Association of the SHOX2 and RASSF1A methylation levels with the pathological evolution of early-stage lung adenocarcinoma.

Background The methylation of SHOX2 and RASSF1A shows promise as a potential biomarker for the early screening of lung cancer, offering a solution to remedy the limitations of morphological diagnosis. The aim of this study is to diagnose lung adenocarcinoma by measuring the methylation levels of SHOX2 and RASSF1A, and provide an accurate pathological diagnosis to predict the invasiveness of lung cancer prior to surgery.Material and methods The methylation levels of SHOX2 and RASSF1A were quantified using a LungMe® test kit through methylation-specific PCR (MS-PCR). The diagnostic efficacy of SHOX2 and RASSF1A and the cutoff values were validated using ROC curve analysis. The hazardous factors influencing the invasiveness of lung adenocarcinoma were calculated using multiple regression.Results: The cutoff values of SHOX2 and RASSF1A were 8.3 and 12.0, respectively. The sensitivities of LungMe® in IA, MIA and AIS patients were 71.3% (122/171), 41.7% (15/36), and 16.1% (5/31) under the specificity of 94.1% (32/34) for benign lesions. Additionally, the methylation level of SHOX2, RASSF1A and LungMe® correlated with the high invasiveness of clinicopathological features, such as age, gender, tumor size, TNM stage, pathological type, pleural invasion and STAS. The tumor size, age, CTR values and LungMe® methylation levels were identified as independent hazardous factors influencing the invasiveness of lung adenocarcinoma.Conclusion: SHOX2 and RASSF1A combined methylation can be used as an early detection indicator of lung adenocarcinoma. SHOX2 and RASSF1A combined (LungMe®) methylation is significantly correlated to age, gender, tumor size, TNM stage, pathological type, pleural invasion and STAS. The SHOX2 and RASSF1A methylation levels, tumor size and CTR values could predict the invasiveness of the tumor prior to surgery, thereby providing guidance for the surgical procedure.

Roles of glutamic pyruvate transaminase 2 in reprogramming of airway epithelial lipidomic and metabolomic profiles after smoking.

Metabolic abnormalities represent one of the pathological features of chronic obstructive pulmonary disease (COPD). Glutamic pyruvate transaminase 2 (GPT2) is involved in glutamate metabolism and lipid synthesis pathways, whilst the exact roles of GPT2 in the occurrence and development of COPD remains uncertain. This study aims at investigating how GPT2 and the associated genes modulate smoking-induced airway epithelial metabolism and damage by reprogramming lipid synthesis. The circulating or human airway epithelial metabolomic and lipidomic profiles of COPD patients or cell-lines explored with smoking were assessed to elucidate the pivotal roles of GPT2 in reprogramming processes. We found that GPT2 regulate the reprogramming of lipid metabolisms caused by smoking, especially phosphatidylcholine (PC) and triacylglycerol (TAG), along with changes in the expression of lipid metabolism-associated genes. GPT2 modulated cell sensitivities and survival in response to smoking by enhancing mitochondrial functions and maintaining lipid and energy homeostasis. Our findings provide evidence for the involvement of GPT2 in the reprogramming of airway epithelial lipids following smoking, as well as the molecular mechanisms underlying GPT2-mediated regulation, which may offer an alternative of therapeutic strategies for chronic lung diseases.

Achieving Negatively Charged Pt Single Atoms on Amorphous Ni(OH)2 Nanosheets with Promoted Hydrogen Absorption in Hydrogen Evolution.

Single-atom (SA) catalysts with nearly 100% atom utilization have been widely employed in electrolysis for decades, due to the outperforming catalytic activity and selectivity. However, most of the reported SA catalysts are fixed through the strong bonding between the dispersed single metallic atoms with nonmetallic atoms of the substrates, which greatly limits the controllable regulation of electrocatalytic activity of SA catalysts. In this work, Pt-Ni bonded Pt SA catalyst with adjustable electronic states was successfully constructed through a controllable electrochemical reduction on the coordination unsaturated amorphous Ni(OH)2 nanosheet arrays. Based on the X-ray absorption fine structure analysis and first-principles calculations, Pt SA was bonded with Ni sites of amorphous Ni(OH)2, rather than conventional O sites, resulting in negatively charged Ptδ-. In situ Raman spectroscopy revealed that the changed configuration and electronic states greatly enhanced absorbability for activated hydrogen atoms, which were the essential intermediate for alkaline hydrogen evolution reaction. The hydrogen spillover process was revealed from amorphous Ni(OH)2 that effectively cleave the H-O-H bond of H2O and produce H atom to the Pt SA sites, leading to a low overpotential of 48 mV in alkaline electrolyte at -1000 mA cm-2 mg-1Pt, evidently better than commercial Pt/C catalysts. This work provided new strategy for the controllable modulation of the local structure of SA catalysts and the systematic regulation of the electronic states.

Amorphous Bismuth-Tin Oxide Nanosheets with Optimized C-N Coupling for Efficient Urea Synthesis.

Closing the carbon and nitrogen cycles by electrochemical methods using renewable energy to convert abundant or harmful feedstocks into high-value C- or N-containing chemicals has the potential to transform the global energy landscape. However, efficient conversion avenues have to date been mostly realized for the independent reduction of CO2 or NO3-. The synthesis of more complex C-N compounds still suffers from low conversion efficiency due to the inability to find effective catalysts. To this end, here we present amorphous bismuth-tin oxide nanosheets, which effectively reduce the energy barrier of the catalytic reaction, facilitating efficient and highly selective urea production. With enhanced CO2 adsorption and activation on the catalyst, a C-N coupling pathway based on *CO2 rather than traditional *CO is realized. The optimized orbital symmetry of the C- (*CO2) and N-containing (*NO2) intermediates promotes a significant increase in the Faraday efficiency of urea production to an outstanding value of 78.36% at -0.4 V vs RHE. In parallel, the nitrogen and carbon selectivity for urea formation is also enhanced to 90.41% and 95.39%, respectively. The present results and insights provide a valuable reference for the further development of new catalysts for efficient synthesis of high-value C-N compounds from CO2.

Isorhamnetin: what is the in vitro evidence for its antitumor potential and beyond?

Isorhamnetin (ISO) is a phenolic compound belonging to flavonoid family, showcasing important in vitro pharmacological activities such as antitumor, anti-inflammation, and organ protection. ISO is predominantly extracted from Hippophae rhamnoides L. This plant is well-known in China and abroad because of its "medicinal and food homologous" characteristics. As a noteworthy natural drug candidate, ISO has received considerable attention in recent years owing to its low cost, wide availability, high efficacy, low toxicity, and minimal side effects. To comprehensively elucidate the multiple biological functions of ISO, particularly its antitumor activities and other pharmacological potentials, a literature search was conducted using electronic databases including Web of Science, PubMed, Google Scholar, and Scopus. This review primarily focuses on ISO's ethnopharmacology. By synthesizing the advancements made in existing research, it is found that the general effects of ISO involve a series of in vitro potentials, such as antitumor, protection of cardiovascular and cerebrovascular, anti-inflammation, antioxidant, and more. This review illustrates ISO's antitumor and other pharmacological potentials, providing a theoretical basis for further research and new drug development of ISO.

A Pharmacist-Led Intervention of Dispensing Naloxone to a Patient Population at Risk of Opioid-Related Harm.

BACKGROUND: Even though pharmacists are fully capable of dispensing naloxone under protocols, there are barriers perceived by pharmacists, such as determining which patients are at high risk. OBJECTIVE(S): The study objectives were to 1) determine the impact of pharmacist-led identification of patients at a high risk of opioid-related harm and pharmacist intervention by providing naloxone counseling; and 2) identify patient-reported barriers for receiving naloxone recommended by pharmacists under the Missouri Standing Protocol. METHODS: Pharmacists developed a standardized process in their workflow to identify patients at high risk of opioid-related harm defined by the Centers for Disease Control and Prevention guidelines, and attempted to call the patient prior to the patient's arrival to counsel the patient on naloxone. Primary outcomes included the number of at-risk patients identified, the number of patients who were willing to receive naloxone, and the number of patients who picked up naloxone at the pharmacy. Secondary outcomes included patient-reported barriers. Descriptive statistics, bivariate correlations, and Chi-square tests were used to analyze the data. RESULTS: Fifty patients participated in the study, of whom the average age was 56 years, 52% were male, and 56% were African American. Forty-one patients were willing to receive naloxone from pharmacists under the Missouri Standing Protocol, and 36 were dispensed naloxone from the pharmacy. Fourteen patients reported barriers to receiving naloxone, including transportation, cost, and waiting time at the pharmacy. The correlations show that not understanding need and not wanting to keep naloxone on hand were negatively associated with the patient's willingness to receive naloxone (p<0.01). Chi-squared tests supported the relationships revealed by the correlations. CONCLUSION: Pharmacists were able to identify patients who were at high risk for opioid-related harm and then counseled them on naloxone. Pharmacists also identified patient-reported barriers to further expand access to naloxone.

[Identification and expression of genome of uridine diphosphate glycosyltransferase (UGT) gene family from Chrysanthemum indicum].

Uridine diphosphate glycosyltransferase(UGT) is involved in the glycosylation of a variety of secondary metabolites in plants and plays an important role in plant growth and development and regulation of secondary metabolism. Based on the genome of a diploid Chrysanthemum indicum, the UGT gene family from Ch. indicum was identified by bioinformatics methods, and the physical and chemical properties, subcellular localization prediction, conserved motif, phylogeny, chromosome location, gene structure, and gene replication events of UGT protein were analyzed. Transcriptome and real-time fluorescence quantitative polymerase chain reaction(PCR) were used to analyze the expression pattern of the UGT gene in flowers and leaves of Ch. indicum. Quasi-targeted metabolomics was used to analyze the differential metabolites in flowers and leaves. The results showed that a total of 279 UGT genes were identified in the Ch. indicum genome. Phylogenetic analysis showed that these UGT genes were divided into 8 subfamilies. Members of the same subfamily were distributed in clusters on the chromosomes. Tandem duplications were the main driver of the expansion of the UGT gene family from Ch. indicum. Structural domain analysis showed that 262 UGT genes had complete plant secondary metabolism signal sequences(PSPG box). The analysis of cis-acting elements indicated that light-responsive elements were the most ubiquitous elements in the promoter regions of UGT gene family members. Quasi-targeted metabolome analysis of floral and leaf tissue revealed that most of the flavonoid metabolites, including luteolin-7-O-glucoside and kaempferol-7-O-glucoside, had higher accumulation in flowers. Comparative transcriptome analysis of flower and leaf tissue showed that there were 72 differentially expressed UGT genes, of which 29 genes were up-regulated in flowers, and 43 genes were up-regulated in leaves. Correlation network and phylogenetic analysis showed that CindChr9G00614970.1, CindChr2G00092510.1, and CindChr2G00092490.1 may be involved in the synthesis of 7-O-flavonoid glycosides in Ch. indicum, and real-time fluorescence quantitative PCR analysis further confirmed the reliability of transcriptome data. The results of this study are helpful to understand the function of the UGT gene family from Ch. indicum and provide data reference and theoretical basis for further study on the molecular regulation mechanism of flavonoid glycosides synthesis in Ch. indicum.

Population genetic variation and geographic distribution of suitable areas of Coptis species in China.

Introduction: The rhizomes of Coptis plants have been used in traditional Chinese medicine over 2000 years. Due to increasing market demand, the overexploitation of wild populations, habitat degradation and indiscriminate artificial cultivation of Coptis species have severely damaged the native germplasms of species in China. Methods: Genome-wide simple-sequence repeat (SSR) markers were developed using the genomic data of C. chinensis. Population genetic diversity and structure of 345 Coptis accessions collected from 32 different populations were performed based on these SSRs. The distribution of suitable areas for three taxa in China was predicted and the effects of environmental variables on genetic diversity in relation to different population distributions were further analyzed. Results: 22 primer pairs were selected as clear, stable, and polymorphic SSR markers. These had an average of 16.41 alleles and an average polymorphism information content (PIC) value of 0.664. In the neighbor-joining (N-J) clustering analysis, the 345 individuals clustered into three groups, with C. chinensis, C. chinensis var. brevisepala and C. teeta being clearly separated. All C. chinensis accessions were further divided into four subgroups in the population structure analysis. The predicted distributions of suitable areas and the environmental variables shaping these distributions varied considerably among the three species. Discussion: Overall, the amount of solar radiation, precipitation and altitude were the most important environmental variables influencing the distribution and genetic variation of three species. The findings will provide key information to guide the conservation of genetic resources and construction of a core reserve for species.

A novel long non-coding RNA LINC00524 facilitates invasion and metastasis through interaction with TDP43 in breast cancer.

Breast cancer (BC) remains a significant health concern worldwide, with metastasis being a primary contributor to patient mortality. While advances in understanding the disease's progression continue, the underlying mechanisms, particularly the roles of long non-coding RNAs (lncRNAs), are not fully deciphered. In this study, we examined the influence of the lncRNA LINC00524 on BC invasion and metastasis. Through meticulous analyses of TCGA and GEO data sets, we observed a conspicuous elevation of LINC00524 expression in BC tissues. This increased expression correlated strongly with a poorer prognosis for BC patients. A detailed Gene Ontology analysis suggested that LINC00524 likely exerts its effects through RNA-binding proteins (RBPs) mechanisms. Experimentally, LINC00524 was demonstrated to amplify BC cell migration, invasion and proliferation in vitro. Additionally, in vivo tests showed its potent role in promoting BC cell growth and metastasis. A pivotal discovery was LINC00524's interaction with TDP43, which leads to the stabilization of TDP43 protein expression, an element associated with unfavourable BC outcomes. In essence, our comprehensive study illuminates how LINC00524 accelerates BC invasion and metastasis by binding to TDP43, presenting potential avenues for therapeutic interventions.

Novel Uncertainty Quantification through Perturbation-Assisted Sample Synthesis.

This paper introduces a novel Perturbation-Assisted Inference (PAI) framework utilizing synthetic data generated by the Perturbation-Assisted Sample Synthesis (PASS) method. The framework focuses on uncertainty quantification in complex data scenarios, particularly involving unstructured data while utilizing deep learning models. On one hand, PASS employs a generative model to create synthetic data that closely mirrors raw data while preserving its rank properties through data perturbation, thereby enhancing data diversity and bolstering privacy. By incorporating knowledge transfer from large pre-trained generative models, PASS enhances estimation accuracy, yielding refined distributional estimates of various statistics via Monte Carlo experiments. On the other hand, PAI boasts its statistically guaranteed validity. In pivotal inference, it enables precise conclusions even without prior knowledge of the pivotal's distribution. In non-pivotal situations, we enhance the reliability of synthetic data generation by training it with an independent holdout sample. We demonstrate the effectiveness of PAI in advancing uncertainty quantification in complex, data-driven tasks by applying it to diverse areas such as image synthesis, sentiment word analysis, multimodal inference, and the construction of prediction intervals.

Effective oxygen activation on polyoxometalate-based hybrids for epoxidation of alkenes.

Two polyoxometalate-based hybrids, [M(btap)3(H2O)3(HPW12O40)]·xH2O (M-PW, M = Co/Mn, btap = 3,5-bis(1',2',4'-triazol-1'-yl)pyridine) were synthesized. Co-PW exhibited higher activity and selectivity towards olefin epoxidation than Mn-PW due to the synergistic effect between CoII and PW, in which the Co centers activate O2 to ˙O2- and further binding of free H+ from PW affords the active peroxyacid.

Role and regulation of FOXO3a: new insights into breast cancer therapy.

Breast cancer is the most common malignancy in the world, particularly affecting female cancer patients. Enhancing the therapeutic strategies for breast cancer necessitates identifying molecular drug targets that effectively eliminate tumor cells. One of these prominent targets is the forkhead and O3a class (FOXO3a), a member of the forkhead transcription factor subfamily. FOXO3a plays a pivotal role in various cellular processes, including apoptosis, proliferation, cell cycle regulation, and drug resistance. It acts as a tumor suppressor in multiple cancer types, although its specific role in cancer remains unclear. Moreover, FOXO3a shows promise as a potential marker for tumor diagnosis and prognosis in breast cancer patients. In addition, it is actively influenced by common anti-breast cancer drugs like paclitaxel, simvastatin, and gefitinib. In breast cancer, the regulation of FOXO3a involves intricate networks, encompassing post-translational modification post-translational regulation by non-coding RNA (ncRNA) and protein-protein interaction. The specific mechanism of FOXO3a in breast cancer urgently requires further investigation. This review aims to systematically elucidate the role of FOXO3a in breast cancer. Additionally, it reviews the interaction of FOXO3a and its upstream and downstream signaling pathway-related molecules to uncover potential therapeutic drugs and related regulatory factors for breast cancer treatment by regulating FOXO3a.

Zeaxanthin impairs angiogenesis and tumor growth of glioblastoma: An in vitro and in vivo study.

OBJECTIVES: To investigate the therapeutic effects of Zeaxanthin (Zea), one of the oxidized xanthophyll carotenoids belonging to the isoprenoids, on inhibiting the angiogenesis and tumor growth of glioblastoma (GBM) via an in vitro and in vivo study. METHODS: The effects of Zea on the proliferation, adhesion, migration and invasion of human GBM cell lines were detected by cell proliferation assay, cell adhesion assay and Transwell assay. The effect of Zea on angiogenesis was detected by rat aortic ring assay and human umbilical vein endothelial cells (HUVEC) in vitro tube formation assay. The effects of Zea on PARP, Caspase 3 and VEGFR2 phosphorylation as well as VEGFR2's downstream signaling pathway were detected by Western blot. The in vivo human GBM xenograft mouse model was employed to study the therapeutic efficacy of Zea. RESULTS: Zea impaired the proliferation, adhesion, migration and invasion of U87 and U251 cells as well as HUVECs. Rat aortic ring experiments displayed Zea significantly inhibited angiogenesis during VEGF-induced microvascular germination. In vitro and in vivo vascular experiments verified that Zea inhibited VEGF-induced HUVEC proliferation and capillary-like tube formation. Additionally, Zea induced GBM cells apoptosis via increasing the expression of cleaved PARP and Caspase 3. In HUVECs and U251 GBM cells, Zea down-regulated VEGF-induced activation of the VEGFR2 kinase pathway. Meanwhile the expression of p-AKT, p-ERK, p-STAT3 and FAK were all attenuated in U251 cells. Moreover, the effects of Zea on GBM cells proliferation could be blocked by VEGFR2 kinase inhibitor SU5408. These results suggest that Zea may hinder GBM angiogenesis and tumor growth through down-regulating a cascade of oncogenic signaling pathways, both through the inhibition of angiogenesis and the anti-tumor mechanism of a direct cytotoxic effect. Besides, Zea inhibits GBM angiogenesis and tumor growth exemplified through a xenograft mouse model in vivo. CONCLUSION: Zea impairs angiogenesis and tumor growth of GBM both in vitro and in vivo. It can be declared that Zea is a potential valuable anticancer candidate for the future treatment strategy of GBM.

ORTEGA v1.0: an open-source Python package for context-aware interaction analysis using movement data.

BACKGROUND: Interaction analysis via movement in space and time contributes to understanding social relationships among individuals and their dynamics in ecological systems. While there is an exciting growth in research in computational methods for interaction analysis using movement data, there remain challenges regarding reproducibility and replicability of the existing approaches. The current movement interaction analysis tools are often less accessible or tested for broader use in ecological research. RESULTS: To address these challenges, this paper presents ORTEGA, an Object-oRiented TimE-Geographic Analytical tool, as an open-source Python package for analyzing potential interactions between pairs of moving entities based on the observation of their movement. ORTEGA is developed based on one of the newly emerged time-geographic approaches for quantifying space-time interaction patterns among animals. A case study is presented to demonstrate and evaluate the functionalities of ORTEGA in tracing dynamic interaction patterns in animal movement data. Besides making the analytical code and data freely available to the community, the developed package also offers an extension of the existing theoretical development of ORTEGA for incorporating a context-aware ability to inform interaction analysis. CONCLUSIONS: ORTEGA contributes two significant capabilities: (1) the functions to identify potential interactions (e.g., encounters, concurrent interactions, delayed interactions) from movement data of two or more entities using a time-geographic-based approach; and (2) the capacity to compute attributes of potential interaction events including start time, end time, interaction duration, and difference in movement parameters such as speed and moving direction, and also contextualize the identified potential interaction events.

A novel heterozygous frameshift mutation in the KRT6A gene responsible for an uncommon phenotype of pachyonychia congenita: One case report and review of literature.

Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely KRT6A, KRT6B, KRT6C, KRT16 or KRT17. Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the KRT6A gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of KRT6A was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the KRT6A gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the KRT6A gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.

A Pilot Study to Explore the Effect of Long Acting Injectable Antipsychotics on Aggression.

Objectives: To explore the effect of switching from an oral antipsychotic to a long-acting injectable (LAI) antipsychotic on aggression, in terms of the changes of verbal and physical aggression, interventions required, self-injurious behavior, use of seclusion or restraint, antipsychotic medication refusal, and use of antipsychotics as needed (PRN). Methods: This was a retrospective chart review at a long-term state forensic psychiatric facility. Patients treated with an oral antipsychotic for at least 6 months and then switched to a LAI antipsychotic for an additional 6 months during an 80-month period were included. Results: Out of 70 patients evaluated, 18 were the study subjects. The median age of the cohort was 38 years with a majority being male. Of the seven patients who had an incident of aggression, two had an increase in aggressive incidents following the switch, three had a decrease, and two had no change. Thirty-six interventions occurred while patients were on an oral antipsychotic, which decreased by 30.6% to 25 interventions after the switch. Three patients had an incident of self-injurious behavior, and 6 patients required restraints/seclusions. Of the eight patients who had retrievable medication refusal and antipsychotic PRN use information, five had a decrease in antipsychotic medication refusals and five had an increase in PRN antipsychotic use after the switch. Conclusion: The switch from an oral antipsychotic to a LAI antipsychotic did not appear to significantly increase or decrease incidents of aggression or self-injurious behavior, but seemed to decrease the number of restraints/seclusions required.

Evaluating the comprehensive diagnosis efficiency of lung cancer, including measurement of SHOX2 and RASSF1A gene methylation.

Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P < 0.01), as opposed to those with low expression of Ki67, but RASSF1A methylation did not show this phenomenon (P = 0.35). Furthermore, CEA, SCCA, and CYFRA21-1 showed positive detection rates of 48.8%, 26.2%, and 55.8%, respectively. Finally, we present a comprehensive lung cancer diagnostic work-up, including LumgMe® methylation. The combined analysis of SHOX2 and RASSF1A methylation serves as a powerful complement and extension to conventional methods, enhancing the accuracy of a lung cancer diagnosis with satisfactory sensitivity and specificity.

LD-UNet: A long-distance perceptual model for segmentation of blurred boundaries in medical images.

The blurriness of boundaries in medical image target regions hinders further improvement in automatic segmentation accuracy and is a challenging problem. To address this issue, we propose a model called long-distance perceptual UNet (LD-UNet), which has a powerful long-|distance perception ability and can effectively perceive the semantic context of an entire image. Specifically, LD-UNet utilizes global and local long-distance induction modules, which endow the model with contextual semantic induction capabilities for long-distance feature dependencies. The modules perform long-distance semantic perception at the high and low stages of LD-UNet, respectively, effectively improving the accuracy of local blurred information assessment. We also propose a top-down deep supervision method to enhance the ability of the model to fit data. Then, extensive experiments on four types of tumor data with blurred boundaries are conducted. The dataset includes nasopharyngeal carcinoma, esophageal carcinoma, pancreatic carcinoma, and colorectal carcinoma. The dice similarity coefficient scores obtained by LD-UNet on the four datasets are 73.35%, 85.93%, 70.04%, and 82.71%. Experimental results demonstrate that LD-UNet is more effective in improving the segmentation accuracy of blurred boundary regions than other methods with long-distance perception, such as transformers. Among all models, LD-UNet achieves the best performance. By visualizing the feature dependency field of the models, we further explore the advantages of LD-UNet in segmenting blurred boundaries.

Deciphering the heterogeneity of neutrophil cells within circulation and the lung cancer microenvironment pre- and post-operation.

Neutrophils play a crucial role in the immune system within tumor microenvironment. At present, numerous studies have explored the changes of neutrophils' automatic killing effect and cellular communication with other immune cells under pathological conditions through single-cell sequencing. However, there remains a lack of definite conclusion about the identification criteria of neutrophil subgroups. Here, we collected tumor and para-carcinoma tissues, pre- and postoperative blood from patients with non-small cell lung cancer (NSCLC), and performed single-cell RNA (scRNA) sequencing to evaluate the distribution of neutrophil subgroups. We have developed a computational method of over expression rate (OER) to evaluate the specificity of neutrophil subgroups, in order to target gene panels with potential clinical application value. In addition, OER was used to evaluate specificity of neutrophil subsets in healthy people and patients with various diseases to further validate the feasibility of this evaluation system. As a result, we found the specificity of Neu_ c1_ IL1B and Neu_ c2_ cxcr4 (low) in postoperative blood has increased, while that of IL-7R + neutrophils has decreased, indicating that these groups of cells possibly differentiated or migrated to other subgroups in the state of lung cancer. In addition, seven gene panels (Neu_c3_CST7, RSAD2_Neu, S100A2/Pabpc1_Neu, ISG15/Ifit3_Neu, CD74_Neu, PTGS2/Actg1_Neu, SPP1_Neu) were high specific in all the four NSCLC-associated samples, meaning that changes in the percentage of these cell populations would have a high degree of confidence in assessing changes of disease status. In conclusion, combined consideration of the distribution characteristics of neutrophil subgroups could help evaluate the diagnosis and prognosis of NSCLC.