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Objective: Neuronal precursor cells expressed developmentally down‐regulated 4 (Nedd4) are believed to play a critical role in promoting the degradation of substrate proteins and are involved in numerous biological processes. However, the role of Nedd4 in intracerebral hemorrhage (ICH) remains unknown. This study aims to investigate the regulatory role of Nedd4 in the ICH model. Methods: Male C57BL/6J mice were induced with ICH. Subsequently, the levels of glutathione peroxidase 4 (GPX4), malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, as well as the expression of divalent metal transporter 1 (DMT1) and Nedd4 were assessed after ICH. Furthermore, the impact of Nedd4 overexpression was evaluated through analyses of hematoma area, ferroptosis, and neurobehavioral function. The mechanism underlying Nedd4‐mediated degradation of DMT1 was elecidated using immunoprecipitation (IP) after ICH. Results: Upon ICH, the level of DMT1 in the brain increased, but decreased when Nedd4 was overexpressed using Lentivirus, suggesting a negative correlation between Nedd4 and DMT1. Additionally, the degradation of DMT1 was inhibited after ICH. Furthermore, it was found that Nedd4 can interact with and ubiquitinate DMT1 at lysine residues 6, 69, and 277, facilitating the degradation of DMT1. Functional analysis indicated that overexpression of Nedd4 can alleviate ferroptosis and promote recovery following ICH. Conclusion: The results demonstrated that ferroptosis occurs via the Nedd4/DMT1 pathway during ICH, suggesting it potential as a valuable target to inhibit ferroptosis for the treatment of ICH. [ABSTRACT FROM AUTHOR]

Objective: Microglial polarization plays a critical role in neuroinflammation and may be a potential therapeutic target for ischemic stroke. This study was to explore the role and underlying molecular mechanism of Circular RNA PTP4A2 (circPTP4A2) in microglial polarization after ischemic stroke. Methods: C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO), while primary mouse microglia and BV2 microglial cells experienced oxygen glucose deprivation/reperfusion (OGD/R) to mimic ischemic conditions. CircPTP4A2 shRNA lentivirus and Colivelin were used to knock down circPTP4A2 and upregulate signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. Microglial polarization was assessed using immunofluorescence staining and Western blot. RNA pull‐down and RNA binding protein immunoprecipitation (RIP) were applied to detect the binding between circPTP4A2 and STAT3. Results: The levels of circPTP4A2 were significantly increased in plasma and peri‐infarct cortex in tMCAO mice. CircPTP4A2 knockdown reduced infarct volume, increased cortical cerebral blood flow (CBF), and attenuated neurological deficits. It also decreased pro‐inflammatory factors levels in peri‐infarct cortex and plasma, and increased anti‐inflammatory factors concentrations 24 h post‐stroke. In addition, circPTP4A2 knockdown suppressed M1 microglial polarization and promoted M2 microglial polarization in both tMCAO mice and OGD/R‐induced BV2 microglial cells. Moreover, circPTP4A2 knockdown inhibited the phosphorylation of STAT3 induced by oxygen–glucose deprivation. In contrast, increased phosphorylation of STAT3 partly counteracted the effects of circPTP4A2 knockdown. RNA pull‐down and RIP assays further certified the binding between circPTP4A2 and STAT3. Conclusion: These results revealed regulatory mechanisms of circPTP4A2 that stimulated neuroinflammation by driving STAT3‐dependent microglial polarization in ischemic brain injury. CircPTP4A2 knockdown reduced cerebral ischemic injury and promoted microglial M2 polarization, which could be a novel therapeutic target for ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: Accumulating studies have shown that circulating circular RNAs (circRNAs) represent novel biomarkers for many human diseases. We investigated whether plasma circPTP4A2 and circTLK2 levels are associated with stroke severity, infarct volume, stroke etiology, and functional outcome in acute ischemic stroke (AIS) patients. Methods: We applied quantitative real‐time PCR (qPCR) to measure plasma circPTP4A2 and circTLK2 levels of 236 AIS patients within 72 h of symptoms onset and 136 healthy controls. We further assessed the National Institutes of Health Stroke Scale (NIHSS), infarct size, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and the 90‐day modified Rankin scale (mRS) for each patient. Results: At admission, plasma circPTP4A2 and circTLK2 levels in patients with moderate to severe stroke were significantly higher compared to those with mild stroke. Logistic regression and receiver‐operating characteristic (ROC) curve analyses indicated that they might function as predictive biomarkers for moderate to severe stroke. We also observed a medium positive correlation between these two circRNAs and NIHSS. Plasma circPTP4A2 and circTLK2 levels were slight positively correlated with cerebral infarct volume only in anterior circulation infarction (ACI) patients. Levels of both circPTP4A2 and circTLK2 were closely related with large artery atherosclerosis (LAA) stroke. Moreover, changes within 7 days after admission in circPTP4A2 and circTLK2 were able to predict unfavorable clinical outcome 90 days after AIS. Interpretation: These results demonstrate that plasma circPTP4A2 and circTLK2 strongly correlated with severity, subtypes and prognosis of AIS, and they could serve as promising biomarkers. [ABSTRACT FROM AUTHOR]

Aim: To examine the expression profile of FMO1 in papillary thyroid cancer (PTC) and its prognostic value in recurrence-free survival (RFS). Methods: A retrospective analysis was performed using data from the Cancer Genome Atlas and Human Protein Atlas. Results: The most frequent variants of PTC had decreased FMO1 expression compared with their respective adjacent normal tissues. However, even under the best cut-off model, high FMO1 expression was only significantly associated with better RFS in classical PTC (p < 0.001), but not in other two variants. High FMO1 expression independently predicted favorable RFS (hazard ratio: 0.202; 95% CI: 0.084-0.487; p < 0.001) in classical PTC. Conclusion: High FMO1 expression might serve as a biomarker that independently predicts favorable RFS in classical PTC patients. [ABSTRACT FROM AUTHOR]

Abstracts The bottom-gate structure ZnO based thin film transistors (ZnO-TFTs) using Bi 1.5 Zn 1.0 Nb 1.5 O 7 (BZN) thin films as gate insulator were fabricated on Pt/SiO 2 /Si substrate by radio frequency magnetic sputtering at room temperature. We investigated the effect of thicknesses (100 nm, 170 nm, 250 nm, and 330 nm) of BZN thin films on the performance of BZN thin films and ZnO-TFTs. The results show that 170-nm-thick BZN thin film obtained high dielectric constant of 71, low roughness of 3.51 nm and low leakage current density of 10 −7 A/cm 2 , which is approximately one order magnitude lower than that of 100-nm-thick BZN thin film. Also, we concluded that the electrical performance of ZnO-TFTs using 170-nm-thick BZN thin film as gate insulator is enhanced remarkably. On/off current ratio (1.1 × 10 5 ) and field effect mobility (0.22 cm 2 /Vs) of ZnO-TFTs are approximately one order magnitude and seven times larger, respectively than that of ZnO-TFTs using 100 nm-thick BZN thin film as gate insulator. Meanwhile, surface states density (3.21 × 10 12 ) of ZnO-TFTs is reduced three times. [ABSTRACT FROM AUTHOR]

Objective: Klebsiella pneumoniae (Kp) bloodstream infections (BSI) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for Kp BSI., Methods: We retrospectively analyzed 72 patients suspected with bloodstream infection and mNGS Kp positive in peripheral blood, who were hospitalized in our hospital from January 2022 to January 2023. Clinical data and laboratory parameters were collected. All patients had blood drawn and other samples for blood mNGS, blood cultures (BC) and other cultures (OC). The accuracy of mNGS results was analyzed according to infection site, clinical indicators, therapeutic effect and routine culture results. The detection of pathogenic microorganisms by blood mNGS and routine culture was compared., Results: Among 72 infection patients, 29 cases (40.28%) were BC positive, 43 cases (59.72%) were other culture (OC) positive, 16 cases (22.22%) were both BC and OC positive, 56 cases were positive for both mNGS and routine culture. Among the 56 double-positive cases, mNGS and conventional cultures were completely consistent in 27 cases, partially consistent in 15 cases, and completely inconsistent in 14 cases. Using the clinical diagnosis as the reference standard, There were 51 cases consistent with the results of mNGS with Kp BSI, the clinical consistency was 70.83% (51/72). The coincidence rate of mNGS and clinical diagnosis was higher than that of BC (54.17%, 39/72), indicating a statistically significant difference between the two methods ( P <0.01)., Conclusions: Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of Kp BSI. Although it cannot replace blood culture detection technology, it can be used as a supplement to provide stronger diagnostic capabilities for BSI and optimize treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Liu, Zhang, Cui, Zhu, Li, Wang and Wang.)