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Public health measures to prevent, detect, and respond to events are essential to control public health risks, including infectious disease outbreaks, as highlighted in the International Health Regulations (IHR). In light of the outbreak of 2019 novel coronavirus disease (COVID-19), we aimed to review existing health security capacities against public health risks and events. We used 18 indicators from the IHR State Party Annual Reporting (SPAR) tool and associated data from national SPAR reports to develop five indices: (1) prevent, (2) detect, (3) respond, (4) enabling function, and (5) operational readiness. We used SPAR 2018 data for all of the indicators and categorised countries into five levels across the indices, in which level 1 indicated the lowest level of national capacity and level 5 the highest. We also analysed data at the regional level (using the six geographical WHO regions). Of 182 countries, 52 (28%) had prevent capacities at levels 1 or 2, and 60 (33%) had response capacities at levels 1 or 2. 81 (45%) countries had prevent capacities and 78 (43%) had response capacities at levels 4 or 5, indicating that these countries were operationally ready. 138 (76%) countries scored more highly in the detect index than in the other indices. 44 (24%) countries did not have an effective enabling function for public health risks and events, including infectious disease outbreaks (7 [4%] at level 1 and 37 [20%] at level 2). 102 (56%) countries had level 4 or level 5 enabling function capacities in place. 32 (18%) countries had low readiness (2 [1%] at level 1 and 30 [17%] at level 2), and 104 (57%) countries were operationally ready to prevent, detect, and control an outbreak of a novel infectious disease (66 [36%] at level 4 and 38 [21%] at level 5). Countries vary widely in terms of their capacity to prevent, detect, and respond to outbreaks. Half of all countries analysed have strong operational readiness capacities in place, which suggests that an effective response to potential health emergencies could be enabled, including to COVID-19. Findings from local risk assessments are needed to fully understand national readiness capacities in relation to COVID-19. Capacity building and collaboration between countries are needed to strengthen global readiness for outbreak control. None.

Ginkgo biloba L., an ancient dioecious gymnosperm, is now cultivated worldwide for landscaping and medical purposes. A novel biflavonoid—amentoflavone 7′′-O-β-d-glucopyranoside (1)—and four known biflavonoids were isolated and identified from the male flowers of Ginkgo. The anti-proliferative activities of five biflavonoids were evaluated on different cancer lines. Bilobetin (3) and isoginkgetin (4) exhibited better anti-proliferative activities on different cancer lines. Their effects were found to be cell-specific and in a dose and time dependent manner for the most sensitive HeLa cells. The significant morphological changes validated their anticancer effects in a dose-dependent manner. They were capable of arresting the G2/M phase of the cell cycle, inducing the apoptosis of HeLa cells dose-dependently and activating the proapoptotic protein Bax and the executor caspase-3. Bilobetin (3) could also inhibit the antiapoptotic protein Bcl-2. These might be the mechanism underlying their anti-proliferation. In short, bilobetin (3) and isoginkgetin (4) might be the early lead compounds for new anticancer agents.

Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.

Background Pumpkins ( Cucurbita moschata ; Cucurbitaceae) are valued for their fruits and seeds and are rich in nutrients. Carotenoids and sugar contents, as main feature of pumpkin pulp, are used to determine the fruit quality. Results Two pumpkin germplasms, CMO-X and CMO-E, were analyzed regarding the essential quality traits such as dry weight, soluble solids, organic acids, carotenoids and sugar contents. For the comparison of fruit development in these two germplasms, fruit transcriptome was analyzed at 5 different developmental stages from 0 d to 40 d in a time course manner. Putative pathways for carotenoids biosynthesis and sucrose metabolism were developed in C. moschata fruit and homologs were identified for each key gene involved in the pathways. Gene expression data was found consistent with the accumulation of metabolites across developmental stages and also between two germplasms. PSY , PDS , ZEP , CRTISO and SUS , SPS , HK , FK were found highly correlated with the accumulation of carotenoids and sucrose metabolites, respectively, at different growth stages of C. moschata as shown by whole transcriptomic analysis. The results of qRT-PCR analysis further confirmed the association of these genes. Conclusion Developmental regulation of the genes associated with the metabolite accumulation can be considered as an important factor for the determination of C. moschata fruit quality. This research will facilitate the investigation of metabolic profiles in other cultivars.

Glycolysis, a series of oxidative reactions used to metabolize glucose and provide energy to host cells, is also required for respiratory syncytial virus (RSV) infection. However, the role of glycolysis during RSV infection and its underlying molecular mechanisms remain to be further explored. In this study, we investigated the function of hypoxia-inducible factor (HIF)-1α-mediated glycolysis in HEp-2 cells and mouse models during RSV infection. The results showed that RSV infection activated the insulin receptor (IR)-PI3K-Akt axis, upregulated the translation and activity of HIF-1α, increased the expression of glucose transporters (Glut1, Glut3, and Glut4), hexokinase (HK) 1 and 2, and platelet-type phosphofructokinase (PFKP), and promoted glucose uptake and glycolysis. In addition, mitochondrial damage induced by RSV resulted in the generation of large amounts of reactive oxygen species (ROS) in infected cells, which contributed to the stabilization and activation of HIF-1α. An energy map of the glycolytic ATP production rate (Glyco-ATP) versus the mitochondrial ATP production rate (mito-ATP) confirmed a switch from oxidative phosphorylation (OXPHOS) to glycolysis. Inhibition of IR-PI3K-Akt signaling, ROS, or HIF-1α effectively reversed the RSV-induced increase in glycolysis by blocking HIF-1α activation. Importantly, HIF-1α-mediated glycolysis provided energy for the production of progeny RSV virions. The production of infectious virions was nearly abolished after knocking down HIF-1α. PX-478, an orally active HIF-1α inhibitor, effectively inhibited RSV infection in vivo . Collectively, these results indicate the role of HIF-1α-mediated glycolysis in RSV infection and highlight HIF-1α as a potential target for anti-RSV drug development. Respiratory syncytial virus (RSV) is the leading etiological agent of lower respiratory tract illness. However, efficacious vaccines or antiviral drugs for treating RSV infections are currently not available. Indeed, RSV depends on host cells to provide energy needed to produce progeny virions. Glycolysis is a series of oxidative reactions used to metabolize glucose and provide energy to host cells. Therefore, glycolysis may be helpful for RSV infection. In this study, we show that RSV increases glycolysis by inducing the stabilization, transcription, translation, and activation of hypoxia-inducible factor (HIF)-1α in infected cells, which is important for the production of progeny RSV virions. This study contributes to understanding the molecular mechanism by which HIF-1α-mediated glycolysis controls RSV infection and reveals an effective target for the development of highly efficient anti-RSV drugs.

This study aimed to investigate the role of apoptotic bodies (Abs) from the oxidative stressed endplate chondrocytes in regulating mineralization and potential mechanisms. Endplate chondrocytes were isolated from rats and treated with H2O2 to induce oxidative stress. The calcium deposition for matrix mineralization in the cells was examined by histological staining. The expression levels of calcification‐related genes in individual groups of cells were determined by quantitative real time‐PCR (qRT‐PCR). Subsequently, extracellular vesicles (EVs) were purified and characterized. The effect of treatment with H2O2 and/or Abs on the mineralization, extracellular PPi metabolism and related gene expression were determined. Oxidative stress significantly increased the mineralization and promoted the generation of main Abs from endplate chondrocytes. Abs were effectively endocytosed by endplate chondrocytes and co‐localized with collagen (COL)‐II in the cytoplasm, which enhanced the mineralization, alkaline phosphatase (ALP), osteocalcin (OCN), Runt‐related transcription factor 2 (RUNX2) and COL‐I expression in endplate chondrocytes. Furthermore, treatment either H2O2 or Abs significantly decreased PPi, but increased Pi production and treatment with both further enhancing the changes in endplate chondrocytes. Similarly, treatment either H2O2 or Abs significantly decreased the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ankylosis protein (ANK) expression and ENPP1 promoter activity, but increased the tissue‐nonspecific alkaline phosphatase (TNAP) expression and TNAP promoter activity in endplate chondrocytes. Oxidative stress promoted the generation of Abs, which might enhance the oxidative stress‐mediated mineralization in endplate chondrocytes by regulating the PPi metabolism.

Disturbances or defects in the process of wound repair can disrupt the delicate balance of cells and molecules necessary for complete wound healing, thus leading to chronic wounds or fibrotic scars. Myofibroblasts are one of the most important cells involved in fibrotic scars, and reprogramming provides a potential avenue to increase myofibroblast clearance. Although myofibroblasts have long been recognized as terminally differentiated cells, recent studies have shown that myofibroblasts have the capacity to be reprogrammed into adipocytes. This review intends to summarize the potential of reprogramming myofibroblasts into adipocytes. We will discuss myofibroblast lineage tracing, as well as the known mechanisms underlying adipocyte regeneration from myofibroblasts. In addition, we investigated different changes in myofibroblast gene expression, transcriptional regulators, signalling pathways and epigenetic regulators during skin wound healing. In the future, myofibroblast reprogramming in wound healing will be better understood and appreciated, which may provide new ideas for the treatment of scarless wound healing.

This article investigated the potential of fly ash (FA)/blast furnace slag- (BFS-) based geopolymer as a novel backfilling material. The effects of NaOH concentration and FA/BFS mass ratio were explored through XRD, FTIR, and TG-DTG analyses. The results indicated that the reaction products and strengths of geopolymer depended on the NaOH concentration and types of source materials. Slump, final setting time, and setting ratio increased as a function of FA content. However, the increase in FA content reduced the compressive strength and microstructure of the backfilling material (BM) due to the lower reactivity than BFS. Microstructure analysis reveals that the matrix tends to be denser with the BFS content and NaOH concentration increase.

This paper studied the relationship between personality traits and mental health conditions of medical personnel to provide a basis and reference for the implementation of targeted education on mental health. A self-report inventory, the Symptom Checklist-90 (SCL-90), was used to investigate the mental health status of 548 medical personnel dealing with the new coronavirus pneumonia in eight provinces and cities of China. The overall mean SCL-90 score and mean values of factors (somatization, obsessive-compulsive, anxiety, phobic anxiety, and psychoticism) of the medical personnel were significantly higher than in the norm group (p < 0.05), while their average interpersonal sensitivity score was significantly lower (p < 0.01). In addition, personal factors affecting the mental health status of medical personnel were identified (all p < 0.05). The overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China.

A rapid and convenient homogeneous aptamer sensor with high sensitivity is highly desirable for the electrochemical detection of tumor biomarkers. In this work, a homogeneous electrochemical aptamer sensor is demonstrated based on a two-dimensional (2D) nanocomposite probe and nanochannel modified electrode, which can realize sensitive detection of carcinoembryonic antigen (CEA). Using π-π stacking and electrostatic interaction, CEA aptamer (Apt) and cationic redox probe (hexaammineruthenium(III), Ru(NH3)63+) are co-loaded on graphite oxide (GO), leading to a 2D nanocomposite probe (Ru(NH3)63+/Apt@GO). Vertically ordered mesoporous silica-nanochannel film (VMSF) is easily grown on the supporting indium tin oxide (ITO) electrode (VMSF/ITO) using the electrochemical assisted self-assembly (EASA) method within 10 s. The ultrasmall nanochannels of VMSF exhibits electrostatic enrichment towards Ru(NH3)63+ and size exclusion towards 2D material. When CEA is added in the Ru(NH3)63+/Apt@GO solution, DNA aptamer recognizes and binds to CEA and Ru(NH3)63+ releases to the solution, which can be enriched and detected by VMSF/ITO electrodes. Based on this mechanism, CEA can be an electrochemical detection ranging from 60 fg/mL to 100 ng/mL with a limit of detection (LOD) of 14 fg/mL. Detection of CEA in human serum is also realized. The constructed homogeneous detection system does not require the fixation of a recognitive aptamer on the electrode surface or magnetic separation before detection, demonstrating potential applications in rapid, convenient and sensitive electrochemical sensing of tumor biomarkers.