The roles of lncRNA AP001469.3 in clinical implications, immune landscape and carcinogenesis of colorectal cancer.

Background: Previously, long non-coding RNA (lncRNA) gene AP001469.3 was reported to participate in the construction of an immune-related lncRNA signature, which showed promising clinical predictive value in colorectal cancer (CRC) patients. However, the clinical and immunological significance and biological function of AP001469.3 in CRC remain unclear. In this study, we aim to explore the roles of AP001469.3 in CRC progression, thereby opening an avenue for CRC treatment. Methods: Our study collected data from The Cancer Genome Atlas (TCGA) database and investigated the role of AP001469.3 in CRC through bioinformatics analysis. Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) methods evaluated the immune infiltration. The biological functions of AP001469.3 in CRC were validated by in vitro experiments. Gene set enrichment analysis (GSEA) was used to estimate the enrichment of functional pathways and gene signatures. Results: In this work, high expression of AP001469.3 was found in CRC and was positively associated with tumor-node-metastasis (TNM) stage in CRC. AP001469.3 expression had a strong relationship with microsatellite instability (MSI) in colon adenocarcinoma (COAD). Additionally, AP001469.3 expression was associated with StromalScore, ImmuneScore, ESTIMATEScore, immune cell infiltration (ICI) levels and immune checkpoint (ICP) genes expression in CRC. Subsequent results showed that immunotherapy could be more effective in CRC patients with low-AP001469.3 expression using the immunophenoscore (IPS). We confirmed that the transcript of AP001469.3 gene ENST00000430259 was highly expressed in CRC tissues and cell lines. In vitro experiments indicated that ENST00000430259 knockdown reduced the proliferation, migration and invasion of CRC cells. Finally, our GSEA results showed that the majority of the differentially enriched signaling pathways between the high- and low-AP001469.3 expression groups were immune-related. Conclusions: Taken together, our study demonstrates that lncRNA gene AP001469.3 is associated with immunological characteristics in CRC and promotes malignant progression of CRC. Moreover, AP001469.3 can be potentially used as an immunotherapeutic indicator and a therapeutic target for CRC patients.

Advanced theory of mind and children's prosocial lie-telling in middle childhood: A training study.

Children's advanced theory of mind (AToM) is concurrently associated with their prosocial lie-telling. However, the causal link between AToM and prosocial lie-telling has not yet been demonstrated. To address this gap, the current study adopted a training paradigm and investigated the role of AToM in children's prosocial lie-telling in middle childhood. A total of 66 9- and 10-year-old children who did not demonstrate any prosocial lie-telling in a disappointment gift paradigm at the baseline were recruited and randomly assigned to either the experimental group (n = 32) or an active control group (n = 34). The experimental group underwent a conversation-based training program of four sessions. The results showed significantly greater gains in AToM at the posttest for the experimental group children compared with the control group children, controlling for family socioeconomic status, children's literacy score, working memory, and inhibition. More important, the experimental group children were more likely to tell prosocial lies than the control group, even after controlling for the pretest AToM and other covariates. However, the training effects faded at the 6-month follow-up test after the training's completion. These findings provide the first evidence for the causal role of AToM in the development of prosocial lie-telling in middle childhood. The fade-out effect is discussed in the context of educational interventions.

Endoscopic Endonasal Reconstruction of Intraoperative Cerebrospinal Fluid Leak in Different Skull Base Regions: Outcomes, Meningitis, and Risk Factors.

OBJECTIVES: Various nonvascularized or vascularized techniques have been adopted in endoscopic endonasal surgery (EES) for repairing intraoperative cerebrospinal fluid (CSF) leaks after tumor resection. Vascularized nasoseptal flaps, free nasoseptal grafts, free turbinate grafts, and fascia lata and mashed muscle are frequently used. Outcomes of those grafts applied in the defects of different regions need to be clarified. METHODS: The data from a series of 162 patients with skull base tumor who underwent EES that had intraoperative CSF leak between Jan 2012 and Jan 2021 were retrospectively analyzed. The regions included anterior skull base, sellar region, clivus and infratemporal fossa. Repair failure rate (RFR), meningitis rate, and associated risk factors were assessed. RESULTS: In total, 172 reconstructions were performed in 162 patients for the 4 sites of the skull base. There were 7 cases (4.3%) that had postoperative CSF leaks, which required second repair. The RFR for anterior skull base, sellar region, clivus, and infratemporal fossawas 2.6%, 2.2%, 16.7%, and 0%, respectively. The clivus defect was an independent risk factor for repair failure (P < 0.01). The postoperative meningitis rate was 5.6%. Repair failure was an independent risk factor for meningitis (P < 0.01). CONCLUSIONS: Vascularized nasoseptal flap, free nasoseptal graft, free turbinate graft, and fascia lata and mashed muscle are reliable autologous materials for repairing the dural defects in different regions during EES. Clivus reconstruction remains a great challenge, which had a higher RFR and meningitis rate. Repair failure is significantly associated with postoperative meningitis.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Chiral quasi bound states in the continuum for augmented reality.

Augmented Reality technology enables users to interact with virtual imagines and the real world. The emergence of AR has propelled the development of the next generation of optical devices towards miniaturization, lightweight design, and enhanced light field manipulation capabilities. However, current AR glass still suffer from shortcomings of low efficiency. This work proposes a near-eye display device based on bilayer chiral quasi-BIC (Bound States in the continuum) nonlocal metasurfaces which can reflect narrow bandwidth RGB light with high efficiency while being able to see the natural environment clearly. At the same time, the geometric phase is introduced to realize oblique emission and reflective focusing. Due to its ability to manipulate narrowband light fields, it can reduce the interaction of metasurfaces and environment light, and has potential applications in the fields of imaging and near-eye display.

Detailed Characterization of Pore Results of Continental Shale Reservoir in Fengcheng Formation, Mahu Sag.

The exploration potential of shale oil in the Fengcheng Formation of the Mahu Sag, located in the Junggar Basin, is significant. However, there is a notable dearth of research on shale oil within this formation. This study addresses this gap by focusing on the pore structure and associated development factors of the Fengcheng Formation in Mahu Sag. A total of 113 samples from well X of the Fengcheng Formation were meticulously selected for analysis. The mineral components and pore structure of these samples were characterized using advanced techniques, including X-ray diffraction (XRD), low-temperature nitrogen adsorption (LTNA), high-pressure mercury injection (HPMI), and scanning electron microscopy (SEM). The findings reveal that, despite a relatively low content of clay minerals in the Fengcheng Formation, their presence is intricately linked to pore development. The high content of feldspar in the formation contributes significantly to the formation of clay minerals through dissolution processes. This dual influence plays a crucial role in shaping the overall pore development within the Fengcheng Formation. In addition, a comparative analysis was conducted with shale samples from other wells within the Fengcheng Formation in Mahu Sag, as well as from different basins, such as the Songliao Basin and Ordos Basin. Different from Qingshankou Formation in Songliao Basin and Yanchang Formation in Ordos Basin, the samples from Fengcheng Formation in Mahu Sag are composed of a large number of felic minerals and carbonate minerals with less clay minerals. This study underscores the paramount importance of mineral components and their respective content in influencing the pore development of shale oil reservoirs. The unique characteristics of the Fengcheng Formation in Mahu Sag, as revealed through comprehensive analyses, contribute valuable insights to the understanding of shale oil exploration potential in the Junggar Basin.

Integrin αvß3 and LHRH Receptor Double Directed Nano-Analogue Effective Against Ovarian Cancer in Mice Model.

Introduction: The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvß3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LP-PTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects. Methods: LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice. Results: The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytotoxicity, and hand a more potent inhibitory effect on tumor spheroids of A2780 cells. It also showed enhanced co-localization with endosomes or lysosome in A2780 cells, improved tumor-targeting capability, and demonstrated an enhanced anti-tumor effect in LHRHR-positive ovarian cancers. Conclusion: The designed LHRHa-RGD-LP-PTX liposomes significantly enhanced the tumor-targeting ability and therapeutic efficacy for LHRH receptor-positive ovarian cancers.

On-device phase engineering.

In situ tailoring of two-dimensional materials' phases under external stimulus facilitates the manipulation of their properties for electronic, quantum and energy applications. However, current methods are mainly limited to the transitions among phases with unchanged chemical stoichiometry. Here we propose on-device phase engineering that allows us to realize various lattice phases with distinct chemical stoichiometries. Using palladium and selenide as a model system, we show that a PdSe2 channel with prepatterned Pd electrodes can be transformed into Pd17Se15 and Pd4Se by thermally tailoring the chemical composition ratio of the channel. Different phase configurations can be obtained by precisely controlling the thickness and spacing of the electrodes. The device can be thus engineered to implement versatile functions in situ, such as exhibiting superconducting behaviour and achieving ultralow-contact resistance, as well as customizing the synthesis of electrocatalysts. The proposed on-device phase engineering approach exhibits a universal mechanism and can be expanded to 29 element combinations between a metal and chalcogen. Our work highlights on-device phase engineering as a promising research approach through which to exploit fundamental properties as well as their applications.

Eosinophil extracellular traps in eosinophilic chronic rhinosinusitis induce Charcot-Leyden crystal formation and eosinophil recruitment.

Eosinophil extracellular traps (EETs) are implicated in various eosinophil-associated diseases; however, their role in chronic rhinosinusitis (CRS) remains unclear. In the present study, 57 CRS patients were enrolled, and immunofluorescence was used to analyze EETs in eosinophilic (eCRS) and non-eosinophilic (Non-eCRS) tissues. MSD was used to examine IL-4, IL-5, and IL-13 concentrations in tissue homogenates. Charcot-Leyden crystals (CLCs) protein expression was detected in PMA, PMA+DNase I, and blank control eosinophils using ELISA. Eotaxin-3 mRNA and protein levels were measured in human nasal epithelial cells (HNECs) cultured with EETs, EETs+DNase I, DNase I, and unstimulated eosinophils using PCR and ELISA. EETs were significantly increased in eCRS tissues compared with Non-eCRS (P<0.001), and correlated with VAS and Lund-Mackay CT scores. IL-5 expression was related to EETs formation (r = 0.738, P<0.001). PMA-stimulated eosinophils exhibited higher CLCs protein levels (P<0.01). Co-culturing HNECs with EETs significantly increased eotaxin-3 mRNA and protein levels (P<0.0001, P<0.001) compared with other groups. The study suggests EETs formation is elevated in eCRS patients and is involved in CLCs formation and chemokine secretion, promoting eosinophilic inflammation.

Targeting the adenosine signaling pathway in macrophages for cancer immunotherapy.

One of the ways in which macrophages support tumorigenic growth is by producing adenosine, which acts to dampen antitumor immune responses and is generated by both tumor and immune cells in the tumor microenvironment (TME). Two cell surface expressed molecules, CD73 and CD39, boost catalytic adenosine triphosphate, leading to further increased adenosine synthesis, under hypoxic circumstances in the TME. There are four receptors (A1, A2A, A2B, and A3) expressed on macrophages that allow adenosine to perform its immunomodulatory effect. Researchers have shown that adenosine signaling is a key factor in tumor progression and an attractive therapeutic target for treating cancer. Several antagonistic adenosine-targeting biological therapies that decrease the suppressive action of tumor-associated macrophages have been produced and explored to transform this result from basic research into a therapeutic advantage. Here, we'll review the newest findings from studies of pharmacological compounds that target adenosine receptors, and their potential therapeutic value based on blocking the suppressive action of macrophages in tumors.

Patterns of Olfactory Impairment Among Patients with Uncontrolled Chronic Rhinosinusitis.

OBJECTIVES: Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test. METHODS: A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS. RESULTS: Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS. CONCLUSION: Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2341-2348, 2024.

Single-cell integrated transcriptomics reveals the role of keratinocytes in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignant tumor with significant morbidity and mortality. Understanding the molecular mechanisms of HNSCC and identifying prognostic markers and therapeutic targets are crucial for improving patient outcomes. In this study, we utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to comprehensively analyze HNSCC at the cellular level. We identified keratinocytes as the predominant cell type in tumor samples, suggesting their potential role in HNSCC development. Through hdWGCNA co-expression network analysis, we identified gene modules associated with HNSCC progression. Furthermore, we constructed a prognostic model based on specific genes and demonstrated its robust predictive performance in multiple datasets. The model exhibited strong correlations with immune cell infiltration patterns and signaling pathways related to tumor progression. Additionally, drug sensitivity analysis revealed potential chemotherapeutic targets for HNSCC treatment. Our findings provide valuable insights into the molecular characteristics and immune microenvironment of HNSCC, offering new perspectives for prognosis prediction and therapeutic interventions in clinical practice. Further research is warranted to validate and expand upon these findings, ultimately improving patient outcomes in HNSCC.

Picture book reading improves children's learning understanding.

Mental state reasoning is an integral part of children's teaching and learning understanding. This study investigated whether a picture book reading approach focusing on mental state discourse and contrasting perspectives in a preschool classroom setting would improve children's teaching and learning understanding and school readiness. In total, 104 children from four classrooms aged between 46 and 64 months (53 girls, M = 54.03 months, SD = 3.68) participated in the study. Half of the classrooms were randomly assigned to an experimental group where teachers read picture books rich in mental state discourse and engaged in intensive discussions with children for eight weeks. Children's false belief understanding and teaching and learning understanding were measured before and after the eight-week period. The result revealed that picture book reading improved children's learning understanding with a medium effect size, controlling for demographic variables, children's verbal ability, inhibition, and initial false belief understanding. The experimental group children further demonstrated more advanced school readiness 18 months after the intervention ended in a follow-up study using a teacher questionnaire.