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Abstract Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.

The Newmark method is a classic method for evaluating the permanent displacements of a slope under seismic loads. This study aims at proposing a three-dimensional nested Newmark method (3D-NNM) in the framework of the kinematic theorem of limit analysis. The classical three-dimensional rotational failure mechanism is discretized into a series of nested rotating wedges, each of which is subjected to a corresponding yield acceleration determined by employing the work rate balance, and each of which produces relative displacements under seismic excitations when it exceeds the yield acceleration. The total permanent displacement profile is further obtained by integration of the relative displacements from the slope toe to the slope crest. The obtained results show that the proposed 3D-NNM can effectively evaluate the permanent displacement profile of slopes under earthquakes, and the proposed 3D-NNM improves the Leshchinsky’s 2D nested Newmark method by 30.7%; the obtained total horizontal displacement at the slope middle height reduces with the number of nested blocks, but increases with the increasing of the slope-width-to-height ratios. Besides, the traditional Newmark method with a single sliding block tends to overestimate the permanent displacements of slope under seismic shakings.

This study aimed to design an evaluation scale of traditional Chinese medicine (TCM) confidence and then evaluate its validity and reliability.

Alpelisib selectively inhibits the p110α catalytic subunit of PI3Kα and is approved for treatment of breast cancers harboring canonical PIK3CA mutations. In head and neck squamous cell carcinoma (HNSCC), 63% of PIK3CA mutations occur at canonical hotspots. The oncogenic role of the remaining 37% of PIK3CA noncanonical mutations is incompletely understood. We report a patient with HNSCC with a noncanonical PIK3CA mutation (Q75E) who exhibited a durable (12 months) response to alpelisib in a phase II clinical trial. Characterization of all 32 noncanonical PIK3CA mutations found in HNSCC using several functional and phenotypic assays revealed that the majority (69%) were activating, including Q75E. The oncogenic impact of these mutations was validated in 4 cellular models, demonstrating that their activity was lineage independent. Further, alpelisib exhibited antitumor effects in a xenograft derived from a patient with HNSCC containing an activating noncanonical PIK3CA mutation. Structural analyses revealed plausible mechanisms for the functional phenotypes of the majority of the noncanonical PIK3CA mutations. Collectively, these findings highlight the importance of characterizing the function of noncanonical PIK3CA mutations and suggest that patients with HNSCC whose tumors harbor activating noncanonical PIK3CA mutations may benefit from treatment with PI3Kα inhibitors.

We outline a framework for elucidating tumor genetic complexity through multidimensional protein-protein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified association of the fibroblast growth factor receptor tyrosine kinase 3 with Daple, a guanine-nucleotide exchange factor, resulting in activation of Gαi- and p21-activated protein kinase 1/2 to promote cancer cell migration. Additionally, we observe mutation-enriched interactions between the human epidermal growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo. We anticipate that the application of this framework will be valuable for translating genetic alterations into a molecular and clinical understanding of the underlying biology of many disease areas.

Background:Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer’s disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly.Methods:In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia.Results:The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells.Conclusion:Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7-related microglial inflammation.

Head and neck squamous cell carcinoma (HNSCC) is a highly morbid, genetically unstable disease derived from the mucoepithelium of the upper aerodigestive tract. Recent characterization of this disease has implicated the PI3K-Akt-mTOR pathway as one of the most frequently dysregulated pathways. As such, there are several classes of PI3K inhibitors currently undergoing clinical trials. In this article, we review the PI3K pathway, mutations of this pathway in HNSCC, drugs that target PI3K, the impact of these agents on the PI3K and GSK-3 signaling axes, ongoing clinical trials evaluating PI3K inhibitors, and the challenges of using these drugs in the clinic. This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.

Oil is a significant source of fatty acids and various trace functional components, and plays a vital role in regulating human health. The macro- and micro-components in oils are closely related to nutritional health. This paper introduces the future development goals and strategies of healthy oils from two aspects of precise nutrition and moderate processing. Firstly, precise nutrition based on life cycle and physiological state is a priority research area of lipid science. On the other hand, moderate processing will retain nutrients such as vitamin E, phytosterols, and squalene to a greater extent, and avoid the formation of risk factors such as trans fatty acids, 3-chloropropanol esters, and glycidyl esters. Moderate processing not only ensures the safety of oil, but also reduces the loss of healthy and beneficial fat concomitants, which is the development direction of oil engineering research. Therefore, under the dual demands of nutrition and safety, accurate nutrition and moderate processing of oils will help the implementation of "Healthy China" and "Double- Carbon" strategies. Future healthy oils will not only provide basic nutrition and flavor, but also give specific health functions to people with different life cycles, such as infants, children, adolescents, adults and the elderly, and maintain the homeostasis of people with different physiological states including pregnant and lactating women.

Background & Aims: Approximately one-third of colorectal cancers develop from serrated lesions (SLs), including hyperplastic polyp (HP), sessile serrated lesion (SSL), traditional serrated adenoma (TSA), and SSL with dysplasia (SSLD) through the serrated neoplasia pathway, which progresses faster than the conventional adenoma-carcinoma pathway. We sought to depict the currently unclarified molecular and immune alterations by the single-cell landscape in SLs. Methods: We performed single-cell RNA sequencing of 16 SLs (including 4 proximal HPs, 5 SSLs, 2 SSLDs, and 5 TSAs) vs 3 normal colonic tissues. Results: A total of 60,568 high-quality cells were obtained. Two distinct epithelial clusters with redox imbalance in SLs were observed, along with upregulation of tumor-promoting SerpinB6 that regulated ROS level. Epithelial clusters of SSL and TSA showed distinct molecular features: SSL-specific epithelium manifested overexpressed proliferative markers with Notch pathway activation, whereas TSA-specific epithelium showed Paneth cell metaplasia with aberrant lysozyme expression. As for immune contexture, enhanced cytotoxic activity of CD8+ T cells was observed in SLs; it was mainly attributable to increased proportion of CD103+CD8+ tissue-resident memory T cells, which might be regulated by retinoic acid metabolism. Microenvironment of SLs was generally immune-activated, whereas some immunosuppressive cells (regulatory T cells, anti-inflammatory macrophages, MDK+IgA+ plasma cells, MMP11-secreting PDGFRA+ fibroblasts) also emerged at early stage and further accumulated in SSLD. Conclusion: Epithelial, immune, and stromal components in the serrated pathway undergo fundamental alterations. Future molecular subtypes of SLs and potential immune therapy might be developed.

In this paper, 25 sampling points of overlying deposits in Tonglushan mining area, Daye City, Hubei Province, China were tested for heavy metal content to explore pollution characteristics, pollution sources and ecological risks of heavy metals in sediments. A geo-accumulation index method was used to evaluate the degree of heavy metal pollution in the sediment. The mean sediment quality guideline quotient was used for evaluating the ecological risk level of heavy metal in the sediment. And a method of correlation analysis, clustering analysis, and principal component analysis was used for preliminary analysis on the source of heavy metal in the sediment. It was indicated that there was extremely heavy metal pollution in the sediment, among which Cd was extremely polluted, Cu strongly contaminated, Zn, As, and Hg moderately contaminated, and Pb, Cr, and Ni were slightly contaminated. It was also indicated by the mean sediment quality guideline-quotient result that there was a high ecological risk of heavy metals in the sediment, and 64% of the sample sites had extremely high hidden biotoxic effects. For distribution, the contamination of branches was worse than that of the main channel of Daye Dagang, and the deposition of each heavy metal was mainly influenced by the distance from this sample site to the sewage draining exit of a tailings pond. The source analysis showed that the heavy metals in the sediment come from pollution discharging of mining and beneficiation companies, tailings ponds, smelting companies, and transport vehicles. In the study area, due to the influence of heavy metal discharging from these sources, the ecotoxicity of heavy metals in the sediment was extremely high, and Cd was the most toxic pollutant. The research figured out the key restoration area and elements for ecological restoration in the sediment of the Tonglüshan mining area, which could be referenced by monitoring and governance of heavy metal pollution in the sediment of the polymetallic mining area.©2022 China Geology Editorial Office.