Progressive myoclonic ataxia as an initial symptom of typical type I sialidosis with NEU1 mutation.

OBJECTIVE: Expand genetic screening for atypical Type I sialidosis (ST-1) could address its underdiagnosed in both progressive myoclonic ataxia (PMA) and ataxia patients. To evaluate the potential founder effect of mutation in the population. METHODS: We enrolled 231 patients with PMA or ataxia from the First Affiliated Hospital of Fujian Medical University. Through Whole Exome Sequencing and Sanger sequencing, we identified the causative gene in patients. Haplotype analysis was employed to explore a potential founder effect of the NEU1 c.544A>G mutation. RESULTS: A total of 31 patients from 23 unrelated families were genetically diagnosed with ST-1. A significant 80.6% of these patients were homozygous for the c.544A>G mutation. We discovered six different NEU1 variants, including two novel mutations: c.951_968del and c.517T>G. The mean age of onset was 18.0 ± 7.1 years. The clinical spectrum of ST-1 featured ataxia and myoclonus as the most common initial symptoms. Over 40% suffered from controlled generalized tonic-clonic seizures. Mobility and independence varied greatly across the cohort. Cherry-red spots were rare, occurring in just 9.5% (2/21) of patients. Brain MRIs were typically unremarkable, except for two patients with unusual findings. EEGs showed diffuse paroxysmal activity in 17 patients. The c.544A>G mutation in NEU1 is a founder variant in Fujian, with a unique haplotype prevalent in East Asians. INTERPRETATION: ST-1 should be suspected in patients with PMA or ataxia in Southeast China, even without macular cherry-red spots and seizures, and the premier test could be a variant screening of the founder variant NEU1 c.544A>G.

PARP inhibitors enhance antitumor immune responses by triggering pyroptosis via TNF-caspase 8-GSDMD/E axis in ovarian cancer.

BACKGROUND: In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses. METHODS: To decode the immune responses reshaped by PARPis, we conducted T-cell receptor (TCR) sequencing and immunohistochemical (IHC) analyses of paired clinical specimens before and after niraparib monotherapy obtained from a prospective study, as well as ID8 mouse ovarian tumors. To validate the induction of immunogenic cell death (ICD) by PARPis, we performed immunofluorescence/IHC staining with homologous recombination deficiency tumor cells and patient-derived xenograft tumor tissues, respectively. To substantiate that PARPis elicited tumor cell pyroptosis, we undertook comprehensive assessments of the cellular morphological features, cleavage of gasdermin (GSDM) proteins, and activation of TNF-caspase signaling pathways through genetic downregulation/depletion and selective inhibition. We also evaluated the critical role of pyroptosis in tumor suppression and immune activation following niraparib treatment using a syngeneic mouse model with implanting CRISPR/Cas9 edited Gsdme-/ - ID8 tumor cells into C57BL/6 mice. RESULTS: Our findings revealed that PARPis augmented the proportion of neoantigen-recognized TCR clones and TCR clonal expansion, and induced an inflamed TIME characterized by increased infiltration of both innate and adaptive immune cells. This PARPis-strengthened immune response was associated with the induction of ICD, specifically identified as pyroptosis, which possessed distinctive morphological features and GSDMD/E cleavage. It was validated that the cleavage of GSDMD/E was due to elevated caspase 8 activity downstream of the TNFR1, rather than FAS and TRAIL-R. On PARP inhibition, the NF-κB signaling pathway was activated, leading to increased secretion of TNF-α and subsequent initiation of the TNFR1-caspase 8 cascade. Impeding pyroptosis through the depletion of Gsdme significantly compromised the tumor-suppressing effects of PARP inhibition and undermined the anti-immune response in the syngeneic ID8 mouse model. CONCLUSIONS: PARPis induce a specific type of ICD called pyroptosis via TNF-caspase 8-GSDMD/E axis, resulting in an inflamed TIME and augmentation of tumor-targeting immune responses. These findings deepen our understanding of PARPis activities and point toward a promising avenue for synergizing PARPis with immunotherapeutic interventions. TRIAL REGISTRATION NUMBER: NCT04507841.

Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma.

BACKGROUND: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the post-platinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 50% of patients with aUC can tolerate platinum-containing treatment, treatments combining first-line ICIs with non-platinum drugs are urgently needed. Therefore, we assessed the safety and efficacy of the anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first-line therapy in aUC (NCT04603846). METHODS: This was a multi-center, single-arm, phase Ib study that enrolled patients with treatment-naive aUC. Patients received Socazolimab (5 mg/kg) and nab-paclitaxel (260 mg/m2) Q3w. The primary endpoint was safety and tolerability of the combination regimen. Second endpoints were the objective response rate (ORR) and progression-free survival. RESULTS: Between September, 2020 and September, 2021, 20 patients with urothelial carcinoma were enrolled, arising from renal pelvis (5), bladder (8), and ureter (7). After a median follow-up of 17 months, the median number of treatment cycles was 12. No patients had dose limiting toxicity. All patients had treatment-related adverse events (TRAEs), most of which were grade 1 or 2. The common TRAEs (≥20%) were peripheral neurotoxicity, alopecia, rash, increased ALT, weight loss, weakness, pruritus, increased AST, increased γGT, increased ALP, neutropenia, emesis, and anorexia. Nine patients (45%) developed grade 3 TRAEs including peripheral neurotoxicity (30.0%), increased ALT (10.0%), and increased γGT (5.0%). Two patients (10%) discontinued treatment because of grade 3 mouth ulcer (n = 1) and grade 2 lung fibrosis (n = 1). No grade 4-5 TRAEs were observed. Among the 17 patients who had received at least one tumor assessment, ORR was 58.8% (95% CI, 32.9%-81.6%) and the median progression-free survival was 8.3 months (95% CI, 5.2-19.5). The median duration of response was 13.3 months (95% CI, 2.0-20.1), and the overall survival was 19.5 months (95% CI, 11.2-not reached). CONCLUSION: Socazolimab combined with nab-paclitaxel has shown good safety and promising antitumor activity as first-line therapy in patients with advanced urothelial carcinoma.

Phosphorus modifies the association between body mass index and uric acid: Results from NHANES 2007-2018.

INTRODUCTION: Studies in recent years have shown that high uric acid causes harm to the human body, which has become a serious public health problem. Elevated serum uric acid has been shown to be associated with obesity, but the relationship between BMI and uric acid (UA) remains controversial. Although the association between BMI and UA has been well studied, the effect of phosphorus levels in vivo on this association remains unclear. This study aimed to determine the relationship between BMI and serum uric acid and the effect of phosphorus on the relationship between the two. RESEARCH DESIGN AND METHODS: The present study analyzed data from the National Health and Nutrition Examination Survey (NHANES) continuous 2007-2018 cycle. We included 10786 participants aged 20 years and over. Multivariable linear regression was performed to assess the association between BMI and serum uric acid. phosphorus was stratified into low phosphorus (<3.3 mg/dl), middle phosphorus (3.3-3.9 mg/dl) and high phosphorus (>3.9 mg/dl). Correction of the effect of phosphorus was assessed by testing the interaction between BMI and UA in multivariate linear regression. RESULTS: In this cross-sectional study, we found that BMI was positively associated with UA in the female population but not significantly in the male population or in the total population. In multiple regression analysis, UA was 0.51 higher in the highest female BMI group than in the lowest group (p = 0.0001). The relationship between BMI and UA differed significantly by gender under the influence of phosphorus, with men and women in Model II having a greater elevation of UA in men than in women within most groups. (BMI >30, phosphorus >3.9 mg/dl, ß:0.83 95% CI: 0.43, 1.23 vs ß: 0.79 95% CI: 0.30, 1.29). In addition, phosphorus significantly altered the positive association between BMI and UA in most models. CONCLUSION: Our results indicate significant associations between BMI and uric acid in women, with higher BMI values likely to be associated with a higher risk of hyperuricemia, suggesting that uric acid levels in obese people should be closely monitored in clinical practice. Phosphorus and BMI have an interactive effect in elevating UA and should be noted as indicators of phosphorus in clinical practice.

Evaluating the detection of barbiturates in dried blood spots: A comparative analysis using gas chromatography-mass spectrometry, gas chromatography-tandem mass spectrometry, and liquid chromatography-tandem mass spectrometry with different extraction methods.

Rapid and accurate characterization and quantitation of blood barbiturates and their combination drugs are very important for the clinical treatment of acute barbiturate poisoning. A comparison of dried blood spot (DBS) and traditional liquid-liquid extraction (LLE) in the pre-treatment stage, as well as a comparison of gas chromatography-mass spectrometry (GC-MS), gas chromatography-tandem mass spectrometry (GC-MS/MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) as instrumental analysis methods, revealed differences in the analysis results of barbiturates and their combination drugs under different conditions. Based on these findings, we introduce a DBS-GC-MS/MS method. The developed and validated method showed good selectivity, sensitivity (LOD: 0.1 µg mL-1, LOQ: 0.2 µg mL-1), linearity (R2>0.9992), trueness (<15 %, except for carbamazepine, at 29.4 %), and precision (<15 %). Recovery was also good for most target compounds, but significant matrix effects were evident. Compared with the LLE method, the DBS method has the benefits of easy sample collection, storage, and transport, as well as simple pre-treatment and reduced reagent and energy consumption. Compared to LC-MS/MS, GC-MS/MS requires no switching between positive and negative ion modes and uses the MRM detection mode, meaning that more information about the sample compounds can be obtained in less analysis time. Using actual sample analysis, we have demonstrated the advantages of the DBS-GC-MS/MS method for the qualitative and quantitative analysis of barbiturates and poisoning events due to combinations of these drugs. Comparison of the three instruments and the two treatment methods revealed their analysis characteristics. From the perspective of practical application, the broad practical value and advantages of DBS should be embraced in more applications, and future analytical laboratory development should continue to recognize GC-MS/MS as a useful supplement to LC-MS/MS.

Ambient Moisture-Induced Self Alignment of Polarization in Ferroelectric Hafnia.

The discovery of nanoscale ferroelectricity in hafnia (HfO2) has paved the way for next generation high-density, non-volatile devices. Although the surface conditions of nanoscale HfO2 present one of the fundamental mechanism origins, the impact of external environment on HfO2 ferroelectricity remains unknown. In this study, the deleterious effect of ambient moisture is examined on the stability of ferroelectricity using Hf0.5Zr0.5O2 (HZO) films as a model system. It is found that the development of an intrinsic electric field due to the adsorption of atmospheric water molecules onto the film's surface significantly impairs the properties of domain retention and polarization stability. Nonetheless, vacuum heating efficiently counteracts the adverse effects of water adsorption, which restores the symmetric electrical characteristics and polarization stability. This work furnishes a novel perspective on previous extensive studies, demonstrating significant impact of surface water on HfO2-based ferroelectrics, and establishes the design paradigm for the future evolution of HfO2-based multifunctional electronic devices.

Latitudinal responses of litter decomposition to solar radiation.

Photodegradation driven by solar radiation has been confirmed as an important driving factor for litter decomposition. However, previous single-site studies could not quantify the relative contribution of variation in solar radiation to litter decomposition. To address it, we conducted a field experiment in Heshan National Field Research Station of Forest Ecosystem, Guangdong (Heshan Station, south subtropical climate), Jigongshan Ecological Research Station, Xinyang, Henan (Jigongshan Station, north subtropical climate) and Daqinggou Ecological Research Station, Institute of Applied Ecology, Chinese Academy of Sciences (Daqinggou Station, temperate climate) at intervals of 10 degrees. We examined litter decomposition of Populus davidiana and Larix olgensis, two species with significant differences in initial litter quality through an in-situ spectral-attenuation experiment. Treatments included full-spectrum, No-UV-B (attenuating UV-B radiation <315 nm) and No-UV & Blue (attenuating all UV and blue wavelengths <500 nm). After nearly 1-year decomposition, litter dry mass remaining of P. davidiana and L. olgensis under full-spectrum treatment was lowest at Heshan (30.2% and 36.3%), and highest at Jigongshan (37.3% and 45.8%). Among all sites, litter dry mass remaining was lowest under the full-spectrum, and lower than that of No-UV-B and No-UV & blue. UV and blue light significantly increased litter mass loss of P. davidiana and L. olgensis, with contributions of 59.7% and 57.0% (Heshan), 46.4% and 42.1% (Jigongshan), and 39.0% and 45.9% (Daqinggou), respectively. The contribution of UV-A and blue light (315-500 nm) was greater than UV-B (280-315 nm); the cumulative irradiance, soil temperature and moisture were the main driving factors for litter photodegradation.

Characterization of etomidate and emerging analogs in human hair using UHPLC-MS/MS and confirmation in real forensic cases.

The regulation of etomidate, a widely used drug for anesthesia induction and short surgical procedures, has led to the emergence of etomidate analogs such as metomidate, propoxate, and isopropoxate. This study introduces and validates a simple, rapid, and cost-effective ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination and quantification of etomidate, etomidate acid, metomidate, propoxate, and isopropoxate in human hair. Using a five-minute gradient elution on a Phenomenex Kinetex Biphenyl column, the method achieves low limits of quantification (LOQs), ranging from 5 to 20 pg/mg. Method validation confirms robust linear calibration curves for the target substances in hair samples within the range of LOQs to 1000 pg/mg, with average correlation coefficients (r) all exceeding 0.999. The method also achieves acceptable intra-day and inter-day precision (<15 %) and trueness(bias, -10.9 % to 14.4 %). The matrix effect ranges from 46.9 % to 94.2 %, and the extraction recovery rate ranges from 84.5 % to 105 %. When applied to authentic cases, this method successfully identified 56 positive samples. The concentrations of etomidate, etomidate acid, metomidate, propoxate, and isopropoxate in positive samples ranged from 27 to 1.5 × 105 pg/mg, 21 to 1.5 × 103 pg/mg, 18 to 8.7 × 104 pg/mg, 25 to 1.6 × 104 pg/mg, and 22 to 5.0 × 105 pg/mg, respectively.

Chemical constituents with potential cytotoxic activities from Cynanchum otophyllum.

Phytochemical investigation of the chloroform extract of the roots of Cynanchum otophyllum (Asclepiadaceae) led to the isolation of a new cardiac aglycone, characterised as Cynanchin A (1), as well as one known cardenolide (2) and nine known C21 steroidal glycosides (3-10), Their structures were established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. In the present research, the cytotoxic activities of the 11 compounds on five different human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) were evaluated in vitro. Most of the tested compounds showed potent inhibitory activities towards the five cell lines.

Association between serum neurofilament light chains and depression: A cross-sectional study based on NHANES 2013-2014 database.

BACKGROUND: Serum neurofilament light chain (sNfl), identified as a promising biomarker, is a protein released into the bloodstream post-axonal damage. Studies on its correlation with depression, however, remains scarce. The purpose of this study was to investigate the potential relationship between sNfL levels and risk of depression among a representative segment of the U. S. populace. METHODS: This study included 1,909 participants from the 2013-2014 National Health and Nutrition Examination Survey. The 9-item Patient Health Questionnaire (PHQ-9 scale) assessed depression symptoms, while sNfl concentrations were measured using the Attelica fully automated immunoassay system. The logistic regression, restricted cubic splines (RCS), and subgroup analysis were performed to assess the relationship between sNfL, lnsNfL (log-transformed values of sNfl), and depression. RESULTS: After adjusting for sociodemographic variables, lifestyle, and chronic conditions, sNfl and lnsNfL levels positively correlated with depression. A unit increase in sNfL and lnsNfL levels was linked to a 0.7 % and 33.8 % rise in depression risk, respectively [OR (95 % CI): 1.007 (1.000, 1.014), p = 0.041 for sNfl; 1.338 (1.015, 1.764), p = 0.039 for lnsNfl]. Additionally, a positive linear association was observed between lnsNfl levels and the risk of depression (p for overall = 0.039, p for nonlinear = 0.189 in RCS). No significant differences were observed across subgroups between lnsNfl and depression, with no significant impact on this relationship from subgroups (All p for interaction >0.05). CONCLUSION: The findings of our study suggest a significant positive correlation between sNfl and depression, warranting further investigation into the molecular dynamics linking sNfL to depression and subgroup variability.

Five New Species of Wood-Decaying Brown-Rot Fungi within Postiaceae (Polyporales, Basidiomycota) from Xinjiang, Northwest China.

Brown-rot fungi are an important group of wood-decaying fungi, but there has been limited research on the species diversity of brown-rot fungi in Xinjiang, China. During an investigation of brown-rot fungi in Xinjiang, from July 2018 to July 2023, five new species belonging to the family Postiaceae were discovered based on morphological and molecular evidence. Amaropostia altaiensis is characterized by a conchate pileus, circular pores (5-8 per mm), and growing on Populus. Amaropostia tianshanensis is characterized by a flabelliform-to-conchate pileus, angular pores (5-6 per mm), and growing on Picfea. Cyanosporus latisporus is characterized by a hirsute and dark greyish blue pileal surface with fresh, larger pores (3-6 per mm) and broad basidiospores (4.3-5.9 × 1.4-2 µm). Cyanosporus tianshanensis is characterized by a smooth and white-to-cream pileal surface with fresh, smaller pores (6-9 per mm). Osteina altaiensis is characterized by a light mouse-grey-to-honey-yellow pileal surface, smaller pores (4-6 per mm), and slightly wide basidiospores (5-6 × 1.7-2.2 µm). Each of these five new species form independent lineages in phylogenetic analyses based on the seven gene loci (ITS + nLSU + nSSU + mtSSU + TEF1 + RPB1 + RPB2). This research enriches the diversity of brown-rot fungi species, while also demonstrating the substantial discovery potential and research value of brown-rot fungi in Xinjiang.

Design, synthesis, and biological evaluation of imidazolylacetophenone oxime derivatives as novel brain-penetrant agents for Alzheimer's disease treatment.

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC50 value of 0.49 µM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aß42 aggregation. Moreover, the selected nuclide [18F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment.

Monitoring of ketamine-based emerging contaminants in wastewater: a direct-injection method and fragmentation pathway study.

The ketamine (KET) and its analogs consumed by humans are becoming emerging contaminants (ECs), as they at present in surface waters after being carried through wastewater systems. Drugs in wastewater can be analyzed using the direct-injection method, a simple wastewater analysis (WWA) method that can provide objective, continuous and nearly to real-time findings. This article describes an ultra-high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification and confirmation of seven KET-based ECs in wastewater by direct injection. After optimization of the UPLC-MS/MS and sample pretreatment conditions, the method was validated and applied to samples (n = 157) collected from several wastewater treatment plants (WWTPs) in southern China in which KET had the highest detection rate. The established direct-injection method was not only simple to perform but also had better sensitivity, shorter detection times, and analyzed more KET-based ECs than currently published methods, meeting the requirements for the monitoring and high-throughput analysis of common KET-based ECs. We also analyzed the fragmentation pathway of KET-based ECs to obtain product ion information on other unknown substances. Additional studies are needed to establish a comprehensive direct-injection screening method of ECs in wastewater on model-based assessment.

Detection of "smoke powder" etomidate and its metabolite etomidate acid in blood and urine by UHPLC-MS/MS: Application in authentic cases.

Recently, etomidate has been widely used as an alternative in illicit drug market. It is usually added to regular cigarette tobacco (commonly known as "cigarette powder") or mixed in e-cigarette oil sold through the Internet, retail stores, or entertainment outlets and other channels. An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed to quantify etomidate and etomidate acid in human blood and urine. The limit of detection (LOD) of etomidate and etomidate acid in blood are 0.5 ng/mL and 2 ng/mL, respectively, and the lower limit of quantification (LLOQ) are 1 ng/mL and 5 ng/mL, respectively. The LOD of etomidate and etomidate acid in urine are1 ng/mL and 2 ng/mL, respectively, and the LLOQ are 2 ng/mL and 5 ng/mL, respectively. The precision, accuracy, recoveries and matrix effects of etomidate and etomidate acid determinations in blood and urine met the requirements for methodological validation. The method was successfully applied to the identification and quantification of etomidate and etomidate acid in blood and urine of 62 forensic cases. The concentration of etomidate ranged from 1.52 to 8.41 ng/mL (positive cases, n=5) and the concentration of etomidate acid ranged from 2.76 to 112 ng/mL (positive cases, n=5) in blood. The concentrations of etomidate and etomidate acid in urine samples were 2.64-79,300 ng/mL (positive cases, n=59) and 6.11-518,000 ng/mL (positive cases, n=60), respectively. Therefore, the concentration of etomidate in blood and urine is mostly higher than that of etomidate.

[A headspace injection double-column dual-detector gas chromatography system for the analysis of 12 volatile compounds such as ethanol in human blood].

Based on the technical methods of GB/T 42430-2023 and GA/T 204-2019, this study established an analytical method for headspace injection double-column dual-detector (hydrogen flame ion detector) gas chromatography for the simultaneous analysis of at least 12 volatile compounds, including ethanol, in human blood using two different equipment platforms and chromatographic columns. A 100 µL blood or urine sample and a 0.04 g/L tert-butanol working solution prepared as an internal standard are introduced into the headspace sample bottle and then sealed, mixed, and placed on the headspace sampler rack. Using different equipment platforms and columns, methodological parameters such as the limit of detection (LOD), limit of quantification (LOQ), precision, and accuracy of the method were systematically evaluated. The chromatographic separation of acetone, alcohols and benzenes using the established method was satisfactory. The linear ranges, linear correlation coefficients (r), and LODs of acetone and six alcohols, including ethanol, were 0.10-3.00 g/L, >0.997, and 0.05 g/L, respectively. The LOQs were 0.10 g/L for all other compounds, excluding n-propanol (0.005 g/L). Additionally, the linear ranges, r values, LODs, and LOQs of benzene and four benzene derivatives were 0.05-50 mg/L, >0.995, 0.02 mg/L, and 0.05 mg/L, respectively (Column J&W DB-BAC1 UI and Column Rtx-BAC-PLUS 2). The average recoveries of compounds on J&W DB-BAC1 UI and Rtx-BAC-PLUS 2 columns ranged from 92.2% to 111.6%, and the relative standard deviations (RSDs, n=6) ranged from 0.4% to 7.4%. The LOD, LOQ, precision, accuracy, and linearity of the established method met the requirements of relevant standards, and no significant differences arose between the methodological parameters of the two platforms. CNAS-GL006 (2019) and JJF 1059.1-2012 were used as guides to evaluate the uncertainty of ethanol on two different sets of equipment platforms and chromatographic columns. The ethanol uncertainty was mainly derived from the calibration curve; however, the confidence probability was 95% (k=2). According to the analysis of the verification samples and real samples, the established method is suitable for the high-precision quantitative analysis of acetone and six alcohols and five benzene derivatives in human blood and other body fluids. It can be used in practical scenarios such as judicial identification and the detection of poisons.

Effects of ball milling treated wheat flour and maltodextrin on the texture and oil absorption properties of fried batter-coated cashews and almonds.

In this study, the effects of wheat flour treated with ball milling (BM) and maltodextrin on the oil absorption and textural characteristics of fried batter-coated cashews and almonds (BCAs) were investigated. The result showed that the crystallinity of the starch granules in wheat flour decreased after the BM treatment. Furthermore, the ΔH of the batter decreased as the BM time was elongated, but the addition of maltodextrin had no significant impact on ΔH. Both BM-treated wheat flour and maltodextrin increased the fracturability and decreased the oil content of the fried BCAs' batter. The addition of BM-treated wheat flour and maltodextrin decreased the oil content of the batter from 28.93% to 18.75% for batter-coated cashews and from 30.92% to 18.61% for batter-coated almonds. Overall, the addition of BM-treated wheat flour and maltodextrin in batter is an effective approach to decrease oil content and improve the textural quality of fried BCAs.

Feasibility and Success of Muscular Ventricular Septal Defect Occluders and Mushroom-Shaped Occluders in Transcatheter Patent Ductus Arteriosus Closure in Low-Weight Children: A Propensity Score-Matched Retrospective Analysis from a Chinese National Regional Health Center.

INTRODUCTION: Muscular ventricular septal defect occluders (MVSDOs) have been attempted as an option in low-weight patients with patent ductus arteriosus (PDA). However, few studies have assessed the safety of transcatheter patent ductus arteriosus closure (TCPC) using MVSDO. Therefore, we compared the outcomes in low-weight patients who used MVSDO and mushroom-shaped occluder (MSO). METHODS: Medical records of children under 10 kg (n = 417) who underwent TCPC from 2015 to 2021 at a Chinese health center were reviewed. They were divided into MSO (n = 372) and MVSDO (n = 45) groups. A 1:1 propensity score matching (PSM) was done considering gender, height, weight, body surface area (BSA), PDA diameter, and BSA-corrected PDA diameter. RESULTS: All 45 children in the MVSDO group (mean weight: 5.92 ± 1.32 kg) achieved successful immediate occlusion. One case in the MVSDO group experienced device migration within 24 h requiring unplanned surgery. MVSDO significantly ameliorated pulmonary artery hypertension. After PSM, each group comprised 41 children. The MVSDO group had a smaller effect on platelet counts (MVSDO vs. MSO = 259.85 ± 114.82 vs. 356.12 ± 134.37, p < 0.001), a reduced incidence of thrombocytopenia (MVSDO vs. MSO = 2/41 vs. 7/41, p = 0.001), and a higher rate of residual shunting (MVSDO vs. MSO = 16/41 vs. 5/41, p = 0.005), compared with the MSO group. Thrombocytopenia resolved during hospitalization and micro-shunts disappeared by 6 months. No pulmonary artery or descending aortic secondary stenosis was observed in 1-year follow-up. CONCLUSIONS: MVSDO used in low-weight children is feasible, with high success and satisfactory postoperative and short-term follow-up outcomes, including lower thrombocytopenia incidence, compared to MSO. Further long-term studies with larger samples are recommended.

Mechanistic insights into cadmium exacerbating 2-Ethylhexyl diphenyl phosphate-induced human keratinocyte toxicity: Oxidative damage, cell apoptosis, and tight junction disruption.

Organophosphate flame retardants 2-ethylhexyldiphenyl phosphate (EHDPP) and cadmium (Cd) are ubiquitous in environmental matrices, and dermal absorption is a major human exposure pathway. However, their detrimental effects on the human epidermis remain largely unknown. In this study, human keratinocytes (HaCaT cells) were employed to examine the toxicity and underlying mechanisms of co-exposure to EHDPP and Cd. Their influence on cell morphology and viability, oxidative damage, apoptosis, and tight junction were determined. The results showed that co-exposure decreased cell viability by >40 %, induced a higher level of oxidative damage by increasing the generation of reactive oxygen species (1.3 folds) and inhibited CAT (79 %) and GPX (90 %) activities. Moreover, Cd exacerbated EHDPP-induced mitochondrial disorder and cellular apoptosis, which was evidenced by a reduction in mitochondrial membrane potential and an elevation of cyt-c and Caspase-3 mRNA expression. In addition, greater loss of ZO-1 immunoreactivity at cellular boundaries was observed after co-exposure, indicating skin epithelial barrier function disruption, which may increase the human bioavailability of contaminants via the dermal absorption pathway. Taken together, oxidative damage, cell apoptosis, and tight junction disruption played a crucial role in EHDPP + Cd triggered cytotoxicity in HaCaT cells. The detrimental effects of EHDPP + Cd co-exposure were greater than individual exposure, suggesting the current health risk assessment or adverse effects evaluation of individual exposure may underestimate their perniciousness. Our data imply the importance of considering the combined exposure to accurately assess their health implication.