Clinical application of an optimized reference measurement procedure for serum digoxin using bracketing calibration method by ID-LC-MS/MS.

Digoxin, a cardiac glycoside, is widely used in the treatment of cardiovascular diseases. Due to its narrow therapeutic range, precise monitoring of its blood concentration is essential. A reference measurement procedure (RMP) is pivotal for ensuring result accuracy and comparability. The RMP for serum digoxin by ID-LC-MS/MS was optimized with sample pre-treatment and detection processes, and the bracketing calibration method was used, which facilitates more accurate measurement, especially for extreme concentrations. The performance of this optimized RMP was thoroughly evaluated. The limit of detection (LoD) was 0.05 ng/mL (0.06 nmol/L) and the lowest limit of quantification (LLoQ) was 0.10 ng/mL (0.13 nmol/L). The intra- and inter-assay imprecisions were 2.24%, 2.51%, 1.40% and 1.72%, 1.65%, 0.97% at 0.5, 2.0, 5.0 ng/mL, respectively. Recoveries were 99.63 to 101.42% and the linear response ranged from 0.1 to 10.0 ng/mL. The relative bias was 0.41% and 2.00% of our results compared with the median of all participating reference laboratories for IFCC-RELA (External Quality Assessment Scheme for Reference Laboratories in Laboratory Medicine) 2023A and 2023B. The uncertainty, calibration and measurement capability (CMC) of this method were also evaluated. The optimized RMP was applied in the Trueness Verification Plan of Southern China, which indicates significant differences among clinical systems, highlighting the need for standardization efforts. In addition, two commonly used clinical systems which employed immunoassay methods were compared with this optimized RMP, and 26 individual serum samples were analyzed. The good correlations indicate the feasibility of standardization for serum digoxin. The optimized RMP serves as an accurate reference baseline for routine methods, aiming to enhance the accuracy and precision of measurements in clinical laboratories.

Dynamic responses of the inter-microbial synergism and thermodynamic conditions attribute to the inhibition-and-relief effects of chitosan towards anaerobic digestion.

Wide commercial applications of chitosan in food preservation and green packaging fields inevitably lead to the universal existence in food, as well as the food waste (FW) processing system. However, whether and how the chitosan, a class of biomacromolecule substances, lead to dysfunction of anaerobic digestion (AD) process of FW remains less understood. Herein, chitosan exhibited an inhibition-and-relief effect with the AD process proceeding, and 80 mg/g-FW of chitosan decreased the net methane yield of FW by 24.7 %. The dynamic effect was ascribed to the varied fates of chitosan and the coupling biotic/abiotic influencing on multi-steps. Chitosan enhanced substrate flocs agglomeration, restraining the release of organics to liquid phase and reducing the binding affinity to enzymes. Among the various microorganisms involved in different steps, chitosan severely inhibited aceticlastic and hydrogenotrophic methanogen at the levels of microbial abundance, activity and function. Genome-centric metagenomics analyses revealed that transient chitosan decreased the coenzyme-based synergism of various microbial taxa involved in acetic acid generation/consumption metabolisms, including syntrophic propionate-oxidizing bacteria, syntrophic butyrate-oxidizing bacteria and methanogen. With the elimination of chitosan, these inhibitions were relieved, and the accumulated acetic acid and the more favorable thermodynamic conditions finally attributed to the recovery of AD performance.

Identification of mitochondria-related genes as diagnostic biomarkers for diabetic nephropathy and their correlation with immune infiltration: New insights from bioinformatics analysis.

BACKGROUND: Diabetic nephropathy (DN) is a common and severe microvascular complication of diabetes. Mitochondrial dysfunction and immune inflammation are important factors in the pathogenesis of DN. However, the specific mechanisms and their intricate interactions in DN remain unclear. Besides, there are no effective specific predictive or diagnostic biomarkers for DN so far. Therefore, this study aims to elucidate the role of mitochondrial-related genes and their possibility as predictive or diagnostic biomarkers, as well as their crosstalk with immune infiltration in the progression of DN. METHODS: Based on the GEO database and limma R package, the differentially expressed genes (DEGs) of DN were identified. Mitochondrial-related DEGs (MitoDEGs) were then obtained by intersecting these DEGs with mitochondria-related genes from the MitoCarta 3.0 database. Subsequently, the candidate hub genes were further screened by gene co-expression network analysis (WGCNA), and verified mRNA levels of these genes by real-time quantitative PCR (qRT-PCR) in high-glucose-treated human proximal tubular (HK-2) cells. The verified hub genes were utilized to construct a combined diagnostic model for DN, with its diagnostic efficacy assessed across the GSE30122 and GSE96804 datasets. Additionally, the immune infiltration pattern in DN was assessed with the CIBERSORT algorithm, and the Nephroseq v5 database was used to analyze the correlation between hub genes and clinical features of DN. RESULTS: Seven mitochondria-related candidate hub genes were screened from 56 MitoDEGs. Subsequently, the expression levels of six of them, namely EFHD1, CASP3, AASS, MPC1, NT5DC2, and BCL2A1, exhibited significant inter-group differences in the HK-2 cell model. The diagnostic model based on the six genes demonstrated good diagnostic efficacy in both training and validation sets. Furthermore, correlation analysis indicated that EFHD1 and AASS, downregulated in DN, are positively correlated with eGFR and negatively with serum creatinine. Conversely, CASP3, NT5DC2, and BCL2A1, upregulated in DN, show opposite correlations. In addition, spearman analysis revealed that the six hub genes were significantly associated with the infiltration of immune cells, including M1 and M2 macrophages, mast cells, resting NK cells, gamma delta T cells, and follicular helper T cells. CONCLUSION: This study elucidated the characteristics of mitochondria-related genes and their correlation with immune cell infiltration in DN, providing new insights for exploring the pathogenesis of DN and facilitating the identification of new potential biomarkers and therapeutic targets.

Absolute quantitation of human serum cystatin C: candidate reference method by 15N-labeled recombinant protein isotope dilution UPLC-MS/MS.

OBJECTIVES: Serum cystatin C (CysC) is a reliable and ideal endogenous marker for accurately assessing early changes in glomerular filtration rate (GFR), surpassing the limitations of creatinine-based estimated GFR. To improve the precision of GFR calculation, the development of strategies for accurately measuring serum CysC is crucial. METHODS: In this study, the full-length CysC pure product and fully recombinant 15N-labeled CysC internal standard were subjected to protein cleavage. Subsequently, an LC-MS/MS method was developed for the absolute quantification of serum CysC. The traceability of the method was assigned calibrator using the amino acid reference measurement procedure (RMP). It involved calibrating the instrument using an amino acid reference material with known amino acid concentrations for calibration and comparison purposes. RESULTS: The total imprecision of the method was determined to be ≤8.2 %, and a lower functional limit of quantification (LLoQ) was achieved. The recoveries ranged from 97.36 to 103.26 %. The relative bias between this candidate RMP for measurement of ERM-DA471-IFCC and the target value was 1.74 %. The linearity response was observed within the concentration range of 0.21-10.13 mg/L, with a high R2 value of 0.999. The results obtained using our method was consistent with those obtained using other certified RMPs. CONCLUSIONS: With the establishment of this highly selective and accurate serum CysC measurement method, it is now possible to assess the correlation between immunoassay results of serum CysC and the intended target when discrepancies are suspected in the clinical setting.

Synergies quantification and evolution on air pollutant and CO2 emissions driven by different socio-economic effects.

Realizing a synergistic reduction of air pollutant and CO2 emissions (APCE) is an important approach to promote a green socio-economic transformation in China, and it can provide a solid foundation for the achievement of clean energy production and climate action under a sustainable development goal framework. The objective of this study is to explore the quantitative relationship and evolution of synergies between APCE in industrial sectors driven by different socio-economic effects from 2007 to 2020 in China. The results indicated that the main sectors of pollutant emissions had consistency, however, large differences in the reduction efficiency of emissions exist among pollutants. The efficiency in reducing CO2 emissions was about 48% lower when compared with reductions of SO2 (95%), NOx (86%), and smoke and dust (83%) emissions from 2007 to 2020. The effects of improved technology were the main contributor to a reduction in pollutant emissions, but the synergies between APCE driving by it were not achieved. While the synergies between APCE driven by structure and final demand effects were significant. The synergies between NOx and CO2 emissions were stronger driven by final demand structure and type effects, with correlation coefficients of 1.06 and 1.13, respectively. Besides, the degree of synergistic reduction between APCE in most industrial sectors was around zero. Therefore, the efficiency of synergistic pollution reduction should be improved with the development of a synergistic governance system for industrial sectors. The structural decomposition analysis based on input-output model combined with the cross-elasticity analysis method to quantitively synergies between APCE from the consumption (demand) perspective, considering the connections between industrial sectors with socio-economic developing, which would contribute to the industrial synergistic reduction and green transformation as the consumption driven gradually increasing.

Frontiers and hotspots evolution in mild cognitive impairment: a bibliometric analysis of from 2013 to 2023.

Background: Mild cognitive impairment is a heterogeneous syndrome. The heterogeneity of the syndrome and the absence of consensus limited the advancement of MCI. The purpose of our research is to create a visual framework of the last decade, highlight the hotspots of current research, and forecast the most fruitful avenues for future MCI research. Methods: We collected all the MCI-related literature published between 1 January 2013, and 24 April 2023, on the "Web of Science." The visual graph was created by the CiteSpace and VOSviewer. The current research hotspots and future research directions are summarized through the analysis of keywords and co-cited literature. Results: There are 6,075 articles were included in the final analysis. The number of publications shows an upward trend, especially after 2018. The United States and the University of California System are the most prolific countries and institutions, respectively. Petersen is the author who ranks first in terms of publication volume and influence. Journal of Alzheimer's Disease was the most productive journal. "neuroimaging," "fluid markers," and "predictors" are the focus of current research, and "machine learning," "electroencephalogram," "deep learning," and "blood biomarkers" are potential research directions in the future. Conclusion: The cognition of MCI has been continuously evolved and renewed by multiple countries' joint efforts in the past decade. Hotspots for current research are on diagnostic biomarkers, such as fluid markers, neuroimaging, and so on. Future hotspots might be focused on the best prognostic and diagnostic models generated by machine learning and large-scale screening tools such as EEG and blood biomarkers.

Variation in Long-Term Postoperative Mortality Risk by Race/Ethnicity After Major Non-cardiac Surgeries in the Veterans Health Administration.

BACKGROUND: Few large sample studies have examined whether disparities, as measured by the proxy of race/ethnicity, are observed in long-term mortality after high-risk operations performed in a United States national health system. We compared operation year-related mortality risk by race/ethnicity after high-risk operative interventions among patients receiving care within the VHA. METHODS: From the Veterans Affairs Corporate Data Warehouse and Surgical Quality Improvement Program, data were retrieved for 426,695 patients undergoing high-risk surgical procedures in non-cardiac, general, vascular, thoracic, orthopedic, neurosurgery, and genitourinary specialties between 2000 and 2018. Operation year was used as a surrogate measure of advances in technology and perioperative management. Underrepresented race/ethnicity groups were compared in a binary form with Caucasian/White race, as the reference category. The primary outcome was time to mortality, defined as death occurring at any time, due to any cause, during follow up, and after the initial, eligible surgery. RESULTS: The median follow-up after 537,448 operations among 426,695 patients was 4.8 years. After adjustment for preoperative risk factors and demographics, long-term mortality risk decreased significantly to a hazard ratio of 0.96 (95% confidence interval, 0.962 to 0.964) over calendar time. Long-term mortality was not significantly higher among African Americans/Blacks compared to Caucasians/Whites (p = 0.22). Among Hispanics, differences in mortality risk favored Caucasians/Whites in the early years under study-a difference that dissipated as time progressed. In the most recent years, no difference in mortality was observed among Asian/Native Americans and Caucasians/Whites. CONCLUSIONS: Risk-adjusted long-term mortality after high-risk operations among Veterans Affairs hospitals did not significantly vary between African Americans/Blacks, Hispanics, and Asian/Native Americans groups.

Daily koumiss has positive regulatory effects on blood lipids and immune system: A metabolomics study.

Koumiss, a traditional Mongolian beverage, is believed to possess high nutritional value and potential medical benefits. However, there is a lack of comprehensive research on its potential impact on the human body. Metabolomics, as a sensitive approach in systems biology, offers a new avenue for studying the overall effects of koumiss. In this work, metabolomics was utilized to identify potential biomarkers and pathways associated with koumiss using UPLC-MS detection, pattern recognition analysis, pathway enrichment, network pharmacology. The findings indicated that koumiss exerts a beneficial regulatory influence on lipid metabolism, neurotransmitters, hormones, phospholipids and arachidonic acid metabolism, besides up regulating the content of nutrients. It could reduce the risks of dyslipidemia and inflammatory responses. This study confirmed the benign regulatory effect of koumiss on normal organism from the perspective of endogenous metabolites, and provided objective support for the promotion and application of this ethnic food.

Using machine learning to reveal drivers of soil microplastics and assess their stock: A national-scale study.

The issue of microplastic (MP) contamination in soil is a significant concern. However, due to limited large-scale studies and stock assessments, our understanding of the drivers of their distribution and fate remains incomplete. To address this, we conducted a comprehensive study in China, collected MP data from 621 sites, and utilized machine learning techniques for analysis. Our findings revealed 9 key factors influencing the distribution of soil MPs, highlighting their nonlinear influence processes. Among these factors, atmospheric deposition emerged as the most dominant driver, while wind and precipitation could lead to the transformation of soil from a sink to a source of MPs. MP concentrations in Chinese soils vary from 1.4 to 4333.1 particles/kg, with human activities significantly affecting their distribution, resulting in higher concentrations in the east and lower concentrations in the west. The estimated MP stock in Chinese soils is 1.92 × 1018 particles, equivalent to a mass of 2.11-8.64 million tonnes. This stock alone surpasses that found in global oceans, making global soil the largest reservoir of MPs. Overall, this study enhances our understanding of the environmental behavior of MPs and provides valuable data and theoretical support for the prevention, control, and management of this contamination.

Polyphyly of Boehmeria (Urticaceae) congruent with plastome structural variation.

Boehmeria is a taxonomically challenging group within the nettle family (Urticaceae). The polyphyly of the genus has been proposed by previous studies with respect to five genera (Debregeasia, Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus). Extensive homoplasy of morphological characters has made generic delimitation problematic. Previous studies in other plant groups suggest that plastome structural variations have the potential to provide characters useful in reconstructing evolutionary relationships. We aimed to test this across Boehmeria and its allied genera by mapping plastome structural variations onto a resolved strongly supported phylogeny. In doing so, we expanded the sampling of the plastome to include Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus for the first time. The results of our phylogenomic analyses provide strong support for Sarcochlamys as being more closely related to Leucosyke puya than to Boehmeria and for the clustering of Boehmeria s.l. into four subclades. The sizes of the plastomes in Boehmeria s.l. ranged from 142,627 bp to 170,958 bp. The plastomes recovered a typical quadripartite structure comprising 127~146 genes. We observe several obvious structural variations across the taxa such as gene loss and multiple gene duplication, inverted repeat (IR) contraction and wide expansions, and inversions. Moreover, we recover a trend for these variations that the early clades were relatively conserved in evolution, whereas the later diverging clades were variable. We propose that the structural variations documented may be linked to the adaptation of Boehmeria s.l. to a wide range of habitats, from moist broadleaf forests in Asia to xeric shrublands and deserts in Africa. This study confirms that variation in plastome gene loss/duplication, IR contraction/expansion, and inversions can provide evidence useful for the reconstruction of evolutionary relationships.

An optimized UPLC-MS/MS method for human plasma amyloid-ß 42 and 40 measurement and application in Alzheimer's disease diagnosis.

Critical events in Alzheimer's disease (AD) involve an imbalance between the production and clearance of amyloid-ß (Aß) peptides from the brain. The ratio of Aß42 to Aß40 in plasma was useful for evaluating AD, but quantification is limited by factors including preanalytical analyte loss and insufficient sensitivity. The availability of a targeted UPLC-MS/MS method with adequate analytical sensitivity and accurate values traceable to the SI units is essential for implementing a strategy for assay standardization. A targeted UPLC-MS/MS method for plasma Aß42 and Aß40 quantification was developed based on selected characteristic peptides spiked by 15N-labeled Aß. The calibrator was assigned using an amino acid analysis reference method trace to SI units. UPLC-MS/MS conditions and sample preparation procedures were assessed. 59 plasma samples comparison were used to evaluate immunoassays. Additionally, two clinical cohorts were selected for diagnostic performance evaluation. The LOQ of Aß42 and Aß40 is 10 pg mL-1 and 20 pg mL-1, respectively. The linear range was 10-500 pg mL-1 for Aß42 and 20-1000 pg mL-1 for Aß40, recoveries between 95.3 % and 108.2 % for Aß42, 93.2 % and 104.1 % for Aß40, imprecisions were <7 %. The accuracy of method was validated by analysis of a certified reference material. Clinical cohorts for diagnostic performance evaluation shown that the area under the curve (AUC) for plasma Aß42 and Aß42/Aß40 to differentiate between AD and CN were 0.767 and 0.799, respectively. A robust UPLC-MS/MS method was developed and demonstrated that suitable for a wide range of plasma Aß42 and Aß40. Applied to the investigation of clinically discrepant results, this method can act as an arbiter of the concentration of plasma Aß42 and Aß40 present.

Buyang Huanwu decoction ameliorates myocardial injury and attenuates platelet activation by regulating the PI3 kinase/Rap1/integrin α(IIb)ß(3) pathway.

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese medicine to treat the syndrome of qi deficiency and blood stasis. Platelets play an important role in regulating thrombus and inflammation after ischemic injury, studies have shown that BYHWD regulate myocardial fibrosis and exert anti-inflammatory effects through IL-17 and TLR4 pathways, but the mechanism of platelet activation by BYHWD in stable coronary heart disease is still unknown. In the present study, model of left anterior descending coronary artery ligation was applied to investigate the mechanisms of BYHWD on modulating platelets hyperreactivity and heart function after fibrosis of ischemic myocardial infarction (MI). METHODS: Myocardial infarction model was constructed by ligation of the left anterior descending coronary artery. The rats were randomly divided into five groups: sham, model, MI with aspirin (positive), MI with a low dosage of BYHWD (BYHWD-ld) and MI with a high dosage of BYHWD (BYHWD-hd) for 28 days. RESULTS: Coronary artery ligation prominently induced left ventricle dysfunction, increased cardiomyocyte fibrosis, which was accompanied by platelets with hyperreactivity, and high levels of inflammatory factors. BYHWD obviously reversed cardiac dysfunction and fibrosis, increased the thickness of the left ventricular wall, and inhibited aggregation ratio and CD62p expression. BYHWD restored the mitochondrial respiration of platelets after MI, concomitant with an increased telomere expression and decreased inflammation. According to the result of transcriptome sequencing, we found that 106 differentially expressed genes compared model with BYHWD treatment. Enrichment analysis screened out the Ras-related protein Rap-1 (Rap1) signaling pathway and platelet activation biological function. Quantitative real-time PCR and Western blotting were applied to found that BYHWD reduced the expression of Rap1/PI3K-Akt/Src-CDC42 genes and attenuated the overactivity of PI3 kinase/Rap1/integrin α(IIb)ß(3) pathway. CONCLUSION: BYHWD reduced inflammation and platelet activation via the PI3 kinase/Rap1/integrin α(IIb)ß(3) pathway and improved heart function after MI.

RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

Evaluation and clinical application of a bracketing calibration-based isotope dilution liquid chromatography-tandem mass spectrometry candidate reference measurement procedure for serum theophylline.

A candidate reference measurement procedure (RMP) for serum theophylline via isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. With a single-step precipitation pretreatment and a 6-min gradient elution, the method achieved baseline separation of theophylline and its analogs on a C18-packed column. A bracketing calibration method was used to ensure repeatable signal intensity and high measurement precision. The intra-assay and inter-assay imprecisions were 1.06%, 0.84%, 0.72% and 0.47%, 0.41%, 0.25% at concentrations of 4.22 µg/mL (23.40 µmol/L), 8.45 µg/mL (46.90 µmol/L), and 15.21 µg/mL (84.43 µmol/L), respectively. Recoveries ranged from 99.35 to 102.34%. The limit of detection (LoD) was 2 ng/mL, and the lowest limit of quantification (LLoQ) was 5 ng/mL. The linearity range extended from 0.47 to 60 µg/mL (2.61-333.04 µmol/L). No ion suppression and carry-over (< 0.68%) were observed. The relative bias for this candidate RMP that participated in 2023 External Quality Control for Reference Laboratories (RELA) conducted by the International Federation of Clinical Chemistry (IFCC) was within a range of 0.17 to 0.93%. Furthermore, two clinical immunoassay systems were compared with this candidate RMP, demonstrating good correlations. The results of the Trueness Verification Plan indicate significant differences among routine systems, highlighting the need for standardization efforts. The developed candidate RMP for serum theophylline serves as a precise reference baseline for standardizing clinical systems and assigning values to reference materials.

The relationship between follicle-stimulating hormone and metabolic dysfunction-associated fatty liver disease in men.

OBJECTIVES: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. METHODS: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. RESULT: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. CONCLUSIONS: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.

No genetic link between Parkinson's disease and SARS-CoV-2 infection: a two-sample Mendelian randomization study.

Objective: Existing literature has not clearly elucidated whether SARS-CoV-2 infection increases the incidence of Parkinson's disease or if Parkinson's disease patients are more susceptible to the effects of SARS-CoV-2 infection. To clarify the issue, this study employs a genetic epidemiological approach to investigate the association. Methods: This study utilizes a two-sample Mendelian randomization analysis. The primary analysis employs the inverse variance-weighted (IVW) method, supplemented by secondary analyses including MR-Egger regression, weighted median, IVW radial method, and weighted mode, to evaluate the bidirectional causal relationship between Parkinson's disease and SARS-CoV-2 infection. Results: IVW results showed no genetic causality between SARS-CoV-2 susceptibility, hospitalization rate and severity and Parkinson's disease. (IVW method: p = 0.408 OR = 1.10 95% CI: 0.87 ~ 1.39; p = 0.744 OR = 1.11 95% CI: 0.94 ~ 1.09; p = 0.436 OR = 1.05 95% CI: 0.93 ~ 1.17). Parkinson's disease was not genetically associated with susceptibility to new crown infections, hospitalization rates, and severity (IVW method: p = 0.173 OR = 1.01 95% CI: 0.99 ~ 1.03; p = 0.109 OR = 1.05 95% CI: 0.99 ~ 1.12; p = 0.209 OR = 1.03 95% CI: 0.99 ~ 1.07). MR-Egger regression, weighted median, IVW radial method, and weighted mode results are consistent with the results of the IVW method. Conclusion: This study does not support a genetic link between Parkinson's disease and SARS-CoV-2 infection, and the association observed in previous cohort studies and observational studies may be due to other confounding factors.

Establishment and clinical application of a candidate reference measurement procedure for quantification of urinary vanillylmandelic acid and homovanillic acid using ID-LC-MS/MS method.

Neuroblastoma (NB), an embryonic tumor of the autonomous nervous system, poses a significant threat to the health and lives of children. Accurate measurement of vanillylmandelic acid (VMA) and homovanillic acid (HVA) in human urine is crucial for screening and diagnosis of NB. Although various laboratories have developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect VMA and HVA, the comparability between the results obtained from different laboratories and methods was poor. The absence of reference method for VMA and HVA hinders the standardization of their measurements. Therefore, a candidate reference measurement procedure (cRMP) based on isotope dilution LC-MS/MS (ID-LC-MS/MS) for the detection of VMA and HVA in human urine was established. Urine samples were spiked with VMA-d3 and HVA-d5 as internal standards and extracted using a protein precipitation method. The cRMP exhibited desirable precision with the total imprecision below 5 %. The accuracy of this cRMP was demonstrated by the high analytical recovery (98.64 % - 102.22 % and 98.41 % - 100.97 % for VMA and HVA, respectively), and comparability between different reference systems. The limit of detection for HVA and VMA were 15.625 ng/mL and 3.906 ng/mL, respectively; the quantification limits were 62.5 ng/mL and 7.813 ng/mL, respectively, which can meet the clinical detection requirements. The linear range was from 78.125 ng/mL to 20 µg/mL. Specificity evaluations showed no corresponding interference from structurally similar analogs. In conclusion, we have established a cRMP based on ID-LC-MS/MS for the measurement of VMA and HVA in urine samples, demonstrating well-defined method performance including accuracy, precision, and specificity. This newly established cRMP is suitable for routine assay standardization and evaluation of clinical samples. Furthermore, this method has the potential to significantly enhance the diagnostic accuracy for neuroblastoma.

Revealing mechanisms of NH3 and N2O emissions reduction in the rapid bio-drying of food waste: Insights from organic nitrogen composition and microbial activity.

Inevitably, aerobic biological treatment processes generate emissions of ammonia (NH3) and greenhouse gas (GHGs) emissions, especially nitrous oxide (N2O). The rapid bio-drying process (RBD) for food waste (FW) alleviates issues arising from its substantial growth. However, its emissions of NH3 and N2O remain unknown, and the correlation with nitrogen components in the substrate remains unclear, significantly impeding its widespread adoption. Here, the nitrogen loss and its mechanisms in RBD were investigated, and the results are as follows: The total emission of NH3 and N2O were1.42 and 1.16 mg/kg FW (fresh weight), respectively, achieving a 98 % reduction compared to prior studies. Structural equation modeling demonstrates that acid ammonium nitrogen (AN) decomposition chiefly generates NH3 in compost (p < 0.001). Strong correlation (p < 0.001) exists between amino acid nitrogen (AAN) and AN. In-depth analysis of microbial succession during the process reveals that the enrichment of Brevibacterium, Corynebacterium, Dietzia, Fastidiosipila, Lactobacillus, Mycobacterium, Peptoniphilus, and Truepera, are conducive to reducing the accumulation of AN and AAN in the substrate, minimizing NH3 emissions (p < 0.05). While Pseudomonas, Denitrobacterium, Nitrospira, and Bacillus are identified as key species contributing to N2O emissions during the process. Correlation analysis between physicochemical conditions and microbial succession in the system indicates that the moisture content and NO3- levels during the composting process provide suitable conditions for the growth of bacteria that contribute to NH3 and N2O emissions reduction, these enrichment in RBD process minimizing NH3 and N2O emissions. This study can offer crucial theoretical and data support for the resource utilization process of perishable organic solid waste, mitigating NH3 and GHGs emissions.

Photoreversible Aggregation of the Biliprotein Containing the First and Second GAF Domains of a Cyanobacteriochrome All2699 in Nostoc sp. PCC7120.

As plant photoreceptors, phytochromes are capable of detecting red light and far-red light, thereby governing plant growth. All2699 is a photoreceptor found in Nostoc sp. PCC7120 that specifically responds to red light and far-red light. All2699g1g2 is a truncated protein carrying the first and second GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domains of All2699. In this study, we found that, upon exposure to red light, the protein underwent aggregation, resulting in the formation of protein aggregates. Conversely, under far-red light irradiation, these protein aggregates dissociated. We delved into the factors that impact the aggregation of All2699g1g2, focusing on the protein structure. Our findings showed that the GAF2 domain contains a low-complexity (LC) loop region, which plays a crucial role in mediating protein aggregation. Specifically, phenylalanine at position 239 within the LC loop region was identified as a key site for the aggregation process. Furthermore, our research revealed that various factors, including irradiation time, temperature, concentration, NaCl concentration, and pH value, can impact the aggregation of All2699g1g2. The aggregation led to variations in Pfr concentration depending on temperature, NaCl concentration, and pH value. In contrast, ΔLC did not aggregate and therefore lacked responses to these factors. Consequently, the LC loop region of All2699g1g2 extended and enhanced sensory properties.

Cardiovascular disease and preventive care service utilization among midlife adults: The roles of diagnosis and depression.

Objectives: Secondary preventive care is important for monitoring the progression of cardiovascular disease (CVD). However, the factors that promote secondary prevention were not well understood. This study addressed this gap by investigating the impact of CVD diagnosis on preventive care utilization among midlife adults. Given the high prevalence of depression among this population, it further examined whether depression interacted with CVD diagnosis to affect preventive care utilization. Methods: The study sample included 6,222 midlife adults from six waves of the National Longitudinal Survey of Youth 1979 (NLSY79) collected between 2006 and 2016. Multiple logistic regressions were conducted to examine the relationship between a CVD diagnosis and each of the five types of preventive care utilization: influenza vaccinations, electrocardiography (EKG) and screening for high blood pressure, cholesterol, and blood sugar. Depression was then added to examine its possible moderation effect. Results: The results showed that midlife adults with a CVD diagnosis were more likely to utilize all five types of preventive care services. EKG, the most relevant preventive care type with CVD diagnosis, had the largest strength of likelihood. Depression strengthened the relationship between a CVD diagnosis and the utilization of blood pressure tests, but it showed no associations with other four types of preventive care utilization. Conclusions: The study findings indicate that a CVD diagnosis could serve as an opportunity for promoting secondary preventive care utilization. Future research needs to explore how a CVD diagnosis affects different population groups, and further explore the roles of depression.