Non-volatile Reconfigurable Digital Optical Diffractive Neural Network Based on Phase Change Material

Optical diffractive neural networks have triggered extensive research with their low power consumption and high speed in image processing. In this work, we propose a reconfigurable digital all-optical diffractive neural network (R-ODNN) structure. The optical neurons are built with Sb2Se3 phase-change material, making our network reconfigurable, digital, and non-volatile. Using three digital diffractive layers with 14,400 neurons on each and 10 photodetectors connected to a resistor network, our model achieves 94.46% accuracy for handwritten digit recognition. We also performed full-vector simulations and discussed the impact of errors to demonstrate the feasibility and robustness of the R-ODNN

Data_Sheet_1_Effect of empagliflozin on cytoskeletal repair in the hippocampus of obese mice.xls

ObjectiveWe aimed to investigate the effect of empagliflozin on hippocampal phosphorylated protein levels in obese mice.Materials and methodsSixteen obese mice successfully modeled on high-fat diet were randomly divided into high-fat feeding group (group H) and empagliflozin group (group H + empagliflozin, group E), eight mice in each group, and eight C57BL/6J male normal mice were selected as the control group (normal control, group C). Group E was treated with empagliflozin 10 mg/kg/d for 12 weeks, while mice in groups H and C were treated with equal amounts of saline. The spatial learning memory ability of the mice was determined by the Morris water maze experiment. Further, their body weights and serological indices were measured. Finally, total proteins were extracted from hippocampal tissues for functional analysis by the phosphorylated proteomics method.ResultsThe results showed that escape latency was prolonged, retention time in the target quadrant was shortened, and the number of loop penetrations was reduced in the obese mice induced by a high-calorie diet compared with normal controls, whereas escape latency was shortened, retention time in the target quadrant was increased, and the number of loop penetrations was increased after empagliflozin treatment. Phosphoproteomics in the high-fat/control (H/C), empagliflozin/high-fat (E/H), and E/C groups showed 844, 1,552, and 1,512 differentially significant phosphorylation sites, respectively. The proteins corresponding to these differentially phosphorylated sites were mainly involved in neurodegenerative pathways and actin cytoskeleton regulation. Notably, myosin heavy chain 10 (MYH10), p21 protein-activated kinase 4 (PAK4), phosphatidylinositol 3 -phosphate 5-kinase (PIKfyve), and other differentially phosphorylated proteins were involved in actin cytoskeleton regulation.ConclusionWe concluded that empagliflozin protects cognitive functions by inducing serine phosphorylation in MYH10, PAK4, and PIKfyve in the hippocampal tissue of obese mice.</p

Tyramine-Invertase Bioconjugate-Amplified Personal Glucose Meter Signaling for Ultrasensitive Immunoassay

Highly sensitive and facile detection of low levels of protein markers is of great significance for the early diagnosis and efficacy monitoring of diseases. Herein, aided by an efficient tyramine-signal amplification (TSA) mechanism, we wish to report a simple but ultrasensitive immunoassay with signal readout on a portable personal glucose meter (PGM). In this study, the bioconjugates of tyramine and invertase (Tyr-inv), which act as the critical bridge to convert and amplify the protein concentration information into glucose, are prepared following a click chemistry reaction. Then, in the presence of a target protein, the sandwich immunoreaction between the immobilized capture antibody, the target protein, and the horseradish peroxidase (HRP)-conjugated detection antibody is specifically performed in a 96-well microplate. Subsequently, the specifically loaded HRP-conjugated detection antibodies will catalyze the amplified deposition of a large number of Tyr-inv molecules onto adjacent proteins through highly efficient TSA. Then, the deposited invertase, whose dosage can faithfully reflect the original concentration of the target protein, can efficiently convert sucrose to glucose. The amount of finally produced glucose is simply quantified by the PGM, realizing the highly sensitive detection of trace protein markers such as the carcinoembryonic antigen and alpha fetoprotein antigen at the fg/mL level. This method is simple, cost-effective, and ultrasensitive without the requirement of sophisticated instruments or specialized laboratory equipment, which may provide a universal and promising technology for highly sensitive immunoassay for in vitro diagnosis of diseases

Additional file 1: of Comparison of glycemic improvement between intermittent calorie restriction and continuous calorie restriction in diabetic mice

Figure S1. Food intake of the mice. Figure S2. Comparison of 2–5 regime of intermittent fasting using normal chow with intermittent FMD and matched continuous CR in db/db mice. Figure S3. Fluorescent staining of pancreatic islets in control mice. Figure S4. Fluorescent staining of pancreatic islets in db/db mice after diet intervention. Figure S5. Fluorescent staining of pancreatic islets in STZ-treated mice after diet intervention. Figure S6. Comparison of glycemic control between intermittent FMD and continuous CR in db/db and STZ-treated mice. Figure S7. Comparison between intermittent FMD and continuous CR in db/db mice. Figure S8. Intermittent FMD enhances insulin signaling in the skeletal muscle and liver of the mice. (PDF 1400 kb

Additional file 1: of Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression, restores β cells and reconstructs gut microbiota in mice

Figure S1. Rarefactions curve of gut microbiota in the two groups of mice. Figure S2. Intermittent FMD alters the composition of gut microbiota at species level. Figure S3. Improvement of glucose tolerance and islet area by FMD in type 1 diabetic mice. Table S1. Ingredients of FMD. Table S2. Nutritional information of FMD. Table S3. Nutritional information of normal chow. Table S4. Primer sequences used in RT-PCR with liver tissues. (PDF 695 kb

Energetics and Ionic–Electronic and Geometric Variabilities of Hydroxylammonium-Based Salts

In the present work, we study the formation energy of energetic ionic salts (EISs), as well as the volumetric and electric variabilities of ions involved in EISs, by employing 25 hydroxylammonium cations (HA+) in 22 salts as examples. We identify the viability of a dispersion-corrected density functional theory method, PBE-D3­(BJ), to describe the lattice parameters, with a mean relative deviation of 1.26% and a maximal relative deviation of 2.5%. Thereby, the ionization energy, formation energy, and lattice energy are predicted. The variability of volume (VHA+) is confirmed in different HA+-based salts, as well as between two HA+ of the same lattice with Z′ > 1. The largest difference of VHA+ among the 25 HA+ reaches ∼9%. This variability of VHA+ is originated from the difference in crystal field effects, or intermolecular interactions. That is, the stronger intermolecular hydrogen bond tends to exhibit a stronger drag and pull effect on HA+ and leads to a larger VHA+. In comparison, it exhibits a more significant variability of electricity, as the maximal total Mulliken charge of HA+ (QHA+) is >1.67 times the minimal one. Moreover, the observed QHA+ varying from 0.164 to 0.438 e is much less than the apparent charge of 1 e, suggesting the highly insufficient charge of HA+ in EISs. This means that the ionic bonding does not necessarily govern the intermolecular interactions in common EISs. Besides, an electrostatic potential (ESP) minimum-oxygen balance (OB) correlation is found in the anions countering HA+, as the more negative OB tends to cause a more negative ESP minimum. All of these findings are expected to richen the insight into the nature of EISs as a special group of EMs

Gold-Catalyzed Alkyne Multifunctionalization through an Oxidation–Oxyalkylation–Aryloxylation Sequence

A gold-catalyzed oxidative three-component reaction of terminal alkynes with alcohols and quinone monoimines has been disclosed, affording α-ketoacetals in good to excellent yields. By using quinone monoimines as electrophiles for the interception of the in situ generated gold enolate intermediate, this one-pot process provides an unprecedented method for the polyfunctionalization of terminal alkynes through an oxidation–oxyalkylation–aryloxylation sequence, installing three oxygen atoms on the C–C triple bond

Table5_Low expression of the metabolism-related gene SLC25A21 predicts unfavourable prognosis in patients with acute myeloid leukaemia.XLSX

Acute myeloid leukaemia (AML) is a heterogeneous disease associated with poor outcomes. To identify AML-specific genes with prognostic value, we analysed transcriptome and clinical information from The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) datasets, and Genotype-Tissue Expression (GTEx) project. The metabolism-related gene, SLC25A21 was found to be significantly downregulated in AML, and was associated with high white blood cell (WBC) counts, high pretrial blood (PB) and bone marrow (BM) blast abundance, FLT3 mutation, NPM1 mutation, and death events (all p value <0.05). We validated the expression of SLC25A21 in our clinical cohort, and found that SLC25A21 was downregulated in AML. Moreover, we identified low expression of SLC25A21 as an independent prognostic factor by univariate Cox regression (hazard ratio [HR]: 0.550; 95% Confidence interval [CI]: 0.358–0.845; p value = 0.006) and multivariate Cox regression analysis (HR: 0.341; 95% CI: 0.209–0.557; p value <0.05). A survival prediction nomogram was established with a C-index of 0.735, which indicated reliable prognostic prediction. Subsequently, based on the median SLC25A21 expression level, patients in the TCGA-LAML cohort were divided into low- and high-expression groups. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs highlighted growth factor binding, extracellular structure organization, cytokine‒cytokine receptor interaction, etc. The results of gene set enrichment analysis (GSEA) indicated that the epithelial-mesenchymal transition, KRAS signalling, oxidative phosphorylation, and reactive oxygen species pathways were enriched. Through gene coexpression and protein‒protein interaction (PPI) network analysis, we identified two hub genes, EGFR and COL1A2, which were linked to worse clinical outcomes. Furthermore, we found that lower SLC25A21 expression was closely associated with a significant reduction in the levels of infiltrating immune cells, which might be associated with immune escape of AML cells. A similar trend was observed for the expression of checkpoint genes (CTLA4, LAG3, TIGIT, and HAVCR2). Finally, drug sensitivity testing suggested that the low-expression SLC25A21 group is sensitive to doxorubicin, mitomycin C, linifanib but resistant to JQ1, belinostat, and dasatinib. Hence, our study demonstrated that a low expression level of SLC25A21 predicts an unfavourable prognosis in patients with AML.</p

DataSheet2_Low expression of the metabolism-related gene SLC25A21 predicts unfavourable prognosis in patients with acute myeloid leukaemia.PDF

Acute myeloid leukaemia (AML) is a heterogeneous disease associated with poor outcomes. To identify AML-specific genes with prognostic value, we analysed transcriptome and clinical information from The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) datasets, and Genotype-Tissue Expression (GTEx) project. The metabolism-related gene, SLC25A21 was found to be significantly downregulated in AML, and was associated with high white blood cell (WBC) counts, high pretrial blood (PB) and bone marrow (BM) blast abundance, FLT3 mutation, NPM1 mutation, and death events (all p value <0.05). We validated the expression of SLC25A21 in our clinical cohort, and found that SLC25A21 was downregulated in AML. Moreover, we identified low expression of SLC25A21 as an independent prognostic factor by univariate Cox regression (hazard ratio [HR]: 0.550; 95% Confidence interval [CI]: 0.358–0.845; p value = 0.006) and multivariate Cox regression analysis (HR: 0.341; 95% CI: 0.209–0.557; p value <0.05). A survival prediction nomogram was established with a C-index of 0.735, which indicated reliable prognostic prediction. Subsequently, based on the median SLC25A21 expression level, patients in the TCGA-LAML cohort were divided into low- and high-expression groups. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs highlighted growth factor binding, extracellular structure organization, cytokine‒cytokine receptor interaction, etc. The results of gene set enrichment analysis (GSEA) indicated that the epithelial-mesenchymal transition, KRAS signalling, oxidative phosphorylation, and reactive oxygen species pathways were enriched. Through gene coexpression and protein‒protein interaction (PPI) network analysis, we identified two hub genes, EGFR and COL1A2, which were linked to worse clinical outcomes. Furthermore, we found that lower SLC25A21 expression was closely associated with a significant reduction in the levels of infiltrating immune cells, which might be associated with immune escape of AML cells. A similar trend was observed for the expression of checkpoint genes (CTLA4, LAG3, TIGIT, and HAVCR2). Finally, drug sensitivity testing suggested that the low-expression SLC25A21 group is sensitive to doxorubicin, mitomycin C, linifanib but resistant to JQ1, belinostat, and dasatinib. Hence, our study demonstrated that a low expression level of SLC25A21 predicts an unfavourable prognosis in patients with AML.</p

Table6_Low expression of the metabolism-related gene SLC25A21 predicts unfavourable prognosis in patients with acute myeloid leukaemia.XLSX

Acute myeloid leukaemia (AML) is a heterogeneous disease associated with poor outcomes. To identify AML-specific genes with prognostic value, we analysed transcriptome and clinical information from The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) datasets, and Genotype-Tissue Expression (GTEx) project. The metabolism-related gene, SLC25A21 was found to be significantly downregulated in AML, and was associated with high white blood cell (WBC) counts, high pretrial blood (PB) and bone marrow (BM) blast abundance, FLT3 mutation, NPM1 mutation, and death events (all p value <0.05). We validated the expression of SLC25A21 in our clinical cohort, and found that SLC25A21 was downregulated in AML. Moreover, we identified low expression of SLC25A21 as an independent prognostic factor by univariate Cox regression (hazard ratio [HR]: 0.550; 95% Confidence interval [CI]: 0.358–0.845; p value = 0.006) and multivariate Cox regression analysis (HR: 0.341; 95% CI: 0.209–0.557; p value <0.05). A survival prediction nomogram was established with a C-index of 0.735, which indicated reliable prognostic prediction. Subsequently, based on the median SLC25A21 expression level, patients in the TCGA-LAML cohort were divided into low- and high-expression groups. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs highlighted growth factor binding, extracellular structure organization, cytokine‒cytokine receptor interaction, etc. The results of gene set enrichment analysis (GSEA) indicated that the epithelial-mesenchymal transition, KRAS signalling, oxidative phosphorylation, and reactive oxygen species pathways were enriched. Through gene coexpression and protein‒protein interaction (PPI) network analysis, we identified two hub genes, EGFR and COL1A2, which were linked to worse clinical outcomes. Furthermore, we found that lower SLC25A21 expression was closely associated with a significant reduction in the levels of infiltrating immune cells, which might be associated with immune escape of AML cells. A similar trend was observed for the expression of checkpoint genes (CTLA4, LAG3, TIGIT, and HAVCR2). Finally, drug sensitivity testing suggested that the low-expression SLC25A21 group is sensitive to doxorubicin, mitomycin C, linifanib but resistant to JQ1, belinostat, and dasatinib. Hence, our study demonstrated that a low expression level of SLC25A21 predicts an unfavourable prognosis in patients with AML.</p