Background. The associations between periodontal disease, tooth loss, and lung cancer risk remain debatable. Therefore, the purpose of the present study is to evaluate whether periodontal disease and ...tooth loss are associated with lung cancer risk. Methods. A literature search was performed for relevant studies using PubMed and Embase databases. Risk ratio (RR) with 95% confidence interval (CI) was applied as effect size to summarize the associations between periodontal disease, tooth loss, and lung cancer risk. A further dose-response analysis was also performed. Results. A total of twelve studies comprising 263,238 participants were included. The results indicated that periodontal disease was positively associated with lung cancer risk (RR=1.37, 95%CI=1.16‐1.63). There was a positive association between tooth loss and lung cancer risk (RR=1.69, 95%CI=1.46‐1.96). Moreover, there was a significantly linear dose-response relationship between tooth loss and lung cancer risk, and every 5 increment in tooth loss was associated with 10% increased lung cancer risk. Similar results were obtained in subgroup analysis. Conclusions. Periodontal disease and tooth loss are increased risk factors for lung cancer. Prevention and treatment of periodontal disease may be effective potential prevention strategies for lung cancer.
Traditional methods of depleting tumor-associated myeloid cells
via
chemotherapy can easily lead to the re-recruitment of them, eventually resulting in chemo-resistance and presenting obstacles in ...immunotherapy. Herein, we report a nano-educator (NE) that when loaded with
all trans
retinoic acid (ATRA) and anti-PD-1 antibodies (aPD-1) instructs myeloid cells to assist T cells towards revitalizing anti-PD-1 therapy.
In vivo
, ATRA converts myeloid-derived suppressor cells (MDSCs) into dendritic cells (DCs), which are essential for anti-PD-1 therapy, while intervening in the polarization of macrophages. Furthermore, aPD-1-armed T cells reboot anti-tumor immunity after suppression relief, which exposes tumor-specific antigens and in turn promotes the maturation of transformed DCs. The nano-platform provides shelter for vulnerable immunomodulatory agents and durable drug release to stimulate intensive immune modulation. We established three types of tumor-bearing mice models with different myeloid cell contents to show the spatiotemporal complementarity of ATRA and aPD-1. The NE re-educates the tumor's guard to assist T cells in enhanced immunotherapy, broadening the application of aPD-1 in the treatment of anti-PD-1-resistant tumors.
Traditional methods of depleting tumor-associated myeloid cells
via
chemotherapy can easily lead to the re-recruitment of them, eventually resulting in chemo-resistance and presenting obstacles in immunotherapy.
Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the ...medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC‐sEV is an obstacle for clinical applications. The potential application of MSC‐sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC‐sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC‐sEV, and the methods for obtaining high‐quality human MSC‐sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC‐sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.
Mesenchymal stromal cells‐derived small extracellular vesicle modulate the function of both innate and adaptive immunocytes via encapsulated nucleic acids, proteins, lipids, and other small molecules in small extracellular vesicle. Subsequently, the inflammatory cascade could be raised, such as inflammatory cytokines secretion, immune cell migration, expansion, polarization, and degranulation, which play a role in modulating the allergic response.
The inherent intermittency of solar power due to diurnal and seasonal cycles has usually resulted in the need for alternative generation sources thereby increasing system operation costs. However, ...when solar power is spread over a large geographical area with significant time differences, the intermittency can be significantly reduced and also the electricity market balancing cost. The aim of this article is to address the fundamental scientific question on how the intermittency of solar power generation is affected by aggregation, which is of great interest in the wider power and energy community and would have profound impacts on the solar energy integration into the energy supply and Net-Zero Implementation. This article goes beyond the typical regional analysis by investigating solar power intermittency at 5 aggregation levels from a global perspective based on global 7 year hourly meteorological re-analysis data with a fine spatial resolution of Formula: see text. In the proposed assessment framework, a coefficient of variation (CV) is used to quantify solar power intermittency and hence characterize the potential benefits of wide area solar power aggregation. A duration curve is used to characterize the intermittency in terms of power availability and a probability density function is further employed to investigate the dispersion and scaling behavior of CV at different aggregation levels. The findings indicate that the CV of solar power generation of 'Inner Mongolia' in China drops from 129.65 to 105.65% in the level of 'Asia' (by 24% decrease), to 56.11% in 'Asia-North_America' (by 73.54% decrease) and to the smallest 43.50% in 'Global' (by 86.15% decrease), nearly 3.5 times of that in 'Asia'; (b) the availability of solar power generation increases from 52.17% in Germany, to 73.30% in 'Europe_EU_plus', to 77.82% in 'Europe', to 98.59% in 'Europe-North_America' (80.60% in 'Europe-Africa', 96.90% in 'Europe-Asia'), to 100% in 'Global'. Finally, conclusions and recommendations are provided to support a Net-Zero strategy.
In order to build a high similarity English vocabulary interpretation domain knowledge base and ensure the automatic retrieval effect of high similarity English vocabulary interpretation, this paper ...standardizes the automatic retrieval specification of authoritative interpretation of high similarity English vocabulary knowledge, and takes high similarity English vocabulary as the source corpus of the knowledge base. On the basis of the existing work, this paper attempts to propose an automatic retrieval algorithm of high similarity English word interpretation based on deep learning. The goal is to diversify the sources of high similarity English word knowledge and achieve the accuracy of automatic retrieval of word interpretation while ensuring a certain knowledge coverage. A suitable domain knowledge base of machine-readable dictionary is constructed through a new method It can not only provide accurate knowledge information for high similarity English vocabulary, but also provide retrieval verification for user needs analysis and high similarity English vocabulary indexing of snippet. The experimental results show that the algorithm based on deep learning is effective and can fully meet the research requirements.
Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC‐derived small ...extracellular vesicles (MSC‐sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC‐sEV on DCs in allergic diseases remain unclear.
MSC‐sEV were prepared from the induced pluripotent stem cells (iPSC)‐MSCs by anion‐exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte‐derived DCs were generated and cultured in the presence of MSC‐sEV to differentiate the so‐called sEV‐immature DCs (sEV‐iDCs) and sEV‐mature DCs (sEV‐mDCs), respectively. The phenotypes and the phagocytic ability of sEV‐iDCs were analyzed by flow cytometry. sEV‐mDCs were co‐cultured with isolated CD4+T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated.
We demonstrated that MSC‐sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA‐DR, but had no effects on mDCs with these markers. However, MSC‐sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti‐IL‐10 monoclonal antibody or IL‐10Rα blocking antibody, we identified that sEV‐mDCs suppressed the Th2 immune response by reducing the production of IL‐4, IL‐9, and IL‐13 via IL‐10. Furthermore, sEV‐mDCs increased the level of Treg cells.
Our study identified that mDCs treated with MSC‐sEV inhibited the Th2 responses, providing novel evidence of the potential cell‐free therapy acting on DCs in allergic airway diseases.
MSC‐sEV regulated the differentiation and function of dendritic cells in allergic rhinitis. Peripheral monocytes treated with GM‐CSF, IL‐4, and LPS differentiated into dendritic cells. DCs treated with MSC‐sEV inhibited the type 2 immune response from allergic rhinits. sEV‐mDC exhibited a regulatory phenotype by the production of IL‐10 and induced Treg cells. GM‐CSF: granulocyte‐macrophage colony‐stimulating factor, LPS: lipopolysaccharide, mDCs: mature dendritic cells, MSC: mesenchymal stromal cells, sEV: small extracellular vesicles, Treg: regulatory T.
Inositol polyphosphate 4‐phosphatase type II (INPP4B) is a phosphoinositide phosphatase that plays complex roles in the pathogenesis of different tumors. We aimed to explore the expression, ...clinicopathological significance, and prognostic value of INPP4B in oral squamous cell carcinoma (OSCC). Tissue microarrays that included samples from 176 primary OSCCs, 42 normal mucosae, and 69 dysplastic tissues were used for immunostaining analyses of INPP4B protein. Aperio ScanScope CS scanner and aperio quantification software were used to scan the microarrays and score the staining, respectively. We also evaluated the correlation between INPP4B expression and clinical parameters, pathological grades, node‐positive status, and immune‐related markers. Expression of INPP4B was statistically significantly upregulated in human primary OSCC tissues compared with dysplastic and normal tissues. Additionally, we found that patients with strong expression of INPP4B had a statistically significantly poorer overall survival than patients with weak expression of INPP4B. Furthermore, our study indicated that expression of INPP4B in OSCC was positively associated with expression of p‐S6Ser235/236, p‐CADSer1859, and certain immune checkpoints (B7‐H4, Galectin‐9). Therefore, INPP4B may be an independent prognostic indicator for patients with OSCC, in which it might function as an oncoprotein.
This paper focuses on the development of electric vehicle (EV) charging infrastructure in the UK, which is a vital part of the delivering ultra-low-emission vehicle (ULEV) and will transition into ...low emission energy systems in the near future. Following a brief introduction to global landscape of EV and its infrastructure, this paper presents the EV development in the UK. It then unveils the government policy in recent years, charging equipment protocols or standards, and existing EV charging facilities. Circuit topologies of charging infrastructure are reviewed. Next, three important factors to be considered in a typical site, i. e., design, location and cost, are discussed in detail. Furthermore, the management and operation of charging infrastructure including different types of business models are summarized. Last but not least, challenges and future trends are discussed.
Congenital human cytomegalovirus (HCMV) infection is the leading cause of neurological disabilities in children worldwide, but the mechanisms underlying these disorders are far from well-defined. ...HCMV infection has been shown to dysregulate the Notch signaling pathway in human neural progenitor cells (NPCs). As an important downstream effector of Notch signaling, the transcriptional regulator Hairy and Enhancer of Split 1 (Hes1) is essential for governing NPC fate and fetal brain development. In the present study, we report that HCMV infection downregulates Hes1 protein levels in infected NPCs. The HCMV 72-kDa immediate-early 1 protein (IE1) is involved in Hes1 degradation by assembling a ubiquitination complex and promoting Hes1 ubiquitination as a potential E3 ubiquitin ligase, followed by proteasomal degradation of Hes1. Sp100A, an important component of PML nuclear bodies, is identified to be another target of IE1-mediated ubiquitination. A C-terminal acidic region in IE1, spanning amino acids 451 to 475, is required for IE1/Hes1 physical interaction and IE1-mediated Hes1 ubiquitination, but is dispensable for IE1/Sp100A interaction and ubiquitination. Our study suggests a novel mechanism linking downregulation of Hes1 protein to neurodevelopmental disorders caused by HCMV infection. Our findings also complement the current knowledge of herpesviruses by identifying IE1 as the first potential HCMV-encoded E3 ubiquitin ligase.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Field Trip for Measured Survey of Built Heritage carried out by Tianjin University every summer aims to educate students in each practice session, i.e., on-site data acquisition, condition ...investigation, classification of the component library, taking observation notes, and accomplishing HBIM deliverables. Under the risks posed by the ongoing COVID-19 pandemic, the students could not leave the campus as a provisional arrangement. Only a team of five people was allowed to visit the Kuiwen Pavilion in the Temple of Confucius (Qufu, China). Therefore, the field trip for students had to be replaced with remote solutions, which consists of the following methods: on-site data acquisition; post-processing; online education, observation, modeling, delivery. Kuiwen Pavilion in the Temple of Confucius is a library with the official architectural style of the Ming and Qing Dynasties (14th to 20th century), for which building regulations are commonly recognized, and are suitable for survey education. In this context, this article focuses on the remote practice methods applied and tested throughout the case study. During the practice of the course, students who managed to finish the course, through the virtual tours and other online methods, finally achieved delivery of the HBIM models.
PDF
