Prognostic value and therapeutic potential of NEK family in stomach adenocarcinoma.

Never in mitosis gene A-related kinase (NEK) is an 11-membered family of serine/threonine kinases (NEK1-NEK11), which are known to play important roles in the formation and development of cancer. However, few studies have examined the roles of these kinases in the development of stomach adenocarcinoma (STAD). In this study, we conducted a comprehensive analysis of the relationships between the NEKs family members and STAD. The differential expression of the NEK genes in STAD was validated using The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases, and their prognostic and diagnostic values of NEKs in STAD were assessed using the Kaplan-Meier plotter and TCGA data. The effect of NEK expression on immune cell infiltration in STAD was analysed using the TIMER and TISIDB databases. The expression levels of the majority of the NEK family members were consistently upregulated in STAD, whereas that of NEK10 was downregulated. The upregulation of NEK2/3/4/5/6/8 was closely associated with clinicopathological parameters of patients, and the overexpressed levels of these proteins had good diagnostic value for the disease. NEK1/8/9/10/11 expression correlated with poor overall survival and post-progressive survival, whereas a higher NEK1/6/9/11 level implied worse first progressive survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the NEKs may be related to immunological responses. Additionally, our study confirmed that these kinases correlated with immune cell infiltration and different immune infiltration subtypes in STAD. Our results suggest that NEK9 in particular has the potential to be used as a diagnostic and prognostic biomarker of STAD development and progression and an immune target for treatment of the disease. These findings expand our understanding of the biological functions of the NEK family members in STAD.

Risk Prediction Models for Renal Function Decline After Cardiac Surgery Within Different Preoperative Glomerular Filtration Rate Strata.

BACKGROUND: Our goal was to create a simple risk-prediction model for renal function decline after cardiac surgery to help focus renal follow-up efforts on patients most likely to benefit. METHODS AND RESULTS: This single-center retrospective cohort study enrolled 24 904 patients who underwent cardiac surgery from 2012 to 2019 at Fuwai Hospital, Beijing, China. An estimated glomerular filtration rate (eGFR) reduction of ≥30% 3 months after surgery was considered evidence of renal function decline. Relative to patients with eGFR 60 to 89 mL/min per 1.73 m2 (4.5% [531/11733]), those with eGFR ≥90 mL/min per 1.73 m2 (10.9% [1200/11042]) had a higher risk of renal function decline, whereas those with eGFR ≤59 mL/min per 1.73 m2 (5.8% [124/2129]) did not. Each eGFR stratum had a different strongest contributor to renal function decline: increased baseline eGFR levels for patients with eGFR ≥90 mL/min per 1.73 m2, transfusion of any blood type for patients with eGFR 60 to 89 mL/min per 1.73 m2, and no recovery of renal function at discharge for patients with eGFR ≤59 mL/min per 1.73 m2. Different nomograms were established for the different eGFR strata, which yielded a corrected C-index value of 0.752 for eGFR ≥90 mL/min per 1.73 m2, 0.725 for eGFR 60-89 mL/min per 1.73 m2 and 0.791 for eGFR ≤59 mL/min per 1.73 m2. CONCLUSIONS: Predictors of renal function decline over the follow-up showed marked differences across the eGFR strata. The nomograms incorporated a small number of variables that are readily available in the routine cardiac surgical setting and can be used to predict renal function decline in patients stratified by baseline eGFR.

Risk factors of 30-day and long-term mortality and outcomes in open repair of thoracoabdominal aortic aneurysm.

BACKGROUND: Open repair of thoracoabdominal aortic aneurysm (TAAA) was characterized by significant risk of postoperative mortality and morbidity. The aim of this study was to determine the perioperative predictors of early and long-term mortality in patients undergoing open repair of TAAA. Besides, the postoperative outcomes in patients with open repair of TAAA were described. METHODS: This is a single-center retrospective study, and 146 patients with open repair of TAAA from January 4, 2011, to November 22, 2018 was involved. Categorical variables were analyzed by the Chi-square test or Fisher's exact test, and continuous variables were analyzed by the independent sample t-test and the WilCoxon rank-sum test. Multivariate Logistic regression and Cox regression were applied to identify the predictors of 30-day and long-term mortality, respectively. The Kaplan Meier curves were used to illustrate survival with the Log-rank test. RESULTS: The 30-day mortality was 9.59% (n = 14). Older than 50 years, the intraoperative volume of red blood cell (RBC) and epinephrine use were independently associated with postoperative 30-day mortality in open repair of TAAA. Long-term mortality was 17.12% (n = 25) (median of 3.5 years (IQR = 2-5 years) of follow-up). Prior open thoracoabdominal aortic aneurysm (TAAA) repair, aortic cross-clamping (ACC) time, intraoperative volume of RBC and use of epinephrine were independently correlated with long-term mortality. CONCLUSIONS: Identifying perioperative risk factors of early and long-term mortaliy is crucial for surgeons. Intraoperative volume of RBC and use of epinephrine were predictors of both early and long-term mortality. In addition, patients of advanced age, prior open repair of TAAA and prolonged ACC time should be paid more attention.

The genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia in China: a large cohort study.

BACKGROUND: An intronic GAA repeat expansion in FGF14 was recently identified as a cause of GAA-FGF14 ataxia. We aimed to characterise the frequency and phenotypic profile of GAA-FGF14 ataxia in a large Chinese ataxia cohort. METHODS: A total of 1216 patients that included 399 typical late-onset cerebellar ataxia (LOCA), 290 early-onset cerebellar ataxia (EOCA), and 527 multiple system atrophy with predominant cerebellar ataxia (MSA-c) were enrolled. Long-range and repeat-primed PCR were performed to screen for GAA expansions in FGF14. Targeted long-read and whole-genome sequencing were performed to determine repeat size and sequence configuration. A multi-modal study including clinical assessment, MRI, and neurofilament light chain was conducted for disease assessment. FINDINGS: 17 GAA-FGF14 positive patients with a (GAA)≥250 expansion (12 patients with a GAA-pure expansion, five patients with a (GAA)≥250-[(GAA)n (GCA)m]z expansion) and two possible patients with biallelic (GAA)202/222 alleles were identified. The clinical phenotypes of the 19 positive and possible positive cases covered LOCA phenotype, EOCA phenotype and MSA-c phenotype. Five of six patients with EOCA phenotype were found to have another genetic disorder. The NfL levels of patients with EOCA and MSA-c phenotypes were significantly higher than patients with LOCA phenotype and age-matched controls (p < 0.001). NfL levels of pre-ataxic GAA-FGF14 positive individuals were lower than pre-ataxic SCA3 (p < 0.001) and similar to controls. INTERPRETATION: The frequency of GAA-FGF14 expansion in a large Chinese LOCA cohort was low (1.3%). Biallelic (GAA)202/222 alleles and co-occurrence with other acquired or hereditary diseases may contribute to phenotypic variation and different progression. FUNDING: This study was funded by the National Key R&D Program of China (2021YFA0805200 to H.J.), the National Natural Science Foundation of China (81974176 and 82171254 to H.J.; 82371272 to Z.C.; 82301628 to L.W.; 82301438 to Z.L.; 82201411 to L.H.), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (2020JJ1008 to H.J.), the Key Research and Development Program of Hunan Province (2020SK2064 to H.J.), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to H.J., the Natural Science Foundation of Hunan Province (2024JJ3050 to H.J.; 2022JJ20094 and 2021JJ40974 to Z.C.; 2022JJ40783 to L.H.; 2022JJ40703 to Z.L.), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, 2020LNJJ12 to H.J.), the Central South University Research Programme of Advanced Interdisciplinary Study (2023QYJC010 to H.J.) and the Science and Technology Innovation Program of Hunan Province (2022RC1027 to Z.C.). D.P. holds a Fellowship award from the Canadian Institutes of Health Research (CIHR).

A review of passive acid mine drainage treatment by PRB and LPB: From design, testing, to construction.

An extensive volume of acid mine drainage (AMD) generated throughout the mining process has been widely regarded as one of the most catastrophic environmental problems. Surface water and groundwater impacted by pollution exhibit extreme low pH values and elevated sulfate and metal/metalloid concentrations, posing a serious threat to the production efficiency of enterprises, domestic water safety, and the ecological health of the basin. Over the recent years, a plethora of techniques has been developed to address the issue of AMD, encompassing nanofiltration membranes, lime neutralization, and carrier-microencapsulation. Nonetheless, these approaches often come with substantial financial implications and exhibit restricted long-term sustainability. Among the array of choices, the permeable reactive barrier (PRB) system emerges as a noteworthy passive remediation method for AMD. Distinguished by its modest construction expenses and enduring stability, this approach proves particularly well-suited for addressing the environmental challenges posed by abandoned mines. This study undertook a comprehensive evaluation of the PRB systems utilized in the remediation of AMD. Furthermore, it introduced the concept of low permeability barrier, derived from the realm of site-contaminated groundwater management. The strategies pertaining to the selection of materials, the physicochemical aspects influencing long-term efficacy, the intricacies of design and construction, as well as the challenges and prospects inherent in barrier technology, are elaborated upon in this discourse.

Highly sensitive detection of tryptophan based on Schiff base reaction and surface-enhanced Raman spectroscopy.

In this study, a simple, rapid and sensitive method combining surface-enhanced Raman spectroscopy and Schiff base reaction was developed for the detection of tryptophan. This method does not require product separation to obtain a significant Raman signal of the derivatized product, and the derivatization reaction can be controlled by experimental parameters such as reaction temperature, time, concentration of derivatization reagent and concentration of sodium nitrite. The characteristic peak of the derivative of tryptophan (1620 cm-1) was selected for quantitative analysis, and the intensity of the characteristic Raman spectrum peak showed a linear relationship with the concentration of tryptophan (10-8-10-4 mol/L) in the range of with a correlation coefficient R2 of 0.9922. This assay combines surface-enhanced Raman spectroscopy and Schiff base reaction, which is characterized by high sensitivity and easy operation, and has good application prospects in the detection of tryptophan in food.

Comparison of ozone-based AOPs on the removal of organic matter from the secondary biochemical effluent of coking wastewater.

Advanced oxidation processes (AOPs) based on ozone are gaining continuously growing popularity in wastewater treatment. This study explored the treatment of coking wastewater using a combination of ozonation (O3), ultraviolet (UV), and hydrogen peroxide (H2O2) process expressed by % chemical oxygen demand (COD) removal, % total organic carbon (TOC), % UV254, % fluorescence intensity removal and its electrical energy consumption. The obtained results demonstrated that, the combination of O3, UV, and H2O2 which is denoted by O3/UV/H2O2 in this study achieved great success in COD removal (92.08%), TOC removal (78.25%), and reduction of fluorescence intensity (99.82%). Compared with the O3 and O3/UV processes, O3/UV/H2O2 improved the COD removal by approximately 54-69% and 38-51%, respectively. In addition, the energy consumption was reduced by 53-67%. The TOC removal rate in the effluent ranged 71% and 83%, while the UV254 removal rate was up to 90%. The fluorescence spectroscopy showed that the O3/UV/H2O2 combination process reduced the fluorescence intensity by almost 97% within 10 min. Furthermore, the total polycyclic aromatic hydrocarbons (PAHs) concentration in the effluent was less than 10µg/L (removal efficiency > 80%) and the most toxic benzo(a)pyrene (BaP) was less than 0.03 µg/L (0.018µg/L). In addition, the energy consumption of the O3/UV/H2O2 process was 53-67% lower than those of O3 and O3/UV processes. Furthermore, the energy consumption was 80.26 kWh m-3 after 60 min of reaction time when the COD (69.3 mg/L) met the standard discharge. Finally, the O3/UV/H2O2 process could be an effective method for improving the mineralisation of refractory organic matter.

Guideline for modeling solid-liquid adsorption: Kinetics, isotherm, fixed bed, and thermodynamics.

During the years, adsorption has garnered considerable attention being one of the most cost-effective and efficient methods for separating contaminants out of liquid phase. A comprehensive understanding of adsorption mechanisms entails several crucial steps, including adsorbent characterization, batch and column adsorption tests, fitting of predefined kinetic and isotherm models, and meticulous thermodynamic analysis. These combined efforts serve to provide clarity and insights into the intricate workings of adsorption phenomena. However, the vast amount of literature published in the field each year is riddled with ill-considered model selections and incorrect parameter analyses. Therefore, the aim of this paper is to establish guidelines for the proper employment of these numerous kinetic, isotherm, and fixed-bed models in various applications. A thorough review has been undertaken, encompassing more than 45 kinetic models, 70 isotherm models, and 45 fixed bed models available hitherto, with their classification determined based on the adsorption mechanisms expounded within each of them. Moreover, five general approaches for modifying fixed-bed models were provided. The physical meanings, assumptions, and interconversion relationships of the models were discussed in detail, along with the information criterion used to evaluate their validity. In addition to commonly used activation energy and Gibbs energy analysis, the methods for calculating site energy distribution were also summarized.

An Explainable Machine Learning Model to Predict Acute Kidney Injury After Cardiac Surgery: A Retrospective Cohort Study.

Background: To derive and validate a machine learning (ML) prediction model of acute kidney injury (AKI) that could be used for AKI surveillance and management to improve clinical outcomes. Methods: This retrospective cohort study was conducted in Fuwai Hospital, including patients aged 18 years and above undergoing cardiac surgery admitted between January 1, 2017, and December 31, 2018. Seventy percent of the observations were randomly selected for training and the remaining 30% for testing. The demographics, comorbidities, laboratory examination parameters, and operation details were used to construct a prediction model for AKI by logistic regression and eXtreme gradient boosting (Xgboost). The discrimination of each model was assessed on the test cohort by the area under the receiver operator characteristic (AUROC) curve, while calibration was performed by the calibration plot. Results: A total of 15,880 patients were enrolled in this study, and 4845 (30.5%) had developed AKI. Xgboost model had the higher discriminative ability compared with logistic regression (AUROC, 0.849 [95% CI, 0.837-0.861] vs 0.803[95% CI 0.790-0.817], P<0.001) in the test dataset. The estimated glomerular filtration (eGFR) and creatine on intensive care unit (ICU) arrival are the two most important prediction parameters. A SHAP summary plot was used to illustrate the effects of the top 15 features attributed to the Xgboost model. Conclusion: ML models can provide clinical decision support to determine which patients should focus on perioperative preventive treatment to preemptively reduce acute kidney injury by predicting which patients are not at risk.

SERS detection of foodborne pathogens in beverage with Au nanostars.

The aim of this study is to develop a simple but rapid method for the determination of foodborne pathogens in complex matrices (beverages) by surface enhanced Raman spectroscopy (SERS) combined with Au nanostar solid-phase substrates. The star-shaped singlet Au nanostructure was formed on the surface of a stainless steel sheet by chemical replacement reaction. Rhodamine 6G verified the sensitivity and reproducibility of this substrate, and the relative standard deviations of the SERS intensity at 1312 cm-1, 1364 cm-1, and 1510 cm-1 displacements were 3.40%, 5.64%, and 3.48%, respectively. By detecting four pathogens in beverage samples on Au nanostar substrates, the utility of the SERS assay was demonstrated, while the combination of principal component analysis (PCA) and hierarchical cluster analysis (HCA) further enabled the isolation and identification of pathogens. The results of spiked beverages were validated in conventional culture identification and Vitek 2 Compact biochemical identification system experiments. Thus, this research demonstrated that Au nanostar substrates can be effectively utilized for the recognition of pathogenic bacteria and have immense promise to advance the progress of quick detection of foodborne pathogens and food safety.

Postoperative acute kidney injury after on-pump cardiac surgery in patients with connective tissue disease.

Objective: Patients with connective tissue disease have a poor prognosis after receiving cardiac surgery. This study described the clinical scenarios and investigated factors correlated with acute kidney injury (AKI) after on-pump cardiac surgery in patients with systemic lupus erythematosus (SLE) or vasculitis. Methods: Patients with SLE or vasculitis who underwent on-pump cardiac surgery from March 2002 to March 2022 were enrolled, while patients with preoperative renal dysfunction were excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Uni- and multivariable analyses were performed to identify potential factors associated with postoperative AKI. Results: Among 123 patients enrolled, 39 (31.7%) developed AKI within seven days after receiving on-pump cardiac surgery. Four patients died in the hospital, resulting in an overall in-hospital mortality of 3.3%, and all deaths occurred in the AKI group. Patients in the AKI group also had longer ICU stays (median difference 3.0 day, 95% CI: 1.0-4.0, P < 0.001) and extubation time (median difference 1.0 days, 95% CI: 0-2.0, P < 0.001) than those in the non-AKI group. Multivariable logistic regression revealed that BMI over 24 kg/m2 (OR: 3.00, 95% CI: 1.24-7.28) and comorbid SLE (OR: 4.73, 95% CI: 1.73-12.93) were independently correlated with postoperative AKI. Conclusion: Factors potentially correlated with AKI following on-pump cardiac surgery in patients with connective tissue disease were explored. Clinicians should pay more attention to preoperative evaluation and intraoperative management in patients with risk factors.

Constructing a 3D interconnected network of Ag nanostructures for high-performance SERS detection of food coloring agents.

The design and preparation of various effective three-dimensional (3D) silver nanostructures is a frontier area of research in the field of surface-enhanced Raman scattering (SERS). This paper demonstrates a simple and novel method for the preparation of a substrate, whose surface was covered by a 3D interconnected network of Ag nanostructures, and the resulting network structure surface is free of organic contaminants. The EDS measurements confirm the metallic nature of the formed 3D Ag nanonetwork substrate. Additionally, the influence of experimental parameters on the morphology of the 3D Ag nanonetwork was also investigated, such as reaction time, hydrofluoric acid concentration, silver nitrate concentration and sodium citrate concentration. The 3D Ag nanonetwork has good uniformity. Importantly, the 3D Ag nanonetwork substrate was used to accurately and reliably detect amaranth (AR) and sunset yellow (SY) in beverages, with the lowest detection limit of 3 and 0.1 µg L-1, respectively. Therefore, this substrate is expected to be a promising candidate for SERS detection and offers attractive potential for a wider range of applications.

The response of nitrifying activated sludge to chlorophenols: Insights from metabolism and redox homeostasis.

The specialized wastewater treatment plants for the chemical industry are rapidly developed in China and many other countries. But there is a common bottleneck in that the toxic pollutants in chemical wastewater often cause shock impacts on biological nitrogen removal systems, which directly affects the stability and cost of operation. As the research on nitrification inhibition characteristics is not sufficient till now, there is a great lack of theoretical guidance on the control of the inhibition. This study investigated the response of nitrifying activated sludge to chlorophenols (CPs) inhibition in terms of metabolism disorder and oxidative stress. At the initial stage of reaction (i.e., 1 h), reactive oxygen species (ROS)-induced membrane damage which might account for declining nitrification performance. Simultaneously excessive extracellular polymeric substances (EPS) were secreted to alleviate oxidative stress injury and protected microorganisms to some extent. In particular tyrosine-like substances in LB-EPS with a Fmax increase of 242.30% were confirmed to efficiently resist phenols inhibition. Thus, as the inhibition proceeded, metabolism disorder replaced oxidative stress as the main cause of nitrification inhibition. The affected metabolic processes include weakened enzyme catalysis, restricted electron transport and lessened energy generation. At 4 h, nitrifying production of sludge amended with 5 mg/L chlorophenols was 89.27 ± 9.51%-98.15 ± 9.60% lower than blank, the inhibition could be attributed to comprehensively affected metabolism. The structural equation modeling indicated that phenols restricted nitrification enzymes and bacterial electron transport efficiency which was critical to nitrification performance. Moreover, the lessened energy generation weakens enzyme activity to further suppress nitrification. These findings enriched our knowledge of nitrifiers' responses to CPs inhibition and provided the basis for addressing nitrification inhibition.

Dynamic predictive scores for cardiac surgery-associated agitated delirium: a single-center retrospective observational study.

BACKGROUND: Prevention, screening, and early treatment are the aims of postoperative delirium management. The scoring system is an objective and effective tool to stratify potential delirium risk for patients undergoing cardiac surgery. METHODS: Patients who underwent cardiac surgery between January 1, 2012, and January 1, 2019, were enrolled in our retrospective study. The patients were divided into a derivation cohort (n = 45,744) and a validation cohort (n = 11,436). The AD predictive systems were formulated using multivariate logistic regression analysis at three time points: preoperation, ICU admittance, and 24 h after ICU admittance. RESULTS: The prevalence of AD after cardiac surgery in the whole cohort was 3.6% (2,085/57,180). The dynamic scoring system included preoperative LVEF ≤ 45%, serum creatinine > 100 µmol/L, emergency surgery, coronary artery disease, hemorrhage volume > 600 mL, intraoperative platelet or plasma use, and postoperative LVEF ≤ 45%. The area under the receiver operating characteristic curve (AUC) values for AD prediction were 0.68 (preoperative), 0.74 (on the day of ICU admission), and 0.75 (postoperative). The Hosmer‒Lemeshow test indicated that the calibration of the preoperative prediction model was poor (P = 0.01), whereas that of the pre- and intraoperative prediction model (P = 0.49) and the pre, intra- and postoperative prediction model (P = 0.35) was good. CONCLUSIONS: Using perioperative data, we developed a dynamic scoring system for predicting the risk of AD following cardiac surgery. The dynamic scoring system may improve the early recognition of and the interventions for AD.

Optimizing nitrogenous organic wastewater treatment through integration of organic capture, anaerobic digestion, and anammox technologies: sustainability and challenges.

With China's recent commitment to reducing carbon emissions and achieving carbon neutrality, anaerobic digestion and anaerobic ammonium oxidation (anammox) have emerged as promising technologies for treating nitrogenous organic wastewater. Anaerobic digestion can convert organic matter into volatile fatty acids (VFAs), methane, and other chemicals, while anammox can efficiently remove nitrogen with minimal energy consumption. This study evaluates the principles and characteristics of enhanced chemical flocculation and bioflocculation, as well as membrane separation, for capturing organic matter. Additionally, the paper evaluates the production of acids and methane from anaerobic digestion, exploring the influence of various factors and the need for control strategies. The features, challenges, and concerns of partial nitrification-anammox (PN/A) and partial denitrification-anammox (PD/A) are also outlined. Finally, an integrated system that combined organic capture, anaerobic digestion, and anammox is proposed as a sustainable and effective solution for treating nitrogenous organic wastewater and recovering energy and resources.

Developing a magnetic POCUS-guided bronchoscope for patients with suspected difficult endotracheal intubation in a general tertiary hospital: protocol for a randomised controlled study.

INTRODUCTION: Endotracheal intubation (ETI) is a crucial but risky procedure, especially among patients suspected of difficult endotracheal intubation (DTI). Bronchoscope, as an improved technique commonly used in DTI, might encounter visualisation difficulties. The magnetic point-of-care ultrasound (MGPOCUS) provides a novel visualisation from the outside and enables estimation of the relative position and trajectory of the bronchoscope. The purpose of the study was to evaluate the efficiency of MGPOCUS-guided bronchoscopy, including the time required for successful ETI, the first attempt and overall success rate, the number of attempts, complications, and satisfaction with the visualization of the procedures. METHODS AND ANALYSIS: The study is a randomised, parallel-group, single-blinded, single-centre study. Participants (n=108) will be recruited by the primary anaesthesiologist and randomised to groups of ETI with bronchoscope or MGPOCUS-guided bronchoscope. The primary outcome is the time taken to the first-attempt success ETI. Secondary outcomes include procedure time, the first-attempt and overall success, complications, and satisfaction of visualisation. Cox regression with Bonferroni correction and linear mixed regression will be used to analyse the outcomes. ETHICS AND DISSEMINATION: The trial protocol was approved by the ethics committees at the Peking Union Medical College Hospital (Institutional Review Board #ZS-3428). Findings will be disseminated through conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05647174.

Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study.

BACKGROUND: The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA. METHODS: We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients. Propensity score matching (PSM) was used to balance the age between the three groups. The pNfL levels between groups were compared using Kruskal-Wallis test. Linear mixed models were performed to explore the disease progression-associated factors in longitudinal MSA cohort. Random forest model as a complement to linear models was employed to quantify the importance of predictors. RESULTS: Before and after matching the age by PSM, the pNfL levels could reliably differentiate MSA from HC and PD groups, but only had mild potential to distinguish PD from HC. By combining linear and nonlinear models, we demonstrated that pNfL levels at baseline, rather than the change rate of pNfL, displayed potential prognostic value for progression of MSA. The combination of baseline pNfL levels and other modifiers, such as subtypes, Hoehn-Yahr stage at baseline, was first shown to improve the diagnosis accuracy. CONCLUSIONS: Our study contributed to a better understanding of longitudinal dynamics of pNfL in MSA, and validated the values of pNfL as a non-invasive sensitive biomarker for the diagnosis and progression. The combination of pNfL and other factors is recommended for better monitoring and prediction of MSA progression.

Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography.

BACKGROUND: Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. OBJECTIVE SPINOCEREBELLAR ATAXIA TYPE 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging. METHODS: We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts. All participants received SV2A-PET imaging using 18 F-SynVesT-1 for synaptic density assessment. Specifically, cohort 1 received standard PET procedure and quantified neurofilament light chain (NfL), and cohort 2 received simplified PET procedure for exploratory purpose. Bivariate correlation was performed between synaptic loss and clinical as well as genetic assessments. RESULTS: In cohort 1, significant reductions of synaptic density were observed in cerebellum and brainstem in SCA3 ataxia stage compared to preataxic stage and controls. Vermis was found significantly involved in preataxic stage compared to controls. Receiver operating characteristic (ROC) curves highlighted SV2A of vermis, pons, and medulla differentiating preataxic stage from ataxic stage, and SV2A combined with NfL improved the performance. Synaptic density was significantly negatively correlated with disease severity in cerebellum and brainstem (International Co-operative Ataxia Rating Scale: ρ ranging from -0.467 to -0.667, P ≤ 0.002; Scale of Assessment and Rating of Ataxia: ρ ranging from -0.465 to -0.586, P ≤ 0.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure. CONCLUSIONS: We first identified in vivo synaptic loss was related to disease severity of SCA3, suggesting SV2A PET could be a promising clinical biomarker for disease progression of SCA3. © 2023 International Parkinson and Movement Disorder Society.

Combining thin-film microextraction and surface enhanced Raman spectroscopy to sensitively detect thiram based on 3D silver nanonetworks.

By coupling thin-film microextraction (TFME) with surface enhanced Raman scattering (SERS), a facile method was developed for the determination of thiram in the complex matrix (orange juice or grape peel). The substrate of TFME was made by self-assembling silver sol on the silicon wafer to form a three-dimensional (3D) silver nanonetwork structure, without adding any template, which was used for TFME and SERS detection, respectively. The substrate exhibits high reproducibility with a relative standard deviation of about 7.32 % in spot and spot SERS intensity. The SERS signal intensity at a shift of 1384 cm-1 and the thiram concentration showed good linearity in the range of 0.01-5 µg/L and the linear correlation coefficient was 0.9912. The detection limit for thiram was found to be 0.01 µg/L. The TFME-SERS method was applied for the determination of thiram in fruit juice and the results were obtained very well. Therefore, this method is expected to play a role in the detection of trace pollutants.