Identification of an HLA-A*11:01-restricted neoepitope of mutant PIK3CA and its specific T cell receptors for cancer immunotherapy targeting hotspot driver mutations.

Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.

Smart Temperature Sensor Design and High-Density Water Temperature Monitoring in Estuarine and Coastal Areas.

Acquiring in situ water temperature data is an indispensable and important component for analyzing thermal dynamics in estuarine and coastal areas. However, the long-term and high-density monitoring of water temperature is costly and technically challenging. In this paper, we present the design, calibration, and application of the smart temperature sensor TS-V1, a low-power yet low-cost temperature sensor for monitoring the spatial-temporal variations of surface water temperatures and air temperatures in estuarine and coastal areas. The temperature output of the TS-V1 sensor was calibrated against the Fluke-1551A sensor developed in the United States and the CTD-Diver sensor developed in the Netherlands. The results show that the accuracy of the TS-V1 sensor is 0.08 °C, while sensitivity tests suggest that the TS-V1 sensor (comprising a titanium alloy shell with a thermal conductivity of 7.6 W/(m °C)) is approximately 0.31~0.54 s/°C slower than the CTD-Diver sensor (zirconia shell with thermal conductivity of 3 W/(m °C)) in measuring water temperatures but 6.92~10.12 s/°C faster than the CTD-Diver sensor in measuring air temperatures. In addition, the price of the proposed TS-V1 sensor is only approximately 1 and 0.3 times as much as the established commercial sensors, respectively. The TS-V1 sensor was used to collect surface water temperature and air temperature in the western part of the Pearl River Estuary from July 2022 to September 2022. These data wells captured water and air temperature changes, frequency distributions, and temperature characteristics. Our sensor is, thus, particularly useful for the study of thermal dynamics in estuarine and coastal areas.

HPV+ HNSCC-derived exosomal miR-9-5p inhibits TGF-ß signaling-mediated fibroblast phenotypic transformation through NOX4.

Human papillomavirus (HPV) is a significant risk factor for head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients have a higher survival rate, which may be related to its unique tumor microenvironment. Exosomes are emerging as a communication tool between tumor cells and the tumor microenvironment, including cancer-associated fibroblasts (CAFs). In this study, 111 clinical samples tissues and public sequencing data were analyzed. Our study found fewer CAFs infiltrated in HPV+ HNSCC, and poor CAF infiltration level was associated with a good prognosis. HPV+ HNSCC cell-derived exosomes can significantly reduce the phenotypic transformation of fibroblasts. miR-9-5p, as a miRNA enriched in HPV+ HNSCC cell-derived exosomes, can be transferred to fibroblasts. miR-9-5p mimic transfection decreased the expression of NOX4 and the level of intracellular reactive oxygen species (ROS), which inhibited the transforming growth factor beta 1(TGF-ß1)-induced increase of αSMA levels. Therefore, these results indicated that HPV+ HNSCC-derived exosomal miR-9-5p inhibits TGF-ß signaling-mediated fibroblast phenotypic transformation through NOX4, which is related to the excellent prognosis of HPV patients.

Random color filters based on an all-dielectric metasurface for compact hyperspectral imaging.

Metasurface filters are a compact, lightweight, and inexpensive solution for the miniaturized hyperspectral imaging system. However, the emerging applicability of these filters is limited by the trade-off between spatial and spectral resolutions. In this study, we establish and experimentally demonstrate a compact hyperspectral photodetection method using random all-dielectric metasurface filters that are directly integrated on the detectors. Based on compressive sensing algorithms, the compact photodetectors can accurately reconstruct the incident spectrum in the visible range. The minimum full width at half maximum (FWHM) of the spectrum reconstructed is 4.8 nm, which fully satisfies the requirements of hyperspectral imaging. The proposed method may be applied in the design, development, and measurement of compact hyperspectral imaging systems.

A Blockchain-Based Product Traceability System with Off-Chain EPCIS and IoT Device Authentication.

Blockchain-based traceability systems are a promising approach because they are decentralized, transparent, and tamper proof; however, if all traceability data are uploaded to a blockchain platform, it may affect the efficiency or even lead to data explosion. Additionally, it is difficult to guarantee the reliability of the original data source of massive Internet of Things (IoT) devices. Furthermore, when different enterprise nodes adopt different data storage structures, the costs that are associated with data sharing will increase. In this paper, we have proposed a trustworthy product traceability system that is based on hyperledger fabric and Electronic Product Code Information Service (EPCIS), which is not only capable of making products traceable, but it can also authenticate and authorize the IoT devices that are used for data collection. First, we adopted the on-chain and off-chain collaborative management mechanism in order to alleviate data explosion on the chain. Second, we proposed a scheme to authenticate and authorize devices based on blockchain. Third, we complied with EPCIS and Core Business Vocabulary (CBV) standards and provided the EPCIS location discovery service in order to improve the interactivity. Finally, we implemented and tested the proposed traceability system and compared it with the existing research. The proposed solution provides product information traceability, data tamper proofing, data confidentiality, and data source reliability.

Characteristics of B lymphocyte infiltration in HPV+ head and neck squamous cell carcinoma.

Human papillomavirus (HPV) is an important etiological factor of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients usually have a better prognosis, which probably results from the higher infiltration of B lymphocytes. This study was purposed to detect the infiltration of B lymphocyte subsets and the correlation between B lymphocyte subsets and the prognosis in HPV-related HNSCC. In this study, 124 HPV+ and 513 HPV- HNSCC samples were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database for transcriptomic analysis. Infiltration of B lymphocytes subsets was detected with 7 HPV+ HNSCC and 13 HPV- HNSCC tissues through immunohistochemistry and immunofluorescence. One HPV- HNSCC sample was detected with single-cell sequencing for chemokine analysis. In the results, the infiltration of plasma cells (CD19+ CD38+ ) and memory B cells (MS4A1+ CD27+ ) was higher in HPV+ HNSCC samples. High infiltration of plasma cells and memory B cells was related to a better prognosis. High density of B lymphocytes was positively correlated with high CXCL13 production mainly from CD4+ T lymphocytes in HNSCC. These results indicated that a high density of plasma cells and memory B cells could predict excellent prognosis. CD4+ T lymphocytes might affect B lymphocytes and their subsets through the CXCL13/CXCR5 axis in HNSCC.

Cellular heterogeneity landscape in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a highly malignant tumor originated from respiratory system. Although there have been many improvements in therapy until now, reducing the high mortality remains difficult. Understanding the cellular heterogeneity of LSCC could contribute to improve this problem. Single-cell RNA sequencing was applied to dissect the cell composition and molecular characteristics of LSCC tissues. Immunohistochemistry staining of the LSCC tissues was performed to identify the spatial location of tumor cells. Survival analysis of marker genes was executed in The Cancer Genome Atlas to verify the correlation between each cell clusters and patients' prognosis. The LSCC tissue cells were finely grouped into various clusters, including tumor cells, immune cells, epithelial cells, fibroblasts and endothelial cells. Notably, in tumor cells, keratinocyte-like cells were in the core of tumor while malignant proliferating cells were located at the tumor edge. The malignant proliferating cells were correlated with poor prognosis. In summary, this is the first study to delineate a landscape of the LSCC intratumor heterogeneity. Our work might help researchers have a better understanding for tumor progression.

Alleviation of drought stress and the physiological mechanisms in Citrus cultivar (Huangguogan) treated with methyl jasmonate.

The role of exogenous methyl jasmonate (MeJA) in alleviating drought stress was investigated on Huangguogan. Except for intercellular CO2 concentration, MeJA had little effect on net photosynthetic rate, stomatal conductance, and transpiration rate under drought stress. Compared with drought stress, MeJA significantly alleviated the decrease of chlorophyll content. However, chlorophyll a/b ratio was significantly increased. MeJA significantly increased proline and soluble sugar contents, significantly decreased the O2 -· and H2O2 levels, and increased SOD and POD activities. In addition, the MDA content of drought stress was the highest of all treatments. MeJA significantly reduced MDA content in drought-stressed Huangguogan leaves. Although the Ascorbic acid (AsA) contents of 500 and 1000 mg L-1 MeJA treatments were lower than that of 250 mg L-1 MeJA, but all concentration of MeJA treatments delayed the decline of AsA content. Therefore, MeJA could induce drought stress tolerance by increasing the osmotic adjustment substances and antioxidant activities.

Transcriptomic response of Ralstonia solanacearum to antimicrobial Pseudomonas fluorescens SN15-2 metabolites.

To develop efficient biocontrol agents, it is essential to investigate the response of soil-borne plant pathogens to such agents. For example, the response of Ralstonia solanacearum, the tomato wilt pathogen, to antimicrobial metabolites of Pseudomonas fluorescens is unknown. Thus, we assessed the effects of P. fluorescens SN15-2 fermentation broth on R. solanacearum by transmission electron microscopy and transcriptome technology. RNA sequencing identified 109 and 155 genes that are significantly upregulated and downregulated, respectively, in response to P. fluorescens metabolites, many of which are associated with the cell membrane and cell wall, and with nucleotide acid metabolism, iron absorption, and response to oxidative stress. This study highlights the effectiveness of P. fluorescens metabolites against the tomato wilt pathogen and helps clarify the underlying molecular mechanisms.

Transumbilical Endoscopic Resection of Intra-abdominal Mesenchymal Tumor.

Gastrointestinal stromal tumors (GISTs) typically occur in the stomach and proximal small intestine but can also be found in any other part of the digestive tract, including the abdominal cavity, albeit rarely. In the present case, the tumor was resected endoscopically through the anterior gastric wall. Computed tomography (CT) scan and gastroscopy of a 60-year-old woman revealed submucosal lesions in the gastric body. The possibility of a stromal tumor was considered more likely. The endoscopic surgery was performed under endotracheal anesthesia. After a solution had been injected at the lesion site in the stomach, the entire gastric wall was dissected to expose the tumor. As the lesion was in the abdominal cavity and its base was attached to the abdominal wall, it was accessed using a sterilized PCF colonoscope. A sodium chloride injection was administered at the base. The tumor was then peeled along its boundaries using the hooking and excision knife combined with the precutting knife. Subsequently, the tumor was pulled into the stomach through the incision made in the stomach and then extracted externally through the upper digestive tract using the ERCP spiral mesh basket. After confirming the absence of bleeding at the incision site, the endoscope was returned to the stomach, and the stomach opening was closed using purse-string sutures. The patient recovered satisfactorily following the surgery and was discharged on day 4. Histological examination revealed a low-risk stromal tumor (spindle cell type, <5 mitosis/50 high-power fields [HPF]). Immunohistochemistry revealed positive staining for CD34 and CD117, negative staining for SMA, positive staining for DOG1, and negative staining for S100. Additionally, the expression of ki67 was 3%.

The Lithofacies of Sandstones Interbedded with Shales: Implication for Organic Matter Accumulation of Triassic Deep Lacustrine Setting, Southern Ordos Basin.

The sandstones interbedded with shales in the lacustrine black shale have great potential to become important targets for oil and gas exploration, but there has been a lack of systematic research regarding their types and genesis. This study focused on the investigation of the Triassic Chang 73 member deep lacustrine sandstone. Eleven lithofacies are identified and classified into three different types of deposits: ash fall and intra- and extra-basinal turbidite deposits. Vitric tuff, pumice-bearing shale, and ash are the main ash fall lithofacies. The presence of reverse grading and a significant concentration of plant fragments/micas suggest extra-basinal turbidite deposits. However, the collapse of deltaic intrabasinal sediments has been well sorted and does not contain plant debris and low-density materials. These three different types of sediments combined with a humid climate are the main causes for the deposition of a large number of sandstone layers in the deep lacustrine environment. Furthermore, the abundant volcanic eruptions are associated with increased organic matter accumulation and promoted the bloom of algae. In addition, the generated oil in the black shales would then migrate and accumulate in the interbedded sandstones. This research provides geological evidence for the prospective prediction of lacustrine shale oil accumulations.

A Highly Flexible Piezoelectric Ultrasonic Sensor for Wearable Bone Density Testing.

Driven by the loss of bone calcium, the elderly are prone to osteoporosis, and regular routine checks on bone status are necessary, which mainly rely on bone testing equipment. Therefore, wearable real-time healthcare devices have become a research hotspot. Herein, we designed a high-performance flexible ultrasonic bone testing system using axial transmission technology based on quantitative ultrasound theory. First, a new rare-earth-element-doped PMN-PZT piezoelectric ceramic was synthesized using a solid-state reaction, and characterized by X-ray diffraction and SEM. Both a high piezoelectric coefficient d33 = 525 pC/N and electromechanical coupling factors of k33 = 0.77, kt = 0.58 and kp = 0.63 were achieved in 1%La/Sm-doped 0.17 PMN-0.47 PZ-0.36 PT ceramics. Combining a flexible PDMS substrate with an ultrasonic array, a flexible hardware circuit was designed which includes a pulse excitation module, ultrasound array module, amplification module, filter module, digital-to-analog conversion module and wireless transmission module, showing high power transfer efficiency and power intensity with values of 35% and 55.4 mW/cm2, respectively. Finally, the humerus, femur and fibula were examined by the flexible device attached to the skin, and the bone condition was displayed in real time on the mobile client, which indicates the potential clinical application of this device in the field of wearable healthcare.

Diagnosis of Alzheimer's disease via resting-state EEG: integration of spectrum, complexity, and synchronization signal features.

Background: Alzheimer's disease (AD) is the most common neurogenerative disorder, making up 70% of total dementia cases with a prevalence of more than 55 million people. Electroencephalogram (EEG) has become a suitable, accurate, and highly sensitive biomarker for the identification and diagnosis of AD. Methods: In this study, a public database of EEG resting state-closed eye recordings containing 36 AD subjects and 29 normal subjects was used. And then, three types of signal features of resting-state EEG, i.e., spectrum, complexity, and synchronization, were performed by applying various signal processing and statistical methods, to obtain a total of 18 features for each signal epoch. Next, the supervised machine learning classification algorithms of decision trees, random forests, and support vector machine (SVM) were compared in categorizing processed EEG signal features of AD and normal cases with leave-one-person-out cross-validation. Results: The results showed that compared to normal cases, the major change in EEG characteristics in AD cases was an EEG slowing, a reduced complexity, and a decrease in synchrony. The proposed methodology achieved a relatively high classification accuracy of 95.65, 95.86, and 88.54% between AD and normal cases for decision trees, random forests, and SVM, respectively, showing that the integration of spectrum, complexity, and synchronization features for EEG signals can enhance the performance of identifying AD and normal subjects. Conclusion: This study recommended the integration of EEG features of spectrum, complexity, and synchronization for aiding the diagnosis of AD.

CENPM upregulation by E5 oncoprotein of human papillomavirus promotes radiosensitivity in head and neck squamous cell carcinoma.

OBJECTIVES: This study aims to investigate how human papillomavirus (HPV) affects the key gene in the biological behaviors of head and neck squamous cell carcinoma (HNSCC) that leads to better response to radiotherapy. MATERIALS AND METHODS: The expression of key gene CENPM was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data and HPV positive and HPV negative HNSCC tumors and cells. Assays with siRNAs, CRISPR/Cas9-based models, Western blot, qRT-PCR, ChIP, etc., were used to explore how HPV affects CENPM and response to radiotherapy for HNSCC. RESULTS: CENPM occupies the hub in the HPV-related gene network. HPV-positive HNSCC showed higher level of CENPM expression comparing with HPV-negative HNSCC. HPV E5 has the most pronounced impact on CENPM (R = 0.44, p = 0.00081). This might result from the binding of transcription factor E2F1 to CENPM. We further found that inhibition of CENPM expression in HPV-positive HNSCC cell line SCC47 increased resistance to X-ray radiation by approximately 59% under 2 Gy irradiation, which may be resulted from a reduced proportion of mitotic cells. CONCLUSION: HPV E5 enhances CENPM expression by transcription factor E2F1 in HNSCC, which results in a radiosensitive profile in cell cycle redistribution of HNSCC. Thus, HPV infection in HNSCC provides profound evidence that underscores the magnitude of E2F1 control of CENPM expression illustrating the potential clinical benefit of CENPM examination for difficult-to-treat HPV-negative cancers.

Recent Advances on Conducting Polymers Based Nanogenerators for Energy Harvesting.

With the rapid growth of numerous portable electronics, it is critical to develop high-performance, lightweight, and environmentally sustainable energy generation and power supply systems. The flexible nanogenerators, including piezoelectric nanogenerators (PENG) and triboelectric nanogenerators (TENG), are currently viable candidates for combination with personal devices and wireless sensors to achieve sustained energy for long-term working circumstances due to their great mechanical qualities, superior environmental adaptability, and outstanding energy-harvesting performance. Conductive materials for electrode as the critical component in nanogenerators, have been intensively investigated to optimize their performance and avoid high-cost and time-consuming manufacture processing. Recently, because of their low cost, large-scale production, simple synthesis procedures, and controlled electrical conductivity, conducting polymers (CPs) have been utilized in a wide range of scientific domains. CPs have also become increasingly significant in nanogenerators. In this review, we summarize the recent advances on CP-based PENG and TENG for biomechanical energy harvesting. A thorough overview of recent advancements and development of CP-based nanogenerators with various configurations are presented and prospects of scientific and technological challenges from performance to potential applications are discussed.

Applications and analytical tools of cell communication based on ligand-receptor interactions at single cell level.

BACKGROUND: Cellular communication is an essential feature of multicellular organisms. Binding of ligands to their homologous receptors, which activate specific cell signaling pathways, is a basic type of cellular communication and intimately linked to many degeneration processes leading to diseases. MAIN BODY: This study reviewed the history of ligand-receptor and presents the databases which store ligand-receptor pairs. The recently applications and research tools of ligand-receptor interactions for cell communication at single cell level by using single cell RNA sequencing have been sorted out. CONCLUSION: The summary of the advantages and disadvantages of analysis tools will greatly help researchers analyze cell communication at the single cell level. Learning cell communication based on ligand-receptor interactions by single cell RNA sequencing gives way to developing new target drugs and personalizing treatment.

Physiological and Transcriptomic Analyses Reveal Exogenous Trehalose Is Involved in the Responses of Wheat Roots to High Temperature Stress.

High temperature stress seriously limits the yield and quality of wheat. Trehalose, a non-reducing disaccharide, has been shown involved in regulating plant responses to a variety of environmental stresses. This study aimed to explore the molecular regulatory network of exogenous trehalose to improve wheat heat tolerance through RNA-sequencing technology and physiological determination. The physiological data and RNA-seq showed that trehalose reduced malondialdehyde content and relative conductivity in wheat roots, and affecting the phenylpropane biosynthesis, starch and sucrose metabolism, glutathione metabolism, and other pathways. Our results showed that exogenous trehalose alleviates the oxidative damage caused by high temperature, coordinating the effect of wheat on heat stress by re-encoding the overall gene expression, but two wheat varieties showed different responses to high temperature stress after trehalose pretreatment. This study preliminarily revealed the effect of trehalose on gene expression regulation of wheat roots under high temperature stress, which provided a reference for the study of trehalose.

Correction: Understanding the spatial dimension of natural language by measuring the spatial semantic similarity of words through a scalable geospatial context window.

[This corrects the article DOI: 10.1371/journal.pone.0236347.].

Drought resistance in Harumi tangor seedlings grafted onto different rootstocks.

In this study we analysed the influence of drought stress on the leaf morphological characteristics, osmotic adjustment substances, antioxidant enzymes, and resistance-related photosynthetic physiological indices of Harumi tangor plants grafted onto Poncirus trifoliata (Pt), Citrus junos (Cj), and Citrus tangerine (Ct). The leaf relative water content and leaf area of the three rootstocks decreased with increasing drought stress, with the smallest decrease in Cj. The relative conductivity and malondialdehyde content increased with increasing drought stress. Proline, total soluble sugar, soluble protein, and activities of superoxide dismutase, ascorbate peroxidase, and catalase increased with drought stress but decreased under severe drought stress, with Cj exhibiting the greatest increase in enzyme activity. The net photosynthetic rate, stomatal conductance, transpiration rate, and chlorophyll a and b content were all lower than those of the control, whereas intercellular CO2 concentration increased with increasing drought stress. The initial fluorescence and maximal quantum yield of PSII were approximately equal for all rootstocks but increased with increasing drought stress severity. The combined analysis of physiological indicators, membership function, and principal components indicated that the drought resistance of grafted H. tangor decreased in the order Cj > Ct > Pt.

Understanding the spatial dimension of natural language by measuring the spatial semantic similarity of words through a scalable geospatial context window.

Measuring the semantic similarity between words is important for natural language processing tasks. The traditional models of semantic similarity perform well in most cases, but when dealing with words that involve geographical context, spatial semantics of implied spatial information are rarely preserved. Geographic information retrieval (GIR) methods have focused on this issue; however, they sometimes fail to solve the problem because the spatial and textual similarities of words are considered and calculated separately. In this paper, from the perspective of spatial context, we consider the two parts as a whole-spatial context semantics, and we propose a method that measures spatial semantic similarity using a sliding geospatial context window for geo-tagged words. The proposed method was first validated with a set of simulated data and then applied to a real-world dataset from Flickr. As a result, a spatial semantic similarity model at different scales is presented. We believe this model is a necessary supplement for traditional textual-language semantic analyses of words obtained by word-embedding technologies. This study has the potential to improve the quality of recommendation systems by considering relevant spatial context semantics, and benefits linguistic semantic research by emphasising the spatial cognition among words.