Spatio-Temporal Modeling for Flash Memory Channels Using Conditional Generative Nets

We propose a data-driven approach to modeling the spatio-temporal characteristics of NAND flash memory read voltages using conditional generative networks. The learned model reconstructs read voltages from an individual memory cell based on the program levels of the cell and its surrounding cells, as well as the specified program/erase (P/E) cycling time stamp. We evaluate the model over a range of time stamps using the cell read voltage distributions, the cell level error rates, and the relative frequency of errors for patterns most susceptible to inter-cell interference (ICI) effects. We conclude that the model accurately captures the spatial and temporal features of the flash memory channel

Neurologic Abnormalities in Workers of a 1-Bromopropane Factory

We reported recently that 1-bromopropane (1-BP; n-propylbromide, CAS Registry no. 106-94-5), an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP), showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34–49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system

Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1

PurposeSpermatogonial stem cells (SSCs) are essential for maintaining reproductive function in males. B-lymphoma Mo-MLV insertion region 1 (BMI1) is a vital transcription repressor that regulates cell proliferation and differentiation. However, little is known about the role of BMI1 in mediating the fate of mammalian SSCs and in male reproduction. This study investigated whether BMI1 is essential for male reproduction and the role of alpha-tocopherol (α-tocopherol), a protective agent for male fertility, as a modulator of BMI1 both in vitro and in vivo.MethodsMethyl thiazolyl tetrazolium (MTT) and 5-ethynyl-2′-deoxyuridine (EDU) assays were used to assess the effect of BMI1 on the proliferative ability of the mouse SSC line C18-4. Real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence were applied to investigate changes in the mRNA and protein expression levels of BMI1. Male mice were used to investigate the effect of α-tocopherol and a BMI1 inhibitor on reproduction-associated functionality in vivo.ResultsAnalysis revealed that BMI1 was expressed at high levels in testicular tissues and spermatogonia in mice. The silencing of BMI1 inhibited the proliferation of SSCs and DNA synthesis and enhanced the levels of γ-H2AX. α-tocopherol enhanced the proliferation and DNA synthesis of C18-4 cells, and increased the levels of BMI1. Notably, α-tocopherol rescued the inhibition of cell proliferation and DNA damage in C18-4 cells caused by the silencing of BMI1. Furthermore, α-tocopherol restored sperm count (Ctrl vs. PTC-209, p = 0.0034; Ctrl vs. PTC-209 + α-tocopherol, p = 0.7293) and normalized sperm malformation such as broken heads, irregular heads, lost and curled tails in vivo, as demonstrated by its antagonism with the BMI1 inhibitor PTC-209.ConclusionAnalysis demonstrated that α-tocopherol is a potent in vitro and in vivo modulator of BMI1, a transcription factor that plays an important role in in SSC proliferation and spermatogenesis. Our findings identify a new target and strategy for treating male infertility that deserves further pre-clinical investigation

Self‐Assembly of Therapeutic Peptide into Stimuli‐Responsive Clustered Nanohybrids for Cancer‐Targeted Therapy

Clinical translation of therapeutic peptides, particularly those targeting intracellular protein–protein interactions (PPIs), has been hampered by their inefficacious cellular internalization in diseased tissue. Therapeutic peptides engineered into nanostructures with stable spatial architectures and smart disease targeting ability may provide a viable strategy to overcome the pharmaceutical obstacles of peptides. This study describes a strategy to assemble therapeutic peptides into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to tumor microenvironment. As a proof of concept, an anticancer peptide termed β‐catenin/Bcl9 inhibitors is copolymerized with gold ion and assembled into a cluster of nanohybrids (pCluster). Through a battery of in vitro and in vivo tests, it is demonstrated that pClusters potently inhibit tumor growth and metastasis in several animal models through the impairment of the Wnt/β‐catenin pathway, while maintaining a highly favorable biosafety profile. In addition, it is also found that pClusters synergize with the PD1/PD‐L1 checkpoint blockade immunotherapy. This new strategy of peptide delivery will likely have a broad impact on the development of peptide‐derived therapeutic nanomedicine and reinvigorate efforts to discover peptide drugs that target intracellular PPIs in a great variety of human diseases, including cancer.A strategy for clinical translation of therapeutic peptides by assembling them into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to the tumor microenvironment, is presented. An anticancer peptide termed β‐catenin/Bcl9 inhibitor is assembled into a cluster of nanohybrids termed pCluster, which potently inhibits tumor growth as well as metastasis, and synergizes with immunotherapy, while maintaining a highly favorable biosafety profile.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/1/adfm201807736.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/2/adfm201807736-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/3/adfm201807736_am.pd

Physicochemical properties, antioxidant activities and hypoglycemic effects of soluble dietary fibers purified from Lentinula edodes

Abstract Lentinula edodes (L. edodes), which imparts various health benefits to humans, is considered a novel source of soluble dietary fiber (SDF). In this study, ultrasonic-assisted hot-water method was used to extract SDF (U-SDF) from L. edodes, and physicochemical, antioxidant and hypoglycemic properties of the U-SDF were investigated. Physicochemical properties of U-SDF showed that water solubility, water holding capacity, swelling capacity, and oil holding capacity were higher than that the SDF extracted using hot water method without ultrasonication. The DPPH, •OH, and •O2- radical clearance rates indicated that U-SDF exhibited better antioxidant activities. U-SDF also exhibited notable α-amylase and α-glucosidase inhibition activities. Treatment with U-SDF alleviated glucose and peroxidation metabolism disorders in vivo. Histological analysis indicated that U-SDF improved the oxidative tissue damage in diabetic mice. These results provided a theoretical basis for the development and utilization of SDF derived from L. edodes

Effects of Microwave Treatment on Structure, Functional Properties and Antioxidant Activities of Germinated Tartary Buckwheat Protein

Tartary buckwheat protein (TBP) has promise as a potential source of novel natural nutrient plant protein ingredients. The modulating effects of microwave pretreatment at varying powers and times on the structure, functional properties, and antioxidant activities of germinated TBP were investigated. Compared with native germinated TBP, after microwave pretreatment, the content of free sulfhydryl groups in the germinated TBP increased, and the secondary structure changes showed a significant decrease in α-helix and an increase in random coil contents, and the intensity of the ultraviolet absorption peak increased (p < 0.05). In addition, microwave pretreatment significantly improved the solubility (24.37%), water-holding capacity (38.95%), emulsifying activity index (17.21%), emulsifying stability index (11.22%), foaming capacity (71.43%), and foaming stability (33.60%) of germinated TBP (p < 0.05), and the in vitro protein digestibility (5.56%) and antioxidant activities (DPPH (32.35%), ABTS (41.95%), and FRAP (41.46%)) of germinated TBP have also been improved. Among different treatment levels, a microwave level of 300 W/50 s gave the best results for the studied parameters. Specifically, microwave pretreatment could be a promising approach for modulating other germinated plant protein resources, as well as expanding the application of TBP

Baicalin-Copper Complex Modulates Gut Microbiota, Inflammatory Responses, and Hormone Secretion in DON-Challenged Piglets

The present experiment assessed the inflammatory responses, hormone secretion, and gut microbiota of weanling piglets administered baicalin-copper complex (BCU) or deoxynivalenol (DON) supplementation diets. Twenty-eight piglets were randomly assigned to four groups: control diet (Con group), a 4 mg DON/kg diet (DON group), a 5 g BCU/kg diet (BCU group), a 5 g BCU + 4 mg DON/kg diet (DBCU group). After 14 days, the results showed that dietary BCU supplementation remarkably increased the relative abundance of Clostrium bornimense and decreased the relative abundance of Lactobacillus in the DBCU group (p < 0.05). BCU decreased the serum concentration of IgG, IL-2, IFN-γ, and IgA in DON treated piglets (p < 0.05), and promoted the serum concentration of IL-1β, IgG, IL-2, IFN-γ, IgA, IL-6, IgM, and TNFα in normal piglets (p < 0.05). BCU increased the concentrations of serum IGF1, insulin, NPY, GLP-1, and GH, and decreased the concentrations of serum somatostatin in no DON treated piglets (p < 0.05). Dietary BCU supplementation significantly promoted the secretion of somatostatin, and inhibited the secretion of leptin in piglets challenged with DON (p < 0.05). BCU regulated the expression of food intake-related genes in the hypothalamus and pituitary of piglets. Collectively, dietary BCU supplementation alleviated inflammatory responses and regulated the secretion of appetite-regulating hormones and growth-axis hormones in DON challenged piglets, which was closely linked to changes of intestinal microbes

Dietary Addition of Antioxidant Complex Packs and Functional Amino Acids Can Improve the Digestion, Absorption, and Immunity of Huanjiang Minipigs

To study the effect of functional amino acids and the antioxidant function compound package on Huanjiang minipigs and to lay a foundation for the formulation of green and efficient feed for Huanjiang minipigs, we added functional amino acids and the antioxidant function compound package to piglet feed for 28 days. After feeding, we detected the growth performance, biochemical indexes, inflammatory indexes, and intestinal disaccharidase of piglets. It was found that functional amino acids and the antioxidant compound package had certain effects on the growth performance and biochemical indexes of piglets and could reduce the level of IL-6 and increase the level of LZM and SIgA of piglets, and the levels of lactase and maltase in the intestine also increased significantly. The results showed that the compound package of functional amino acids and antioxidation could improve the growth performance and immunity of piglets and promote the digestion and absorption of nutrients in piglets