Explore the vast range of titles available.

The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF -like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications. The characterisation of the papillary thyroid carcinoma (PTC) tumour microenvironment remains crucial. Here, the authors perform single-cell RNA sequencing in 11 patients and identify potential opportunities for the use of immunotherapy and its combination with anti-angiogenic therapy in PTC.

SO2F2 and SOF2 are the main components from the decomposition of insulation gas SF6. Photoacoustic spectroscopy (PAS) has been acknowledged as an accurate sensing technique. Polar material adsorption for SO2F2 and SOF2 in the photoacoustic gas cell of PAS may affect detection efficiency. In this paper, the optical gas-cell dynamic adsorptions of four different materials and the detection effects on SO2F2 and SOF2 are theoretically analyzed and experimentally demonstrated. The materials, including grade 304 stainless steel (SUS304), grade 6061 aluminum alloy (Al6061), polyvinylidene difluoride (PVDC), and polytetrafluoroethylene (PTFE), were applied inside the optical gas cell. The results show that, compared with metallic SUS304 and Al6061, plastic PVDC and PTFE would reduce the gas adsorption of SO2F2 and SOF2 by 10 to 20% and shorten the response time during gas exchange. The complete gas defusing period in the experiment was about 30 s. The maximum variations of the 90% rising time between the different adsorption materials were approximately 3 s for SO2F2 and 6 s for SOF2, while the generated photoacoustic magnitudes were identical. This paper explored the material selection for PAS-based gas sensing in practical applications.

Landslides involving solid–fluid interaction such as submarine landslides and landslide dams occur frequently around the world, which may bring severe damage to human lives and properties. Investigation of such landslides is thus of significance to hazard prevention and mitigation. To conduct the analysis, there are three key points to be addressed: (a) the landslide failure process, (b) the free surface flow, and (c) the solid–fluid interaction process. Discontinuous deformation analysis (DDA) method is suitable for analyzing discontinuous blocky systems and has outstanding advantages in simulating the landslide failure process. Meanwhile, smoothed particle hydrodynamics (SPH) method is well-suited for modeling the free surface flow. However, the consideration of solid–fluid interaction in these two methods is seldom, which somehow restricts their applications. With the aim to take advantages of these two methods, a coupled DDA–SPH method in two-dimensional case is proposed, in which the solid–fluid interaction is forced using a penalty approach. The SPH formulations are implemented into DDA code. Several numerical examples are presented to check the validity of the proposed method. A dam-break test is first investigated to show the success of implementing SPH into DDA code for modeling the fluid flow in later simulations of fluid–solid systems. Subsequently, the performance of the coupled DDA–SPH method is validated through a submarine rigid landslide, and the simulation results are in good agreement with the experimental data. Further, an extension study on the submarine deformable landslide is performed, in which the landslide mass consists of multiple blocks and a sensitivity analysis on the interface friction angle between blocks is conducted. Finally, a designed landslide dam is simulated to show the applicability and feasibility of the coupled DDA–SPH method.

Molecular ions are relatively cold in the E region ionosphere; however, they can upwell to the magnetosphere during geomagnetically active times. Resonance between electrostatic ion cyclotron (EIC) waves is a potential pathway to energize molecular ions. In this work, the E region ionospheric plasma was modeled in the laboratory, and EIC waves were excited by a nonuniform field‐aligned current. The EIC wave was excited even when the ion neutral collision frequency is much higher than the ion cyclotron frequency, and the fundamental frequency was observed to be below the ion cyclotron frequency. In addition, the wave dispersion of the collisional EIC wave was calculated, which shows a consistent trend with experimental results as the collisions increasing. Therefore, this work suggests that EIC waves can be excited in the E region ionospheric‐like plasma, which can support the explanation of the energization of molecular ions in the E region ionosphere. Plain Language Summary Spacecraft observed the presence of molecular ions in the topside ionosphere (600–1,000 km) and the magnetosphere during geomagnetically active times, and the potential mechanisms responsible for the acceleration of these molecular ions are still not fully understood. The resonance between electrostatic ion cyclotron (EIC) waves and molecular ions is a potential pathway to energize the molecular ions. However, most previous works on EIC waves were studied in collisionless plasma similar to the magnetospheric plasma, which is different from the E region ionospheric plasma. A typical characteristic of E region ionospheric plasma is the partially ionized effect, which introduces new physical processes that do not occur in collisionless plasmas. In this work, strong collisions that occurred in the E region ionosphere were simulated in the laboratory, and the current‐driven electrostatic ion cyclotron waves were observed in the modeled ionosphere. It is found that electrostatic ion cyclotron waves can be generated in the E region ionospheric‐like plasma. This work provides solid experimental evidence that electrostatic ion cyclotron instability can exist in weakly ionized plasmas of the E region ionosphere, and can be applied to explain the transverse ion heating of bulk ions in the bottomside ionosphere. Key Points The E region ionospheric‐like collisional plasma was modeled in the laboratory EIC waves were excited by field aligned current in the ionospheric‐like plasma This work can be applied to explain the energization of molecular ions in the E region ionosphere

The roots and rhizomes of Panax ginseng C.A. Mey are commonly used herbal medicine in Asian countries. These components contain a large number of secondary metabolites known as ginsenosides, which serve as primary active ingredient. Environmental factors significantly influence the production of secondary metabolites, which are crucial for enhancing plant adaptability to ecological stress. P . ginseng is a shady plant that thrives in a constantly humid and temperate environment. However, it cannot withstand excessive moisture, making soil moisture a significant ecological stress affecting P . ginseng survival. In this study, we applied a water spray to maintain a water-saturated surface on 5-year-old fresh P . ginseng roots for a duration of 5 days, to establish a short-term water stress condition. The results revealed a notable increase in superoxide anion (O 2 ·- ), hydrogen peroxide (H 2 O 2 ), and NADPH oxidase (NOX) activity ( p < 0.01), as well as malondialdehyde (MDA) contents ( p < 0.01) in both the main root and fibrous root of P . ginseng . Additionally, superoxide dismutase (SOD), catalase (CAT), peroxides (POD), ascorbate peroxidase (APX) and glutathione reductase (GR) activities also elevated significantly under water stress ( p < 0.01). Ascorbic acid (AsA), glutathione (GSH) and oxidized glutathione (GSSG) contents also showed a marked increase ( p < 0.01). The main root treated with water showed the most positive impact on the 5 th day. Water stress boosted the activities of key enzymes including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), farnesyl pyrophosphate synthase (FPS), squalene synthase (SS), squalene epoxidase (SE), and dammarenediol-II synthase (DS) involved in the ginsenoside biosynthesis pathway ( p <0.01). This resulted in a significant an increase in the level of ginsenosides Rg 1 , Rb 1 , Rf, Rg 2 +Rh 1 , Rc, and Rb 3 , by 42.4%, 21.0%, 15.7%, 157.9%, 18.3%, and 10.6% respectively, and an increase of 40.1% in total saponins content. Similarly, the fibrous root changes in the treated sample showed the most positive impact on the 4 th day. Specifically, Rg 1 , Re, Rb 1 , Rf, Rg 2 +Rh 1 , Rc, Ro, and Rb 2 increased by 41.8%, 20.5%, 17.3%, 84.3%, 30.7%, 35.6%, 8.6%, and 7.6%, respectively, and an increase of 4.2% in total saponins content. Furthermore, 1,3-disphosphoglycerate (1,3-DPG) contents and phosphoenolpyruvate carboxylase (PEPC) activities, which are key intermediate of primary metabolism, were significantly elevated under water stress ( p < 0.01). This indicates that the primary source of the raw materials used in the biosynthesis of secondary metabolites is sugars. Pharmacodynamic analysis demonstrated that water stress could increase the contents of ginsenosides, improve the quality of ginseng, and enhance the efficacy of ginseng root to a certain extent.

Background Weedy rice competes for nutrients and living space with cultivated rice, which results in serious reductions in rice production. The rhizosphere bacterial community plays an important role in nutrient competition between species. It is therefore important to clarify the differences in the diversities of the inter rhizosphere bacterial community between cultivated rice and weedy rice. The differences in compositions and co-occurrence networks of the rhizosphere bacterial community of cultivated rice and weedy rice are largely unknown and thus the aim of our study. Results In our study, the different rhizosphere bacterial community structures in weedy rice (AW), cultivated rice (AY) and cultivated rice surrounded by weedy rice (WY) were determined based on 16S rRNA gene sequencing. The majority of the WY rhizosphere was enriched with unique types of microorganisms belonging to Burkholderia. The rhizosphere bacterial community showed differences in relative abundance among the three groups. Network analysis revealed a more complex co-occurrence network structure in the rhizosphere bacterial community of AW than in those of AY and WY due to a higher degree of Microbacteriaceae and Micrococcaceae in the network. Both network analysis and functional predictions reveal that weedy rice contamination dramatically impacts the iron respiration of the rhizosphere bacterial community of cultivated rice. Conclusions Our study shows that there are many differences in the rhizosphere bacterial community of weedy rice and cultivated rice. When cultivated rice was disturbed by weedy rice, the rhizosphere bacterial community and co-occurrence network also changed. The above differences tend to lead to a nutritional competitive advantage for weedy rice in paddy soils.

The roots of Panax ginseng C. A. Meyer (ginseng) are one of the traditional medicinal herbs in Asian countries and is known as the “king of all herbs”. The most important active components of ginseng are the secondary metabolite saponins, which are closely related to ecological stress. Unsuitable ecological stress can generate a large amount of reactive oxygen species (ROS), by which the secondary metabolism is regulated, and the quality of herbs can be significantly improved. The purpose of this study was to investigate the effect of sodium nitroprusside (SNP) treatment on the quality of fresh ginseng roots. In this study, 5-year-old fresh ginseng was exposed to 0.1, 0.5, and 2 mmol/L SNP, a nitric oxide (NO) donor for five consecutive days. SNP significantly increased the levels of O 2 ·− , H 2 O 2 , malondialdehyde (MDA), NADPH oxidase (NOX), superoxide dismutase (SOD), catalase (CAT), peroxides (POD), ascorbate peroxidase (APX), glutathione reductase (GR), ascorbate (AsA) and GSH/GSSG. The main root treated by 0.5 mmol/L SNP for three days was the best, with the activities of the key enzymes of the ginsenoside synthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), farnesyl pyrophosphate synthase (FPS), squalene synthase (SS), squalene epoxidase (SE), and dammarane diol-II synthase (DS) activities increased markedly; the ginsenosides Rg 1  + Re, Rb 1 , Rf, Rc, Rg 2  + Rh 1 and the total ginsenoside contents increased by 51.0%, 77.7%, 44.6%, 26.8%, 63.2% and 48.2%, respectively, but only a trace amount of the ginsenoside monomer Rb 2 decreased 23.4%. The fibrous roots treated by 0.1 mmol/L SNP for four days showed the best effect, HMGCR, FPS, SS, SE, and DS also increased significantly; ginsenosides Rg 1  + Re, Rb 1 , Ro, Rc, Rf, Rb 3 , Rb 2 , and total saponin contents increased 37.6%, 47.8%, 34.2%, 75.1%, 51.0%, 49.4%, 28.3%, and 20.4%, respectively. The 1,3-diphosphoglycerate (1,3-DPG) and phosphoenolpyruvate carboxylase (PEPC), related to primary metabolism, were also significantly elevated. The Morris water maze (MWM), histopathological analysis and oxidative stress indexes in brain tissues were used to evaluate the anti-aging effect, indicating that the SNP-treated ginseng further ameliorated D-gal-induced the impaired memory function and oxidative stress in mice, implying the efficacy of SNP-treated ginseng was better than untreated ginseng’s. SNP can build the physiological state of ginseng under ecological stress, stimulate the antioxidant protection mechanism, increase the secondary metabolites, and improve the quality of ginseng.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia among humans, with its incidence increasing significantly with age. Despite the high frequency of AF in clinical practice, its etiology and management remain elusive. To develop effective treatment strategies, it is imperative to comprehend the underlying mechanisms of AF; therefore, the establishment of animal models of AF is vital to explore its pathogenesis. While spontaneous AF is rare in most animal species, several large animal models, particularly those of pigs, dogs, and horses, have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic options. This review aims to provide a comprehensive discussion of various animal models of AF, with an emphasis on the unique features of each model and its utility in AF research and treatment. The data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

ObjectivesWe aimed to investigate the association between the albumin-corrected anion gap (ACAG) and the prognosis of cardiogenic shock (CS).DesignA multicentre retrospective cohort study.SettingData were collected from the Medical Information Mart for Intensive Care (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD) datasets.Participants808 and 700 individuals from the MIMIC-IV and eICU-CRD, respectively, who were diagnosed with CS.Primary and secondary outcomesThe primary endpoint was short-term all-cause mortality, including intensive care unit (ICU), in-hospital and 28-day mortality. The secondary endpoints were the 28-day free from the ICU duration and the length of ICU stay.ResultsCS patients were divided into two groups according to the admission ACAG value: the normal ACAG group (≤20 mmol/L) and the high ACAG group (> 20 mmol/L). CS patients with higher ACAG values exhibited increased short-term all-cause mortality rates, including ICU mortality (MIMIC-IV cohort: adjusted HR: 1.43, 95% CI=1.05–1.93, p=0.022; eICU-CRD cohort: adjusted HR: 1.38, 95% CI=1.02–1.86, p=0.036), in-hospital mortality (MIMIC-IV cohort: adjusted HR: 1.31, 95% CI=1.01–1.71, p=0.03; eICU-CRD cohort: adjusted HR: 1.47, 95% CI=1.12–1.94, p=0.006) and 28-day mortality (adjusted HR: 1.42, 95% CI: 1.11 to 1.83, p=0.007). A positive linear correlation was observed between the ACAG value and short-term mortality rates via restricted cubic splines. Compared with the AG, the ACAG presented a larger area under the curve for short-term mortality prediction. In addition, the duration of intensive care was longer, whereas the 28-day free from the ICU duration was shorter in patients with a higher ACAG value in both cohorts.ConclusionThe ACAG value was independently and strongly associated with the prognosis of patients with CS, indicating that the ACAG value is superior to the conventional AG value.

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Inflammation plays an important role in the initiation and perpetuation of AF. The present study was conducted to characterize immune clusters in nonparoxysmal AF and to distinguish immune subtypes of nonparoxysmal AF. Immune-related algorithms (CIBERSORT, ESTIMATE, and ssGSEA) were used to evaluate the immune cluster characterization and cell abundance, and multivariable logistics analysis was performed to determine the most relevant immune cells. We identified differentially expressed genes (DEGs) and used consensus clustering analysis to identify nonparoxysmal AF subtypes. Weighted gene coexpression network analysis (WGCNA) was used for finding highly correlated gene sets and attach to external sample traits. And it was conducted twice to identify the immune- and subtype- related modules. Finally, Metascape was used to compare the biological functions of the two nonparoxysmal AF subtypes we obtained. CytoHubba was used to identify the hub genes of these two subtypes. Based on the results of bioinformatics analysis, regulatory T cells, resting NK cells, active mast cells and neutrophils were considered to be closely related to nonparoxysmal AF. The brown module was identified as the most relevant module to the above immune cells by WGCNA. We identified two major nonparoxysmal AF subtypes by consensus clustering analysis and their enriched biological functions by Metascape. The hub genes are TYROBP, PTPRC, ITGB2, SPI1, PLEK, and CSF1R in permanent AF and JAM3, S100P, ARPC5, TRIM34, and GREB1L in persistent AF. This study revealed two major nonparoxysmal AF subtypes and eleven hub genes, which provide potential therapeutic targets for anti-inflammatory treatments of nonparoxysmal AF.