Molecular epidemiology and resistance mechanisms of tigecycline-non-susceptible Acinetobacter baumannii isolated from a tertiary care hospital in Chongqing, China.

We studied 34 isolates of Tigecycline-Non-Susceptible A. baumannii (TNAB) obtained from clinical specimens at a large tertiary care hospital in Chongqing, China. These 34 strains belonged to 8 different clones including ST195 (35.3%) and ST208 (17.7%). EBURST analysis found that these 8 ST types belonged to the Clonal Complex 92. Tigecycline resistance-associated genes adeR, adeS, adeL, adeN, rrf, rpsJ, and trm were detected in most strains. The expression level of the resistance-nodulation-cell division (RND) efflux pumps in TNAB strains was higher than the reference strain ATCC19606. 58.8% of strains had a decrease in the tigecycline minimum inhibitory concentration (MIC) after the addition of carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The TNAB strains in our hospital have a high degree of affinity and antibiotic resistance. Regular surveillance should be conducted to prevent outbreaks of TNAB epidemics.

METTL14 is decreased and regulates m6 A modification of α-synuclein in Parkinson's disease.

N6-methyladenosine (m6A), an emerging modification of messenger RNA, has been implicated in many biological processes. However, its role in Parkinson's disease (PD) remains largely unknown. Here, we investigated the role of m6A modification and its underlying mechanism in PD. First, 86 individuals with PD and 86 healthy controls were recruited from a pilot multicenter cohort. Levels of m6A and its modulators in peripheral blood mononuclear cells of patients with PD and controls were measured using an m6A RNA methylation quantification kit and quantitative real-time PCR. The underlying mechanism of m6A modification in PD was investigated in vitro through RNA immunoprecipitation assay, RNA stability assay, gene silencing or overexpression, western blot, and confocal immunoassay. The results show that mRNA levels of m6A, METTL3, METTL14, and YTHDF2 in patients with PD were significantly lower than in healthy controls, and METTL14 was the main factor involved in abnormal m6A modification. Area under the curve (AUC) analysis suggests METTL14 may provide excellent diagnostic capability for PD, especially when combined with plasma α-synuclein (α-syn). Spearman correlation analysis identified that METTL14 was moderately negatively correlated with plasma α-syn and the motor function of PD. Mechanistic experiments demonstrated that Mettl14 targets and regulates the expression of the α-syn gene using its methylation function. Overexpression of Mettl14 dramatically increased m6 A modification of α-syn mRNA and weakened its stability. Further results suggest that α-syn mRNA was modified by Mettl14 binding of an m6 A motif in the coding region of α-syn mRNA, while the reading protein Ythdf2 was involved in recognizing m6 A-modified α-syn mRNA. Taken together, our results reveal the potential of METTL14 as a novel diagnostic biomarker for PD and identify modification of pathogenic α-syn protein by METTL14 via an m6 A-YTHDF2-dependent mechanism.

Nickel-Catalyzed Reductive Cross-Coupling of Allylammonium Salts with Alkyl Iodides.

An unprecedented reductive cross-coupling reaction of allylammonium salts with alkyl electrophiles has been established through C-N bond cleavage. A range of allylammonium bromides smoothly participated in the nickel-catalyzed zinc-mediated allyl-alkyl cross-electrophile coupling reaction with alkyl iodides, delivering structurally diverse alkene products in moderate to good yields with high linear selectivity. Preliminary mechanistic experiments are consistent with the formation of an alkyl radical from the alkyl iodide.

Effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery: A meta-analysis.

We performed a meta-analysis to evaluate the effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery. A systematic literature search up to June 2022 was performed and 6026 subjects with lower gastrointestinal surgery at the baseline of the studies; 3090 of them were using the wound protector, and 2936 were using no wound protector. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery using the dichotomous methods with a random or fixed-effect model. The surgical site wound infection was significantly lower with single-ring wound protectors (OR, 0.53; 95% CI, 0.39-0.83, P = .004), and dual-ring wound protectors (OR, 0.44; 95% CI, 0.35-0.56, P < .001) in subjects with lower gastrointestinal surgery compared with no wound protector. The surgical site wound infection was significantly lower with single-ring wound protectors, and dual-ring wound protectors in subjects with lower gastrointestinal surgery compared with no wound protector. The analysis of outcomes should be with caution because of the low sample size of 5 out of 28 studies in the meta-analysis and a low number of studies in certain comparisons.

The potential protective role of Parkinson's disease against hypothyroidism: co-localisation and bidirectional Mendelian randomization study.

Background: The association between hypothyroidism and Parkinson's disease (PD) has sparked intense debate in the medical community due to conflicting study results. A better understanding of this association is crucial because of its potential implications for both pathogenesis and treatment strategies. Methods: To elucidate this complex relationship, we used Bayesian co-localisation (COLOC) and bidirectional Mendelian randomization (MR) analysis. COLOC was first used to determine whether hypothyroidism and PD share a common genetic basis. Subsequently, genetic variants served as instrumental variables in a bidirectional MR to explore causal interactions between these conditions. Results: COLOC analysis revealed no shared genetic variants between hypothyroidism and PD, with a posteriori probability of hypothesis 4 (PPH4) = 0.025. Furthermore, MR analysis indicated that hypothyroidism does not have a substantial causal effect on PD (OR = 0.990, 95% CI = 0.925, 1.060, p = 0.774). Conversely, PD appears to have a negative causal effect on hypothyroidism (OR = 0.776, 95% CI = 0.649, 0.928, p = 0.005). Conclusion: Our findings suggest the absence of shared genetic variants between hypothyroidism and PD. Interestingly, PD may inversely influence the risk of developing hypothyroidism, a finding that may inform future research and clinical approaches.

Essential oil from Fructus Alpiniae zerumbet ameliorates vascular endothelial cell senescence in diabetes by regulating PPAR-γ signalling: A 4D label-free quantitative proteomics and network pharmacology study.

ETHNOPHARMACOLOGICAL RELEVANCE: Vascular endothelial cell senescence is associated with cardiovascular complications in diabetes. Essential oil from Fructus Alpiniae zerumbet (Pers.) B.L.Burtt & R.M.Sm. (EOFAZ) has potentially beneficial and promising diabetes-related vascular endothelial cell senescence-mitigating effects; however, the underlying molecular mechanisms remain unclear. AIM OF THE STUDY: To investigate the molecular effects of EOFAZ on vascular endothelial cell senescence in diabetes. MATERIALS AND METHODS: A diabetes mouse model was developed using a high-fat and high-glucose diet (HFD) combined with intraperitoneal injection of low-dose streptozotocin (STZ, 30 mg/kg) and oral treatment with EOFAZ. 4D label-free quantitative proteomics, network pharmacology, and molecular docking techniques were employed to explore the molecular mechanisms via which EOFAZ alleviates diabetes-related vascular endothelial cell senescence. A human aortic endothelial cells (HAECs) senescence model was developed using high palmitic acid and high glucose (PA/HG) concentrations in vitro. Western blotting, immunofluorescence, SA-ß-galactosidase staining, cell cycle, reactive oxygen species (ROS), cell migration, and enzyme linked immunosorbent assays were performed to determine the protective role of EOFAZ against vascular endothelial cell senescence in diabetes. Moreover, the PPAR-γ agonist rosiglitazone, inhibitor GW9662, and siRNA were used to verify the underlying mechanism by which EOFAZ combats vascular endothelial cell senescence in diabetes. RESULTS: EOFAZ treatment ameliorated abnormal lipid metabolism, vascular histopathological damage, and vascular endothelial aging in diabetic mice. Proteomics and network pharmacology analysis revealed that the differentially expressed proteins (DEPs) and drug-disease targets were associated with the peroxisome proliferator-activated receptor gamma (PPAR-γ) signalling pathway, a key player in vascular endothelial cell senescence. Molecular docking indicated that the small-molecule compounds in EOFAZ had a high affinity for the PPAR-γ protein. Western blotting and immunofluorescence analyses confirmed the significance of DEPs and the involvement of the PPAR-γ signalling pathway. In vitro, EOFAZ and rosiglitazone treatment reversed the effects of PA/HG on the number of senescent endothelial cells, expression of senescence-related proteins, the proportion of cells in the G0/G1 phase, ROS levels, cell migration rate, and expression of pro-inflammatory factors. The protective effects of EOFAZ against vascular endothelial cell senescence in diabetes were aborted following treatment with GW9662 or PPAR-γ siRNA. CONCLUSIONS: EOFAZ ameliorates vascular endothelial cell senescence in diabetes by activating PPAR-γ signalling. The results of the present study highlight the potential beneficial and promising therapeutic effects of EOFAZ and provide a basis for its clinical application in diabetes-related vascular endothelial cell senescence.

Efficacy of probiotics on nonalcoholic fatty liver disease: A meta-analysis.

OBJECTIVES: The intestinal flora is closely related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study intends to systematically evaluate the efficacy and safety of probiotics in the treatment of NAFLD through a meta-analysis of published randomized controlled trials. METHODS: This study was conducted through a search of published randomized controlled trials using probiotic-related drugs for the treatment of nonalcoholic fatty liver disease (up to April 6, 2022). The JADAD evaluation table was used to evaluate the quality of the literatures included in the search, and the risk of bias was evaluated according to the Cochrane evaluation manual. Finally, RevMan5.4 software was used for meta-analysis. RESULTS: A total of 21 randomized clinical trials involving 1037 patients with NAFLD were included in this study. Meta-analysis results showed that after probiotic intervention, liver function, blood lipid level, blood glucose levels and insulin levels were significantly reduced, which had a good effect on improving hepatic steatosis. However, it did not significantly improve BMI, inflammatory factors, or homeostasis model assessment of insulin resistance. Through the subgroup analysis of the course of treatment, it was found that ALT, GGT, TG, and blood sugar improved better in the probiotic treatment course of greater than or equal to 12 weeks. CONCLUSION: This study shows that the use of probiotics therapy has a good regulating effect on liver function, steatosis, blood glucose level, insulin level and blood lipid level in NAFLD patients.

Experimental Study on the Mechanism of Radial Change of Simulated Enrichment Nutrient Solution Injection into Coal Seams.

This paper deals with enhanced coal bed methane recovery and geological CO2 storage, combined with the dual effect of increasing coal-bed methane and achieving carbon emission reduction. Coal of different particle sizes were loaded into acrylic tanks of a certain height, and peristaltic pumps were used to enrich nutrient solution and CO2 into different layers of coal seams, to monitor the liquid phase pH, COD, OD600, aromatic structure, HCO3-, three-dimensional fluorescence data of the upper, middle, and lower layers, and the specific surface area of coal Poreginseng. The following conclusions were drawn: (1) the reaction with CO2 resulted in a lower pH than that without CO2, with weak acidity and higher concentration of HCO3- ions. The OD600 concentration and activity of the bacterial solution were stronger. Most of the solution was dominated by Clostridium acidophilum, and the three-dimensional fluorescence results are also shown. (2) Coal samples with small particle sizes had a larger surface area, more contact area with bacterial liquid, and a more complete reaction, so the physical property transformation of coal reservoirs with small particle sizes was more obvious, and the COD change was the largest. (3) The upper and middle layers were exposed to more bacterial fluid and CO2, resulting in a more complete degradation reaction.

The emerging role of circular RNAs in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. It involves a gradual loss of dopaminergic neurons in the substantia nigra. Although many studies have been conducted, the underlying molecular pathways of PD remain largely unknown. Circular RNAs (circRNAs), a novel class of non-coding RNAs with a covalently closed loop structure, are common in the brain. They are stable, conserved molecules that are widely expressed in eukaryotes in tissue-, cell-, and development-specific patterns. Many circRNAs have recently been identified in nervous system diseases, and some circRNA expression profiles have been linked to PD. Given that recent research has indicated the essential roles of various circRNAs in the development and progression of neurodegenerative diseases, the identification of individual circRNAs may be a promising strategy for finding new treatment targets for PD. Moreover, the search for circRNAs with high specificity and sensitivity will open up new avenues for the early diagnosis and treatment of PD. Herein, we address the biogenesis, properties, and roles of circRNAs and review their potential utility as biomarkers and therapeutic targets in PD.

HfO2-based ferroelectric thin film and memory device applications in the post-Moore era: A review.

The rapid development of 5G, big data, and Internet of Things (IoT) technologies is urgently required for novel non-volatile memory devices with low power consumption, fast read/write speed, and high reliability, which are crucial for high-performance computing. Ferroelectric memory has undergone extensive investigation as a viable alternative for commercial applications since the post-Moore era. However, conventional perovskite-structure ferroelectrics (e.g., PbZr x Ti1- x O3) encounter severe limitations for high-density integration owing to the size effect of ferroelectricity and incompatibility with complementary metal-oxide-semiconductor technology. Since 2011, the ferroelectric field has been primarily focused on HfO2-based ferroelectric thin films owing to their exceptional scalability. Several reviews discussing the control of ferroelectricity and device applications exist. It is believed that a comprehensive understanding of mechanisms based on industrial requirements and concerns is necessary, such as the wake-up effect and fatigue mechanism. These mechanisms reflect the atomic structures of the materials as well as the device physics. Herein, a review focusing on phase stability and domain structure is presented. In addition, the recent progress in related ferroelectric memory devices and their challenges is briefly discussed.

Long-term spatiotemporal and highly specific imaging of the plasma membrane of diverse plant cells using a near-infrared AIE probe.

Fluorescent probes are valuable tools to visualize plasma membranes intuitively and clearly and their related physiological processes in a spatiotemporal manner. However, most existing probes have only realized the specific staining of the plasma membranes of animal/human cells within a very short time period, while almost no fluorescent probes have been developed for the long-term imaging of the plasma membranes of plant cells. Herein, we designed an AIE-active probe with NIR emission to achieve four-dimensional spatiotemporal imaging of the plasma membranes of plant cells based on a collaboration approach involving multiple strategies, demonstrated long-term real-time monitoring of morphological changes of plasma membranes for the first time, and further proved its wide applicability to plant cells of different types and diverse plant species. In the design concept, three effective strategies including the similarity and intermiscibility principle, antipermeability strategy and strong electrostatic interactions were combined to allow the probe to specifically target and anchor the plasma membrane for an ultralong amount of time on the premise of guaranteeing its sufficiently high aqueous solubility. The designed APMem-1 can quickly penetrate cell walls to specifically stain the plasma membranes of all plant cells in a very short time with advanced features (ultrafast staining, wash-free, and desirable biocompatibility) and the probe shows excellent plasma membrane specificity without staining other areas of the cell in comparison to commercial FM dyes. The longest imaging time of APMem-1 can be up to 10 h with comparable performance in both imaging contrast and imaging integrity. The validation experiments on different types of plant cells and diverse plants convincingly proved the universality of APMem-1. The development of plasma membrane probes with four-dimensional spatial and ultralong-term imaging ability provides a valuable tool to monitor the dynamic processes of plasma membrane-related events in an intuitive and real-time manner.

Emergence of Tigecycline and Carbapenem-Resistant Citrobacter freundii Co-Carrying tmexCD1-toprJ1, blaKPC-2, and blaNDM-1 from a Sepsis Patient.

Purpose: This research aims to profile ten novel strains of carbapenem-resistant Enterobacteriaceae (CRE) co-carrying blaKPC and blaNDM. Methods: Clinical CRE strains, along with corresponding medical records, were gathered. To ascertain the susceptibility of the strains to antibiotics, antimicrobial susceptibility tests were conducted. To validate the transferability and cost of fitness of plasmids, conjugation experiments and growth curves were employed. For determining the similarity between different strains, ERIC-PCR was utilised. Meanwhile, whole genome sequencing (WGS) was performed to characterise the features of plasmids and their evolutionary characteristics. Results: During the course of this research, ten clinical CRE strains co-carrying blaKPC and blaNDM were gathered. It was discovered that five out of these ten strains exhibited resistance to tigecycline. A closer examination of the mechanisms underlying tigecycline resistance revealed that tmexCD1-toprJ1, blaKPC-2, and blaNDM-1 existed concurrently within a single Citrobacter freundii strain (CF10). This strain, with a minimum inhibitory concentration (MIC) of 32 mg/L to tigecycline, was obtained from a sepsis patient. Furthermore, an investigation of genome evolution implied that CF10 belonged to a novel ST type 696, which lacked analogous strains. Aligning plasmids exposed that similar plasmids all had less than 70% coverage when compared to pCF10-tmexCD1, pCF10-KPC, and pCF10-NDM. It was also found that tmexCD1-toprJ1, blaKPC-2, and blaNDM-1 were transferred by Tn5393, IS5, and Tn6296, respectively. Conclusion: This research presents the first report of coexistence of tmexCD1-toprJ1, blaKPC-2, and blaNDM-1 in a carbapenem and tigecycline-resistant C. freundii strain, CF10. Importance: Tigecycline is considered a "last resort" antibiotic for treating CRE infections. The ongoing evolution of resistance mechanisms to both carbapenem and tigecycline presents an alarming situation. Moreover, the repeated reporting of both these resistance mechanisms within a single strain poses a significant risk to public health. The research revealed that the genes tmexCD1-toprJ1, blaKPC-2, and blaNDM-1, which cause carbapenem and tigecycline-resistance in the same strain, were located on mobile elements, suggesting a potential for horizontal transmission to other Gram-negative bacteria. The emergence of such a multi-resistant strain within hospitals should raise significant concern due to the scarcity of effective antimicrobial treatments for these "superbugs".

The Potential Circular RNAs Biomarker Panel and Regulatory Networks of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease. It has been reported that circular RNAs (circRNAs) play important roles in several neurological diseases. However, the role and regulatory networks of circRNAs in PD are still largely unclear. In this study, we first compared the global expression level of circRNAs from patients with PD and controls using microarray, then the candidate circRNAs were validated in another PD cohort. The possible functions of these candidate circRNAs were analyzed using Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the regulatory networks of these candidate circRNAs were constructed through circRNA-miRNA-mRNA regulatory networks, protein-protein interaction (PPI) networks, and transcription factor-circRNA networks. The results indicated that hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 were significantly more highly expressed in patients with PD, while hsa_circRNA_102850 was lower expressed in patients with PD when compared with controls. A circRNA panel combining the four differentially expressed circRNA showed a high diagnostic ability to distinguish patients with PD from controls (AUC = 0.938). Furthermore, GO and KEGG analysis showed these candidate circRNAs were enriched in PI3K-Akt and MAPK signaling pathways. We established circRNA-miRNA-mRNA regulatory networks and identified 10 hub genes (ESR1, PTEN, SHC1, IGF1R, SMAD2, KRAS, MDM2, HIF1A, BMP4, and ACVR2B) were closely related to PD by using PPI network analysis. Besides, these circRNAs were predicted to be regulated through tyrosine hydroxylase (TH)-relevant transcription factors such as GATA2 and GATA3. In conclusion, our results suggest that the circRNA panel and the established circRNA-miRNA-mRNA regulation networks might provide potential novel biomarkers and therapeutic targets for PD.

Coexistence of Multidrug Resistance and Virulence in a Single Conjugative Plasmid from a Hypervirulent Klebsiella pneumoniae Isolate of Sequence Type 25.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has received considerable attention. Typically, the genetic elements that confer virulence are harbored by nonconjugative plasmids. In this study, we report a CR-hvKP strain, CY814036, of high-risk sequence type 25 (ST25) and the K2 serotype, which is uncommon among K. pneumoniae isolates but caused serious lung infection in a tertiary teaching hospital in China. Whole-genome sequencing (WGS) revealed a rare conjugative plasmid, pCY814036-iucA, carrying a virulence-associated iuc operon (iucABCD-iutA) coding for aerobactin and determinants of multidrug resistance (MDR), coexisting with a conjugative blaKPC-2-bearing plasmid, pCY814036-KPC2, in the same strain. A conjugation assay showed that pCY814036-iucA and pCY814036-KPC2 could be efficiently cotransmitted from CY814036 to Escherichia coli EC600. Further phenotypic investigation, including antimicrobial susceptibility tests, serum resistance assays, and mouse infection models, confirmed that pCY814036-iucA was capable of cotransferring multidrug resistance and hypervirulence features to the recipient. pCY814036-KPC2 also conferred resistance to antibiotics, including ß-lactams and aminoglycosides. Overall, the rare coexistence of a conjugative MDR-virulence plasmid and a blaKPC-2-bearing plasmid in a K. pneumoniae isolate offers a possible mechanism for the formation of CR-hvKP strains and the potential to significantly accelerate the propagation of high-risk phenotypes. IMPORTANCE The increased reporting of carbapenem-resistant hypervirulent K. pneumoniae is considered a worrisome concern to human health care and has restricted the choice of effective antibiotics for clinical treatment. Moreover, virulence plasmids with complete conjugation modules have been identified, which evolved via homologous recombination. Here, we characterize an ST25 CR-hvKP strain, CY814036, harboring both a conjugative MDR-virulence plasmid and a blaKPC-2-bearing plasmid in China. This study highlights that the cotransmission of drug resistance and virulence plasmids increases therapeutic difficulties and worsens clinical prognoses. Also, active surveillance of the conjugative MDR-virulence plasmid is necessary.

Emergence of a Fatal ST11-KL64 Tigecycline-Resistant Hypervirulent Klebsiella pneumoniae Clone Cocarrying blaNDM and blaKPC in Plasmids.

The combination of hypervirulent Klebsiella pneumoniae (hvKP) infection with carbapenem and tigecycline resistance leads to significant challenges to clinical treatment, with limited available antibiotics and poor patient prognoses. The hvKP12 isolate was obtained from a blood sample of a 74-year-old female in a Chinese teaching hospital. Whole-genome sequencing and microbial characterization were performed to understand the evolutionary mechanism of its resistance. The patient infected with hvKP12 died due to pyemia after a 17-day tigecycline treatment. The antimicrobial susceptibility test identified that hvKP12 was resistant to tigecycline and carbapenems. Variants of tet(A) and the overexpression of efflux pumps related to tigecycline resistance were detected in hvKP12. Conjugation experiments with blaNDM and blaKPC plasmids failed in the laboratory environment. Additionally, phylogenetic analysis suggested that hvKP12 was a clinical high-risk clone of ST11-KL64. We found that the blaKPC-2 gene segment was formed by IS26-mediated gene cluster translocation. Interestingly, the evolutionary pathway of hvKP12 suggested that the KPC-2-producing carbapenem-resistant K. pneumoniae (KPC-2-CRKP) strain evolved into a KPC-NDM-CRKP strain by acquiring the NDM plasmid. To our knowledge, this is the first report of tigecycline-resistant ST11-KL64 carbapenem-resistant hvKP (CR-hvKP) bacteria coproducing blaKPC and blaNDM, causing a fatal blood infection. IMPORTANCE Infections with CRKP coproducing KPC and NDM currently have limited clinical antibacterial options, and tigecycline is used as the last line of defense for therapy. However, this study found that CR-hvKP infection with tigecycline resistance, which may lead to many bacteria being resistant to most commonly used antibiotics, brought significant challenges to clinical treatment. The clonal propagation of ST11-KL64 CRKP should receive sufficient attention.

Decreased soluble Nogo-B in serum as a promising biomarker for Parkinson's disease.

Background: Recently, the neurite outgrowth inhibitor-B (Nogo-B) receptor has been reported as a novel candidate gene for Parkinson's disease (PD). Nogo-B receptors need to combine with soluble Nogo-B to exert their physiological function. However, little is known about the relationship between serum soluble Nogo-B and PD. Methods: Serum levels of sNogo-B and α-Synuclein (α-Syn) were measured in a cohort of 53 patients with PD and 49 healthy controls with the ELISA kit method. Results: Serum sNogo-B level is significantly lower in the PD group than that in healthy controls and is negatively correlated with UPDRS-III score (p = 0.049), H&Y stage (p = 0.0108) as well as serum α-Syn level (p = 0.0001). The area under the curve (AUC) of serum sNogo-B in differentiating patients with PD from controls was 0.801 while the AUC of serum α-Syn was 0.93. Combining serum sNogo-B and α-Syn in differentiating patients with PD from HC presented higher discriminatory potential (AUC = 0.9534). Conclusion: Decreased serum sNogo-B may be a potential biomarker for PD. Lower Nogo-B level reflects worse motor function and disease progression of PD. Serum sNogo-B is of added value to serum α-Syn panel in distinguishing PD from controls. Future studies are needed to confirm in larger samples and different populations.

Robustly Stable Ferroelectric Polarization States Enable Long-Term Nonvolatile Storage against Radiation in HfO2-Based Ferroelectric Field-Effect Transistors.

The ferroelectric field-effect transistors (FeFETs) with HfO2-based ferroelectric layers in the gate stacks are emerging as one of the most promising candidates for the next-generation nonvolatile memory devices due to their scalability and compatibility with conventional Si technology. Moreover, owing to the high radiation hardness of the HfO2-based ferroelectric thin films, HfO2-based FeFETs have attracted great interest in the fields of radiation-hard (rad-hard) memory. However, the reliability of their memory states under irradiation, which represents the validity of the stored information, has not been investigated. Here, we focus on the impact of the total ionizing dose (TID) on erased and programmed states of HfO2-based FeFETs. The TID radiation (X-ray) characteristics of erased and programmed HfO2-based FeFETs are characterized using an on-site read operation. Both the erased and programmed states show robust stability under irradiation at a dose rate of 90 rad(Si)/s, and even at 230 rad(Si)/s, only the erased state shows a slight variation. The possible factors contributing to memory state degradation are discussed. Through the analysis of the threshold voltage shift and subthreshold swing evolution, as well as studies of ferroelectric polarization stability under radiation, it is revealed that the erased state degradation is caused by oxide-trapped charges rather than interface degradation or polarization switching. The physical mechanism of the difference in radiation-induced oxide-trapped charges buildup in programmed and erased FeFETs is analyzed to explain different TID radiation characteristics between them. Our work suggests that the HfO2-based FeFETs have great potential in radiation environment applications.