Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. METHODS: Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. RESULTS: From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. CONCLUSIONS: Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

99.92%-Fidelity cnot Gates in Solids by Noise Filtering.

Inevitable interactions with the reservoir largely degrade the performance of entangling gates, which hinders practical quantum computation from coming into existence. Here, we experimentally demonstrate a 99.920(7)%-fidelity controlled-not gate by suppressing the complicated noise in a solid-state spin system at room temperature. We found that the fidelity limited at 99% in previous works results from considering only static classical noise, and, thus, in this work, a complete noise model is constructed by also considering the time dependence and the quantum nature of the spin bath. All noises in the model are dynamically corrected by an exquisitely designed shaped pulse, giving the resulting error below 10^{-4}. The residual gate error is mainly originated from the longitudinal relaxation and the waveform distortion that can both be further reduced technically. Our noise-resistant method is universal and will benefit other solid-state spin systems.

UPLC/Q-TOF-MS-based Metabolomics Study of the Antiosteoporosis Effects of Vaccarin in Ovariectomized Mice.

Osteoporosis is a systemic and metabolic bone disease that usually occurs in postmenopausal women, which mainly manifests as bone loss and increased bone fragility that both facilitate fracture. However, few drugs for osteoporosis have shown good efficacy and limited side effects. Vaccarin has demonstrated its antiosteoporosis effects by inhibiting the formation and osteolytic activities of osteoclasts in our previous investigation. In this study, multivariate statistical analysis and ultrahigh-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry were used to analyze the serum metabolites of ovariectomized mice treated with or without vaccarin. As a result, 9 serum metabolites were identified as biomarkers. The metabolic levels of 3 crucial biomarkers, namely, lysophosphatidylcholine [22 : 6, (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)], 1-linoleoylglycerophosphocholine and 1-palmitoyl-Sn-glycero-3-phosphocholine, that were correlated with glycerophospholipid metabolism increased and then decreased significantly after vaccarin treatment. Molecular docking analysis and osteoclasts differentiation experiment further revealed that vaccarin may bind with phospholipase A2 and downregulated its activity to reduce the osteoclastogenesis. Therefore, the occurrence of osteoporosis is closely related with glycerophospholipid metabolism disorders, and vaccarin exerts antiosteoporosis effects by reducing the levels of glycerophospholipid metabolites.

A Novel Dual-Permanent-Magnet Mechanical Antenna for Pipeline Robot Localization and Communication.

The demand for pipeline inspection has promoted the development of pipeline robots and associated localization and communication technologies. Among these technologies, ultra-low-frequency (30-300 Hz) electromagnetic waves have a significant advantage because of their strong penetration, which can penetrate metal pipe walls. Traditional low-frequency transmitting systems are limited by the size and power consumption of the antennas. In this work, a new type of mechanical antenna based on dual permanent magnets was designed to solve the above problems. An innovative amplitude modulation scheme that involves changing the magnetization angle of dual permanent magnets is proposed. The ultra-low-frequency electromagnetic wave emitted by the mechanical antenna inside the pipeline can be easily received by the antenna outside to localize and communicate with the robots inside. The experimental results showed that when two N38M-type Nd-Fe-B permanent magnets with a volume of 3.93 cm3 each were used, the magnetic flux density reached 2.35 nT at 10 m in the air and the amplitude modulation performance was satisfactory. Additionally, the electromagnetic wave was effectively received at 3 m from the 20# steel pipeline, which preliminarily verified the feasibility of using the dual-permanent-magnet mechanical antenna to achieve localization of and communication with pipeline robots.

Construction of an SNP fingerprinting database and population genetic analysis of 329 cauliflower cultivars.

Cauliflower is one of the most important vegetable crops grown worldwide. However, the lack of genetic diversity information and efficient molecular markers hinders efforts to improve cauliflower. This study aims to construct DNA fingerprints for 329 cauliflower cultivars based on SNP markers and the KASP system. After rigorous filtering, a total of 1662 candidate SNPs were obtained from nearly 17.9 million SNP loci. The mean values of PIC, MAF, heterozygosity and gene diversity of these SNPs were 0.389, 0.419, 0.075, and 0.506, respectively. We developed a program for in silico simulations on 153 core germplasm samples to generate ideal SNP marker sets from the candidates. Finally, 41 highly polymorphic KASP markers were selected and applied to identify 329 cauliflower cultivars, mainly collected from the public market. Furthermore, based on the KASP genotyping data, we performed phylogenetic analysis and population structure analysis of the 329 cultivars. As a result, these cultivars could be classified into three major clusters, and the classification patterns were significantly related to their curd solidity and geographical origin. Finally, fingerprints of the 329 cultivars and 2D barcodes with the genetic information of each sample were generated. The fingerprinting database developed in this study provides a practical tool for identifying the authenticity and purity of cauliflower seeds and valuable genetic information about the current cauliflower cultivars.

The abdominal-transhiatal surgical approach versus the thoracoabdominal surgical approach in Siewert type II adenocarcinoma of the esophagogastric junction: protocol for a multicenter prospective, open, parallel, and randomized controlled trial.

BACKGROUND: To date, Siewert type II adenocarcinoma of the esophagogastric junction (ST-II AEG) can be removed radically utilizing either the abdominal-transhiatal (TH) or the right thoracoabdominal (RTA) approaches. Because of a paucity of high-quality direct evidence, the appropriate surgical approach for ST-II AEG remains debatable. In the present, only several retrospective studies are available, representing ambiguous results. Thus, prospective randomized clinical trials are demanded to compare the survival, oncological outcomes, safety and efficiency and life quality between the TH and RTA approach in patients with resectable AEG of Siewert type II. METHODS: A prospective, multicenter, open, randomized, and parallel controlled study named S2AEG will be conducted. Three hundred and twelve patients who match the inclusion criteria but not the exclusion criteria will be participating in the trial and randomly divided into the TH (156) and RTA (156) cohorts. The primary efficacy endpoint is the 3-year disease-free survival (DFS) following the operation. The rate of R0-resection, the number and site of lymph nodes infiltrated and dissected, postoperative complications, hospital days and life quality are the second endpoints. DISCUSSION: This study is the first prospectively randomized controlled trial aiming to compare the surgical outcomes between TH and RTA approaches in patients with resectable ST-II AEG. It is hypothesized that patients in the TH cohort would harvest equivalent oncological results and survival while maintaining acceptable life quality when compared to patients in the RTA cohort. Our findings will provide high-level clinical evidence for clinical decision-making on the appropriate surgical approach for patients with ST-II AEG. Embarked in November 2019, this research will be completed 3 years after the final participant's enrolment date. TRIAL REGISTRATION: Clinical Trial.gov ID: NCT04910789 May 29, 2021. Name: S2AEG.

A new model of preoperative systemic inflammatory markers predicting overall survival of osteosarcoma: a multicenter retrospective study.

BACKGROUND: The purpose of this study was to investigate the significance of preoperative C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting overall survival (OS) of osteosarcoma, to establish a nomogram of an individualized prognostic prediction model for osteosarcoma. METHODS: Two hundred thirty-five patients with osteosarcoma from multiple centers were included in this study. Receiver operating characteristic (ROC) and Youden index were used to determine the optimal cutoff values ​​for CAR, NLR, and PLR. Univariate analysis using COX proportional hazards model to identify factors associated with OS in osteosarcoma, and multivariate analysis of these factors to identify independent prognostic factors. R software (4.1.3-win) rms package was used to build a nomogram, and the concordance index (C-index) and calibration curve were used to assess model accuracy and discriminability. RESULTS: Univariate analysis revealed that the OS of osteosarcoma is significantly correlated (P < 0.05) with CAR, NLR, PLR, Enneking stage, tumor size, age, neoadjuvant chemotherapy (NACT), and high alkaline phosphatase. Multivariate analysis confirmed that CAR, NLR, Enneking stage, NACT and tumor size are independent prognostic factors for OS of osteosarcoma. The calibration curve shows that the nomogram constructed from these factors has acceptable consistency and calibration capability. CONCLUSION: Preoperative CAR and NLR were independent predictors of osteosarcoma prognosis, and the combination of nomogram model can realize individualized prognosis prediction and guide medical practice.

Identity Test of Single NV

Atomiclike defects in solids are not considered to be identical owing to the imperfections of host lattice. Here, we found that even under ambient conditions, negatively charged nitrogen-vacancy (NV^{-}) centers in diamond could still manifest identical at Hz-precision level, corresponding to a 10^{-7}-level relative precision, while the lattice strain can destroy the identity by tens of Hz. All parameters involved in the NV^{-}-^{14}N Hamiltonian are determined by formulating six nuclear frequencies at 10-mHz-level precision and measuring them at Hz-level precision. The most precisely measured parameter, the ^{14}N quadrupole coupling P, is given by -494 575 4.9(8) Hz, whose precision is improved by nearly 4 orders of magnitude compared with previous measurements. We offer an approach for performing precision measurements in solids and deepening our understandings of NV centers as well as other solid-state defects. Besides, these high-precision results imply a potential application of a robust and integrated atomiclike clock based on ensemble NV centers.

Comparison of robotic- and laparoscopic-assisted gastrectomy in advanced gastric cancer: updated short- and long-term results.

BACKGROUND: Emerging evidence has demonstrated that either laparoscopic-assisted gastrectomy (LAG) or robotic-assisted gastrectomy (RAG) could be adopted as standard treatment for early gastric cancer. However, the long-term survival and recurrence rate after LAG or RAG for locally advanced gastric cancer (AGC) has seldom been reported. METHODS: We retrospectively analyzed the data from 339 patients who underwent LAG and 163 patients who underwent RAG from a prospectively established database in the Chinese People's Liberation Army General Hospital. We compared the short- and long-term oncological outcomes of the RAG group versus the LAG group in the entire cohort, and in a propensity score-matched cohort. RESULTS: Before propensity score matching (PSM), the two groups revealed comparable 3-year overall survival rates (OS, RAG vs. LAG: 76.1 vs. 81.7%, p = 0.118), and recurrence-free survival rates (RFS, RAG vs. LAG: 73.0 vs. 67.6%, p = 0.297). Similar results were obtained in the propensity score-matched cohort; the respective overall survival rates in the propensity score-matched RAG and LAG groups were 76.1 and 79.8% (p = 0.552), and the respective RFS rates were 73.0 and 68.7% (p = 0.386). After PSM, RAG was still associated with a significantly longer mean operating time (249.46 ± 63.26 vs. 232.17 ± 65.39 min, p = 0.008) and higher total costs (133.38 ± 41.62 vs. 95.34 ± 29.39 103 RMB, p < 0.001) than LAG; the two groups did not significantly differ in other surgical and oncological characteristics. CONCLUSION: Although there were some differences in the outcomes of RAG versus LAG in AGC patients, both RAG and LAG were similar in short-term recovery and long-term oncological outcomes.

Constraints on a Spin-Dependent Exotic Interaction between Electrons with Single Electron Spin Quantum Sensors.

A new laboratory bound on the axial-vector mediated interaction between electron spins at micrometer scale is established with single nitrogen-vacancy (NV) centers in diamond. A single crystal of p-terphenyl doped pentacene-d_{14} under laser pumping provides the source of polarized electron spins. Based on the measurement of polarization signal via nitrogen-vacancy centers, we set a constraint for the exotic electron-electron coupling g_{A}^{e}g_{A}^{e}, within the force range from 10 to 900 µm. The obtained upper bound of the coupling at 500 µm is |g_{A}^{e}g_{A}^{e}/4πℏc|≤1.8×10^{-19}, which is one order of magnitude more stringent than a previous experiment. Our result shows that the NV center can be a promising platform for searching for new particles predicted by theories beyond the standard model.

Experimental Adiabatic Quantum Factorization under Ambient Conditions Based on a Solid-State Single Spin System.

The adiabatic quantum computation is a universal and robust method of quantum computing. In this architecture, the problem can be solved by adiabatically evolving the quantum processor from the ground state of a simple initial Hamiltonian to that of a final one, which encodes the solution of the problem. Adiabatic quantum computation has been proved to be a compatible candidate for scalable quantum computation. In this Letter, we report on the experimental realization of an adiabatic quantum algorithm on a single solid spin system under ambient conditions. All elements of adiabatic quantum computation, including initial state preparation, adiabatic evolution (simulated by optimal control), and final state read-out, are realized experimentally. As an example, we found the ground state of the problem Hamiltonian S_{z}I_{z} on our adiabatic quantum processor, which can be mapped to the factorization of 35 into its prime factors 5 and 7.

A novel endoscopy image fusion system: combine white light imaging and compound band imaging.

PURPOSE: White light imaging (WLI) is a commonly seen examination mode in endoscopy. The particular light in compound band imaging (CBI) can highlight delicate structures, such as capillaries and tiny structures on the mucosal surface. These two modes complement each other, and doctors switch between them manually to complete the examination. This paper proposes an endoscopy image fusion system to combine WLI and CBI. METHODS: We add a real-time rotatable color wheel in the light source device of the AQ-200 endoscopy system to achieve rapid imaging of two modes at the same position of living tissue. The two images corresponding to the pixel level can avoid registration and lay the foundation for image fusion. We propose a multi-scale image fusion framework, which involves Laplacian pyramid (LP) and convolutional sparse representation (CSR) and strengthens the details in the fusion rule. RESULTS: Volunteer experiments and ex vivo pig stomach trials are conducted to verify the feasibility of our proposed system. We also conduct comparative experiments with other image fusion methods, evaluate the quality of the fused images, and verify the effectiveness of our fusion framework. The results show that our fused image has rich details, high color contrast, apparent structures, and clear lesion boundaries. CONCLUSION: An endoscopy image fusion system is proposed, which does not change the doctor's operation and makes the fusion of WLI and CBI optical staining technology a reality. We change the light source device of the endoscope, propose an image fusion framework, and verify the feasibility and effectiveness of our scheme. Our method fully integrates the advantages of WLI and CBI, which can help doctors make more accurate judgments than before. The endoscopy image fusion system is of great significance for improving the detection rate of early lesions and has broad application prospects.

Independent associations of education, intelligence, and cognition with gastrointestinal diseases and the mediating effects of risk factors: a Mendelian randomization study.

Background: Education, intelligence and cognition affect occupational performance and socioeconomic status and may influence virous diseases development. However, the impact of these factors on gastrointestinal diseases and their mediating risk factors remains unclear. Methods: We utilized genome-wide association studies from European ancestry populations to perform two-sample Mendelian randomization analyses, aiming to estimate genetic instruments associated with education, intelligence, or cognition in relation to 24 gastrointestinal diseases Subsequently, we evaluated 14 potential mediators of this association and calculated the corresponding mediated proportions through two-step Mendelian randomization analyses. Result: As the dominant factor in gastrointestinal diseases, education had a statistically significant association with 2 gastrointestinal diseases (acute pancreatitis, gastroesophageal reflux) and a suggestive association with 6 diseases (cirrhosis, alcoholic liver disease, cholecystitis, cholelithiasis, chronic gastritis and gastric ulcer). Of the 14 mediators, smoking and adiposity traits played a major role in mediating the effects. Conclusion: The study demonstrated the causal, independent impact of education on specific gastrointestinal diseases. Smoking and adiposity traits emerged as primary mediators, illuminating potential avenues for targeted interventions for prevention of them.

Comprehensive advancement in endoscopy: optical design, algorithm enhancement, and clinical validation for merged WLI and CBI imaging.

As endoscopic imaging technology advances, there is a growing clinical demand for enhanced imaging capabilities. Although conventional white light imaging (WLI) endoscopy offers realistic images, it often cannot reveal detailed characteristics of the mucosa. On the other hand, optical staining endoscopy, such as Compound Band Imaging (CBI), can discern subtle structures, serving to some extent as an optical biopsy. However, its image brightness is low, and the colors can be abrupt. These two techniques, commonly used in clinical settings, have complementary advantages. Nonetheless, they require different lighting conditions, which makes it challenging to combine their imaging strengths on living tissues. In this study, we introduce a novel endoscopic imaging technique that effectively combines the advantages of both WLI and CBI. Doctors don't need to manually switch between these two observation modes, as they can obtain the image information of both modes in one image. We calibrated an appropriate proportion for simultaneous illumination with the light required for WLI and CBI. We designed a new illumination spectrum tailored for gastrointestinal examination, achieving their fusion at the optical level. Using a new algorithm that focuses on enhancing specific hemoglobin tissue features, we restored narrow-band image characteristics lost due to the introduction of white light. Our hardware and software innovations not only boost the illumination brightness of the endoscope but also ensure the narrow-band feature details of the image. To evaluate the reliability and safety of the new endoscopic system, we conducted a series of tests in line with relevant international standards and validated the design parameters. For clinical trials, we collected a total of 256 sets of images, each set comprising images of the same lesion location captured using WLI, CBI, and our proposed method. We recruited four experienced clinicians to conduct subjective evaluations of the collected images. The results affirmed the significant advantages of our method. We believe that the novel endoscopic system we introduced has vast potential for clinical application in the future.

Genomic analyses reveal the stepwise domestication and genetic mechanism of curd biogenesis in cauliflower.

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.

Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer.

BACKGROUND: The current prognostic significance of perigastric tumor deposits (TDs) in gastric cancer (GC) remains unclear. AIM: To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC. METHODS: This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1, 2012 to December 31, 2017 at the Chinese PLA General Hospital. According to the presence of perigastric TDs or not, the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching. The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling. The Kaplan-Meier method was used to plot survival curves. Multivariate Cox regression modeling and the log-rank test were used to analyze the data. RESULTS: Perigastric TDs were found to be positive in 339 (5.09%) of the 6672 patients with GC, among whom 237 were men (69.91%) and 102 were women (30.09%) (2.32:1). The median age was 59 years (range, 27 to 78 years). Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients (P < 0.05). The 1-, 3-, and 5-year overall survival rates of GC patients with TDs were 68.3%, 19.6%, and 11.2%, respectively, and these were significantly poorer than those without TDs of the same stages. There was significant variation in survival according to TD locations among the GC patients (P < 0.05). A new TNM staging framework for GC was formulated according to TD location. When TDs appear in the gastric body, the original stages T1, T2, and T3 are classified as T4a with the new framework, and the original stages T4a and T4b both are classified as T4b. When TDs appear in the lesser curvature, the previous stages N0, N1, N2, and N3 now both are classified as N3. When TDs appear in the greater curvature or the distant tissue, the patient should be categorized as having M1. With the new GC staging scheme including TDs, the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs. CONCLUSION: TDs are a poor prognostic factor for patients with primary GC. The location of TDs is associated with the prognosis of patients with primary GC. Accordingly, we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.

Sub-nanotesla sensitivity at the nanoscale with a single spin.

High-sensitivity detection of the microscopic magnetic field is essential in many fields. Good sensitivity and high spatial resolution are mutually contradictory in measurement, which is quantified by the energy resolution limit. Here we report that a sensitivity of 0.5 nT/[Formula: see text] at the nanoscale is achieved experimentally by using nitrogen-vacancy defects in diamond with depths of tens of nanometers. The achieved sensitivity is substantially enhanced by integrating with multiple quantum techniques, including real-time-feedback initialization, dynamical decoupling with shaped pulses and repetitive readout via quantum logic. Our magnetic sensors will shed new light on searching new physics beyond the standard model, investigating microscopic magnetic phenomena in condensed matters, and detection of life activities at the sub-cellular scale.

Analysis of scRNA-seq and bulk RNA-seq demonstrates the effects of EVI2B or CD361 on CD8+ T cells in osteosarcoma.

Osteosarcoma (OS) is a common primary malignant tumor of the bone in children and adolescents. The five-year survival rate is estimated to be ~70% based on the currently available treatment modalities. It is well known that tumor-infiltrating immune cells (TIICs) that are the most important components in the tumor microenvironment can exert a killing effect on tumor cells. Therefore, in the present study, 85 RNA-sequencing OS samples were categorized into high- and low-immune score groups with ESTIAMATE. Based on the immune score groups, 474 differentially expressed genes (DEGs) were acquired using the LIMMA package of R language. Subsequently, 86 DEGs were taken through univariate COX regression analysis, of which 14 were screened out by least absolute shrinkage and selection operator regression analysis. Furthermore, multivariate COX regression analysis was performed to obtain 4 DEGs. Finally, ecotropic virus integration site 2B (EVI2B) or CD361 gene was screened out via Kaplan-Meier analysis. In addition, CIBERSORT algorithm was used to evaluate the proportion of 22 kinds of TIICs in OS. Correlation analysis revealed that the high expression level of EVI2B can elevate the infiltrated proportion of CD8+ T cells. Moreover, analysis of single cell RNA-sequencing transcriptome datasets and immunohistochemical staining uncovered that EVI2B was mainly expressed on CD8+ T cells and that EVI2B could promote the expression of granzyme A and K of CD8+ T cells to exhibit a potent killing effect on tumor cells. Therefore, EVI2B was identified as a protective immune-related gene and contributed to good prognosis in OS patients.

L-kynurenine induces NK cell loss in gastric cancer microenvironment via promoting ferroptosis.

BACKGROUND: Natural killer (NK) cells play a major role in body's fighting against various types of cancers. Their infiltration in the tumor microenvironment (TME) of gastric cancer (GC) are significantly decreased, which has been reported as a robust prognostic marker. However, the causes leading to NK cells loss in GC TME remains poorly understood. METHODS: We constructed a non-contact co-culturing system and humanized xenograft tumor mice model to detect the influence of GC microenvironment on NK-92 or primary human NK cells viability by flow cytometry. Then through using the specific inhibitors for different types of cell death and examining the surrogate markers, we confirmed ferroptosis in NK cells. Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells. RESULTS: We found L-KYN, mainly generated through indoleamine 2, 3-dioxygenase (IDO) from GC cells, impaired NK cells viability in TME. Further analysis revealed L-KYN induced ferroptosis in NK cells via an AHR-independent way. Moreover, we found NK cells with higher GPX4 expression showed resistance to L-KYN induced ferroptosis. Based on this, we generated GPX4 over-expressed NK-92 cells, and found these cells showed therapeutic potential towards GC. CONCLUSIONS: Our study revealed a novel mechanism to explain the decline of NK cell number in GC TME. Notably, we also developed a potential immunotherapy strategy, which might be beneficial in clinical treatment in the future.

Circ_0001060 Upregulates and Encourages Progression in Osteosarcoma.

Circular RNA (circRNA) is involved in the occurrence and development of various cancers. To this day, the expression and mechanism of circRNA in osteosarcoma (OS) remain unclear. We previously found that circ_0001060 was highly expressed in OS tumor tissues. In this work, we identified that high level expression of circ_0001060 was significantly associated with late clinical stage, larger tumor volume, higher frequency of metastasis, and poor prognosis in OS patients. Furthermore, we confirmed that silencing circ_0001060 inhibited the proliferation and migration of OS cell. Using bioinformatics analysis, we built three circRNA-miRNA-mRNA regulatory modules (circ_0001060-miR-203a-5p-TRIM21, circ_0001060-miR-208b-5p-MAP3K5, and circ_0001060-miR-203a-5p-PRKX), suggesting that these signaling axes may be involved in the inhibitory effect of circ_0001060 on OS. To sum up, circ_0001060 is a novel tumor biomarker for OS as well as a potential therapeutic target.