Summary
Currently severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission has been on the rise worldwide. Predicting outcome in COVID‐19 remains challenging, and the search for more ...robust predictors continues. We made a systematic meta‐analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non‐severe patients of COVID‐19, serum levels of Interleukins (IL)‐2, IL‐2R, IL‐4, IL‐6, IL‐8, IL‐10 and tumor necrosis factor α were significantly up‐regulated in severe patients, with the largest inter‐group differences observed for IL‐6 and IL‐10. In contrast, IL‐5, IL‐1β and Interferon (IFN)‐γ did not show significant inter‐group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+CD25+CD127‐ Treg, together with CD19+ B cells count and CD16+CD56+ NK cells were all consistently and significantly depressed in severe group than in non‐severe group. SARS‐CoV‐2 specific IgA and IgG antibodies were significantly higher in severe group than in non‐severe group, while IgM antibody in the severe patients was slightly lower than those in the non‐severe patients, and IgE antibody showed no significant inter‐group differences. The combination of cytokines, especially IL‐6 and IL‐10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS‐CoV‐2 infection.
Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) ...signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling.
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•Tetherin negatively regulates RLR-mediated type I IFN signaling•Tetherin promotes the autophagic degradation of MAVS via NDP52•Tetherin-NDP52 degrades MAVS relying on the ubiquitination modification of MAVS•Tetherin recruits MARCH8 to catalyze the K27-linked ubiquitination of MAVS at lysine 7
Jin et al. demonstrate that IFN-induced Tetherin recruits MARCH8 to mediate the K27-linked ubiquitination of MAVS for NDP52-dependent autophagic degradation, serving as a suppressor to prevent the sustained activation of RLR-mediated type I IFN signaling via a negative feedback loop.
Tissue engineering is promising in realizing successful treatments of human body tissue loss that current methods cannot treat well or achieve satisfactory clinical outcomes. In scaffold-based bone ...tissue engineering, a high performance scaffold underpins the success of a bone tissue engineering strategy and a major direction in the field is to produce bone tissue engineering scaffolds with desirable shape, structural, physical, chemical and biological features for enhanced biological performance and for regenerating complex bone tissues. Three-dimensional (3D) printing can produce customized scaffolds that are highly desirable for bone tissue engineering. The enormous interest in 3D printing and 3D printed objects by the science, engineering and medical communities has led to various developments of the 3D printing technology and wide investigations of 3D printed products in many industries, including biomedical engineering, over the past decade. It is now possible to create novel bone tissue engineering scaffolds with customized shape, architecture, favorable macro-micro structure, wettability, mechanical strength and cellular responses. This article provides a concise review of recent advances in the R & D of 3D printing of bone tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of bone tissue engineering scaffolds through 3D printing.
•3D printing of bioceramic pastes followed by sintering improves bone formation.•Cryogenic 3D printing of drug loaded polymer solution supports cell differentiation.•Surface modification of 3D printed scaffolds improves the cellular responses.
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Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this ...paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 μM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form β of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1β and TNF-α in serum. In conclusion, oral administration of crystal form β of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.
We aimed to investigate the hesitancy and willingness of parents to vaccinate themselves and their children with a booster dose against severe acute respiratory syndrome coronavirus 2 and related ...factors. We conducted a cross‐sectional study in Puyang city, China. The information was collected, including demographic characteristics, willingness to receive a booster dose of coronavirus disease 2019 (COVID‐19) vaccine, and attitudes and concerns toward COVID‐19 and vaccines. Vaccine hesitancy was assessed in individuals completing the first two doses and booster eligible, while vaccine willingness was assessed in those completing the first two doses and not yet booster eligible. Among the participants completing two primary doses while not meeting the booster criteria, 95.4% (1465/1536) and 95.0% (1385/1458) had a willingness to a booster dose of COVID‐19 vaccine for themselves and their children, respectively. Among the participants who met the booster criteria, 40.3% had vaccine hesitancy. Vaccine hesitancy and unwillingness tended to occur in people who were younger, less educated, less healthy, and with unsureness of vaccines' efficacy and adverse events (AE). The younger age of children, children in poorer health, and concern about the efficacy and AE of vaccines contributed to the participants' unwillingness to vaccinate their children. We observed a high willingness to the booster dose of COVID‐19 vaccine both for the parents and their children, regardless of the eligibility to a booster dose. However, 40% of people had delayed vaccination behaviors. The promotion of scientific knowledge of vaccines' effectiveness and safety is needed, especially for people in poor health and parents with young children. Timely disclosure of AE caused by COVID‐19 vaccines and proper aiding offered to people encountering AE are suggested.
Myocardial infarction (MI) is accompanied by severe energy deprivation and extensive epigenetic changes. However, how energy metabolism and chromatin modifications are interlinked during MI and heart ...repair has been poorly explored. Here, we examined the effect of different carbon sources that are involved in the major metabolic pathways of acetyl-CoA synthesis on myocardial infarction and found that elevation of acetyl-CoA by sodium octanoate (8C) significantly improved heart function in ischemia reperfusion (I/R) rats. Mechanistically, 8C reduced I/R injury by promoting histone acetylation which in turn activated the expression of antioxidant genes and inhibited cardiomyocyte (CM) apoptosis. Furthermore, we elucidated that 8C-promoted histone acetylation and heart repair were carried out by metabolic enzyme medium-chain acyl-CoA dehydrogenase (MCAD) and histone acetyltransferase Kat2a, suggesting that 8C dramatically improves cardiac function mainly through metabolic acetyl-CoA-mediated histone acetylation. Therefore, our study uncovers an interlinked metabolic/epigenetic network comprising 8C, acetyl-CoA, MCAD, and Kat2a to combat heart injury.
Summary
Coxsackievirus A6 (CV‐A6) has been associated with increasingly occurred sporadic hand‐foot‐mouth disease (HFMD) cases and outbreak events in many countries. In order to understand ...epidemiological characteristics of CV‐A6, we collected the information describing HFMD caused by CV‐A6 to describe the detection rate, severe rate and onychomadesis rate, which is defined as one or more nails defluvium, caused by CV‐A6 from 2007 to 2017. The results showed that there was an outbreak of CV‐A6 every other year, and overall trend of the epidemic of CA6‐associated HFMD was increasing in China. The detection rate of CV‐A6 in other countries was 32.0% (95% CI: 25.0%~40.0%) before 2013 and 28.0% (95% CI: 20.0%~36.0%) after 2013, respectively. Although the severe rate of HFMD caused by CV‐A6 was low (0.10%, 95% CI: 0.01%~0.20%), CV‐A6 can cause a high incidence of onychomadesis (28.0%, 95%CI: 21.9%‐34.3%). Thus, it would be worthwhile to research and develop an effective multivalent vaccine for CV‐A6 to achieve a more powerful prevention of HMFD.
To evaluate the impact of momentary intervention on the willingness and actual uptake of influenza vaccination among the elderly in China.
A cross-sectional study assessed the willingness of the ...elderly to receive influenza vaccination, and an momentary intervention aimed to increase vaccination willingness among those initially unwilling. The elderly reporting a willingness were offered free influenza vaccination through a community intervention program.
A total of 3138 participants were recruited in this study, and 61.3 % (95 % CI 59.6 %–63.0 %) were willing to receive influenza vaccination at baseline. The willingness rate of influenza vaccination increased to 79.8 % (95 % CI 78.4 %–81.2 %), with an increase of 18.5 % (95 % CI 16.3 %–20.7 %) after momentary intervention. The influenza vaccination rate was 40.4 % (95 % CI 38.5 %–42.3 %) before and 53.9 % (95 % CI 52.0 %–55.8 %) after momentary intervention with an increase of 13.5 % (95 % CI 10.9 %–16.2 %). There was no significant difference in influenza vaccination rates between the initially willing people and those who changed to be willing to receive influenza vaccination after momentary intervention (vaccination rates: 78.0 % vs. 81.3 %).
Momentary intervention has been shown to effectively enhance the willingness of the elderly to receive influenza vaccination, thereby facilitating the translation of this intention into actual behavior.
Diabetic complications pose a significant threat to life and have a negative impact on quality of life in individuals with diabetes. Among the various factors contributing to the development of these ...complications, endothelial dysfunction plays a key role. The main mechanism underlying endothelial dysfunction in diabetes is oxidative stress, which adversely affects the production and availability of nitric oxide (NO). Flavonoids, a group of phenolic compounds found in vegetables, fruits, and fungi, exhibit strong antioxidant and anti-inflammatory properties. Several studies have provided evidence to suggest that flavonoids have a protective effect on diabetic complications. This review focuses on the imbalance between reactive oxygen species and the antioxidant system, as well as the changes in endothelial factors in diabetes. Furthermore, we summarize the protective mechanisms of flavonoids and their derivatives on endothelial dysfunction in diabetes by alleviating oxidative stress and modulating other signaling pathways. Although several studies underline the positive influence of flavonoids and their derivatives on endothelial dysfunction induced by oxidative stress in diabetes, numerous aspects still require clarification, such as optimal consumption levels, bioavailability, and side effects. Consequently, further investigations are necessary to enhance our understanding of the therapeutic potential of flavonoids and their derivatives in the treatment of diabetic complications.
Deep brain stimulation (DBS) and stereo-electroencephalography (SEEG) electrode implantation are the most important and frequent manipulations in nonhuman primates (NHP) neuromodulation research. ...However, traditional methods tend to be arduous and inaccurate.
Twelve adult male rhesus monkeys were selected for the study, with six subthalamic nucleus (STN) DBS, six anterior nucleus of the thalamus (ANT) DBS and six hippocampus-SEEG (Hippo-SEEG) electrodes implantation. Mean Euclidean errors of entrance and the target were calculated by postoperative image fusion, and the correlation between entrance and target error, as well as the differences among the various manipulations, were analyzed. The accuracy of target was further confirmed by gross anatomy examination. Moreover, the time consumption was recorded.
The mean (±SD) Euclidean errors of the target point and entry point of the three manipulations were STN-DBS: 1.05 ± 0.54 mm and 0.52 ± 0.17 mm; ANT-DBS: 1.12 ± 0.74 mm and 0.58 ± 0.24 mm; and Hippo-SEEG: 2.68 ± 1.03 mm and 1.47 ± 0.63 mm. Significant differences were observed in both target and entry point errors between the DBS and Hippo-SEEG groups, with superior accuracy in the DBS group. The entrance errors had a significantly positive correlation with the target errors in the STN-DBS and Hippo-SEEG groups. Moreover, the time consumption in robotic surgery was much shorter than that in the traditional method, without any severe complications.
The application of robot-assisted lead implantation in NHP neuromodulation research is feasible, accurate, safe, and efficient, and can prospectively be beneficial to neurological studies.
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