Tumor immunity: A brief overview of tumor­infiltrating immune cells and research advances into tumor­infiltrating lymphocytes in gynecological malignancies (Review).

Tumor immunity is a promising topic in the area of cancer therapy. The 'soil' function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor-infiltrating immune cells in the TME, especially the tumor-infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: 'Tumor microenvironment'; 'TME'; 'tumor-infiltrating immunity cells'; 'gynecologic malignancies'; 'the adoptive cell therapy (ACT) of TILs'; and 'TIL-ACT' (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor-infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy.

Effects of exogenous salicylic acid on starch physicochemical properties and in vitro digestion under heat stress during the grain-filling stage in waxy maize.

Waxy maize starch serves as a pivotal component in global food processing and industrial applications, while high temperature (HT) during the grain-filling stage seriously affects its quality. Salicylic acid (SA) has been recognized for its role in enhancing plant heat resistance. Nonetheless, its regulatory effect on the quality of waxy maize starch under HT conditions remains unclear. In this study, two waxy maize varieties, JKN2000 (heat-tolerant) and SYN5 (heat-sensitive) were treated with SA after pollination and then subjected to HT during the grain-filling stage to explore the effect of SA on grain yield and starch quality. The results indicate that exogenous SA under HT treatment led to an increase in kernel weight and starch content in both varieties. Moreover, SA reduced the HT-induced holes on the surfaces of starch granules, enlarged the starch granule size, elevated the amylopectin branching degree, and reduced amylopectin average chain length. Consequently, improvements of pasting viscosity and the decrease of retrogradation percentage of starch were observed with SA under HT. Exogenous SA reduced HT-induced rapidly digestible starch content in SYN5, but had no significant effect on that in JKN2000. In summary, SA pretreatment effectively alleviated the detrimental effects of HT on starch pasting and thermal properties of waxy maize.

Three-dimensional covalent organic frameworks with nia nets for efficient separation of benzene/cyclohexane mixtures.

The synthesis of three-dimensional covalent organic frameworks with highly connected building blocks presents a significant challenge. In this study, we report two 3D COFs with the nia topology, named JUC-641 and JUC-642, by introducing planar hexagonal and triangular prism nodes. Notably, our adsorption studies and breakthrough experiments reveal that both COFs exhibit exceptional separation capabilities, surpassing previously reported 3D COFs and most porous organic polymers, with a separation factor of up to 2.02 for benzene and cyclohexane. Additionally, dispersion-corrected density functional theory analysis suggests that the good performance of these 3D COFs can be attributed to the incorporation of highly aromatic building blocks and the presence of extensive pore structures. Consequently, this research not only expands the diversity of COFs but also highlights the potential of functional COF materials as promising candidates for environmentally-friendly separation applications.

Spatial predictions of groundwater potential using automated machine learning (AutoML): a comparative study of feature selection and training sample size in Qinghai Province, China.

Predicting groundwater potential is crucial for identifying the spatial distribution of groundwater in a region. It serves as an essential guide for the development, utilization, and protection of groundwater resources. Previous studies have primarily emphasized finding the most accurate prediction model for groundwater potential while giving less attention to the selection of training features and sample sizes. This study aims to predict groundwater potential within Qinghai Province using automated machine learning technology and assess the influence of sample sizes and feature selection on prediction accuracy. Sixteen groundwater conditioning factors were categorized into categorical and numerical variables. Four feature selection modes were utilized as input in training the model. The results indicated that, except for correlations between evaporation and landforms (- 0.8) and precipitation and normalized difference vegetation index (0.8), the Pearson correlation coefficients among the remaining sixteen factors were ≤ 0.5 or ≥ - 0.5. The models XGB-ALL, RF-Entropy, ET-CRITIC, and XGB-PCA yielded accuracy scores of 0.783, 0.685, 0.745, and 0.703, and area under curve (AUC) of 0.819, 0.724, 0.779, and 0.747, respectively. If enough samples are available with the tree model, an increased number of features can improve prediction accuracy. The principal component analysis method showed difficulty in reducing the dimensionality of the input space, while the Entropy method proved efficient. The accuracy and AUC value of the prediction model improved with an increasing number of samples. Training with 8 features and 200 data points achieved an accuracy of 0.745, sufficient to evaluate regional groundwater potential. As for training with 600 samples, the model's performance accuracy rose to 0.9, enabling precise groundwater potential prediction. The outputs of this research can provide decision-makers in groundwater resource management in Qinghai Province with crucial theoretical and practical support. The lessons learned can have future applications in similar situations.

Endovascular Interventional Procedure is a Significant Risk Factor of Postsurgical Gout: A Retrospective Cohort Study.

INTRODUCTION: Surgery is a risk factor for flares in people with gout. However, gout flares after endovascular interventional procedures are not well understood. The aim of this study was to evaluate the clinical features and risk factors for gout flare that develop during the postsurgical period including endovascular procedures. METHODS: We enrolled 222 patients with gout who developed postsurgical gout and 196 controls who had histories of gout but did not develop gout flares after surgery within 20 days. Clinical characteristics of patients who developed a postsurgical gout flare were compared with the controls. RESULTS: The rate of endovascular interventional procedures was higher (38.74% vs. 13.48%, P < 0.001) in the flare group than in the no-flare group and lower in orthopedic surgery (13.96% vs. 41.84%, P < 0.001). The Cox model showed that endovascular interventional procedures (HR, hazard ratio 1.752; 95% CI, confidence interval 1.126-2.724, P = 0.013) and presurgical uric acid levels of ≥ 7 mg/dl (HR 1.489; 95% CI 1.081-2.051, P = 0.015) were significantly associated with increased risks of postsurgical gout flare, and taking colchicine before surgery were significantly associated with decreased risk of postsurgical gout flare (HR 0.264; 95% CI 0.090-0.774, P = 0.015). There was no significant difference in the types of endovascular interventional procedures between the flare group and the no-flare group. CONCLUSIONS: Patients with a history of gout should be more alert to recurrence gout flares after endovascular interventional procedures. Adequate presurgical control of serum uric acid levels and/or prophylactic treatment with colchicine will help prevent gout flares during the postsurgical period.

BMP4 participates in the pathogenesis of PCOS by regulating glucose metabolism and autophagy in granulosa cells under hyperandrogenic environment.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disease characterized by ovulation dysfunction with multiple etiologies and manifestations, and it is widely believed that the disorders of hyper-androgen and glucose metabolism play a key role in its progression. There has been evidence that bone morphogenetic protein 4 (BMP4) is essential for the regulation of granulosa cells, but whether it regulates metabolism level of granulosa cells under hyperandrogenic environment remains unclear. In this study, Gene Expression Omnibus, clinical data and serum of PCOS patient were collected to detect androgen and BMP4 levels. KGN cells exposed to androgens as a model for simulating PCOS granulosa cells. Lactate/pyruvate kits, and Extracellular Acidification Rate and Oxygen Consumption Rate assay were performed to detect glycolysis and autophagy levels of granulosa cells. Lentivirus infection was used to investigate the effects of BMP4 on granulosa cells. RNA-seq were performed to explore the special mechanism. We found that BMP4 was increased in PCOS patients with hyper-androgen and granulosa cells with dihydrotestosterone treatment. Mechanically, on the one hand, hyperandrogenemia can up-regulate BMP4 secretion and induce glycolysis and autophagy levels. On the other hand, we found that hyperandrogenic-induced YAP1 upregulation may mediate BMP4 to increase glycolysis level and decrease autophagy, which plays a protective role in granulosa cells to ensure subsequent energy utilization and mitochondrial function. Overall, we innovated on the protective effect of BMP4 on glycolysis and autophagy disorders induced by excessive androgen in granulosa cells. Our study will provide guidance for future understanding of PCOS from a metabolic perspective and for exploring treatment options.

Primary acinic cell carcinoma of the breast: A case report and literature review.

Acinic cell carcinoma (ACCA), a type of malignant epithelial neoplasm, tends to occur in the parotid gland, and is occasionally found within the breast. Published literature regarding primary ACCA of the breast is scarce, and the number of reports may be fewer than 100. At present, full clinical details have not been published. As an extremely rare disorder, ACCA cannot be definitively diagnosed depending on microscopic structure alone and often requires the assistance of immunohistochemistry. Currently, universal therapies are not available. Here, we present a 47-year-old patient with a history of a palpable mass in the outer upper quadrant of the left breast for more than 2 years, which had obviously increased in size in the last half year. This patient was definitively diagnosed with primary ACCA of the breast. Neoadjuvant chemotherapy was performed preoperatively, and drug sensitivity tests based on primary tumor cells were conducted after surgery and successfully screened chemotherapy schemes for the patient's greater benefit. The whole treatment course followed the guidelines for invasive breast cancer. The patient was free of symptoms for 14 months after surgery. Long-term follow-up is in progress. Altogether, to further broaden the understanding of primary ACCA of the breast, we detail the diagnosis and treatment of one patient and review the relevant literature.

Transcriptome Screening of Long Noncoding RNAs and Their Target Protein-Coding Genes Unmasks a Dynamic Portrait of Seed Coat Coloration Associated with Anthocyanins in Tibetan Hulless Barley.

Many plants have the capability to accumulate anthocyanins for coloration, and anthocyanins are advantageous to human health. In the case of hulless barley (Hordeum vulgare L. var. nudum), investigation into the mechanism of anthocyanin formation is limited to the level of protein-coding genes (PCGs). Here, we conducted a comprehensive bioinformatics analysis to identify a total of 9414 long noncoding RNAs (lncRNAs) in the seed coats of purple and white hulless barley along a developmental gradient. Transcriptome-wide profiles of lncRNAs documented several properties, including GC content fluctuation, uneven length, a diverse range of exon numbers, and a wide variety of transcript classifications. We found that certain lncRNAs in hulless barley possess detectable sequence conservation with Hordeum vulgare and other monocots. Furthermore, both differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) were concentrated in the later seed development stages. On the one hand, DElncRNAs could potentially cis-regulate DEPCGs associated with multiple metabolic pathways, including flavonoid and anthocyanin biosynthesis in the late milk and soft dough stages. On the other hand, there was an opportunity for trans-regulated lncRNAs in the color-forming module to affect seed coat color by upregulating PCGs in the anthocyanin pathway. In addition, the interweaving of hulless barley lncRNAs and diverse TFs may function in seed coat coloration. Notably, we depicted a dynamic portrait of the anthocyanin synthesis pathway containing hulless barley lncRNAs. Therefore, this work provides valuable gene resources and more insights into the molecular mechanisms underlying anthocyanin accumulation in hulless barley from the perspective of lncRNAs, which facilitate the development of molecular design breeding in crops.

Recognition of the Subtypes Classification and Diagnostic Signature Based on RNA N6-Methyladenosine Regulators in Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is a common reproductive disease in female patients that seriously affects the quality of life of patients. N6-methyladenosine (m6A), as the most common modification, plays an important role in various biological behaviors; however, the relationship between m6A and RSA is still unknown. In the present study, we utilized RNA sequencing data and clinical information of RSA patients and normal women in the GEO database to identify the expression profiles of m6A regulators in RSA. Based on the m6A regulators' expression profiles, we constructed a random forest model consisting of 4 genes to predict the prevalence of RSA patients, including FMR1, METTL14, LRPPRC, and RBMX. The predictive performance of the nomogram was constructed and validated. Not only that, consensus clustering was performed to divide RSA patients into 3 clusters based on the expression of m6A regulators and calculated the m6A scores and immune infiltration of patients in different clusters. It was found that the TH1-type immune response was dominant in the A cluster, the B-type immune activity was poor, and the C cluster was the strongest. In addition, on the basis of m6A typing, we further used the differentially expressed genes between clusters to perform consensus clustering verification, and the results were consistent with the previous findings. In conclusion, the m6A regulators played an indispensable role in the occurrence of RSA, and the m6A-based typing could effectively identify the immune characteristics of different RSA patients to a certain extent, providing a new direction and strategy for the diagnosis and treatment of RSA patients.

Long-Term Stable Complementary Electrochromic Device Based on WO3 Working Electrode and NiO-Pt Counter Electrode.

Complementary electrochromic devices (ECDs) composed of WO3 and NiO electrodes have wide applications in smart windows. However, they have poor cycling stability due to ion-trapping and charge mismatch between electrodes, which limits their practical application. In this work, we introduce a partially covered counter electrode (CE) composed of NiO and Pt to achieve good stability and overcome the charge mismatch based on our structure of electrochromic electrode/Redox/catalytic counter electrode (ECM/Redox/CCE). The device is assembled using a NiO-Pt counter electrode with WO3 as the working electrode, and PC/LiClO4 containing a tetramethylthiourea/tetramethylformaminium disulfide (TMTU/TMFDS2+) redox couple as the electrolyte. The partially covered NiO-Pt CE-based ECD exhibits excellent EC performance, including a large optical modulation of 68.2% at 603 nm, rapid switching times of 5.3 s (coloring) and 12.8 s (bleaching), and a high coloration efficiency of 89.6 cm2·C-1. In addition, the ECD achieves a good stability of 10,000 cycles, which is promising for practical application. These findings suggest that the structure of ECC/Redox/CCE could overcome the charge mismatch problem. Moreover, Pt could enhance the Redox couple's electrochemical activity for achieving high stability. This research provides a promising approach for the design of long-term stable complementary electrochromic devices.

Proton and Redox Couple Synergized Strategy for Aqueous Low Voltage-Driven WO3 Electrochromic Devices.

Aqueous electrolytes possess non-combustible and eco-friendly features compared to organic electrolytes, leading them to be more suitable for application in smart windows for daily use. However, limited by the narrow electrochemical window of water (1.23 V), its use in conventional electrochromic devices (ECDs) would result in irreversible performance loss, which arises from decomposition caused by high voltage. Here, we propose a synergistic scheme combining a redox couple-catalytic counter electrode (RC-CCE) strategy with protons as guest ions. With the help of the intelligent matching of the reaction potentials of the RC and amorphous WO3 electrochromic electrodes and the highly active and fast kinetic features of protons, it successfully reduces the working voltage range of the device to 1.1 V. The assembled HClO4-ECD can possess an overall modulation rate (350-1200 nm) of 0.43 and 0.94 at -0.1 and -0.7 V, respectively, and a modulation of 66.8% at 600 nm at -0.7 V. Moreover, compared with other guest ions, the proton-based ECD exhibits higher coloration efficiency, a broader color modulation capability, and better stability. In addition, the house model equipped with the proton-based ECD effectively blocks solar radiation, which provides a potential solution for the design of aqueous smart windows.

Groundwater potential assessment using GIS-based ensemble learning models in Guanzhong Basin, China.

Groundwater plays a crucial role in sustaining industrial and agricultural production and meeting the water demands of the growing population in the semi-arid Guanzhong Basin of China. The objective of this study was to evaluate the groundwater potential of the region through the use of GIS-based ensemble learning models. Fourteen factors, including landform, slope, slope aspect, curvature, precipitation, evapotranspiration, distance to fault, distance to river, road density, topographic wetness index, soil type, lithology, land cover, and normalized difference vegetation index, were considered. Three ensemble learning models, namely random forest (RF), extreme gradient boosting (XGB), and local cascade ensemble (LCE), were trained and cross-validated using 205 sets of samples. The models were then applied to predict groundwater potential in the region. The XGB model was found to be the best, with an area under the curve (AUC) value of 0.874, followed by the RF model with an AUC of 0.859, and the LCE model with an AUC of 0.810. The XGB and LCE models were more effective than the RF model in discriminating between areas of high and low groundwater potential. This is because most of the RF model's prediction outcomes were concentrated in moderate groundwater potential areas, indicating that RF is less decisive when it comes to binary classification. In areas predicted to have very high and high groundwater potential, the proportions of samples with abundant groundwater were 33.6%, 69.31%, and 52.45% for RF, XGB, and LCE, respectively. In contrast, in areas predicted to have very low and low groundwater potential, the proportions of samples without groundwater were 57.14%, 66.67%, and 74.29% for RF, XGB, and LCE, respectively. The XGB model required the least amount of computational resources and achieved the highest accuracy, making it the most practical option for predicting groundwater potential. The results can be useful for policymakers and water resource managers in promoting the sustainable use of groundwater in the Guanzhong Basin and other similar regions.

Topological Isomerism in Three-Dimensional Covalent Organic Frameworks.

Although isomerism is a typical and significant phenomenon in organic chemistry, it is rarely found in covalent organic framework (COF) materials. Herein, for the first time, we report a controllable synthesis of topological isomers in three-dimensional COFs via a distinctive tetrahedral building unit under different solvents. Based on this strategy, both isomers with a dia or qtz net (termed JUC-620 and JUC-621) have been obtained, and their structures are determined by combining powder X-ray diffraction and transmission electron microscopy. Remarkably, these architectures show a distinct difference in their porous features; for example, JUC-621 with a qtz net exhibits permanent mesopores (up to ∼23 Å) and high surface area (∼2060 m2 g-1), which far surpasses those of JUC-620 with a dia net (pore size of ∼12 Å and surface area of 980 m2 g-1). Furthermore, mesoporous JUC-621 can remove dye molecules efficiently and achieves excellent iodine adsorption (up to 6.7 g g-1), which is 2.3 times that of microporous JUC-620 (∼2.9 g g-1). This work thus provides a new way for constructing COF isomers and promotes structural diversity and promising applications of COF materials.

The potential evaluation of groundwater by integrating rank sum ratio (RSR) and machine learning algorithms in the Qaidam Basin.

Groundwater is a vital resource in arid areas that sustains local industrial development and environmental preservation. Mapping groundwater potential zones and determining high-potential regions are essential for the responsible use of the local groundwater resource. When utilizing machine learning or deep learning algorithms to forecast groundwater potential in arid areas, difficulties such as inaccurate and overfitting predictions might occur due to a shortage of borehole samples. In this study, a database of groundwater conditioning factors with a size of 275,157 × 9 was created in the Qaidam Basin, and 85 known borehole samples were collected. The groundwater potential was evaluated using a combination of rank sum ratio (RSR), projection pursuit regression (PPR) and random forest (RF) algorithms, resulting in four models: PPR, RSR-PPR, RSR-RF, and RF. Results indicated that the groundwater potential was higher in mountainous regions surrounding the Qaidam Basin and decreased progressively towards the central and northwestern regions where most industries and facilities are located. The two primary factors, according to the PPR and RF models, were evapotranspiration (0.246, 0.225) and landform (0.176, 0.294). In terms of their ability to accurately forecast the borehole samples, the four models ranked as follows: RF > RSR-RF > RSR-PPR > PPR. The accuracy of the four models in the low-potential area was 0.73 (PPR), 0.60 (RSR-PPR), 0.87 (RSR-RF), and 0.80 (RF), respectively. However, the RF model showed overfitting due to a lack of samples, especially in high-potential regions, which limits its applicability. The RSR-RF method was applied directly to evaluate the entire factor database, avoiding the risk of overfitting caused by a limited number of training samples. The results demonstrate that the RSR-RF model is effective for classifying groundwater potential types in samples and mapping groundwater potential of the study area. This research presents a novel approach for groundwater potential predictions in areas with insufficient sample sizes, providing a reference for policymakers and researchers.

Effectiveness and Safety of Belimumab in Chinese Lupus Patients: A Multicenter, Real-World Observational Study.

Objective: The effectiveness and safety of belimumab in Chinese lupus patients with different disease activities were investigated in a real-world setting. Method: Patients who received 10 mg/kg belimumab intravenously on weeks 0, 2, and 4, and then every 4 weeks on a background of standard-of-care (SoC) therapy and had a follow-up of more than 6 months were enrolled from four centers in China. They were stratified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score at baseline as the moderate/severe (SELENA-SLEDAI > 6) or mild subgroups (SELENA-SLEDAI ≤ 6). Attainment of the Lupus Low Disease Activity State (LLDAS) or remission on treatment was analyzed in all patients. The SLE Responder Index 4 (SRI-4) and SELENA-SLEDAI Flare Index (SFI) were evaluated for patients with moderate/severe disease and mild disease, respectively. Patients in the control arm with SoC alone from previous metformin lupus trials were selected by propensity score matching (PSM) as the reference group. Results: 224 SLE patients with a mean follow-up of 11.7 months receiving belimumab were enrolled in this observational study, of which 126 and 98 were in the moderate/severe and mild subgroup, respectively. At 12 months, 54.76% of the patients attained LLDAS and 28.57% attained remission. Lower daily prednisone at baseline were independently associated with 12-month LLDAS. Further, 87% of the subgroup with moderate/severe disease achieved SRI-4 at 12 months and a high SLEDAI at baseline was its predictive factor. For the mild subgroup, a reduced flare rate was observed compared with PSM reference (17.5%, vs. 38.6%, p = 0.021). Infection events, particularly viral infections and pneumonia were recorded in 7 and 6 patients, respectively. Conclusion: Our real-world data supported the effectiveness and safety of belimumab in Chinese lupus patients.

Response of waxy maize (Zea mays L. var. ceratina Kulesh) leaf photosynthesis to low temperature during the grain-filling stage.

Low temperature (LT) during the grain-filling stage is an important factor that affects the source-sink relationship and leads to yield loss in maize (Zea mays L). In this study, field and pot trials were conducted to investigate the effects of LT during the grain-filling stage on leaf photosynthesis, antioxidant system, hormones, and grain yield of waxy maize cultivars Suyunuo 5 (S5) and Yunuo 7 (Y7). The results showed that LT treatment inhibited the chlorophyll biosynthesis and reduced the photosynthetic pigment levels during grain-filling stage. Ribulose-1,5-bisphosphate carboxylase and phosphoenolpyruvate carboxylase activities, photosynthetic rate, transpiration rate, and stomatal conductance decreased under LT treatment during the grain-filling stage. Furthermore, LT treatment increased the contents of malondialdehyde and reactive oxygen species, and decreased the activities of catalase, superoxide dismutase, peroxidase, and ascorbate peroxidase in the ear leaves, which accelerated the oxidative damage of leaf. The LT treatment also raised abscisic acid content and reduced indole acetic acid content in the ear leaves during grain-filling stage. The results of field and pot trials were verified by each other, but the field effect was greater than that of pot. Overall, LT treatment reduced the waxy maize dry matter accumulation after silking by affecting the physiological and biochemical processes of leaves, and ultimately decreased grain yield.

Comparison of the physicochemical properties of starches from maize reciprocal F1 hybrids and their parental lines.

Heterosis on maize yield and quality is highly variable and depends on parental selection. This study investigated and compared the starch structure and physicochemical properties among four sweet-waxy maize lines, four waxy maize lines, and their eight reciprocal F1 hybrids. Compared with the sweet-waxy maize, waxy maize and F1 hybrids had lower extent of branching of amylopectin and relative crystallinity, and larger starch granule size. Waxy maize starch had higher breakdown viscosity and retrogradation percentage, and lower setback viscosity and gelatinization enthalpy than the sweet-waxy maize starch. Meanwhile, the peak and setback viscosities, and retrogradation enthalpy of most F1 hybrid starches were higher than those of their female parent, while gelatinization enthalpy was the opposite. The F1 hybrid starches had higher onset temperature and retrogradation percentage and lower gelatinization enthalpy than their male parent in general. In conclusion, this study provides a framework for the production of new hybrids.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unveils heterogeneity and establishes a novel signature for prognosis and tumor immune microenvironment in ovarian cancer.

Ovarian cancer is a highly heterogeneous gynecological malignancy that seriously affects the survival and prognosis of female patients. Single-cell sequencing and transcriptome analysis can effectively characterize tumor heterogeneity to better study the mechanism of occurrence and development. In this study, we identified differentially expressed genes with different differentiation outcomes of tumor cells by analyzing a single-cell dataset. Based on the differentially expressed genes, we explored the differences in function and tumor microenvironment among clusters via consensus clustering. Meanwhile, WGCNA was employed to obtain key genes related to ovarian cancer. On the basis of the TCGA and GEO datasets, we constructed a risk model consisting of 7 genes using the LASSO regression model, and successfully verified that the model was characterized as an independent prognostic factor, efficiently predicting the survival prognosis of patients. In addition, immune signature analysis showed that patients in the high-risk group exhibited lower anti-tumor immune cell infiltration and immunosuppressive status, and had poorer responsiveness to chemotherapeutic drugs and immunotherapy. In conclusion, our study provided a 7-gene prognostic model based on the heterogeneity of OC cells for ovarian cancer patients, which could effectively predict the prognosis of patients and identify the immune microenvironment status of patients.

Neutrophil Extracellular Trap-Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout.

OBJECTIVE: Gout flares that occur during urate-lowering therapy (ULT) are typically related to the shrinkage of tophi due to aggregated neutrophil extracellular traps (NETs) that have captured monosodium urate crystals in the tissues. The present study was undertaken to analyze the blocking effect of α1 -antitrypsin on neutrophil elastase, and it was found that α1 -antitrypsin induced rapid inflammation in the presence of unstable tophi. METHODS: Cell-free DNA levels in serum samples were compared between patients who experienced a varying number of gout flares. We investigated whether cell-free DNA in serum samples and α1 -antitrypsin could be altered after the initiation of ULT. In mice, an injection of monosodium urate monohydrate (MSU) crystals was used to form a mimic of tophi in the peritoneal cavity, which was then analyzed using immunofluorescence staining. Finally, we investigated the relapse of inflammation by analyzing the levels of α1 -antitrypsin in 2 kinds of artificial tophi and in tophus-bearing mice. RESULTS: Levels of cell-free DNA in serum samples correlated with the number of flares experienced by patients with tophaceous gout. ULT induced an increase in cell-free DNA in the serum of patients with tophi. Increases in levels of α1 -antitrypsin were seen in patients with tophi who received ULT. Chalk-like tophi removed from the peritoneal cavity of mice after MSU crystals induced inflammation showed abundant coexpression of interleukin-1ß (IL-1ß) and IL-6-associated NETs. A relapse in inflammation was induced by α1 -antitrypsin during the spontaneous resolution of MSU crystal-induced peritonitis. We observed that α1 -antitrypsin blocks cytokine degradation by neutrophil elastase during the resolution phase of tophi. CONCLUSION: ULT causes shrinkage of the tophi reflected by an increase in the levels of cell-free DNA in serum. In the resolution phase of tophi in mice, NET-associated neutrophil elastase degrades proinflammatory cytokines and, thus, ameliorates inflammation.