Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health
. Despite intense research efforts, how, when and where ...new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing
of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China
. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
The HEPS project Jiao, Yi; Xu, Gang; Cui, Xiao-Hao ...
Journal of synchrotron radiation,
November 2018, Letnik:
25, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The High Energy Photon Source (HEPS), a 6 GeV green‐field diffraction‐limited storage ring light source, will be built in Beijing, China. The HEPS design has been evolving for about ten years, and is ...now mostly finished and ready for construction. The storage ring is based on a modified hybrid seven‐bend achromat (7BA) design, where bending magnets with reverse bending angles and longitudinal gradients are adopted to reach an ultralow natural emittance of 34.2 pm with a circumference of 1360.4 m. The central slice of the dipole in the middle of the modified hybrid 7BA, with flexible magnetic field, is used as the source of the bending‐magnet beamline. Moreover, alternating high‐ and low‐beta sections are specially designed to generate and deliver X‐ray synchrotron radiation with high brightness of 5 × 1022 photons s−1 mm−2 mrad−2 (0.1% bandwidth)−1. Here, the HEPS storage ring design and solutions to the challenges inherent in this ultralow‐emittance design are presented.
Details of the High Energy Photon Source (HEPS), a 6 GeV green‐field diffraction‐limited storage ring light source to be built in China, are presented.
X‐ray imaging technology has achieved important applications in many fields and has attracted extensive attentions. Dynamic X‐ray flexible imaging for the real‐time observation of the internal ...structure of complex materials is the most challenging type of X‐ray imaging technology, which requires high‐performance X‐ray scintillators with high X‐ray excited luminescence (XEL) efficiency as well as excellent processibility and stability. Here, a macrocyclic bridging ligand with aggregation‐induced emission (AIE) feature was introduced for constructing a copper iodide cluster‐based metal–organic framework (MOF) scintillator. This strategy endows the scintillator with high XEL efficiency and excellent chemical stability. Moreover, a regular rod‐like microcrystal was prepared through the addition of polyvinyl pyrrolidone during the in situ synthesis process, which further enhanced the XEL and processibility of the scintillator. The microcrystal was used for the preparation of a scintillator screen with excellent flexibility and stability, which can be used for high‐performance X‐ray imaging in extremely humid environments. Furthermore, dynamic X‐ray flexible imaging was realized for the first time. The internal structure of flexible objects was observed in real time with an ultrahigh resolution of 20 LP mm−1.
High performance dynamic X‐ray flexible imaging in extremely humid environments was achieved using copper iodide cluster‐based MOF microcrystal scintillator, which shows a high X‐ray absorption efficiency, environmental friendliness, good stability and excellent processability.Twitter: High Performance Dynamic X‐ray Flexible Imaging Realized Using a Copper Iodide
Coronavirus disease 2019 (COVID‐19) is a novel type of highly contagious pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Despite the strong efforts taken to ...control the epidemic, hundreds of thousands of people were infected worldwide by 11 March, and the situation was characterized as a pandemic by the World Health Organization. Pregnant women are more susceptible to viral infection due to immune and anatomic alteration, though hospital visits may increase the chance of infection, the lack of medical care during pregnancy may do more harm. Hence, a well‐managed system that allows pregnant women to access maternal health care with minimum exposure risk is desired during the outbreak. Here, we present the managing processes of three pregnant women who had fever during hospitalization in the gynecology or obstetrics department, and then, we further summarize and demonstrate our maternal health care management strategies including antenatal care planning, patient triage based on the risk level, admission control, and measures counteracting emergencies and newly discovered high‐risk cases at in‐patient department. In the meantime, we will explain the alterations we have done throughout different stages of the epidemic and also review relative articles in both Chinese and English to compare our strategies with those of other areas. Although tens of COVID‐19 cases were confirmed in our hospital, no nosocomial infection has occurred and none of the pregnant women registered in our hospital was reported to be infected.
Highlights
Demonstration of three cases of pregnant women who developed a fever during hospitalization.
BackgroundTryptophan catabolites suppress immunity. Therefore, blocking tryptophan catabolism with indoleamine 2,3-dioxygenase (IDO) inhibitors is pursued as an anticancer strategy.MethodsThe ...intracellular level of tryptophan and kynurenine was detected by mass spectrum analysis. The effect of tryptophan and IDO inhibitors on cell surface programmed cell death protein 1 (PD-1) level were measured by flow cytometry. A set of biochemical analyses were used to figure out the underlying mechanism. In vitro co-culture system, syngeneic mouse models, immunofluorescent staining, and flow cytometry analysis were employed to investigate the role of tryptophan and IDO inhibitor in regulating the cytotoxicity of CD8+ T cells.ResultsHere, we reported that IDO inhibitors activated CD8+ T cells also by accumulating tryptophan that downregulated PD-1. Tryptophan and IDO inhibitors administration, both increased intracellular tryptophan, and tryptophanyl-tRNA synthetase (WARS) overexpression decreased Jurkat and mice CD8+ T cell surface PD-1. Mechanistically, WARS tryptophanylated lysine 1136 of and activated E3 ligase TRIP12 to degrade NFATc1, a PD-1 transcription activator. SIRT1 de-tryptophanylated TRIP12 and reversed the effects of tryptophan and WARS on PD-1. Tryptophan or IDO inhibitors potentiated CD8+ T cells to induce apoptosis of co-cultured cancer cells, increased cancer-infiltrating CD8+ T cells and slowed down tumor growth of lung cancer in mice.ConclusionsOur results revealed the immune-activating efficacy of tryptophan, and suggested tryptophan supplemental may benefit IDO inhibitors and PD-1 blockade during anticancer treatments.
Elevation in homocysteine (Hcy) level is associated with insulin resistance; however, the causality between them and the underlying mechanism remain elusive. Here, we show that Hcy induces insulin ...resistance and causes diabetic phenotypes by protein cysteine-homocysteinylation (C-Hcy) of the pro-insulin receptor (pro-IR). Mechanistically, Hcy reacts and modifies cysteine-825 of pro-IR in the endoplasmic reticulum (ER) and abrogates the formation of the original disulfide bond. C-Hcy impairs the interaction between pro-IR and the Furin protease in the Golgi apparatus, thereby hindering the cleavage of pro-IR. In mice, an increase in Hcy level decreases the mature IR level in various tissues, thereby inducing insulin resistance and the type 2 diabetes phenotype. Furthermore, inhibition of C-Hcy in vivo and in vitro by overexpressing protein disulfide isomerase rescues the Hcy-induced phenotypes. In conclusion, C-Hcy in the ER can serve as a potential pharmacological target for developing drugs to prevent insulin resistance and increase insulin sensitivity.
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•Increased levels of Hcy decrease the abundance of IR-α and IR-β•Hcy reacts with pro-IR through its thiol group and thus regulates pro-IR cleavage•Furin plays an important role in cleavage of pro-IR into its mature/active forms•Inhibition of cysteine- homocysteinylation refreshes the insulin signal
Zhang et al. show that homocysteine (Hcy) induces insulin resistance and causes diabetic phenotypes by protein cysteine-homocysteinylation of the pro-insulin receptor. The findings suggest that cysteine-homocysteinylation in the endoplasmic reticulum could be an ideal therapeutic target to prevent insulin resistance.
Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and ...impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global
knockout (
) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α (TNF-α), we determined that recombinant omentin-1 reduces the production of pro-inflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the pro-inflammatory cytokines.
Due to the wet and dynamic environment of the oral cavity, the healing of intraoral wounds, such as tooth extraction wounds, requires stable and firm wound dressings. In clinical practice, cotton ...balls and gauzes, sponge plugs, or sutures are used to treat extraction wounds, but none of these means can continuously isolate the wound from the intraoral environment and facilitate ideal healing conditions. Herein, inspired by the natural extracellular matrix, a family of wound dressings is developed for intraoral wound repair. Infiltrating a ductile long‐chain hydrogel network into a prefabricated, sturdy macromolecular meshwork and in situ crosslinking endowed the composite hydrogel with controllable swelling behaviors and robust mechanical properties. The macromolecular meshwork functioned as the backbone to support the composite and restricts the swelling of the long‐chain hydrogel network. In vitro tests verified that this wound dressing can provide durable protection for intraoral wounds against complex irritations. Furthermore, accelerated wound healing occurred when the wound dressing is applied in vivo on a canine tooth extraction model, due to the effective reduction of acute inflammation. These results suggest that this family of bioinspired hydrogels has great potential for application as intraoral wound dressing.
An extracellular matrix‐mimicking hydrogel wound dressing is designed as tooth extraction adhesive wound dressing for intraoral application. The hydrogel exhibits excellent anti‐swelling efficiency, along with consistent mechanical and adhesive robustness in aqueous environments. In vitro and in vivo tooth extraction models demonstrate the stability of hydrogels as physical and antibacterial barriers for intraoral wounds, leading to continuous protection and effective healing acceleration.
Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial ...structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high‐glucose and high‐fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high‐glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin ‐induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase SOD, malondialdehyde MDA, gp91phox, Cyt‐Cyto C), enhanced cell apoptosis (Bax/Bcl‐2, Cleaved caspase‐3, TUNEL‐positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1‐Foxo1 and PI3K‐Akt pathways.
The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how ...circulating cancer cells released through these “leaky” vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer.
•CEVs promote the metastasis of gastric cancer by disrupting endothelial integrity.•CEVs induce vascular leakage by activating endothelial cells and inducing cytoskeletal reorganization.•Dynasore and lactadherin could reduce CEV-induced metastasis.
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