Integral Operators Between Fock Spaces∗

In this paper, the authors study the integral operator Sφf(z) = Z C φ(z, w)f(w)dλα(w) induced by a kernel function φ(z, ·) ∈ F ∞α between Fock spaces. For 1 ≤ p ≤ ∞, they prove that Sφ : F 1 α → F p α is bounded if and only if sup a∈C kSφkakp,α < ∞, (?) where ka is the normalized reproducing kernel of F 2 α; and, Sφ : F 1 α → F p α is compact if and only if lim |a|→∞ kSφkakp,α = 0. When 1 < q ≤ ∞, it is also proved that the condition (?) is not sufficient for boundedness of Sφ : F q α → F p α . In the particular case φ(z, w) = eαzw?(z ? w) with ? ∈ F 2 α, for 1 ≤ q < p < ∞, they show that Sφ : F p α → F q α is bounded if and only if ? = 0; for 1 < p ≤ q < ∞, they give sufficient conditions for the boundedness or compactness of the operator Sφ : F p α → F q α.     

Human Serum Amyloid a Impaired Structural Stability of High-Density Lipoproteins (HDL) and Apolipoprotein (Apo) A-I and Exacerbated Glycation Susceptibility of ApoA-I and HDL

Human serum amyloid A (SAA) is an exchangeable apolipoprotein (apo) in high-density lipoprotein (HDL) that influences HDL quality and functionality, particularly in the acute phase of inflammation. On the other hand, the structural and functional correlations of HDL containing SAA and apoA-I have not been reported. The current study was designed to compare the change in HDL quality with increasing SAA content in the lipid-free and lipid-bound states in reconstituted HDL (rHDL). The expressed recombinant human SAA1 (13 kDa) was purified to at least 98% and characterized in the lipid-free and lipid-bound states with apoA-I. The dimyristoyl phosphatidylcholine (DMPC) binding ability of apoA-I was impaired severely by the addition of SAA, while SAA alone could not bind with DMPC. The recombinant human SAA1 was incorporated into the rHDL (molar ratio 95:5:1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC): cholesterol: apoA-I) with various apoA-I:SAA molar ratios from 1:0 to 1:0.5, 1:1 and 1:2. With increasing SAA1 content, the rHDL particle size was reduced from 98 Å to 93 Å, and the α-helicity of apoA-I:SAA was decreased from 73% to 40% for (1:0) and (1:2), respectively. The wavelength maximum fluorescence (WMF) of tryptophan in rHDL was red-shifted from 339 nm to 345 nm for (1:0) and (1:2) of apoA-I:SAA, respectively, indicating that the addition of SAA to rHDL destabilized the secondary structure of apoA-I. Upon denaturation by urea treatment from 0 M to 8 M, SAA showed only a 3 nm red-shift in WMF, while apoA-I showed a 16 nm red-shift in WMF, indicating that SAA is resistant to denaturation and apoA-I had higher conformational flexibility than SAA. The glycation reaction of apoA-I in the presence of fructose was accelerated up to 1.8-fold by adding SAA in a dose-dependent manner than that of apoA-I alone. In conclusion, the incorporation of SAA in rHDL impaired the structural stability of apoA-I and exacerbated glycation of HDL and apoA-I.     

一致空间的理想导集映射

本文介绍一致空间的理想导集映射,并对这些映射的像展开研究.同时,介绍I-Hurewicz有界性的概念,研究I-Hurewicz有界性的基础拓扑运算性质.最后,得到一致空间中I-Hurewicz有界性的一个等价刻画.     

Synthesis and Systematic Study on the Effect of Different PEG Units on Stability of PEGylated,Integrin-αvβ6-Specific A20FMDV2 Analogues in Rat Serum and Human Plasma

A20FMDV2 is a 20-mer peptide that exhibits high selectivity and affinity for the tumour-related αvβ6 integrin that can compete with extracellular ligands for the crucial RGD binding site, playing a role as a promising αvβ6-specific inhibitor for anti-cancer therapies. Unfortunately, the clinical value of A20FMDV2 is limited by its poor half-life in blood caused by rapid renal excretion and its reported high susceptibility to serum proteases. The incorporation of poly (ethylene glycol) chains, coined PEGylation, is a well-established approach to improve the pharmacokinetic properties of drug molecules. Here, we report a systematic study on the incorporation of a varying number of ethylene glycol units (1–20) into the A20FMDV2 peptide to establish the effects of PEGylation size on the peptide stability in both rat serum and human plasma. In addition, the effect of acetyl and propionyl PEGylation handles on peptide stability is also described. Selected peptide analogues were assessed for integrin-αvβ6-targeted binding, showing good specificity and activity in vitro. Stability studies in rat serum established that all of the PEGylated peptides displayed good stability, and an A20FMDV2 peptide containing twenty ethylene glycol units (PEG₂₀) was the most stable. Surprisingly, the stability testing in human plasma identified shorter PEGs (PEG₂ and PEG₅) as more resistant to degradation than longer PEGs, a trend which was also observed with affinity binding to integrin αvβ6.     

Trichoderma Enzymes for Degradation of Aflatoxin B1 and Ochratoxin A

The contamination of agricultural products with mycotoxins causes risks to animal and human health and severe economic losses. Mycotoxicoses can be reduced by preventing fungal infection using chemical and biological approaches. The chemical strategies can release toxic molecules; therefore, strategies for biological control are being evaluated, such as using nontoxic fungi and their metabolites. This work evaluated the effect of exoenzymes produced by the beneficial fungus Trichoderma afroharzianum strain T22 in degrading Aflatoxin B1 (AFB1) and Ochratoxin A (OTA). The ability of Trichoderma to produce hydrolases was stimulated by using different inducing substrates. The highest AFB1 and OTA degradation activity was obtained using a medium containing lyophilized mushrooms and crude fiber. The T. afroharzianum T22’s ability to reduce mycotoxins may be attributed to peroxidase enzymes. This study showed that T. afroharzianum strain T22 or its peroxidase supplementation could represent a sustainable strategy for the degradation of AFB1 and OTA in feed and food products.     

Ultrastructural Damages to H1N1 Influenza Virus Caused by Vapor Essential Oils

Influenza viruses are transmitted from human to human via airborne droplets and can be transferred through contaminated environmental surfaces. Some works have demonstrated the efficacy of essential oils (EOs) as antimicrobial and antiviral agents, but most of them examined the liquid phases, which are generally toxic for oral applications. In our study, we describe the antiviral activity of Citrus bergamia, Melaleuca alternifolia, Illicium verum and Eucalyptus globulus vapor EOs against influenza virus type A. In the vapor phase, C. bergamia and M. alternifolia strongly reduced viral cytopathic effect without exerting any cytotoxicity. The E. globulus vapor EO reduced viral infection by 78% with no cytotoxicity, while I. verum was not effective. Furthermore, we characterized the EOs and their vapor phase by the head-space gas chromatography–mass spectrometry technique, observing that the major component found in each liquid EO is the same one of the corresponding vapor phases, with the exception of M. alternifolia. To deepen the mechanism of action, the morphological integrity of virus particles was checked by negative staining transmission electron microscopy, showing that they interfere with the lipid bilayer of the viral envelope, leading to the decomposition of membranes. We speculated that the most abundant components of the vapor EOs might directly interfere with influenza virus envelope structures or mask viral structures important for early steps of viral infection.     

Drugs Targeting the A3 Adenosine Receptor: Human Clinical Study Data

The A3 adenosine receptor (A3AR) is overexpressed in pathological human cells. Piclidenoson and namodenoson are A3AR agonists with high affinity and selectivity to A3AR. Both induce apoptosis of cancer and inflammatory cells via a molecular mechanism entailing deregulation of the Wnt and the NF-κB signaling pathways. Our company conducted phase I studies showing the safety of these 2 molecules. In the phase II studies in psoriasis patients, piclidenoson was safe and demonstrated efficacy manifested in significant improvements in skin lesions. Namodenoson is currently being developed to treat liver cancer, where prolonged overall survival was observed in patients with advanced liver disease and a Child–Pugh B score of 7. A pivotal phase III study in this patient population has been approved by the FDA and the EMA and is currently underway. Namodenoson is also being developed to treat non-alcoholic steatohepatitis (NASH). A Phase IIa study has been successfully concluded and showed that namodenoson has anti-inflammatory, anti-fibrosis, and anti-steatosis effects. A phase IIb study in NASH is currently enrolling patients. In conclusion, A3AR agonists are promising drug candidates in advanced stages of clinical development and demonstrate safety and efficacy in their targeted indications.     

In Silico Drug Repurposing of FDA-Approved Drugs Highlighting Promacta as a Potential Inhibitor of H7N9 Influenza Virus

Influenza virus infections continue to be a significant and recurrent public health problem. Although vaccine efficacy varies, regular immunisation is the most effective method for suppressing the influenza virus. Antiviral drugs are available for influenza, although two of the four FDA-approved antiviral treatments have resulted in significant drug resistance. Therefore, new treatments are being sought to reduce the burden of flu-related illness. The time-consuming development of treatments for new and re-emerging diseases such as influenza and the high failure rate are increasing concerns. In this context, we used an in silico-based drug repurposing method to repurpose FDA-approved drugs as potential therapies against the H7N9 virus. To find potential inhibitors, a total of 2568 drugs were screened. Promacta, tucatinib, and lurasidone were identified as promising hits in the DrugBank database. According to the calculations of MM-GBSA, tucatinib (−54.11 kcal/mol) and Promacta (−56.20 kcal/mol) occupied the active site of neuraminidase with a higher binding affinity than the standard drug peramivir (−49.09 kcal/mol). Molecular dynamics (MD) simulation studies showed that the C-α atom backbones of the complexes of tucatinib and Promacta neuraminidase were stable throughout the simulation period. According to ADME analysis, the hit compounds have a high gastrointestinal absorption (GI) and do not exhibit properties that allow them to cross the blood–brain barrier (BBB). According to the in silico toxicity prediction, Promacta is not cardiotoxic, while lurasidone and tucatinib show only weak inhibition. Therefore, we propose to test these compounds experimentally against the influenza H7N9 virus. The investigation and validation of these potential H7N9 inhibitors would be beneficial in order to bring these compounds into clinical settings.     

“东方经济”与中国乡村工业化的社会学机制—重访史国衡的个旧矿城研究

本文对“魁阁”社会学家史国衡1940年代在美访学期间的一部未刊稿《个旧矿城》进行了梳理与讨论。史国衡的个旧研究呈现了一个将产业、民情与治理相结合的综合进路,通过对个旧锡业兴衰的个案分析,揭示了传统“东方经济”模式的独特特征以及决定中国乡村工业化成败的社会学机制,同时也以个旧经验对现代化理论、人际关系学派等当时美国社会科学主流范式提出了反思。《个旧矿城》与另一部更为人所熟知的著作《昆厂劳工》共同构成了史国衡关于中国工业化研究的姊妹篇,“工业化的社会基础”是其中一以贯之的核心线索。对史国衡个旧矿城研究的“再发现”,有助于我们重新认识中国早期社会学的工业研究传统,同时也提示我们,当下的乡村工业化乃至乡村振兴仍然需要重视产业的社会基础,处理好经济转型与社会重组之间的辩证关系。     

Solvatochromic Solvent Polarity Measurements In Analytical Chemistry: Synthesiss And Applications Of Et-30

Abstract

The E_T(30) scale of solvent polarity has been shown to be useful in examining many diverse analytical processes. It is based on the charge transfer absorption of 2,6-diphenyl-4-(2,4,6-triphenyl-N-pyridinio)phenolate (referred to as ET-30 in this paper). Unfortunately, use of the E_T(30) scale has been hindered by (a) the lack of a commercial source of the ET-30 dye and (b) the lack of an English language synthetic procedure. Here we discuss recent applications of the E_T(30) scale to analytical techniques, as well as a simplified procedure for the synthesis of ET-30.