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Objectives: Tertiary lymphoid structures (TLSs) are lymphocyte aggregates that play an anti‐tumor role in most solid tumors. However, the functions of TLS in gastric neuroendocrine neoplasms (GNENs) remain unknown. This study aimed to determine the characteristics and prognostic values of TLS in resected GNEN patients. Methods: Haematoxylin–eosin, immunohistochemistry (IHC) and multiple fluorescent IHC staining were used to assess TLS to investigate the correlation between TLSs and clinicopathological characteristics and its prognostic value. Results: Tertiary lymphoid structures were identified in 84.3% of patients with GNEN. They were located in the stromal area or outside the tumor tissue and mainly composed of B and T cells. A high density of TLSs promoted an anti‐tumor immune response in GNEN. CD15+ TANs and FOXP3+ Tregs in TLSs inhibited the formation of TLSs. High TLS density was significantly associated with prolonged recurrence‐free survival (RFS) and overall survival (OS) of GNENs. Univariate and multivariate Cox regression analyses revealed that TLS density, tumor size, tumor–node–metastasis (TNM) stage and World Health Organisation (WHO) classification were independent prognostic factors for OS, whereas TLS density, tumor size and TNM stage were independent prognostic factors for RFS. Finally, OS and RFS nomograms were developed and validated, which were superior to the WHO classification and the TNM stage. Conclusion: Tertiary lymphoid structures were mainly located in the stromal area or outside the tumor area, and high TLS density was significantly associated with the good prognosis of patients with GNEN. Incorporating TLS density into a nomogram may improve survival prediction in patients with resected GNEN. [ABSTRACT FROM AUTHOR]

Immunotherapy, especially with immune checkpoint inhibitors (ICIs), has shown advantages in cancer treatment and is a new hope for patients who have failed multiline therapy. However, in colorectal cancer (CRC), the benefit is limited to a small subset of patients with microsatellite instability‐high (MSI‐H) or mismatch repair‐deficient (dMMR) metastatic CRC (mCRC). In addition, 45% to 60% of dMMR/MSI‐H mCRC patients showed primary or acquired resistance to ICIs. This means that these patients may have potential unknown pathways mediating immune escape. Almost all mismatch repair‐proficient (pMMR) or microsatellite‐stable (MSS) mCRC patients do not benefit from ICIs. In this review, we discuss the mechanisms of action of ICIs and their current status in CRC. We then discuss the mechanisms of primary and acquired resistance to ICIs in CRC. Finally, we discuss promising therapeutic strategies to overcome resistance to ICIs in the clinic. [ABSTRACT FROM AUTHOR]

The precise environmental parameters derived from laser radar scan data can significantly accelerate the process of real-time localization and map-matching technique. One of the research directions is autonomous navigation algorithm based on LiDAR slam. LiDAR has the advantage of having a wide range of accuracy and distance. However, due to the limited amount of LiDAR data available and the influence of sensor noise, it is easy to run into issues such as low accuracy of robot map construction or large positioning errors. At the moment, most of feature extraction algorithms employ an iterative calculation method with high computational complexity and a large amount of computation. Furthermore, due to the dependence of the fixed separation threshold, the algorithms for extracting the linear features of laser radar data are typically undersegment and oversegment. As a result, this paper proposes a radar linear feature fitting algorithm that combines adaptive clustering and corner detection operators. First, bilateral filtering is used to reduce noise and remove invalid data points. Second, the LiDAR data points are classified using adaptive threshold clustering of distance and density. The corner detection operator is applied to the classified data points to determine all possible corners then. Finally, the least square method is used to linearly fit each class and the identified corners within each class. The simulation and experimental results demonstrate that this method avoids the influence of noise points and a fixed segmentation threshold on corner point extraction effectively. The standard variance of length is 9.41 × 10 − 5 m 2 for corner feature extraction and localization in the dataset Cartographer ROS 2D Laser SLAM at Deutsches Museum. When compared to PDBS (point distance based methods) and IEPF (iterative end point fit), only about half the time is used, the accuracy of partition processing is improved by 11.6%, and the accuracy of corner detection is improved by 20.1%. The proposed algorithm can extract the corner features of data frames and linear positioning through experimental verification accurately. The features of the laser scan data that fit are more realistic. It has higher calculation efficiency and position accuracy. It ensures real-time mobile robot map construction and is appropriate for autonomous robot map algorithms developed in embedded systems. [ABSTRACT FROM AUTHOR]

For global navigation satellite system (GNSS), ionospheric disturbances caused by the geomagnetic storm can reduce the accuracy and reliability of precision point positioning (PPP). At present, common stochastic models in GNSS PPP, such as the elevation angle stochastic (EAS) model or carrier‐to‐noise power‐density ratio (C/N0 $C/{N}_{\mathit{0}}$) based SIGMA‐ε $\varepsilon $ model, do not properly consider storm effects on GNSS measurements. To mitigate severe storm effects on GNSS PPP, this study further implements the rate of total electron content index (ROTI) parameter into the EAS model referred to as the EAS‐ROTI model. This model contains two operations. The first one is to adjust variance of GNSS measurements using ROTI observations on EAS model. The second one is to determine the ratio of the priori variance factor between pseudorange and carrier phase measurements during severe storm conditions. The performance of EAS‐ROTI model is verified by using a large number of international GNSS service stations datasets on 17 March and 23 June in 2015. Experimental results indicate that on a global scale, the EAS‐ROTI model improves the PPP accuracy in 3D direction by approximately 12.9%–14.7% compared with the EAS model, and by about 24.8%–45.9% compared with the SIGMA‐ε $\varepsilon $ model. Plain Language Summary: Geomagnetic storm is characterized by strong geomagnetic disturbances caused by solar energy eruption. During the geomagnetically quiet days, the global navigation satellite system (GNSS) precise point positioning (PPP) using the international GNSS service (IGS) precision products and dual‐frequency observations can achieve decimeter or even centimeter level positioning accuracy. However, during the severe geomagnetic storm, the ionospheric disturbances can decrease the quality of GNSS measurements or even cause the signals loss of lock. Though it is difficult to ensure the accuracy and availability of PPP by using traditional GNSS data processing models and methods, in this study, we focus on improving the stochastic model to mitigate the storm effects on GNSS PPP. An improved stochastic model based on rate of total electron content index is established in this study. The PPP experiment is carried out by using abundant GNSS datasets from global IGS stations. Results indicate that the improved stochastic model can effectively improve the positioning accuracy under severe geomagnetic storm conditions. Key Points: Current stochastic models of global navigation satellite system (GNSS) precise point positioning (PPP) do not properly consider the storm effectsRate of total electron content index (ROTI) based stochastic model is established to mitigate severe storm effects on GNSS PPPPositioning accuracy of GNSS PPP based on ROTI‐based stochastic model is generally better than that of PPP with common stochastic models [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum is a critical microbe that contributes to colorectal cancer progression and chemoresistance. However, whether and how F. nucleatum regulates colorectal cancer stem‐like cells (CCSCs) remains unknown. Here, the authors show that F. nucleatum promotes CCSC self‐renewal, and non‐CCSCs to acquire CCSC features by manipulating cellular lipid accumulation. F. nucleatum infection decreases lipid accumulation in CCSCs by enhancing fatty acid oxidation, thus promoting CCSC self‐renewal. In contrast, F. nucleatum increases lipid accumulation in non‐CCSCs by promoting fatty acid formation. Lipids are deposited as lipid droplets, which recruits Numb, a key cell fate regulator, through the AP2A/ACSL3 complex, and MDM2, an E3 ubiquitin ligase, though VCP and UBXD8. On lipid droplets, Numb is degraded by MDM2, activating Notch signaling, thus promoting gain of stem‐like cell features. Their findings demonstrate that F. nucleatum directly manipulates colorectal cancer cell fate and reveal the mechanism of lipid droplet‐mediated Numb degradation for activating Notch signaling. [ABSTRACT FROM AUTHOR]

Geomagnetic storm can affect the performance of Global Navigation Satellite System (GNSS) precise positioning services. To mitigate the adverse effects of strong geomagnetic storms, we propose to establish the geometry‐free (GF) cycle slip threshold model based on ionospheric disturbance index rate of total electron content index to reduce the false detection rate of cycle slip in GNSS precise point positioning (PPP) during strong storm periods, thus improving the accuracy and reliability of GNSS PPP. The performance of our proposed model is validated by using 171 International GNSS Service (IGS) tracking stations data on 8 September 2017. The analysis indicates that compared with conventional PPP scheme, the proposed model can improve the positioning accuracy by approximately 14.0% (36.8%) and 23.1% (51.5%) in the horizonal and vertical components for global (high latitudes) stations. Furthermore, the availability of our proposed model is also validated by PPP experiments using 379 IGS tracking stations data during another strong storm occurred on 26 August 2018. Plain Language Summary: Global Navigation Satellite System (GNSS) precise point positioning (PPP) can achieve decimeter or even millimeter levels of positioning accuracy in general. However, this accuracy will be degraded significantly under the strong geomagnetic storm, which is a major disturbance of Earth's magnetosphere that occurs when there is a very efficient exchange of energy from the solar wind into the space environment surrounding Earth. Strong geomagnetic storm associated with ionospheric disturbances can decrease the quality of GNSS measurements or even result in GNSS signals loss of lock known as cycle slip, thus affecting the availability and reliability of the common data processing methods of GNSS PPP. In this study, we investigate the limitations of common threshold in cycle slip detection of GNSS data processing. It is found that the cycle slip detection observation shows close relationship to ionospheric disturbance index ROTI (rate of total electron content index), so we propose to establish the cycle slip threshold model based on ionospheric disturbance index ROTI. GNSS PPP experiments based on abundant International GNSS Service stations data indicate that the proposed model can effectively improve the positioning accuracy especially those stations located at high latitudes. Key Points: Strong geomagnetic storm can significantly degrade the performance of Global Navigation Satellite System (GNSS) precise point positioning (PPP)Geometry‐free cycle slip detection observation shows close relationship to the ionospheric disturbance index rate of total electron content indexPositioning accuracy of GNSS PPP based on cycle slip threshold model is generally better than that of conventional PPP [ABSTRACT FROM AUTHOR]

Obesity and its related complications pose an increasing threat to human health; however, targetable obesity‐related membrane receptors are not yet elucidated. Here, the membrane receptor CD146 is demonstrated to play an essential role in obesity. In particular, CD146 acts as a new adipose receptor for angiopoietin‐like protein 2 (ANGPTL2), which is thought to act on endothelial cells to activate adipose inflammation. ANGPTL2 binds to CD146 to activate cAMP response element‐binding protein (CREB), which then upregulates CD146 during adipogenesis and adipose inflammation. CD146 is present in preadipocytes and mature adipocytes, where it is mediated by its ligands ANGPTL2 and galectin‐1. In preadipocytes, CD146 ablation suppresses adipogenesis, whereas the loss of CD146 in mature adipocytes suppresses lipid accumulation and enhances energy expenditure. Moreover, anti‐CD146 antibodies inhibit obesity by disrupting the interactions between CD146 and its ligands. Together, these findings demonstrate that ANGPTL2 directly affects adipocytes via CD146 to promote obesity, suggesting that CD146 can be a potential target for treating obesity. [ABSTRACT FROM AUTHOR]

Morus australis distributed widely in China has high value in food and agriculture. Twelve phenolic compounds were isolated and identified as major constituents of M. australis root from Shaanxi province, China, while the protective effect of M. australis root on liver injury has never been determined in detail. In this study, the hepatoprotective ability of M. australis root was investigated in vivo and in vitro. The ethanol‐water extract prepared from M. australis root showed protection on alcohol‐induced liver damage in mice by decreasing the levels of serum alanine aminotransferase, aspartate transaminase, triacylglycerol and malondialdehyde, and by increasing glutathione contents. Furthermore, among 12 major constituents of M. australis root, 10 flavonoids (especially 1) showed protection against carbon tetrachloride (CCl4)‐intoxicated HepG2 cell lines by decreased lactic dehydrogenase levels. In addition a validated HPLC‐DAD method was established for the quantitative analysis of 10 flavonoids in the bioactive extract. Practical applications: Our results showed that M. australis root extract significantly alleviated the liver damage in mice. Ten flavonoids from the root of this plant exhibited protection on CCl4‐intoxicated HepG2 cell lines. This study suggests that Morus australis root has hepatoprotective potential as a promising supplement for the prevention and treatment of liver diseases. [ABSTRACT FROM AUTHOR]

Monocytes and macrophages are critical effectors and regulators of innate immune response. They not only play crucial and distinctive roles in homeostasis, but also contribute to some pathologic processes. The heterogeneity of the macrophage lineage has been widely recognized and, in part, is a result of the specialization of resident macrophages in particular tissue microenvironments. Monocytes are usually known to originate in the bone marrow from a common myeloid progenitor that is shared with neutrophils, and they are then released into the peripheral blood. However, the origin of tissue‐resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. During embryonic organogenesis, macrophages derived from yolk sac and fetal liver precursors are seeded throughout tissues, persisting in the adulthood as resident, self‐maintaining populations. After birth, bone marrow‐derived monocytes can replenish tissue resident macrophages following injury, infection and inflammation. In this review, we will mainly summarize our current understanding on the origin, ontogeny and fates of tissue macrophages and will briefly discuss the molecular regulation of resident macrophage homeostasis in physiological situation. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Airway angiogenesis occurs in asthma, and airway smooth muscle (ASM) cells have been reported to be capable of promoting airway angiogenesis. What is the potential mechanism by which ASM cells harvested from patients with asthma are capable of promoting airway angiogenesis?, What is the main finding and its importance? Endogenous STAT3 mediated the pro-angiogenic ability of ASM cells by directly activating VEGF signalling. These findings contribute to the understanding of airway angiogenesis in pathology and could represent a possible therapeutic target for asthma., Airway angiogenesis indicates the specific vascular structure remodelling that occurs in asthma. Airway smooth muscle (ASM) cells have been reported to be capable of promoting airway angiogenesis; however, the potential mechanism is not yet fully defined. Herein, we investigated the role of signal transducer and activator of transcription 3 (STAT3) in the progress of airway angiogenesis. Western blot analysis showed that STAT3 activation was aberrantly upregulated in ASM tissues of patients with asthma and ASM cells that were exposed to cytokines to imitate the airway conditions in patients with asthma. Compared with the control group, both the inhibition of STAT3 activation and the silencing of endogenous STAT3 in ASM cells significantly reduced the proliferation, migration and tube-forming ability of human lung microvascular endothelial cells induced by the conditioned medium (CM) of ASM cells. The increased proliferation and migration of human aortic vascular smooth muscle cells were also repressed by inhibition of STAT3 in ASM cells. Besides, the increased activity of VEGF signalling was observed in ASM cells and the CM by RT-PCR and Western blotting assay, whereas this increased activity was reduced by STAT3 silencing. Further studies indicated that STAT3 regulated VEGF activation by directly interacting with the binding site on the 5′ region of the VEGF gene. The increase in STAT3-induced pro-angiogenic activity of ASM cells was significantly decreased by administration of VEGF neutralizing antibody. In conclusion, we provided evidence that endogenous STAT3 mediates the pro-angiogenic ability of ASM cells by directly activating VEGF signalling, which could represent a possible therapeutic target for asthma. [ABSTRACT FROM AUTHOR]