Newly Emerging Strategies in Antiviral Drug Discovery: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Anniversary

Viral infections pose a persistent threat to human health. The relentless epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health problem, with millions of infections and fatalities so far. Traditional approaches such as random screening and optimization of lead compounds by organic synthesis have become extremely resource- and time-consuming. Various modern innovative methods or integrated paradigms are now being applied to drug discovery for significant resistance in order to simplify the drug process. This review provides an overview of newly emerging antiviral strategies, including proteolysis targeting chimera (PROTAC), ribonuclease targeting chimera (RIBOTAC), targeted covalent inhibitors, topology-matching design and antiviral drug delivery system. This article is dedicated to Prof. Dr. Erik De Clercq, an internationally renowned expert in the antiviral drug research field, on the occasion of his 80th anniversary.     

Perfect state transfer on weighted graphs of the Johnson scheme

Letters in Mathematical Physics - We characterize quantum perfect state transfer on real-weighted graphs of the Johnson scheme $${\mathcal {J}}(n,k)$$ , which represent spin networks with...     

Upper Bound of the Number of Zeros for Abelian Integrals in a Kind of Quadratic Reversible Centers of Genus One

By using the methods of Picard-Fuchs equation and Riccati equation, we study the upper bound of the number of zeros for Abelian integrals in a kind of quadratic reversible centers of genus one under polynomial perturbations of degree $n$. We obtain that the upper bound is $7[(n-3)/2]+5$ when $n\ge 5$, $8$ when $n=4$, $5$ when $n=3$, $4$ when $n=2$, and $0$ when $n=1$ or $n=0$, which linearly depends on $n$.     

Automatic Search Dense Connection Module for Super-Resolution

The development of display technology has continuously increased the requirements for image resolution. However, the imaging systems of many cameras are limited by their physical conditions, and the image resolution is often restrictive. Recently, several models based on deep convolutional neural network (CNN) have gained significant performance for image super-resolution (SR), while extensive memory consumption and computation overhead hinder practical applications. For this purpose, we present a lightweight network that automatically searches dense connection (ASDCN) for image super-resolution (SR), which effectively reduces redundancy in dense connection and focuses on more valuable features. We employ neural architecture search (NAS) to model the searching of dense connections. Qualitative and quantitative experiments on five public datasets show that our derived model achieves superior performance over the state-of-the-art models.     

绿色氧化合成苯乙酮的研究

研究了以氧气为氧化剂、液相氧化乙苯合成苯乙酮反应的各种影响因素,在优化的反应条件(冰乙酸20mL、乙苯5mL、醋酸钴用量为乙苯的4.2%(物质的量)、Br/Co=2.5(物质的量)、氧气流速为100mL/min、常压、温度80℃和反应时间4h)下,乙苯转化率达到99.94%,苯乙酮收率达到98.49%.     

大型结构大修改下的静力重分析方法

对于大型结构发生参数大修改时, 采用组合近似算法进行结构位移重分析会使所得的近似解与真实解误差较大. 为了解决组合近似算法在大型结构发生参数大修改时的求解精度不足缺陷, 提出了3种改进的结构静力重分析方法. 该3种改进算法都是基于组合近似算法, 并分别通过位移迭代修正、刚度逐步逼近等措施使求解精度不断提高. 通过2个算例验证了3种改进算法的有效性和高效性, 并对3种改进算法之间的求解效率进行了比较.      

TRIM45 causes neuronal damage by aggravating microglia-mediated neuroinflammation upon cerebral ischemia and reperfusion injury

Excessive and unresolved neuroinflammation is a key component of the pathological cascade in brain injuries such as ischemic stroke. Tripartite motif-containing 45 (TRIM45) is a ubiquitin E3 ligase involved in various critical biological processes. However, the role of TRIM45 in cerebral ischemia remains unknown. Here, we found that the TRIM45 protein was highly expressed in the peri-infarct areas of mice subjected to cerebral ischemia and reperfusion injury induced by middle cerebral artery occlusion. This study systemically evaluated the putative role of TRIM45 in the regulation of neuroinflammation during ischemic injury and the potential underlying mechanisms. We found that TRIM45 knockdown significantly decreased proinflammatory cytokine and chemokine production in primary cultured microglia challenged with oxygen-glucose deprivation and reoxygenation (OGD/R) treatment. Mechanistically, we demonstrated that TRIM45 constitutively interacted with TAB2 and consequently facilitated the Lys-63-linked polyubiquitination of TAB2, leading to the formation of the TAB1–TAK1–TAB2 complex and activation of TAK1, which was ultimately followed by activation of the nuclear factor-kappa B (NF-κB) signaling pathway. In an in vitro coculture Transwell system, downregulation of TRIM45 expression also inhibited the OGD/R-induced activation of microglia and alleviated neuronal apoptosis. More importantly, microglia-specific knockdown of TRIM45 in mice significantly reduced the infarct size, mitigated neurological deficit scores, and improved cognitive function after ischemic stroke. Taken together, our study reveals that the TRIM45–TAB2 axis is a crucial checkpoint that controls NF-κB signaling in microglia during cerebral ischemia and reperfusion injury. Therefore, targeting TRIM45 may be an attractive therapeutic strategy.Subject terms: Cell death in the nervous system, Stroke     

Synthesis and Characterization of an α-Fe2O3-Decorated g-C3N4 Heterostructure for the Photocatalytic Removal of MO

This study describes the preparation of graphitic carbon nitride (g-C₃N₄), hematite (α-Fe₂O₃), and their g-C₃N₄/α-Fe₂O₃ heterostructure for the photocatalytic removal of methyl orange (MO) under visible light illumination. The facile hydrothermal approach was utilized for the preparation of the nanomaterials. Powder X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), and Brunauer–Emmett–Teller (BET) were carried out to study the physiochemical and optoelectronic properties of all the synthesized photocatalysts. Based on the X-ray photoelectron spectroscopy (XPS) and UV-visible diffuse reflectance (DRS) results, an energy level diagram vs. SHE was established. The acquired results indicated that the nanocomposite exhibited a type-II heterojunction and degraded the MO dye by 97%. The degradation ability of the nanocomposite was higher than that of pristine g-C₃N₄ (41%) and α-Fe₂O₃ (30%) photocatalysts under 300 min of light irradiation. The formation of a type-II heterostructure with desirable band alignment and band edge positions for efficient interfacial charge carrier separation along with a larger specific surface area was collectively responsible for the higher photocatalytic efficiency of the g-C₃N₄/α-Fe₂O₃ nanocomposite. The mechanism of the nanocomposite was also studied through results obtained from UV-vis and XPS analyses. A reactive species trapping experiment confirmed the involvement of the superoxide radical anion (O₂^•−) as the key reactive oxygen species for MO removal. The degradation kinetics were also monitored, and the reaction was observed to be pseudo-first order. Moreover, the sustainability of the photocatalyst was also investigated.     

一个择一定理及对广义凸规划的应用

本文在实线性空间中得出了广义凸函数的择一定理 ,利用这一定理 ,我们获得广义凸规划的最优性条件