Synthesis and Antioxidant Activity of Cationic 1,2,3-Triazole Functionalized Starch Derivatives

In this study, starch was chemically modified to improve its antioxidant activity. Five novel cationic 1,2,3-triazole functionalized starch derivatives were synthesized by using "click" reaction and N-alkylation. A convenient method for pre-azidation of starch was developed. The structures of the derivatives were analyzed using FTIR and H-1 NMR. The radicals scavenging abilities of the derivatives against hydroxyl radicals, DPPH radicals, and superoxide radicals were tested in vitro in order to evaluate their antioxidant activity. Results revealed that all the cationic starch derivatives (2a-2e), as well as the precursor starch derivatives (1a-1e), had significantly improved antioxidant activity compared to native starch. In particular, the scavenging ability of the derivatives against superoxide radicals was extremely strong. The improved antioxidant activity benefited from the enhanced solubility and the added positive charges. The biocompatibility of the cationic derivatives was confirmed by the low hemolytic rate (<2%). The obtained derivatives in this study have great potential as antioxidant materials that can be applied in the fields of food and biomedicine

Februus: Input Purification Defense Against Trojan Attacks on Deep Neural Network Systems

We propose Februus; a new idea to neutralize highly potent and insidious Trojan attacks on Deep Neural Network (DNN) systems at run-time. In Trojan attacks, an adversary activates a backdoor crafted in a deep neural network model using a secret trigger, a Trojan, applied to any input to alter the model's decision to a target prediction---a target determined by and only known to the attacker. Februus sanitizes the incoming input by surgically removing the potential trigger artifacts and restoring the input for the classification task. Februus enables effective Trojan mitigation by sanitizing inputs with no loss of performance for sanitized inputs, Trojaned or benign. Our extensive evaluations on multiple infected models based on four popular datasets across three contrasting vision applications and trigger types demonstrate the high efficacy of Februus. We dramatically reduced attack success rates from 100% to near 0% for all cases (achieving 0% on multiple cases) and evaluated the generalizability of Februus to defend against complex adaptive attacks; notably, we realized the first defense against the advanced partial Trojan attack. To the best of our knowledge, Februus is the first backdoor defense method for operation at run-time capable of sanitizing Trojaned inputs without requiring anomaly detection methods, model retraining or costly labeled data.Comment: 16 pages, to appear in the 36th Annual Computer Security Applications Conference (ACSAC 2020

Hydrogen atom collisions with a semiconductor efficiently promote electrons to the conduction band

The Born-Oppenheimer approximation is the keystone of modern computational chemistry and there is wide interest in understanding under what conditions it remains valid. Hydrogen atom scattering from insulator, semi-metal and metal surfaces has helped provide such information. The approximation is adequate for insulators and for metals it fails, but not severely. Here we present hydrogen atom scattering from a semiconductor surface: Ge(111)c(2 × 8). Experiments show bimodal energy-loss distributions revealing two channels. Molecular dynamics trajectories within the Born-Oppenheimer approximation reproduce one channel quantitatively. The second channel transfers much more energy and is absent in simulations. It grows with hydrogen atom incidence energy and exhibits an energy-loss onset equal to the Ge surface bandgap. This leads us to conclude that hydrogen atom collisions at the surface of a semiconductor are capable of promoting electrons from the valence to the conduction band with high efficiency. Our current understanding fails to explain these observations. [Abstract copyright: © 2022. The Author(s).

Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs

Body-protective compound (BPC) 157 demonstrates protective effects against damage to various organs and tissues. For future clinical applications, we had previously established a solid-phase synthesis process for BPC157, verified its biological activity in different wound models, and completed preclinical safety evaluations. This study aimed to investigate the pharmacokinetics, excretion, metabolism, and distribution profiles of BPC157. After a single intravenous (IV) administration, single intramuscular (IM) administrations at three doses in successive increments along with repeated IM administrations, the elimination half-life (t1/2) of prototype BPC157 was less than 30 min, and BPC157 showed linear pharmacokinetic characteristics in rats and beagle dogs at all doses. The mean absolute bioavailability of BPC157 following IM injection was approximately 14%–19% in rats and 45%–51% in beagle dogs. Using [3H]-labeled BPC157 and radioactivity examination, we proved that the main excretory pathways of BPC157 involved urine and bile. [3H]BPC157 was rapidly metabolized into a variety of small peptide fragments in vivo, thus forming single amino acids that entered normal amino acid metabolism and excretion pathways. In conclusion, this study provides the first analysis of the pharmacokinetics of BPC157, which will be helpful for its translation in the clinic

Utility of clinical metagenomics in diagnosing malignancies in a cohort of patients with Epstein-Barr virus positivity

BackgroundsDifferentiation between benign and malignant diseases in EBV-positive patients poses a significant challenge due to the lack of efficient diagnostic tools. Metagenomic Next-Generation Sequencing (mNGS) is commonly used to identify pathogens of patients with fevers of unknown-origin (FUO). Recent studies have extended the application of Next-Generation Sequencing (NGS) in identifying tumors in body fluids and cerebrospinal fluids. In light of these, we conducted this study to develop and apply metagenomic methods to validate their role in identifying EBV-associated malignant disease.MethodsWe enrolled 29 patients with positive EBV results in the cohort of FUO in the Department of Infectious Diseases of Huashan Hospital affiliated with Fudan University from 2018 to 2019. Upon enrollment, these patients were grouped for benign diseases, CAEBV, and malignant diseases according to their final diagnosis, and CNV analysis was retrospectively performed in 2022 using samples from 2018 to 2019.ResultsAmong the 29 patients. 16 of them were diagnosed with benign diseases, 3 patients were diagnosed with CAEBV and 10 patients were with malignant diseases. 29 blood samples from 29 patients were tested for mNGS. Among all 10 patients with malignant diagnosis, CNV analysis suggested neoplasms in 9 patients. Of all 19 patients with benign or CAEBV diagnosis, 2 patients showed abnormal CNV results. The sensitivity and specificity of CNV analysis for the identification for tumors were 90% and 89.5%, separately.ConclusionsThe application of mNGS could assist in the identification of microbial infection and malignancies in EBV-related diseases. Our results demonstrate that CNV detection through mNGS is faster compared to conventional oncology tests. Moreover, the convenient collection of peripheral blood samples adds to the advantages of this approach

Increased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration

Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration. Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold. Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29(+)/CD90(+) double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups. Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for clinical application in the future

HDAC Inhibitors Act with 5-aza-2′-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells

5-aza-2′-deoxycytidine (5-aza-CdR) is used extensively as a demethylating agent and acts in concert with histone deacetylase inhibitors (HDACI) to induce apoptosis or inhibition of cell proliferation in human cancer cells. Whether the action of 5-aza-CdR in this synergistic effect results from demethylation by this agent is not yet clear. In this study we found that inhibition of cell proliferation was not observed when cells with knockdown of DNA methyltransferase 1 (DNMT1), or double knock down of DNMT1-DNMT3A or DNMT1-DNMT3B were treated with HDACI, implying that the demethylating function of 5-aza-CdR may be not involved in this synergistic effect. Further study showed that there was a causal relationship between 5-aza-CdR induced DNA damage and the amount of [3H]-5-aza-CdR incorporated in DNA. However, incorporated [3H]-5-aza-CdR gradually decreased when cells were incubated in [3H]-5-aza-CdR free medium, indicating that 5-aza-CdR, which is an abnormal base, may be excluded by the cell repair system. It was of interest that HDACI significantly postponed the removal of the incorporated [3H]-5-aza-CdR from DNA. Moreover, HDAC inhibitor showed selective synergy with nucleoside analog-induced DNA damage to inhibit cell proliferation, but showed no such effect with other DNA damage stresses such as γ-ray and UV, etoposide or cisplatin. This study demonstrates that HDACI synergistically inhibits cell proliferation with nucleoside analogs by suppressing removal of incorporated harmful nucleotide analogs from DNA

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data