KNN set similarity search is a foundational operation in various realistic applications in cloud computing. However, for security consideration, sensitive data will always be encrypted before ...uploading to the cloud servers, which makes the search processing a challenging task. In this paper, we focus on the problem of KNN set similarity search over the encrypted datasets. We use Yao’s garbled circuits and secret sharing as underlying tools. To achieve better querying efficiency, we construct a secure R-Tree index structure based on a novel secure grouping protocol, which enables grouping appropriate private values in an oblivious way. Along with several elaborately designed secure arithmetic subroutines, we propose an efficient secure and verifiable KNN set similarity search framework over outsourced clouds. Theoretically, we analyze the complexity of our schemes in detail, and prove the security in the presence of semi-honest adversaries. Finally, we evaluate the performance and feasibility of our proposed methods by extensive experiments.
Spinetoram is an important semi-synthetic insecticide extensively applied in agriculture. It is neurotoxic to insects, primarily by acting on acetylcholine receptors (nAChRs). However, few studies ...have examined the neurotoxicity of spinetoram in human beings. In this study, various concentrations (5, 10, 15, and 20 μM) of spinetoram were employed to expose SH-SY5Y cells in order to study the neurotoxic effects of spinetoram. The results showed that spinetoram exposure markedly inhibited cell viability and induced oxidative stress. It also induced mitochondrial membrane potential collapse (ΔΨm), and then caused a massive opening of the mitochondrial permeability transition pore (mPTP), a decrease in ATP synthesis, and Ca
overloading. Furthermore, spinetoram exposure induced cellular autophagy, as evidenced by the formation of autophagosomes, the conversion of LC3-I into LC3-II, down-regulation of p62, and up-regulation of beclin-1. In addition, we observed that p-mTOR expression decreased, while p-AMPK expression increased when exposed to spinetoram, indicating spinetoram triggered AMPK/mTOR-mediated autophagy. Complementarily, the effect of spinetoram on neurobehavior was studied using the zebrafish model. After being exposed to different concentrations (5, 10, and 20 μg/mL) of spinetoram, zebrafish showed neurobehavioral irregularities, such as reduced frequency of tail swings and spontaneous movements. Similarly, autophagy was also observed in zebrafish. In conclusion, spinetoram exposure produced potential neurotoxicity through autophagy mediated by mitochondrial damage. The experimental data and results of the neurotoxicity study of spinetoram provided above are intended to serve as reference for its safety assessment.
Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms underlying the involvement of ...gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.
Anti-CD19 chimeric antigen receptor (CAR)-T cells not only target CD19-positive malignant lymphoma cells but also normal B cells. The utility of CAR-T cell therapy has been reported in rheumatoid ...arthritis and systemic lupus erythematosus; however, its use in Sjögren's disease (SjD) remains unknown. In this study, we describe the case of a 76-year-old woman with active SjD for 10 years who was diagnosed with diffuse large B-cell lymphoma. After receiving anti-CD19 CAR-T cell therapy, she achieved complete remission (CR) on day 28. Since the onset of her 10-year history with SjD, she was negative for antinuclear antibodies and anti-Ro-52 for the first time on day 90 after CAR-T cell therapy. Six months after CAR-T cell therapy, the CR status was maintained, serum cytokine levels returned to their normal levels, and dry mouth symptoms improved. The EULAR Sjögren's Syndrome Disease Activity Index score decreased from 5 to 2, indicating a partial remission of SjD activity compared with that before CAR-T cell treatment. In the early stage of treatment, she presented with grade 2 cytokine release syndrome and grade 1 neurotoxicity, which were completely controlled after an active intervention. This case highlights the potential application of CAR-T cells in treating autoimmune diseases, such as SjD.
Mesenchymal stem cells (MSCs) can differentiate into diverse cell types under specific conditions. Dysfunction in the osteogenic differentiation of MSCs can result in bone metabolism-related ...diseases, including osteoporosis. Accumulating evidence has revealed that long non-coding RNA (lncRNAs) play critical regulatory roles during MSC differentiation.
In the present study, we identified an evolutionarily conserved lncRNA expressed during the osteogenic differentiation of MSCs, which we termed LINC01119. We first identified LINC01119 as a negative regulator of the osteogenic differentiation of MSCs.
LINC01119 knockdown markedly induced calcium deposition in bone marrow MSCs and promoted the osteogenic differentiation of MSCs. More importantly, we demonstrated the underlying molecular basis through which LINC01119 regulates osteogenesis via the Wnt pathway by targeting FZD4. Furthermore, we observed that transcription factor EBF3 could directly bind the promoter site of LINC01119.
We first explored the molecular regulatory mechanism of LINC01119 during the osteogenic differentiation of MSCs and revealed that LINC01119 negatively regulates osteogenesis through the Wnt pathway by targeting FZD4.
The phenomenon of color change is an important signal to diagnose the quality of lubrication oils.
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Dose the blackened lubrication oil needs to be replaced for flying safety? Since ...there is very limited room for inaccurate assessment of oil quality due to strict flying safety standards, much aviation lubrication oil is disposed in advance long before their service life. More important, aircrafts still face the fatal challenges from unpredictable lubrication oil deterioration.
Color change is surely a significant signal to diagnose the quality of lubrication oils. Based on the colorimeter, the color numbers of the testing lubrication oils are measured in this paper to identify the color variation degree of the oxidized lubrication oils. Then the molecular structures of the oxidized lubrication oils are investigated to find the intrinsic relationship between the oxidation products and color numbers. Based on key performances of the oxidized oil samples, the oil quality is undoubtfully deteriorated which is coincident with the variation of color number. The color numbers of the used aviation lubrication oils could provide an alternative way to readily and quickly measure the decline degree and residual lifetime.
The invention and use of chelating purification products directed at atmospheric particulate matter 2.5 (PM2.5) are beneficial in preventing cytotoxicity and bodily harm. However, natural plant ...active compounds that minimize the adverse effect of PM2.5 are rarely reported. Chlorella pyrenoidosa extracts (CPEs), a nutritional supplement derived from Chlorella vulgaris, have been shown to have antioxidant and anti-inflammatory effects. Here, we discovered that CPEs extracted with crushing cell extraction technology can attenuate the negative impacts of PM2.5. Furthermore, CPE intervention can protect against DNA damage and unstable genomic structure due to PM2.5 exposure. Moreover, CPE intervention restored mRNA and protein expression of the DNA misincorporation repair mechanism gene, nudix hydrolase 1 (NUDT1), and 8-oxoguanine DNA glycosylase (OGG1). In vivo damage protection experiments revealed that CPEs reduced PM2.5-induced hepatotoxicity of zebrafish larvae and effectively prevented the death of adult zebrafish exposed to PM2.5. Briefly, CPEs can attenuate cytotoxicity, resist DNA damage, relieve PM2.5-induced hepatotoxicity, and improve cell purification activity, making them ideal for use as a protective factor or functional ingredient in the cosmetics and health food industries.
The clinical and molecular characteristics of localized diffuse large B-cell lymphoma (DLBCL) with single nodal (SN) or single extranodal (SE) involvement remain largely elusive in the rituximab era. ...The clinical data of 181 patients from a retrospective cohort and 108 patients from a phase 3 randomized trial NHL-001 (NCT01852435) were reviewed. Meanwhile, genetic aberrations, gene expression pattern, and tumor immunophenotype profile were revealed by DNA and RNA sequencing of 116 and 53 patients, respectively. SE patients showed similar clinicopathological features as SN patients, except for an increased percentage of low-intermediate risk in the National Comprehensive Cancer Network–International Prognostic Index. According to the molecular features, increased
MPEG1
mutations were observed in SN patients, while SE patients were associated with upregulation of TGF-β signaling pathway and downregulation of T-cell receptor signaling pathway. SE patients also presented immunosuppressive status with lower activity of killing of cancer cells and recruiting dendritic cells. Extranodal involvement had no influence on progression-free survival (PFS) or overall survival (OS) in localized DLBCL. Serum lactate dehydrogenase >3 upper limit of normal was an independent adverse prognostic factor for OS, and
ATM
mutations were related to inferior PFS. Although the overall prognosis is satisfactory, specific clinical, genetic, and microenvironmental factors should be considered for future personalized treatment in localized DLBCL.
Background As an original traditional Chinese medicinal formula, Qin Huang formula (QHF) is used as adjuvant therapy for treating lymphoma in our hospital and has proven efficacy when combined with ...chemotherapy. However, the underlying mechanisms of QHF have not been elucidated. Methods A network pharmacological-based analysis method was used to screen the active components and predict the potential mechanisms of QHF in treating B cell lymphoma. Then, a murine model was built to verify the antitumor effect of QHF combined with Adriamycin (ADM) in vivo. Finally, IHC, ELISA, .sup.18F-FDG PET-CT scan, and western blot were processed to reveal the intriguing mechanism of QHF in treating B cell lymphoma. Results The systemic pharmacological study revealed that QHF took effect following a multiple-target and multiple-pathway pattern in the human body. In vivo study showed that combination therapy with QHF and ADM potently inhibited the growth of B cell lymphoma in a syngeneic murine model, and significantly increased the proportion of tumor infiltrating CD4+ and CD8+ T cells in the tumor microenvironment (TME). Furthermore, the level of CXCL10 and IL-6 was significantly increased in the combination group. Finally, the western blot exhibited that the level of TLR2 and p38 MAPK increased in the combination therapy group. Conclusion QHF in combination of ADM enhances the antitumor effect of ADM via modulating tumor immune microenvironment and can be a combination therapeutic strategy for B cell lymphoma patients. Keywords: Qin Huang formula, B-cell lymphoma, Tumor microenvironment, Tumor-infiltrating lymphocytes, Toll-like receptor, Systemic pharmacology
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