Association between platelet count and the risk and progression of hand, foot, and mouth disease among children

OBJECTIVE: We aimed to evaluate the association between platelet (PLT) count and the risk and progression of hand, foot, and mouth disease (HFMD). METHODS: In total, 122 HFMD patients and 40 healthy controls were enrolled in the study. The differences between variables among the different subgroups were compared. Logistic regression analyses were performed to assess the relationship between various parameters and HFMD risk/progression. Sensitivity analysis was conducted by detecting the trend of the association between PLT count quartiles and HFMD risk/progression. A generalized additive model was used to identify the nonlinear relationship between PLT count and HFMD risk/ progression. The relationship between gender and PLT count as well as the risk/progression of HFMD was detected using a stratified logistic regression model. RESULTS: Significant differences were observed in terms of age, male/female ratio, white blood cell (WBC) count, and PLT count between patients with stage I-II, III-IV HFMD and healthy controls. Moreover, the alanine aminotransferase and magnesium levels between patients with stage I-II and III-IV HFMD significantly differed. Moreover, a significant difference was noted in the male/female ratio among the different PLT groups. The group with a low PLT count had a lower risk of HFMD progression than the group with a high PLT count (Q4) (p=0.039). Lower age, male gender, and WBC count were found to be associated with HFMD risk. Meanwhile, PLT count was correlated to HFMD progression. The sensitivity analysis yielded a similar result using the minimally adjusted model (p for trend=0.037), and minimal changes were observed using the crude and fully adjusted model (p for trend=0.054; 0.090). A significant nonlinear relationship was observed between PLT count and HFMD progression after adjusting for age, gender, and WBC (p=0.039). CONCLUSIONS: PLT was independently associated with HFMD progression in a nonlinear manner

CL-SCA: Leveraging Contrastive Learning for Profiled Side-Channel Analysis

Side-channel analysis based on machine learning, especially neural networks, has gained significant attention in recent years. However, many existing methods still suffer from certain limitations. Despite the inherent capability of neural networks to extract features, there remains a risk of extracting irrelevant information. The heavy reliance on profiled traces makes it challenging to adapt to remote attack scenarios with limited profiled traces. Besides, attack traces also contain critical information that can be used in the training process to assist model learning. In this paper, we propose a side-channel analysis approach based on contrastive learning named CL-SCA to address these issues. We also leverage a stochastic data augmentation technique to assist model to effectively filter out irrelevant information from the profiled traces. Through experiments of different datasets from different platforms, we demonstrate that CL-SCA significantly outperforms various conventional machine learning side-channel analysis techniques. Moreover, by incorporating attack traces into the training process using our approach, known as CL-SCA+, it becomes possible to achieve even greater enhancements. This extension can further improve the effectiveness of key recovery, which is fully verified through experiments on different datasets

The Broad Host Range Phage vB_CpeS_BG3P Is Able to Inhibit Clostridium perfringens Growth

Clostridium perfringens is an important pathogen for both humans and animals, causing human foodborne disease and necrotic enteritis in poultry. In the present study, a C. perfringens-specific phage, vB_CpeS_BG3P (designated as BG3P hereafter), was isolated from chicken farm sewage. Both electron microscopy and phylogenetic analysis suggested that phage BG3P is a novel phage belonging to Siphoviridae family. Phage BG3P exhibited a broad host range against different C. perfringens isolates (90.63% of strains were infected). Sequencing of the complete genome revealed a linear double-stranded DNA (43,528 bp) with 28.65% GC content. After sequence analysis, 73 open reading frames (orf s) were predicted, of which only 13 were annotated with known functions. No tRNA and virulence encoding genes were detected. It should be noted that the protein of orf 15 has 97.92% homology to C. perfringens-specific chloramphenicol resistance protein, which has not been reported for any C. perfringens phage. Phylogenetic analysis of the ssDNA binding protein demonstrated that this phage is closely related to C. perfringens phages phiSM101 and phi3626. In considering future use as an antimicrobial agent, some biological characteristics were observed, such as a good pH (3–11) stability and moderate temperature tolerance (<60 C). Moreover, bacteriophage BG3P showed a good antimicrobial effect against C. perfringens liquid cultures. Thus, phage treatment with MOI ≥ 100 completely inhibited bacterial growth compared to untreated cultures. Although phage BG3P shows good lytic efficiency and broad host range in vitro, future development and application may need to consider removal of the chloramphenicol-like resistance gene or exploring its lysin for future antibacterial applications.This work was supported by the National Key Research and Development Program of China (No. 2018YFE0101900) and the Jiangsu Agricultural Science and Technology Foundation (No. cx(21)1004)

Monitoring the therapeutic efficacy of CA4P in the rabbit VX2 liver tumor using dynamic contrast-enhanced MRI

PURPOSE:The present work aims to evaluate whether dynamic contrast-enhanced magnetic resonance Imaging (DCE-MRI) can monitor non-invasively the blocking effect on microvessels of the Combretastatin-A4-phosphate (CA4P) and assess the therapeutic efficacy. METHODS:Forty rabbits were implanted the VX2 tumors specimens. Two weeks later, serial MRI (T1 weighted image, T2 weighted image and DCE) were performed at 0 h, 4 h, 24 h, 3 d and 7 d after CA4P (10 mg/kg) or saline treatment. The parameters of DCE (Ktrans, Kep, Ve and iAUC60) of enhancement tumor portions were measured. Then all the tumor samples were stained to count microvessel density (MVD). At last, two-way repeated measures ANOVA was used to analyze the difference between and within groups. The correlation between the Ktrans, Kep, Ve, iAUC60 and MVD was analyzed by using the Pearson correlation analysis and Spearman's rank correlation.RESULTS:The Ktrans and iAUC60 in the CA4P group were lower than the values of the control group at 4 h after treatment, which have significant differences (D-value: -0.133 min-1, 95%CI: -0.169~-0.097 min-1，F = 59.109, p 0.05). CONCLUSION:The blocking effect of microvessels after CA4P treatment can be evaluated by DCE-MRI, and the parameters of quantitative Ktrans and semi- quantitative iAUC60 can assess the change of the tumor angiogenesis noninvasively

Manganese causes neurotoxic iron accumulation via translational repression of Amyloid Precursor Protein (APP) and H-Ferritin

For more than 150 years, it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD‐like syndromes. However, the mechanisms of Mn toxicity are still poorly understood. Here, we demonstrate that Mn dose‐ and time‐dependently blocks the protein translation of amyloid precursor protein (APP) and heavy‐chain Ferritin (H‐Ferritin), both iron homeostatic proteins with neuroprotective features. APP and H‐Ferritin are post‐transcriptionally regulated by iron responsive proteins, which bind to homologous iron responsive elements (IREs) located in the 5′‐untranslated regions (5′‐UTRs) within their mRNA transcripts. Using reporter assays, we demonstrate that Mn exposure repressed the 5′‐UTR‐activity of APP and H‐Ferritin, presumably via increased iron responsive proteins‐iron responsive elements binding, ultimately blocking their protein translation. Using two specific Fe2+‐specific probes (RhoNox‐1 and IP‐1) and ion chromatography inductively coupled plasma mass spectrometry (IC‐ICP‐MS), we show that loss of the protective axis of APP and H‐Ferritin resulted in unchecked accumulation of redox‐active ferrous iron (Fe2+) fueling neurotoxic oxidative stress. Enforced APP expression partially attenuated Mn‐induced generation of cellular and lipid reactive oxygen species and neurotoxicity. Lastly, we could validate the Mn‐mediated suppression of APP and H‐Ferritin in two rodent in vivo models (C57BL6/N mice and RjHan:SD rats) mimicking acute and chronic Mn exposure. Together, these results suggest that Mn‐induced neurotoxicity is partly attributable to the translational inhibition of APP and H‐Ferritin resulting in impaired iron metabolism and exacerbated neurotoxic oxidative stress

LR12 Promotes Liver Repair by Improving the Resolution of Inflammation and Liver Regeneration in Mice with Thioacetamide- (TAA-) Induced Acute Liver Failure

Background. Triggering receptor expressed on myeloid cells-1 (TREM-1) controls the mobilization of inflammatory cells in response to injury and consequently enhances liver damage. LR12 is a TREM-1 inhibitory peptide. However, the role of LR12 in acute liver failure (ALF) has remained elusive. This study was aimed at indicating whether LR12 could promote liver repair in mice with thioacetamide- (TAA-) induced ALF. Methods. BALB/c mice were intraperitoneally injected with TAA, followed by intravenous injection of LR12. Damage and regeneration of the liver were assessed. LO2 cells and macrophages were used to assess the therapeutic effects of LR12. Results. Mice treated with TAA for 24 h developed ALF, while liver inflammation was alleviated after LR12 treatment. Moreover, LR12 promoted hepatocyte regeneration in mice with TAA-induced ALF. In vitro, the supernatant from TAA+LR12-treated macrophages promoted the proliferation of LO2 cells. Cytokine protein microarray analysis suggested that LR12 promoted the secretion of C-C chemokine ligand 20 (CCL20) from macrophages. Besides, neutralization of CCL20 blocked the effects of LR12, thus inhibited the proliferation of LO2 cells in vitro, aggregated the liver inflammation, and restrained hepatocyte regeneration in ALF mice in vivo. Furthermore, we also found that LR12 activated the p38 mitogen-activated protein kinase (MAPK) pathway in hepatocytes through promoting the secretion of CCL20 from macrophages. Conclusions. LR12 could improve the resolution of inflammation and liver regeneration in mice with TAA-induced ALF by promoting the secretion of CCL20 from macrophages and activating the p38 MAPK pathway. Therefore, LR12 could be an attractive therapeutic target for the treatment of ALF.Peer Reviewe

Hydrothermal Synthesis of CaAl-LDH Intercalating with Eugenol and Its Corrosion Protection Performances for Reinforcing Bar

Layered double hydroxides (LDHs) intercalating with a corrosion inhibitor for slowing down the corrosion of a reinforcing bar has attracted considerable attention. However, achieving high-loading capacity of organic inhibitor in LDH with high efficiency and long-term protection characteristics remains an important challenge. In this work, the CaAl-LDH intercalating with eugenol (EG) was synthesized via a continuous hydrothermal method. The prepared LDHs were characterized by SEM, XRD, UV-vis absorption spectra and TGA. Additionally, the corrosion protection performances of LDH-EG for steel bar were studied in detail via the electrochemical method. The results show that the loading amount of EG in LDHs was about 30% and about 80% EG could be released from LDH-EG within 4 h in SCPs containing 3.5% NaCl. The electrochemical test results show that the Rct value (105~106 Ω · cm2) of steel-mortar incorporated with LDH-EG has increased by 3–4 orders of magnitude compared to the specimen without LDHs (102~103 Ω · cm2) after 16 dry–wet cycles corrosion test. The significantly improved protection capability is mainly derived from two aspects: one is the filling effect of LDH, which can fill the pores of mortar and improve the impermeability; another reason is that the intercalated EG can slowly diffuse out of the inner structure of LDHs in a controllable way and result in a relatively long-term effect of corrosion inhibition

Construction and Characterization of TiN/Si₃N₄ Composite Insulation Layer in TiN/Si₃N₄/Ni₈₀Cr₂₀ Thin Film Cutting Force Sensor

The measurement of cutting force is an effective method for machining condition monitoring in intelligent manufacturing. Titanium nitride films and silicon nitride films were prepared on 304 stainless steel substrates by DC-reactive magnetron sputtering and plasma-enhanced chemical vapor deposition (PECVD). The effects of substrate negative bias and nitrogen flow on the surface microstructures of TiN film were investigated. The smoothness of the film is optimal when the bias voltage is −60 V. X-ray diffraction (XRD) analysis was performed on the samples with the optimal smoothness, and it was found that when the nitrogen flow rate was higher than 2 sccm, the titanium nitride film had a mixed phase of TiN(111) and (200). It is further revealed that the change of peak intensity of TiN(200) can be enhanced by nitrogen flow. Through atomic force microscopy (AFM), it is found that the stronger the intensity of the TiN (200) peak, the smoother the surface of the film is. Finally, the effect of different film thicknesses on the hardness and toughness of the TiN/Si3N4 film system was studied by nanoindentation experiments. The nanohardness (H) of the TiN/Si3N4 film can reach 39.2 GPa, the elastic modulus (E) is 480.4 GPa, the optimal toughness value (H3/E2) is 0.261 GPa, and the sample has good insulation performance. Linear fitting of the film’s toughness to nanohardness shows that TiN/Si3N4 films with higher hardness usually have a higher H3/E2 ratio

A Novel Antihypertensive Pentapeptide Identified in Quinoa Bran Globulin Hydrolysates: Purification, In Silico Characterization, Molecular Docking with ACE and Stability against Different Food-Processing Conditions

The addition of food derived antihypertensive peptides to the diet is considered a reasonable way to prevent and lower blood pressure. However, data about stability of antihypertensive peptides against different food-processing conditions are limited. In this study, through Sephadex G-15 gel chromatography and RP-HPLC separation, UPLC-ESI-MS/MS analysis and in silico screening, a novel ACE-inhibitory pentapeptide Ser-Ala-Pro-Pro-Pro (IC50: 915.03 μmol/L) was identified in quinoa bran globulin hydrolysate. The inhibition patterns on angiotensin-I-converting enzyme and safety of SAPPP were studied using molecular docking and in silico predication, respectively. Results demonstrated that SAPPP could noncompetitively bind to active sites PRO519 and SER461 of ACE through short hydrogen bonds. SAPPP was resistant to different pH values (2.0–10.0), pasteurization conditions, addition of Na+, Mg2+, Fe3+ or K+, and the simulated gastrointestinal digestion. In contrast, SAPPP was unstable against heating at 100 °C for more than 50 min and the treatment of Zn2+ (5 mmol/L). These results indicated that peptides derived from quinoa globulin hydrolysates can be added into foods for antihypertension