The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts ...to quantify the age-specific transmissibility using a mathematical model.
An epidemiological model with five compartments (susceptible-exposed-symptomatic-asymptomatic-recovered/removed SEIAR) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model.
The age-specific SEIAR model fitted the data well in each age group (P < 0.001). In Hunan Province, the highest transmissibility was from age group 4 to 3 (median: β
= 7.71 × 10
; SAR
= 3.86 × 10
), followed by group 3 to 4 (median: β
= 3.07 × 10
; SAR
= 1.53 × 10
), group 2 to 2 (median: β
= 1.24 × 10
; SAR
= 6.21 × 10
), and group 3 to 1 (median: β
= 4.10 × 10
; SAR
= 2.08 × 10
). The lowest transmissibility was from age group 3 to 3 (median: β
= 1.64 × 10
; SAR
= 8.19 × 10
), followed by group 4 to 4 (median: β
= 3.66 × 10
; SAR
= 1.83 × 10
), group 3 to 2 (median: β
= 1.21 × 10
; SAR
= 6.06 × 10
), and group 1 to 4 (median: β
= 7.20 × 10
; SAR
= 3.60 × 10
). In Jilin Province, the highest transmissibility occurred from age group 4 to 4 (median: β
= 4.27 × 10
; SAR
= 2.13 × 10
), followed by group 3 to 4 (median: β
= 1.81 × 10
; SAR
= 9.03 × 10
).
SARS-CoV-2 exhibits high transmissibility between middle-aged (45 to 64 years old) and elderly (≥ 65 years old) people. Children (≤ 14 years old) have very low susceptibility to COVID-19. This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.
Background
With the increase in macrolide‐resistant M. pneumoniae infections, off‐label use is difficult to avoid. This study assessed the safety of moxifloxacin in pediatric patients with severe ...refractory M. pneumoniae pneumonia (SRMPP).
Methods
We retrospectively reviewed the medical records of children with SRMPP between January 2017 and November 2020 at Beijing Children's Hospital. They were divided into the moxifloxacin group and azithromycin group according to whether or not moxifloxacin was used. The clinical symptoms, radiographs of both knees, and cardiac ultrasounds of the children were collected after drug withdrawal for at least 1 year. A multidisciplinary team reviewed all adverse events and determined their relationship with moxifloxacin.
Results
A total of 52 children with SRMPP were included in this study (31 in the moxifloxacin group and 21 in the azithromycin group). In the moxifloxacin group, four patients had arthralgia, one had joint effusion, and seven had heart valve regurgitation. In the azithromycin group, three patients had arthralgia, one had claudication, and one had heart valve regurgitation; no obvious knee abnormalities were observed in the radiographs. No statistically significant differences in clinical symptoms or imaging findings were found between the groups. As for the adverse events, 11 patients in moxifloxacin group were deemed to be doubtfully related and one possibly related to moxifloxacin; in the azithromycin group, four patients were regarded to be doubtfully related to azithromycin and one not related.
Conclusion
Moxifloxacin was well tolerated and safe for treating SRMPP in children.
The Toll-like receptor (TLR) family acts as a bridge connecting innate and acquired immunity. TLR10 remains one of the least understood members of this family. Some studies have examined TLR10 ...ligands, dimerization of TLR10 with other TLRs, and downstream signalling pathways and functions, but they have often arrived at conflicting conclusions. TLR10 can induce the production of proinflammatory cytokines by forming homodimers with itself or heterodimers with TLR1 or other TLRs, but it can also inhibit proinflammatory responses when co-expressed with TLR2 or potentially other TLRs. Mutations in the Toll/Interleukin 1 receptor (TIR) domain of TLR10 alter its signalling activity. Polymorphisms in the TLR10 gene can change the balance between pro- and anti-inflammatory responses and hence modulate the susceptibility to infection and autoimmune diseases. Understanding the full range of TLR10 ligands and functions may allow the receptor to be exploited as a therapeutic target in inflammation- or immune-related diseases. Here, we summarize recent findings on the pro- and anti-inflammatory roles of TLR10 and the molecular pathways in which it is implicated. Our goal is to pave the way for future studies of the only orphan TLR thought to have strong potential as a target in the treatment of inflammation-related diseases.
The age-dependent deposition of amyloid-β peptides, derived from amyloid precursor protein (APP), is a neuropathological hallmark of Alzheimer's disease (AD). Despite age being the greatest risk ...factor for AD, the molecular mechanisms linking ageing to APP processing are unknown. Here we show that asparagine endopeptidase (AEP), a pH-controlled cysteine proteinase, is activated during ageing and mediates APP proteolytic processing. AEP cleaves APP at N373 and N585 residues, selectively influencing the amyloidogenic fragmentation of APP. AEP is activated in normal mice in an age-dependent manner, and is strongly activated in 5XFAD transgenic mouse model and human AD brains. Deletion of AEP from 5XFAD or APP/PS1 mice decreases senile plaque formation, ameliorates synapse loss, elevates long-term potentiation and protects memory. Blockade of APP cleavage by AEP in mice alleviates pathological and behavioural deficits. Thus, AEP acts as a δ-secretase, contributing to the age-dependent pathogenic mechanisms in AD.
Oral dysbiosis contributes to periodontitis and has implications for systemic diseases. Diabetes mellitus is a common metabolic disorder characterized by impaired glucose regulation. AMP-activated ...protein kinase (AMPK) plays a vital role in regulating glucose uptake and glycogenesis in the liver. This study aimed to investigate the association between periodontal bacteria and diabetes mellitus. A clinical trial was conducted to explore the association between oral bacteria and hyperglycemia. Additionally, we elucidated the molecular mechanisms by which periodontal bacteria cause insulin resistance. In the clinical trial, we discovered significant alterations in the expression levels of Fusobacterium nucleatum (Fn) and Tannerella forsythia (Tf) in patients with diabetes compared with healthy controls. Furthermore, Fn and Tf levels positively correlated with fasting blood glucose and glycated hemoglobin (HbA1C) levels. Moreover, we explored and elucidated the molecular mechanism by which Fusobacterium nucleatum culture filtrate (FNCF) induces cytokine release via the Toll-like receptor 2 (TLR2) signaling pathway in human gingival epithelial Smulow–Glickman (S–G) cells. This study investigated the effects of cytokines on insulin resistance pathways in liver cells. The use of an extracellular signal-regulated kinase (ERK) inhibitor (U0126) demonstrated that FNCF regulates the insulin receptor substrate 1 and protein kinase B (IRS1/AKT) signaling pathway, which affects key proteins involved in hepatic glycogen synthesis, including glycogen synthase kinase-3 beta (GSK3β) and glycogen synthase (GS), ultimately leading to insulin resistance. These findings suggest that ERK plays a crucial role in hepatocyte insulin resistance.
•Oral microbiome showed a high abundance in patients with diabetes.•Oral microbiome showed a positive correlation with blood glucose levels.•FNCF affected glycogen synthesis, ultimately leading to insulin resistance via ERK.•The ERK plays a crucial role in hepatocyte insulin resistance.
Based on the ligand scaffold of an imidazolyl/benziimidazolyl moiety and a N‐CH2C(=O)NHPh substituent, two series of ligand precursors with ortho hydroxy groups incorporated on the N‐phenyl rings ...were prepared. The structural fine tuning of the ligand scaffold allowed the synthesis of tetranuclear palladium complexes with abnormal N‐heterocyclic carbene (aNHC) ligands. For precursors with C2‐methyl blocking groups, pyridine‐assisted C−H bond activation led to the formation of mononuclear tridentate palladium aNHC complexes or tetranuclear complexes with tridentate CNO donors. Representative mononuclear and tetranuclearpalladium aNHC complexes were structurally characterized by X‐ray diffraction studies, revealing very short Pd−C bond distances. The tetranuclear palladium aNHC complexes were very effective in catalyzing Mizoroki‐Heck coupling reaction, and were capable of employing a range of aryl chlorides including deactivated substrates with low palladium loading of 0.2 mol%.
Purpose
Innovation ecosystem is an emerging and popular concept in both academic and industrial circles. It offers a new perspective for enterprise strategy positioning. A business can create more ...value through a healthy innovation ecosystem. The paper aims to discuss these issues.
Design/methodology/approach
In this paper, the authors utilize a new triple-layer core-periphery framework to analyze Insigma Group’s multi-platform collaboration innovation ecosystem, in order to explore the architecture and heterogeneous functions inside an innovation ecosystem.
Findings
The authors illustrate the components and working mechanisms of the four platforms, which function as ideation, entrepreneurship, financing and investment, and innovation, inside Insigma’s innovation ecosystem in detail, and explain how they interact and collaborate toward a shared aim of the whole innovation ecosystem.
Research limitations/implications
The innovation ecosystem is an emerging concept. In this study, the authors combined two existing analytical frameworks of innovation ecosystem, and proposed a triple-layer core-periphery framework, which enable us to analyze the heterogeneity inside an innovation ecosystem.
Practical implications
The authors discussed the role of government and its policies in shaping the innovation ecosystem at the enterprise level.
Originality/value
The authors believe that this paper provides a holistic study of Insigma’s innovation ecosystem. The triple-layer core-periphery framework can be used to study other enterprise innovation ecosystem in the future.
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