Thiamine Deficiency Causes Long-Lasting Neurobehavioral Deficits in Mice

Thiamine deficiency (TD) has detrimental effects on brain health and neurobehavioral development, and it is associated with many aging-related neurological disorders. To facilitate TD-related neuropsychological studies, we generated a TD mouse model by feeding a thiamine-deficient diet for 30 days, followed by re-feeding the control diet for either one week or 16 weeks as recovery treatment. We then performed neurobehavioral tests in these two cohorts: cohort of one week post TD treatment (1 wk-PTDT) and 16 weeks post TD treatment (16 wks-PTDT). The TD mice showed no significant difference from control in any tests in the 1 wk-PTDT cohort at the age of 13–14 weeks. The tests for the 16 wks-PTDT cohort at the age of 28–29 weeks, however, demonstrated anxiety and reduced locomotion in TD animals in open field and elevated plus maze. In comparison, rotor rod and water maze revealed no differences between TD and control mice. The current findings of the differential effects of the same TD treatment on locomotion and anxiety at different ages may reflect the progressive and moderate change of TD-induced neurobehavioral effects. The study suggests that, even though the immediate neurobehavioral impact of TD is modest or negligible at a young age, the impact could develop and become severe during the aging process

MReD: A Meta-Review Dataset for Structure-Controllable Text Generation

When directly using existing text generation datasets for controllable generation, we are facing the problem of not having the domain knowledge and thus the aspects that could be controlled are limited. A typical example is when using CNN/Daily Mail dataset for controllable text summarization, there is no guided information on the emphasis of summary sentences. A more useful text generator should leverage both the input text and the control signal to guide the generation, which can only be built with a deep understanding of the domain knowledge. Motivated by this vision, our paper introduces a new text generation dataset, named MReD. Our new dataset consists of 7,089 meta-reviews and all its 45k meta-review sentences are manually annotated with one of the 9 carefully defined categories, including abstract, strength, decision, etc. We present experimental results on start-of-the-art summarization models, and propose methods for structure-controlled generation with both extractive and abstractive models using our annotated data. By exploring various settings and analyzing the model behavior with respect to the control signal, we demonstrate the challenges of our proposed task and the values of our dataset MReD. Meanwhile, MReD also allows us to have a better understanding of the meta-review domain.Comment: 15 pages, 5 figures, accepted at ACL 202

Genetic Variants of PICALM rs541458 Modulate Brain Spontaneous Activity in Older Adults With Amnestic Mild Cognitive Impairment

Background: Phosphatidylinositol binding clathrin assembly protein (PICALM) rs541458 C allele has been identified and validated to be associated with a reduction of Alzheimer's disease (AD) risk. Nevertheless, the exact mechanisms through which the variant exert its disease-relevant association remain to be elucidated. This study is to determine whether PICALM rs541458 polymorphism modulates functional magnetic resonance imaging measured brain spontaneous activity in older adults with amnestic mild cognitive impairment (aMCI).Methods: Thirty five aMCI patients and twenty six healthy controls (HC) were enrolled in this study. Each individual was genotyped for rs541458 and scanned with resting-state functional magnetic resonance imaging. Each group was divided into two subgroups (C carriers and TT genotype). Brain activity was measured with amplitude of low-frequency fluctuation (ALFF).Results: The aMCI patients showed decreased ALFF in left inferior frontal gyrus, superior temporal gyrus and insula, while increased ALFF in right cuneus, calcarine, and bilateral posterior cingulate and precuneus. A significant interaction between diagnosis (aMCI vs. HC) and PICALM rs541458 genotype (C carriers vs. TT) on ALFF was observed mainly in the right frontal lobe, with aMCI C carriers and TT genotype in HC showing significantly lower ALFF than HC C carriers. While only negative correlation between ALFF and verbal fluency test was found in HC C carriers (r = −0.543, p = 0.030).Conclusions: This study provided preliminary evidences that PICALM rs541458 variations may modulate the spontaneous brain activity in aMCI patients

High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia

Acute myelogenous leukemia (AML) is a disease that severely affects the physical health of children. Thus, we aimed to identify biomarkers associated with AML prognosis in children. Using transcriptomics on an mRNA dataset from 27 children with non-M3 AML, we selected genes from among those with the top 5000 median absolute deviation (MAD) values for subsequent analysis which showed that two modules were associated with AML risk groups. Thus, enrichment analysis was performed using genes from these modules. A one-way Cox analysis was performed on a dataset of 149 non-M3 AML patients downloaded from the TCGA. This identified four genes as significant: FTH1, RCC2, ABHD17B, and IRAK1. Through survival analysis, FTH1 was identified as a key gene associated with AML prognosis. We verified the proliferative and regulatory effects of ferroptosis on MOLM-13 and THP-1 cells using Liproxstatin-1 and Erastin respectively by CCK-8 and flow cytometry assays. Furthermore, we assayed expression levels of FTH1 in MOLM-13 and THP-1 cells after induction and inhibition of ferroptosis by real-time quantitative PCR, which showed that upregulated FTH1 expression promoted proliferation and inhibited apoptosis in leukemia cells. In conclusion, high expression of FTH1 promoted proliferation and inhibited apoptosis of leukemic cells through the ferroptosis pathway and is thus a potential risk factor that affects the prognosis of non-M3 AML in children

Predicting 18F-FDG SUVs of metastatic pulmonary nodes from CT images in patients with differentiated thyroid cancer by using a convolutional neural network

PurposeThe aim of this study was to predict standard uptake values (SUVs) from computed tomography (CT) images of patients with lung metastases from differentiated thyroid cancer (DTC-LM).MethodsWe proposed a novel SUVs prediction model using 18-layer Residual Network for generating SUVmax, SUVmean, SUVmin of metastatic pulmonary nodes from CT images of patients with DTC-LM. Nuclear medicine specialists outlined the metastatic pulmonary as primary set. The best model parameters were obtained after five-fold cross-validation on the training and validation set, further evaluated in independent test set. Mean absolute error (MAE), mean squared error (MSE), and mean relative error (MRE) were used to assess the performance of regression task. Specificity, sensitivity, F1 score, positive predictive value, negative predictive value and accuracy were used for classification task. The correlation between predicted and actual SUVs was analyzed.ResultsA total of 3407 nodes from 74 patients with DTC-LM were collected in this study. On the independent test set, the average MAE, MSE and MRE was 0.3843, 1.0133, 0.3491 respectively, and the accuracy was 88.26%. Our proposed model achieved high metric scores (MAE=0.3843, MSE=1.0113, MRE=34.91%) compared with other backbones. The predicted SUVmax (R2 = 0.8987), SUVmean (R2 = 0.8346), SUVmin (R2 = 0.7373) were all significantly correlated with actual SUVs.ConclusionThe novel approach proposed in this study provides new ideas for the application of predicting SUVs for metastatic pulmonary nodes in DTC patients

Oxalate as a potent promoter of kidney stone formation

Kidney stones are among the most prevalent urological diseases, with a high incidence and recurrence rate. Treating kidney stones has been greatly improved by the development of various minimally invasive techniques. Currently, stone treatment is relatively mature. However, most current treatment methods are limited to stones and cannot effectively reduce their incidence and recurrence. Therefore, preventing disease occurrence, development, and recurrence after treatment, has become an urgent issue. The etiology and pathogenesis of stone formation are key factors in resolving this issue. More than 80% of kidney stones are calcium oxalate stones. Several studies have studied the formation mechanism of stones from the metabolism of urinary calcium, but there are few studies on oxalate, which plays an equally important role in stone formation. Oxalate and calcium play equally important roles in calcium oxalate stones, whereas the metabolism and excretion disorders of oxalate play a crucial role in their occurrence. Therefore, starting from the relationship between renal calculi and oxalate metabolism, this work reviews the occurrence of renal calculi, oxalate absorption, metabolism, and excretion mechanisms, focusing on the key role of SLC26A6 in oxalate excretion and the regulatory mechanism of SLC26A6 in oxalate transport. This review provides some new clues for the mechanism of kidney stones from the perspective of oxalate to improve the understanding of the role of oxalate in the formation of kidney stones and to provide suggestions for reducing the incidence and recurrence rate of kidney stones

A Major and Stable QTL for Bacterial Wilt Resistance on Chromosome B02 Identified Using a High-Density SNP-Based Genetic Linkage Map in Cultivated Peanut Yuanza 9102 Derived Population

Bacterial wilt (BW) is one of the important diseases limiting the production of peanut (Arachis hypogaea L.) worldwide. The sufficient precise information on the quantitative trait loci (QTL) for BW resistance is essential for facilitating gene mining and applying in molecular breeding. Cultivar Yuanza 9102 is BW resistant, bred from wide cross between cultivated peanut Baisha 1016 and a wild diploid peanut species A. chacoense with BW resistance. In this study, we aim to map the major QTLs related to BW-resistance in Yuanza 9102. A high density SNP-based genetic linkage map was constructed through double-digest restriction-site-associated DNA sequencing (ddRADseq) technique based on Yuanza 9102 derived recombinant inbred lines (RILs) population. The map contained 2,187 SNP markers distributed on 20 linkage groups (LGs) spanning 1566.10 cM, and showed good synteny with AA genome from A. duranensis and BB genome from A. ipaensis. Phenotypic frequencies of BW resistance among RIL population showed two-peak distribution in four environments. Four QTLs explaining 5.49 to 23.22% phenotypic variance were identified to be all located on chromosome B02. The major QTL, qBWB02.1 (12.17–23.33% phenotypic variation explained), was detected in three environments showing consistent and stable expression. Furthermore, there was positive additive effect among these major and minor QTLs. The major QTL region was mapped to a region covering 2.3 Mb of the pseudomolecule B02 of A. ipaensis which resides in 21 nucleotide-binding site -leucine-rich repeat (NBS-LRR) encoding genes. The result of the major stable QTL (qBWB02.1) not only offers good foundation for discovery of BW resistant gene but also provide opportunity for deployment of the QTL in marker-assisted breeding in peanut

Susceptibility of HIV-1 Subtypes B′, CRF07_BC and CRF01_AE that Are Predominantly Circulating in China to HIV-1 Entry Inhibitors

The B', CRF07_BC and CRF01_AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China.The baseline susceptibility of 14 representative HIV-1 isolates (5 CRF07_BC, 4 CRF01_AE, and 5 B'), most of which were R5 viruses, obtained from drug-naïve patients to HIV entry inhibitors, including two fusion inhibitors (enfuvirtide and C34), two CCR5 antagonists (maraviroc and TAK779) and one CXCR4 antagonist (AMD3100), were determined by virus inhibition assay. The sequences of their env genes were amplified and analyzed. These isolates possessed similar susceptibility to C34, but they exhibited different sensitivity to enfuvirtide, maraviroc or TAK779. CRF07_BC isolates, which carried polymorphisms of A578T and V583I in the N-terminal heptad repeat and E630Q, E662A, K665S, A667K and S668N in the C-terminal heptad repeat of gp41, were about 5-fold less sensitive than B' and CRF01_AE isolates to enfuvirtide. Subtype B' isolates with a unique polymorphism site of F317W in V3 loop, were about 4- to 5-fold more sensitive than CRF07_BC and CRF01_AE isolates to maraviroc and TAK779. AMD3100 at the concentration as high as 5 µM exhibited no significant inhibitory activity against any of the isolates tested.Our results suggest that there are significant differences in baseline susceptibility to HIV entry inhibitors among the predominant HIV-1 subtypes in China and the differences may partly result from the naturally occurring polymorphisms in these subtypes. This study provides useful information for rational design of optimal therapeutic regimens for HIV-1-infected patients in China