Traffic-related air pollution (TRAP) is hypothesised to play a role in the development of allergic rhinitis (AR). Prenatal and early-life exposure to traffic-related air pollution is considered ...critical for later respiratory health. However, we could not find any articles systematically reviewing the risk of prenatal and early-life exposure to traffic-related air pollution for allergic rhinitis in children.
A systematic literature search of PubMed, Web of Science and Medline was conducted to identify studies focused on the association between prenatal and early-life exposure to TRAP and AR in children. Other inclusion criteria were: 1) original articles; 2) based upon prospective or retrospective studies or case-control studies; and 3) publications were restricted to English. Literature quality assessment was processed using the Newcastle-Ottawa Scale (NOS) evaluation scale. This systematic literature review has been registered on the prospero (crd.york.ac.uk/prospero) with the following registry number: CRD42022361179.
Only eight studies met the inclusion criteria. The exposure assessment indicators included PM2.5, PM2.5 absorbance, PM10, NOx, CO, and black carbon. On the whole, exposure to TRAP during pregnancy and the first year of life were positively associated with the development of AR in children.
This systematic review presents supportive evidence about prenatal and early-life exposure to TRAP and the risk of AR in children.
Photothermal therapy (PTT) is a promising approach for cancer targeting therapy. However, the temperature-dependent killing of tumor cells in PTT remains unclear. In this study, we report necroptosis ...plays a role in the anti-tumor effects observed in gold nanorod (GNR)-mediated PTT in melanoma. We first synthesized gold nanorods with a targeting adaptor FA (GNRs-FA), which achieved high efficacy of targeted delivery to melanoma cells. We further demonstrated PTT, precipitated by GNRs-FA under the induction of near-infrared laser, was temperature-dependent. Furthermore, the photothermal killing of melanoma cells showed different patterns of cell death depending on varying temperature in PTT. In a lower temperature at 43 °C, the percentages of apoptosis, necroptosis and necrosis of tumor cells were 10.2%, 18.3%, and 17.6%, respectively, suggesting the cell killing is ineffective at lower temperatures. When the temperature increased to 49 °C, the cell death pattern switched to necrosis dominant (52.8%). Interestingly, when the PTT achieved a moderate temperature of 46 °C, necroptosis was significantly increased (35.1%). Additionally, GNRs-FA/PPT-mediated necroptosis was regulated by RIPK1 pathway. Taken together, this study is the first to demonstrate that temperature-dependent necroptosis is an important mechanism of inducing melanoma cell death in GNR-mediated PTT in addition to apoptosis and necrosis.
Bone marrow mesenchymal stem cells (BMSCs) are widely used for therapeutic applications in tissue engineering and regenerative medicine. Nevertheless, the function of BMSCs is adversely affected by ...senescence. Thus, understanding the molecular mechanisms that contribute to BMSC senescence is critical for the development of BMSC-based tissue engineering and regenerative medicine. In this study, senescent BMSCs were characterized with >80 % of BMSCs stained positive for SA-β-gal, increased expressions of senescence-related genes (p16INK4a and p21Waf1). These senescent characters were accompanied by elevated autophagic activity, up-regulation of interleukin 6 (IL-6), IL-8, and FoxO3a. Autophagic activity inhibition alleviated the senescent state with reduced levels of IL-6 and IL-8 during BMSC senescence. The enhanced autophagic activity upregulated the levels of IL-6 and IL-8 which is associated with up-regulation of FoxO3a, and knockdown of FoxO3a reduced IL-6 and IL-8 expression in senescent BMSCs. Therefore, this study indicated the pivotal role of autophagic activity in the expressions of IL-6 and IL-8 during BMSC senescence, which is regulated by FoxO3a.
•Autophagy affects the progression of BMSC senescence.•Autophagic activity modulates the levels of IL-6 and IL-8 during BMSC senescence.•FoxO3a plays a critical role in the expression of IL6 and IL8 that allows autophagy to enhance senescent phenotype of BMSCs.
In this paper, we propose an efficient Newton linearized numerical method for the nonlinear time-fractional parabolic equations with distributed delay based on the Galerkin finite element method in ...space and the nonuniform L1 scheme in time. The term of distributed delay is approximated by using the compound trapezoidal formula. For the constructed numerical scheme, we mainly focus on the unconditional convergence and superconvergence without any time–space ratio restrictions, the key of which is the use of fractional discrete Grönwall inequality and time–space error splitting technique. Numerical tests for several biological models, including the fractional single-species population model with distributed delay, the fractional diffusive Nicholson’s blowflies equation with distributed delay, and the fractional diffusive Mackey-Glass equation with distributed delay, are conducted to confirm the theoretical results. Finally, combined with the nonunifom Alikhanov scheme in time and the FEM in space, we extend a higher-order Newton linearized numerical scheme for the nonlinear time-fractional parabolic equations with distributed delay and give some numerical tests for some biological models.
Activating mutations within the tyrosine kinase (TK) domain of epidermal growth factor receptor (EGFR) gene are observed in 10 ~ 30% of the patients diagnosed with non-small cell lung cancer (NSCLC), ...and are causally related to NSCLC initiation and progression. Treatments with tyrosine kinase inhibitors (TKIs) targeting EGFR significantly improve the outcome of NSCLC patients with EGFR mutation, but are often associated with drug resistance, which is the main cause of treatment failure and cancer relapse. In the present study, by screening the transcriptome of NSCLC patients, we found that EGFR activation is highly correlated with the up-regulation of mitotic regulator, never in mitosis gene A-related kinase 2 (NEK2). NEK2 overexpression is associated with the poor survival of EGFR-mutant patients but not the wild-type patients. Further functional validation revealed that EGFR mutation induces NEK2 expression by activating ERK signaling pathway. Elevated NEK2 level promotes the rapid cell cycle progression and favors the rapid proliferation of EGFR-mutant NSCLC cells. Of note, NEK2 overexpression also impairs the efficacy of TKI treatment via inhibiting apoptosis, while depleting NEK2 suppresses cell growth and restored the sensitivity of TKI in NSCLC cells. Taken together, our study revealed that NEK2 is an oncogene regulated by EGFR mutation and is involved in disease progression and treatment response in NSCLC with EGFR mutation. These findings will pave the road for optimizing personalized treatment strategies to overcome drug resistance and improve the prognosis of lung cancer patients with EGFR mutation.
Instead of the framework of influence-acceptance commonly used in previous studies, the author uses new sources to reexamine John Dewey's visit to China from the perspective of interactive ...experience. This study presents Dewey's lectures in China as the result of interrelationships among a variety of elements - Columbia University, different hosts and audiences, the media, all levels of the Chinese government, the domestic situation in the United States, the international situation, and Dewey's expectations and work - against the general background of China's New Culture Movement and new educational reforms. Dewey's speeches on democracy, science, and new education were remarkably successful in the first year of his visit to China, but began to meet with resistance from some students beginning in June 1920. Because of the Red Scare in the United States, Dewey had to stay in China. In the second year of his visit, he gave warmly welcomed lectures on the same topics in Jiangxi, Fujian, and Guangdong Provinces. With a deeper understanding of China, Dewey not only identified himself with reform plans but also began to pay more attention to China's economic problems. His inquiry into the problems confronting China is a good example of what he advocated in his lectures: seeing democracy, science, and new education as a way of thinking and carrying out actions and making intellectual choices while moving forward.
As a new type of biodegradable implant material, zinc matrix composites have excellent potential in the application of biodegradable implants because of their better corrosion resistance than ...magnesium matrix materials. Our previous studies have shown that graphene nanosheet reinforced zinc matrix composites (Zn-GNS) prepared by spark plasma sintering (SPS) have good mechanical properties and suitable degradation rate. However, the biocompatibility of zinc matrix composites is still a problem of concern. The cytocompatibility and blood compatibility of pure zinc and Zn-GNS composites in vitro were studied. The results showed that Zn-GNS composites had acceptable toxicity to MG-63 human osteosarcoma cells. In addition, the hemolysis rate of pure zinc and its composites were less than 3%, which has no adverse effect on adhered platelets, and has good antithrombotic and antiadhesion platelets properties. In conclusion, the addition of GNS did not adversely affect the biocompatibility of Zn-GNS composites, which indicated that Zn-GNS composites are a promising candidate for bone implantation.
Dendritic cell (DC) based immunotherapy is a promising approach to clinical cancer treatment. miRNAs are a class of small non-coding RNA molecules that bind to RNAs to mediate multiple events which ...are important in diverse biological processes. miRNA mimics and antagomirs may be potent agents to enhance DC-based immunotherapy against cancers. miRNA array analysis was used to identify a representative miR-5119 potentially regulating PD-L1 in DCs. We evaluated levels of ligands of immune cell inhibitory receptors (IRs) and miR-5119 in DCs from immunocompetent mouse breast tumor-bearing mice, and examined the molecular targets of miR-5119. We report that miRNA-5119 was downregulated in spleen DCs from mouse breast cancer-bearing mice. In silico analysis and qPCR data showed that miRNA-5119 targeted mRNAs encoding multiple negative immune regulatory molecules, including ligands of IRs such as PD-L1 and IDO2. DCs engineered to express a miR-5119 mimic downregulated PD-L1 and prevented T cell exhaustion in mice with breast cancer homografts. Moreover, miR-5119 mimic-engineered DCs effectively restored function to exhausted CD8
+
T cells in vitro and in vivo, resulting in robust anti-tumor cell immune response, upregulated cytokine production, reduced T cell apoptosis, and exhaustion. Treatment of 4T1 breast tumor-bearing mice with miR-5119 mimic-engineered DC vaccine reduced T cell exhaustion and suppressed mouse breast tumor homograft growth. This study provides evidence supporting a novel therapeutic approach using miRNA-5119 mimic-engineered DC vaccines to regulate inhibitory receptors and enhance anti-tumor immune response in a mouse model of breast cancer. miRNA/DC-based immunotherapy has potential for advancement to the clinic as a new strategy for DC-based anti-breast cancer immunotherapy.
Abstract
Objective
Adverse events following immunization is an important factor influencing public trust in vaccination. Publicizing its incidence timely can increase public trust. The aim of this ...study is to describe the incidence and characteristics of adverse events following immunization in Jiangsu province of China from 2015 to 2018.
Methods
All information of adverse events following immunization (AEFIs) was gained from Jiangsu Province Vaccination Integrated Service Management Information System. The reported AEFI trend was analyzed using Chi-square test.
Results
A total of 77,980 AEFI cases were reported through the AEFI system; Among which, 77,731 were classified as non-serious AEFI cases and 249 were serious AEFI cases. The male to female ratio was 1.31:1, cases less than 7 years old accounted for 97.7%. The total estimated AEFI rate was 62.70/100,000 doses. By severity, 60.75/100,000, 4.46/100,000 and 0.11/100,000 AEFI cases were common vaccine reaction, rare vaccine reaction, and serious rare vaccine reaction, respectively. The top two serious AEFI were thrombocytopenic purpura and febrile. The incidence rates showed the increasing trend and the linear trend of the increasing incidence rates passed the significant test at 0.05 levels.
Conclusion
The sensitivity of AEFI monitoring in Jiangsu Province is increasing and higher than the national average and most countries. The majority of AEFI cases were common adverse reactions, while the serious vaccine reactions caused by vaccines were extremely low. To elevate the sensitivity of AEFI surveillance may reduce the incidence of developing serious AEFI cases.
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