Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

Development and Validation of a Simoa Assay for Determination of Recombinant Batroxobin in Human Serum

Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies.Therefore,a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101.In this study,a sensitive bioanalytical method was developed and validated,using a Quanterix single molecular array(Simoa)assay.Moreover,to thoroughly assess the platform,enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed,and their performance was compared with that of this novel technology platform.The assay was validated in compliance with the current guidelines.Measurements with the Simoa assay were precise and accurate,presenting a valid assay range from 6.55 to 4000 pg/mL.The intra-and inter-run accuracy and precision were within-19.3%to 15.3%and 5.5%to 17.0%,respectively.S3101 was stable in human serum for 280 days at-20℃and-70℃,for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature(22℃-28℃),respectively,and after five and two freeze-thaw cycles at-70℃and-20oC,respectively.The Simoa assay also demonstrated sufficient dilution linearity,assay sensitivity,and parallelism for quantifying S3101 in human serum.The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.

SoySNP618K array:A high-resolution single nucleotide polymorphism platform as a valuable genomic resource for soybean genetics and breeding

Innovations in genomics have enabled the development of low-cost,high-resolution,single nucleotide polymorphism(SNP)genotyping arrays that accelerate breeding progress and support basic research in crop science.Here,we developed and validated the Soy SNP618 K array(618,888 SNPs)for the important crop soybean.The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions;29.34%of the SNPs mapped to genic regions representing 86.85%of the 56,044annotated high-confidence genes.Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions,highlighting the potential of the Soy SNP618 K array in supporting gene bank management.The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data,suggesting that the ascertainment bias in the Soy SNP618 K array was largely compensated for.Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time,E2 and Gm PRR3 b,and of a new candidate gene,Gm VIP5.Moreover,genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate(>0.65).Thus,the Soy SNP618 K array is a valuable genomic tool that can be used to address many questions in applied breeding,germplasm management,and basic crop research.

Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia with Chromothripsis in an Old Woman

Cell karyotyping in patients with small lymphocytic lymphoma/chronic lymphocytic leukemia （SLL/CLL） is not easy to success, and small genomic lesions （〈5 Mb） are not routinely detected by this method. It is likely that a complete genomic characterization of CLL requires a combination of fluorescence in situ hybridization （FISH）, single nucleotide polymorphism （SNP） array profiling for comprehensive genome-wide analysis of acquired genomic copy number aberrations （aCNAs） and loss-of-heterozygosity （LOH） in dominant clones, and karyotyping for detection of balanced translocations, isochromosomes, and marker chromosomes. SNP array analysis can reveal chromothripsis, a phenomenon by which regions of the cancer genome are shattered and recombined to generate frequent oscillations between the lower and the higher DNA copy number states. This study provided cytogenetic findings in a CLL/SLL patient with v-myc avian myelocytomatosis viral oncogene homolog （C-MYC）-amplification by FISH, in which SNP arrays detected profound genomic upheaval due to chromothripsis that may lead to malignant transformation.