Clinical management controversy caused by a rare case of silver clip detachment and displacement after tubal silver clip sterilization.

Introduction and importance: The treatment of rare long-term complications such as ectopic silver clips after tubal silver clip sterilization, still follows the principle of removing metal foreign body (MFB) in the abdominal cavity: first choice removal, which seems to be a habitual treatment method by clinical gynecologists. However, this measure has recently been greatly questioned. Case presentation: A 54-year-old postmenopausal woman who had undergone tubal sterilization with a silver clip 32 years ago, presented to the emergency department (ED) with severe left upper abdominal colic, paroxysmal, accompanied by vomiting and radiating pain. Her vital signs were stable, and an emergency routine urine test showed microscopic hematuria. Preliminary consideration was given to ureteral stones, and abdominal pain was relieved after treatment. Abdominal computed tomography confirmed the previous consideration, but unexpectedly found that the left tubal sterilization metal clip disappeared and was ectopic in the perihepatic space. Clinical discussion: This traditional conception of removing MFB in the abdominal cavity is often accepted by many surgeons. Based on the management measures of this case and the systematic review of the literature, we found that the detached ectopic silver clip did not cause serious long-term complications, possibly due to its good tissue receptivity and other characteristics. Conclusion: Although an ectopic silver clip is an MFB in the abdominal cavity, it has been increasingly shown that removing the silver clip is not necessary because of the good receptivity of silver to human tissue and the uncertainty of long-term side effects on the human body.

Biogenic secondary organic aerosol participates in plant interactions and herbivory defense.

Biogenic secondary organic aerosols (SOAs) can be formed from the oxidation of plant volatiles in the atmosphere. Herbivore-induced plant volatiles (HIPVs) can elicit plant defenses, but whether such ecological functions persist after they form SOAs was previously unknown. Here we show that Scots pine seedlings damaged by large pine weevils feeding on their roots release HIPVs that trigger defenses in neighboring conspecific plants. The biological activity persisted after HIPVs had been oxidized to form SOAs, which was indicated by receivers displaying enhanced photosynthesis, primed volatile defenses, and reduced weevil damage. The elemental composition and quantity of SOAs likely determines their biological functions. This work demonstrates that plant-derived SOAs can mediate interactions between plants, highlighting their ecological significance in ecosystems.

Associations among dietary 1-carbon metabolism nutrients, genetic risk, and Alzheimer disease: a prospective cohort study.

BACKGROUND: The associations between 1-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B-6, and vitamin B-12) and Alzheimer disease (AD) remains inconclusive. OBJECTIVES: This study aimed to investigate the association of dietary OCM nutrients with subsequent risk of AD and further assess whether participants with high genetic risk for AD might benefit from dietary OCM nutrients. METHODS: We analyzed data from 192,214 participants who completed at least one 24-h dietary questionnaire and had no previous history of AD based on the UK Biobank. Nutrients intake was calculated using McCance and Widdowson's The Composition of Food and USDA's Food and Nutrient Database for Dietary Studies. Cox proportional models with restricted cubic splines were applied to explore the associations. RESULTS: Over a median follow-up of 13.35 y, 959 cases of AD (41 early-onset cases and 918 late-onset cases) were identified. Compared with those in the low-intake OCM group (quartile 1), participants in the high-intake OCM group (quartile 4) had reduced risk of developing AD. The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for methionine, folate, vitamin B-6, and vitamin B-12 intake were 0.66 (0.54, 0.80), 0.71 (0.58, 0.87), 0.71 (0.59, 0.87), and 0.77 (0.64, 0.93), respectively. Similar associations were observed in late-onset AD. In early-onset AD, high methionine and vitamin B-12 intake were associated with 70% (HR: 0.30; 95% CI: 0.10, 0.86) and 71% (HR: 0.29; 95% CI: 0.09, 0.96) reduction in risk, respectively. Participants with low genetic risk and high OCM nutrients intake had >75% reduced AD risk compared with high-risk, low-intake participants. CONCLUSIONS: In this prospective cohort study, we found that higher intake of OCM nutrients is associated with reduced risk of AD. Participants with high genetic risk of AD are more likely to benefit from dietary OCM nutrients intake.

[Spatio-temporal Pattern of Ecosystem Service Value Evolution in the Yihe River Basin in the Context of Land Use Change].

In this study, the modified equivalent factor method was applied to account for the long time series ecosystem service value （ESV） of the Yihe River Basin from 1975 to 2020 in the context of land use change, and the cold hot spot analysis and topographic position analysis methods were introduced to explore the characteristics of its spatial pattern. The results showed that： ① From 1975 to 2020, the land use type of the Yihe River Basin was dominated by arable land, and the land use changes were characterized by the rapid decrease of arable land and the continuous expansion of construction land, a slight increase in the area of forest land and grassland, a contraction of the water body area, and little change in the area of unused land. ② The modified equivalent factor method was more suitable for accounting for the ESV in the basin. From 1975 to 2020, the overall ESV of the basin showed an upward spiral trend （33.369-33.816 billion CNY）, dominated by the regulating services. The ESV of arable land was the highest with a decreasing trend, whereas the ESV of unused land was the lowest. ③ In the horizontal spatial pattern, the hot spot of ESV was near mountains and reservoirs, and the cold spot of ESV was near urban areas. In terms of vertical spatial patterns, with growing topographic gradient, vertical changes in ESV for all land use types showed an increasing trend followed by a decreasing trend. The results of the study revealed the spatial and temporal patterns of ecosystem service values in the Yihe River Basin in the context of land use change and provide a scientific basis for optimizing the land use structure and spatial pattern and enhancing ecosystem services.

Metabolic health and genetic predisposition in inflammatory bowel disease: Insights from a prospective cohort study.

BACKGROUND: Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD. METHOD: This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk. RESULTS: During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27-6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals. CONCLUSION: Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk.

A novel coupling process to replace the traditional multi-stage anammox process-sulfur autotrophic denitrification coupled anammox system.

A novel coupling process to replace the traditional multi-stage anammox process-sulfur autotrophic denitrification (SAD) coupled anaerobic ammonium oxidation (anammox) system was designed, which solved problems of nitrate produced in anammox process and low nitrate conversion rate caused by nitrite accumulation in SAD process. Different filter structures (SAD filter and anammox granular sludge) were investigated to further explore the excellent performance of the novel integrated reactor. The results of sequential batch experiments indicated that nitrite accumulation occurred during SAD, which inhibited the conversion of nitrate to dinitrogen gas. When SAD filter and anammox granular sludge were added to packed bed reactor simultaneously, the nitrate removal rate increased by 37.21% and effluent nitrite concentration decreased by 100% compared to that achieved using SAD. The stratified filter structure solved groove flow. Different proportion influence of SAD filter and anammox granular sludge on the stratified filter structure was evaluated. More suitable ratio of SAD filter to anammox granular sludge was 2:1. Proteobacteria (57.26%), Bacteroidetes (20.12%) and Chloroflexi (9.95%) were the main phyla. The dominant genera of denitrification functional bacteria were Thiobacillus (39.80%), Chlorobaculum (3.99%), norank_f_PHOs-HE36 (2.90%) and Ignavibacterium (2.64%). The dominant genus of anammox bacterium was Candidatus_Kuenenia (3.05%).

Double Reinforcing Strategy with Perpendicular Plate of Ethmoid in Asian Secondary Unilateral Cleft Rhinoplasty: A Finite Element Analysis.

BACKGROUND: Deviation and asymmetry relapse after secondary unilateral cleft rhinoplasty with septal extension graft is a common yet serious problem especially among Asian patients. Therefore, finding an effective approach to reduce deformity relapse remains a great challenge to plastic surgeons. METHODS: In this study, authors established finite element models to simulate different nasal cartilage-corrected options and different reinforcing strategies in secondary unilateral cleft rhinoplasty. A load of 0.01N was given to the nasal tip to simulate the soft tissue pressure, while two loads of 0.5N were separately given to the anterior and posterior part of the septal extension graft to simulate the rhinoplasty condition. Maximum deformations were evaluated to make stability judgments. RESULTS: The maximum deformation of different cartilage correction models in ascending order was: UCL deformity with septum correction, normal nasal cartilage, UCL nasal deformity, and UCL nasal deformity with lower lateral cartilage correction. When applied L-strut reinforcement graft was harvested from the perpendicular plate of the ethmoid bone, the maximum deformation of the models decreased significantly, and strong fixation of the septum could further enhance this decreasing effect. CONCLUSIONS: Correcting the septum and lower lateral cartilage together could improve the structural stability and symmetry in secondary unilateral cleft rhinoplasty. To keep the corrected septum stable and thus reduce deformity relapse, reinforcing the L-strut with perpendicular plate of ethmoid graft while strongly anchoring the septal cartilage to the anterior nasal spine was proved to be effective in both finite element analysis and clinical observation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A GITRL-mTORC1-GM-CSF Positive Loop Promotes Pathogenic Th17 Response in Primary Sjögren Syndrome.

OBJECTIVE: Glucocorticoid-induced tumor necrosis factor receptor superfamily-related protein (GITR), with its ligand (GITRL), plays an important role in CD4+ T cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren syndrome (pSS). METHODS: Patients with pSS and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determined. RNA sequencing was performed to decipher key signal pathways. Nonobese diabetes (NOD) mice were adopted as experimental Sjögren models and recombinant adeno-associated virus (rAAV) transduction was conducted to verify the therapeutic potentials of targeting GITRL in vivo. RESULTS: Serum GITRL was significantly higher in patients with pSS and showed a positive correlation with leukopenia, thrombocytopenia, autoantibodies, lung involvement, and disease activity. Serum GITRL was correlated with Th17-related cytokines. GITRL promoted the expansion of Th17 and Th17.1 cells. Expansion of granulocyte-macrophage colony-stimulating factor positive (GM-CSF+) CD4+ T cells induced by GITRL could be inhibited by blockade of GITRL. Moreover, GM-CSF could stimulate GITRL expression on monocytes. RNA sequencing revealed mammalian target of rapamycin complexes 1 (mTORC1) might be the key modulator. The increased phosphorylation of S6 and STAT3 and the expansion of Th17 and Th17.1 cells induced by GITRL were effectively inhibited by rapamycin, suggesting a GITRL-mTORC1-GM-CSF positive loop in pathogenic Th17 response in pSS. Administration of an rAAV vector expressing short hairpin RNA targeting GITRL alleviated disease progression in NOD mice. CONCLUSION: Our results identified the pathogenic role of GITRL in exacerbating disease activity and promoting pathogenic Th17 response in pSS through a GITRL-mTORC1-GM-CSF loop. These findings suggest GITRL might be a promising therapeutic target in the treatment of pSS.

Acer tegmentosum extract-mediated silver nanoparticles loaded chitosan/alginic acid scaffolds enhance healing of E. coli-infected wounds.

This work developed Acer tegmentosum extract-mediated silver nanoparticles (AgNPs) loaded chitosan (CS)/alginic acid (AL) scaffolds (CS/AL-AgNPs) to enhance the healing of E. coli-infected wounds. The SEM-EDS and XRD results revealed the successful formation of the CS/AL-AgNPs. FTIR analysis evidenced that the anionic group of AL (-COO-) and cationic amine groups of CS (-NH3+) were ionically crosslinked to form scaffold (CS/AL). The CS/AL-AgNPs exhibited significant antimicrobial activity against both Gram-positive (G+) and Gram-negative (G-) bacterial pathogens, while being non-toxic to red blood cells (RBCs), the hen's egg chorioallantoic membrane (HET-CAM), and a non-cancerous cell line (NIH3T3). Treatment with CS/AL-AgNPs significantly accelerated the healing of E. coli-infected wounds by regulating the collagen deposition and blood parameters as evidenced by in vivo experiments. Overall, these findings suggest that CS/AL-AgNPs are promising for the treatment of infected wounds.

Direct mitigation of secondary organic aerosol particulate pollutants by multiphase photocatalysis.

Particulate matter represents one of the most severe air pollutants globally. Organic aerosol (OA) comprises 30-70 % of submicron particle mass in urban areas. An effective way to mitigate OA particulate pollutants is to reduce the formation of secondary organic aerosol (SOA). Here, we studied the effect of titanium dioxide (TiO2) photocatalytic seeds on the formation and mitigation of SOA particles from α-pinene or toluene oxidation in chamber. For the first time, we discovered that under ultraviolet (UV) irradiation, the presence of TiO2 directly removed internally mixed α-pinene SOA mass by 53.7 % within 200 mins, and also directly removed SOA matter in an externally mixed state that is not in direct contact with TiO2 surface: the mass of externally mixed α-pinene SOA was reduced by 21.9 % within 81 mins, and the toluene SOA mass was reduced by 46.6 % in 145mins. In addition, the presence of TiO2 effectively inhibited the formation of SOA particles with a SOA mass yield of zero. This study brings up an innovative concept for air pollution control - the direct photocatalytic degradation of OA with aid of TiO2-based photocatalysts. Our novel findings will potentially bring practical applications in air pollution abatement and regional, even global aerosol-climate interactions.

A comprehensive evaluation of the phenotype-first and data-driven approaches in analyzing facial morphological traits.

The phenotype-first approach (PFA) and data-driven approach (DDA) have both greatly facilitated anthropological studies and the mapping of trait-associated genes. However, the pros and cons of the two approaches are poorly understood. Here, we systematically evaluated the two approaches and analyzed 14,838 facial traits in 2,379 Han Chinese individuals. Interestingly, the PFA explained more facial variation than the DDA in the top 100 and 1,000 except in the top 10 phenotypes. Accordingly, the ratio of heterogeneous traits extracted from the PFA was much greater, while more homogenous traits were found using the DDA for different sex, age, and BMI groups. Notably, our results demonstrated that the sex factor accounted for 30% of phenotypic variation in all traits extracted. Furthermore, we linked DDA phenotypes to PFA phenotypes with explicit biological explanations. These findings provide new insights into the analysis of multidimensional phenotypes and expand the understanding of phenotyping approaches.

Lymphatic endothelial cell-mediated accumulation of CD177+Treg cells suppresses antitumor immunity in human esophageal squamous cell carcinoma.

Regulatory T (Treg) cells are critical in shaping an immunosuppressive microenvironment to favor tumor progression and resistance to therapies. However, the heterogeneity and function of Treg cells in esophageal squamous cell carcinoma (ESCC) remain underexplored. We identified CD177 as a tumor-infiltrating Treg cell marker in ESCC. Interestingly, expression levels of CD177 and PD-1 were mutually exclusive in tumor Treg cells. CD177+ Treg cells expressed high levels of IL35, in association with CD8+ T cell exhaustion, whereas PD-1+ Treg cells expressed high levels of IL10. Pan-cancer analysis revealed that CD177+ Treg cells display increased clonal expansion compared to PD-1+ and double-negative (DN) Treg cells, and CD177+ and PD-1+ Treg cells develop from the same DN Treg cell origin. Importantly, we found CD177+ Treg cell infiltration to be associated with poor overall survival and poor response to anti-PD-1 immunotherapy plus chemotherapy in ESCC patients. Finally, we found that lymphatic endothelial cells are associated with CD177+ Treg cell accumulation in ESCC tumors, which are also decreased after anti-PD-1 immunotherapy plus chemotherapy. Our work identifies CD177+ Treg cell as a tumor-specific Treg cell subset and highlights their potential value as a prognostic marker of survival and response to immunotherapy and a therapeutic target in ESCC.

Diagnosis of small intestinal microperforation by cell morphology detection in abdominal puncture fluid: A case report.

INTRODUCTION AND IMPORTANCE: Although abdominal computed tomography angiography (CTA) may be a gold standard for early diagnosis of small intestinal microperforation, early missed and delayed diagnosis are often important factors leading to poor prognosis. The cellular morphology diagnosis of abdominal puncture fluid (DAPF) or diagnostic peritoneal lavage (DPL) may have unexpected clinical outcomes. CASE PRESENTATION: We report a case of small bowel microperforation which dues to BAT. A 39-year-old male with a chief complaint of "multiple injuries to the whole body from a car accident within 7 hours" was admitted to the trauma center. The first abdominal CTA ruled out perforation of abdominal parenchymatous organs and gastrointestinal tract. Subsequently, the patient underwent emergency surgery for traumatic shock, followed by clinical manifestations of persistent fever and septic shock. After diagnostic abdominal puncture fluid cell morphology examination, intestinal perforation was first considered. CLINICAL DISCUSSION: Routine examination of abdominal puncture fluid can usually roughly determine the condition of visceral trauma, especially quickly and conveniently determine whether there is intra-peritoneal bleeding. However specific diagnostic components which were found in the cell images of abdominal puncture fluid also showed the clinical value of cellular morphology of DAPF. CONCLUSION: The cellular morphology examination of DAPF/DPL may be the simplest, fastest, and most effective method for diagnosing small intestinal perforation due to blunt abdominal trauma(BAT). The value of DAPF /DPL in traumatic gastrointestinal injury cannot be ignored, especially for patients with BAT.

Exercise-based cardiac rehabilitation for patients with coronary heart disease: a systematic review and evidence mapping study.

INTRODUCTION: Exercise-based cardiac rehabilitation (CR) plays a critical role in coronary heart disease (CHD) management. There is a heritage in the effect of exercise-based CR with different exercise programs or intervention settings. This study developed an evidence matrix that systematically assesses, organizes, and presents the available evidence regarding exercise-based CR in CHD management. EVIDENCE ACQUISITION: A comprehensive literature search was conducted across six databases. Two reviewers screened the identified literature, extracted relevant data, and assessed the quality of the studies. An evidence-mapping framework was established to present the findings in a structured manner. Bubble charts were used to represent the included systematic reviews (SRs). The charts incorporated information, exercise prescriptions, outcome indicators, associated P values, research quality, and the number of original studies. A descriptive analysis summarized the types of CR, intervention settings, influential factors, and adverse events. EVIDENCE SYNTHESIS: Sixty-two SRs were included in this analysis, focusing on six exercise types in addition to assessing major adverse cardiovascular events (MACE), cost and rehabilitation outcomes. The most commonly studied exercise types were unspecified (28 studies, 45.2%) and aerobic (11 studies, 17.7%) exercises. All-cause mortality was the most frequently reported MACE outcome (22 studies). Rehabilitation outcomes primarily centered around changes in cardiac function (135 outcomes from 39 SRs). Only 8 (12.9%) studies were rated as "high quality." No significant adverse events were observed in the intervention group. Despite some variations among the included studies, most SRs demonstrated the benefits of exercise in improving one or more MACE or rehabilitation outcomes among CHD patients. CONCLUSIONS: The proportion of high-quality evidence remains relatively low. Limited evidence is available regarding the effectiveness of specific exercise types and specific populations, necessitating further evaluation.

Principal component analysis-assisted zirconium-based metal-organic frameworks/DNA biosensor for the analysis of various phosphates.

Considering the diversity of phosphates and their pivotal roles in physiological processes, detection of various phosphates related to their metabolism is urgent but challenging. Herein, we design a biosensor with zirconium-based MOFs (Zr-MOFs) and fluorophore-modified single-stranded DNA (F-ssDNA) for the analysis of phosphates. Relying on the interaction between Zr clusters and phosphate backbone, F-ssDNA is anchored on the surface of Zr-MOFs, inducing fluorescence resonance energy transfer (FRET) and subsequently quenching the fluorescence of F-ssDNA. Meanwhile, phosphates with different numbers of phosphate groups, molecular structures and coordination environments are able to adjust the FRET between Zr-MOFs and F-ssDNA via a site-occupying effect, recovering the fluorescence of F-ssDNA in distinct cases, which may result in diverse fluorescence signals. Consequently, seventeen phosphates and four phosphate mixtures are discriminated with the assistance of principal component analysis. These results provide new insight into the application of Zr-MOFs and broaden the path for the development of analytical methods for phosphates.

Broadband near-infrared (NIR) emitting Cr3+ -doped La3 Ga5 SnO14 phosphor with long persistent and photostimulated persistent luminescence.

Recently, long persistent phosphors (LPPs) have attracted significant attention as promising candidates for biomedical applications. However, the serious decrease in luminescence intensity in tissue still remains a major challenge. Therefore, exploring more competitive LPPs and achieving reproducible tissue imaging is crucial. In this study, a new series of near-infrared (NIR) phosphors La3 Ga5 Sn1-x O14 :xCr3+ (x = 0.005-0.05) were synthesized using a high-temperature solid-state method. The as-synthesized samples were characterized using X-ray diffraction, diffuse/photoluminescence spectroscopy, fluorescence decay curves, and thermoluminescence spectroscopy. Upon excitation with ultraviolet light, strong emission bands were observed in the range 600-1200 nm with an optimal doping concentration of x = 0.02 mol. Moreover, La3 Ga5 SnO14 :Cr3+ exhibits persistent luminescence due to the presence of suitable energy traps, which prompted the phosphor to emit NIR light even after the removal of the excitation source.

Selective uneven enrichment of soil organic carbon among different-sized sediments under a rain-induced overland flow: 13C stable isotope evidence.

Soil organic carbon (SOC) enrichment varies among sediments of different sizes during rain-induced overland flow erosion. This selective transport of SOC is complex in conjunction with the exposure of labile and stable organic carbon (OC), accompanied by heterogeneous aggregate disintegration under raindrop effects. Utilizing the variations in δ13C values of SOC fractions, we traced this selective transport, linking it to aggregate-wrapped SOC changes during erosion. A modified soil pan facilitated the simultaneous monitoring of splash and sheet erosion via artificially simulated rainfall, with control over the intensity and slope. Aggregate composition, SOC distribution, and δ13C values in the erosion samples were analyzed. The results indicated that distinct sorting existed within the aggregate fragments. Along with SOC variation among different sediment sizes, the proportions of clay and fine silt within sediment aggregates increased as a function of slope and rainfall intensity, whereas particulate OC within aggregates decreased. The SOC enrichment ratios (ERocs) and δ13C values in splash-eroded sediments were positively correlated with those in sheet-eroded sediments. The ERocs in splash-eroded sediments were lower than those in sheet-eroded sediments, but δ13C values were the opposite. Moreover, δ13C values of SOC enriched in sediment particles of all sizes from aggregate stripping were lower than those of the original soil. This indicates that raindrop hits promote heavy C loss during sheet erosion, which is different for mineral-associated and particulate OC. As the slope and rainfall intensity increased, δ13C values for all sediment sizes decreased over the course of erosion. Interestingly, the highest δ13C values were observed under a rainfall intensity of 60 mm h-1, whereas the highest SOC concentrations were noted on a 5° slope. These observations suggest divergent mechanisms affect δ13C values and SOC concentrations in eroded sediments. All these results verified that selective sorting existed for the light SOC fraction. Finally, the internal selective transport of one SOC fraction may explain the enhanced mineralization and reaggregation capacity of the deposited sediments.

Single-Cell RNA Sequencing Pro-angiogenic Macrophage Profiles Reveal Novel Prognostic Biomarkers and Therapeutic Targets for Osteosarcoma.

Osteosarcoma (OS) is a malignant bone tumor that most commonly occurs in children and adolescents. OS patients have a poor prognosis, and 5-year survival rates have rarely improved significantly over the past few decades. OS prognosis may be related to the infiltration of tumor-associated macrophages (TAMs). However, the role of proangiogenic macrophages, a subtype of TAMs, in OS prognosis has not been reported. In this study, seven subtypes of TAMs were identified from single-cell RNA sequencing (scRNA-seq) data that we propose defining as proangiogenic TAMs (Angio-TAMs), interferon-primed TAMs (IFN-TAMs), inflammatory cytokine-enriched TAMs (Inflam-TAMs), immune regulatory TAMs (Reg-TAMs), lipid-associated TAMs (LA-TAMs), and resident-tissue macrophages like TAMs (RTM-TAMs) (containing two subcellular types). In the survival analysis of each macrophage subtype, it was found that patients with Angio-TAMs had the most significant difference in survival. Eight genes associated with Angio-TAMs were obtained by differential expression analysis, and these genes were built into a prognostic model using the LASSO algorithm. Clinical OS case samples were categorized into high-risk and low-risk subgroups using median risk scores. In comparison to the low-risk subgroup, the survival time of the high-risk subgroup was much shorter. Additional studies on immune cell infiltration and immune checkpoint molecule expression in the two risk subgroups were carried out. In immunotherapy response prediction, the Angio-TAM-associated gene risk signature was found to be negatively correlated with immune checkpoint responses. In addition, the associated enriched GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were mainly involved in the malignant progression of tumors. As suggested by these findings, the Angio-TAM gene risk signature may be an underlying prognostic biomarker and novel therapeutic target for OS patients.Kindly check and confirm whether the ESM file is correctly identifiedWe have checked this file and confirmed that it can be correctly identified.

Serum sCD25 is an indicator for rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: CD25 (IL-2Rα) is one of IL-2 receptor's polypeptide subunits, and its soluble form is increased in patients with various inflammatory or autoimmune diseases. This study aimed to evaluate the clinical correlation of serum soluble CD25 (sCD25) with interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: 294 RA patients, including 72 in the discovery cohort (15 patients with ILD, 57 patients without ILD), 222 in the validation cohort (41 patients with ILD and 181 patients without ILD), and 58 healthy controls (HCs) were recruited. High-resolution computed tomography (HRCT) scan provided evidence and patterns of RA-ILD. Serum sCD25 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory data were recorded and the association with sCD25 was also analysed. RESULTS: In the discovery cohort, 16 RA-related molecules including cytokines, chemokines and functional soluble cell surface proteins were investigated. The results showed that sCD25 was significantly higher in RA-ILD than in RA-no-ILD group (p=0.004). ROC analysis also showed RA-ILD was discriminated with RA-no-ILD by sCD25 (AUC=0.695, 95% CI=0.541-0.849). Logistics regression demonstrated that sCD25 was one of the risk factors of RA-ILD. This result was further confirmed in validation cohort (p<0.001). According to the cut-off value in the discovery cohort, the sensitivity and specificity of sCD25 in RA-ILD were 51.2%, 77.3%, respectively. Compared with RA-no-ILD, serum level of sCD25 was also higher in different HRCT patterns including UIP, NSIP and RA-ILA. The ROC curves revealed sCD25 as diagnostic marker in UIP, NSIP and RA-ILA (with AUCs of 0.730, 0.761, and 0. 694, respectively, p<0.05). The result indicated that sCD25 was a biomarker for RA-ILD subtypes. Although sCD25 was not correlated with HRCT scores, it was significantly higher in consolidation pattern by HRCT. CONCLUSIONS: sCD25 was significantly elevated in RA-ILD (including UIP, NSIP and RA-ILA) compared to RA-no-ILD and HCs, which supports their value as a potential biomarker in RA-ILD screening and assessment.