Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, ...and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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•CH25H and its enzymatic product, 25HC, inhibit ZIKV entry in vitro•25HC attenuates ZIKV-associated viremia and disease in mice and non-human primates•25HC prevents ZIKV infection in human cortical organoids•25HC protects fetal mice from microcephaly caused by ZIKV infection
Zika virus (ZIKV) presents a major challenge to the global health system. Li et al. find that 25-hydroxycholesterol (25HC) inhibits ZIKV infection in monkeys and human cortical organoids and protects mice from microcephaly. 25HC has potential as a first-line antiviral agent to combat a broad array of pathogenic species, including ZIKV.
Hypoxia and the Tumor Microenvironment Li, Yue; Zhao, Long; Li, Xiao-Feng
Technology in Cancer Research & Treatment,
2021, Letnik:
20
Book Review, Journal Article
Recenzirano
Odprti dostop
Hypoxia is an important feature of the tumor microenvironment, and is closely associated with cell proliferation, angiogenesis, metabolism and the tumor immune response. All these factors can further ...promote tumor progression, increase tumor aggressiveness, enhance tumor metastatic potential and lead to poor prognosis. In this review, these effects of hypoxia on tumor biology will be discussed, along with their significance for tumor detection and treatment.
Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated ...multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution Ser139→Asn139 (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current ...experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.
We report a 2-family cluster of persons infected with severe acute respiratory syndrome coronavirus 2 in the city of Zhoushan, Zhejiang Province, China, during January 2020. The infections resulted ...from contact with an infected but potentially presymptomatic traveler from the city of Wuhan in Hubei Province.
Fall detection is an important public healthcare problem. Timely detection could enable instant delivery of medical service to the injured. A popular nonintrusive solution for fall detection is based ...on videos obtained through ambient camera, and the corresponding methods usually require a large dataset to train a classifier and are inclined to be influenced by the image quality. However, it is hard to collect fall data and instead simulated falls are recorded to construct the training dataset, which is restricted to limited quantity. To address these problems, a three-dimensional convolutional neural network (3-D CNN) based method for fall detection is developed, which only uses video kinematic data to train an automatic feature extractor and could circumvent the requirement for large fall dataset of deep learning solution. 2-D CNN could only encode spatial information, and the employed 3-D convolution could extract motion feature from temporal sequence, which is important for fall detection. To further locate the region of interest in each frame, a long short-term memory (LSTM) based spatial visual attention scheme is incorporated. Sports dataset Sports-1 M with no fall examples is employed to train the 3-D CNN, which is then combined with LSTM to train a classifier with fall dataset. Experiments have verified the proposed scheme on fall detection benchmark with high accuracy as 100%. Superior performance has also been obtained on other activity databases.
High‐efficiency energy storage technologies and devices have received considerable attention due to their ever‐increasing demand. Na‐related energy storage systems, sodium ion batteries (SIBs) and ...sodium ion capacitors (SICs), are regarded as promising candidates for large‐scale energy storage because of the abundant sources and low cost of sodium. In the last decade, many efforts, including structural and compositional optimization, effective modification of available materials, and design and exploration of new materials, have been made to promote the development of Na‐related energy storage systems. In this Review, the latest developments of micro/nanostructured electrode materials for advanced SIBs and SICs, especially the rational design of unique composites with high thermodynamic stabilities and fast kinetics during charge/discharge, are summarized. In addition to the recent achievements, the remaining challenges with respect to fundamental investigations and commercialized applications are discussed in detail. Finally, the prospects of sodium‐based energy storage systems are also described.
The latest developments of micro/nanostructured electrode materials for sodium‐based electrochemical energy storage devices, sodium ion batteries, and sodium ion capacitors, are reviewed. Especially, the rational design of unique nanocomposites with high thermodynamic stabilities and fast kinetics are comprehensively summarized. On the basis of the recent achievements, the remaining challenges with respect to fundamental investigations and commercialized applications are also discussed along with the prospects of sodium‐based energy storage systems.
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