluoro-2'-deoxy-5-iodo-1-ß-D-arabinofuranosyluracil (123I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here, we tested the enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment in brain tumors after BBB disruption induced by focused ultrasound (FUS) in the presence of microbubbles. We established an orthotopic F98 glioma-bearing rat model with trifusion reporter genes. The results of this study showed that the rat model of HSV1-tk-expressing glioma cells could be successfully detected by SPECT imaging after FUS-induced BBB disruption on day 10 after implantation. Compared to the control group, animals receiving the GCV with or without sonication exhibited a significant antitumor activity (P < 0.05) of glioma cells on day 16 after implantation. Moreover, combining sonication with GCV significantly inhibited tumor growth compared with GCV alone. This study demonstrated that FUS may be used to deliver a wide variety of theranostic agents to the brain for molecular imaging and gene therapy in brain diseases.

Pharmacokinetic analysis and uptake of 18F-FBPA-Fr after ultrasound-induced blood-brain barrier disruption for potential enhancement of boron delivery for neutron capture therapy.

UNLABELLED: Boronophenylalanine has been applied in clinical boron neutron capture therapy for the treatment of high-grade gliomas. The purpose of this study was to evaluate the pharmacokinetics of 4-borono-2-(18)F-fluoro-L-phenylalanine-fructose ((18)F-FBPA-Fr) in F98 glioma-bearing Fischer 344 rats by means of intravenous injection of (18)F-FBPA-Fr both with and without blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). METHODS: Dynamic PET imaging of (18)F-FBPA-Fr was performed on the ninth day after tumor implantation. Blood samples were collected to obtain an arterial input function for tracer kinetic modeling. Ten animals were scanned for approximately 3 h to estimate the uptake of (18)F radioactivity with respect to time for the pharmacokinetic analysis. Rate constants were calculated by use of a 3-compartment model. RESULTS: The accumulation of (18)F-FBPA-Fr in brain tumors and the tumor-to-contralateral brain ratio were significantly elevated after intravenous injection of (18)F-FBPA-Fr with BBB-D. (18)F-FBPA-Fr administration after sonication showed that the tumor-to-contralateral brain ratio for the sonicated tumors (3.5) was approximately 1.75-fold higher than that for the control tumors (2.0). Furthermore, the K1/k2 pharmacokinetic ratio after intravenous injection of (18)F-FBPA-Fr with BBB-D was significantly higher than that after intravenous injection without BBB-D. CONCLUSION: This study demonstrated that radioactivity in tumors and the tumor-to-normal brain ratio after intravenous injection of (18)F-FBPA-Fr with sonication were significantly higher than those in tumors without sonication. The K1/k2 ratio may be useful for indicating the degree of BBB-D induced by FUS. Further studies are needed to determine whether FUS may be useful for enhancing the delivery of boronophenylalanine in patients with high-grade gliomas.

Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.

The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption.

Polarity reversion of the operation mode of HfO2-based resistive random access memory devices by inserting Hf metal layer.

The reversion of polarity within bipolar resistive switching operation occurs in Pt/HfO2/TiN and Pt/Hf/HfO2/TiN resistive random access memory devices. This reversion of voltage polarity is the result of interface generation which induces a conduction mechanism transformation from Poole-Frenkel emission to space charge limited current mechanism. To prove the reversion of polarity, this study uses curve fitting of I-V relations to verify the conduction mechanism theoretically and physical analysis to verify the oxygen ion distribution practically. The proposed Pt/Hf/HfO2/TiN devices exhibit good resistive switching characteristics, such as good uniformity, low voltage operation, robust endurance (10(3) dc sweep), and long retention (3 x 10(4) s at 85 degrees C).

Resistive switching of Au/ZnO/Au resistive memory: an in situ observation of conductive bridge formation.

A special chip for direct and real-time observation of resistive changes, including set and reset processes based on Au/ZnO/Au system inside a transmission electron microscope (TEM), was designed. A clear conducting bridge associated with the migration of Au nanoparticles (NPs) inside a defective ZnO film from anode to cathode could be clearly observed by taking a series of TEM images, enabling a dynamic observation of switching behaviors. A discontinuous region (broken region) nearby the cathode after reset process was observed, which limits the flow of current, thus a high resistance state, while it will be reconnected to switch the device from high to low resistance states through the migration of Au NPs after set process. Interestingly, the formed morphology of the conducting bridge, which is different from the typical formation of a conducting bridge, was observed. The difference can be attributed to the different diffusivities of cations transported inside the dielectric layer, thereby significantly influencing the morphology of the conducting path. The current TEM technique is quite unique and informative, which can be used to elucidate the dynamic processes in other devices in the future.

Improved performance of ZnO-based resistive memory by internal diffusion of Ag atoms.

An Ag/ZnO/Pt memory device, which has much better resistive switching behaviour than Pt/ZnO/Pt device was demonstrated. The detailed resistive mechanisms for the Pt/ZnO/Pt and the Ag/ZnO/Pt systems are proposed and investigated. Microstructures are observed by transmission electron microscope (TEM), indicating that the formation of conducting path for both systems is different. For the Pt/ZnO/Pt device, the conductive filament path is constructed by the oxygen vacancies from top to bottom electrodes under a larger enough bias at a forming process. For the Ag/ZnO/Pt device, the filament path was grown by oxygen vacancies combined with an internal diffusion of Ag atoms under a large bias and can provide the lowest energy barrier for electrons transported between two electrodes during set and reset processes, which reduces formation of other conducting paths after each switching. Accordingly, the stable switching performance of the Ag/ZnO/Pt device can be achieved over 100 cycles even the thickness of ZnO film <25 nm.

ZnO1-x nanorod arrays/ZnO thin film bilayer structure: from homojunction diode and high-performance memristor to complementary 1D1R application.

We present a ZnO(1-x) nanorod array (NR)/ZnO thin film (TF) bilayer structure synthesized at a low temperature, exhibiting a uniquely rectifying characteristic as a homojunction diode and a resistive switching behavior as memory at different biases. The homojunction diode is due to asymmetric Schottky barriers at interfaces of the Pt/ZnO NRs and the ZnO TF/Pt, respectively. The ZnO(1-x) NRs/ZnO TF bilayer structure also shows an excellent resistive switching behavior, including a reduced operation power and enhanced performances resulting from supplements of confined oxygen vacancies by the ZnO(1-x) NRs for rupture and recovery of conducting filaments inside the ZnO TF layer. A hydrophobic behavior with a contact angle of ~125° can be found on the ZnO(1-x) NRs/ZnO TF bilayer structure, demonstrating a self-cleaning effect. Finally, a successful demonstration of complementary 1D1R configurations can be achieved by simply connecting two identical devices back to back in series, realizing the possibility of a low-temperature all-ZnO-based memory system.

Extraction of an input function from dynamic micro-PET images using wavelet packet based sub-band decomposition independent component analysis.

Positron emission tomography (PET) can be used to quantify physiological parameters. However to perform quantification requires that an input function is measured, namely a plasma time activity curve (TAC). Image-derived input functions (IDIFs) are attractive because they are noninvasive and nearly no blood loss is involved. However, the spatial resolution and the signal to noise ratio (SNR) of PET images are low, which degrades the accuracy of IDIFs. The objective of this study was to extract accurate input functions from microPET images with zero or one plasma sample using wavelet packet based sub-band decomposition independent component analysis (WP SDICA). Two approaches were used in this study. The first was the use of simulated dynamic rat images with different spatial resolutions and SNRs, and the second was the use of dynamic images of eight Sprague-Dawley rats. We also used a population-based input function and a fuzzy c-means clustering approach and compared their results with those obtained by our method using normalized root mean square errors, area under curve errors, and correlation coefficients. Our results showed that the accuracy of the one-sample WP SDICA approach was better than the other approaches using both simulated and realistic comparisons. The errors in the metabolic rate, as estimated by one-sample WP SDICA, were also the smallest using our approach.

Reliability characteristics and conduction mechanisms in resistive switching memory devices using ZnO thin films.

In this work, bipolar resistive switching characteristics were demonstrated in the Pt/ZnO/Pt structure. Reliability tests show that ac cycling endurance level above 106 can be achieved. However, significant window closure takes place after about 102 dc cycles. Data retention characteristic exhibits no observed degradation after 168 h. Read durability shows stable resistance states after 106 read times. The current transportation in ZnO films is dominated by the hopping conduction and the ohmic conduction in high-resistance and low-resistance states, respectively. Therefore, the electrical parameters of trap energy level, trap spacing, Fermi level, electron mobility, and effective density of states in conduction band in ZnO were identified.