A Biodegradable Fiber Calcium Ion Sensor by Covalently Bonding Ionophores on Bioinert Nanoparticles.

Implantable sensors, especially ion sensors, facilitate the progress of scientific research and personalized healthcare. However, the permanent retention of implants induces health risks after sensors fulfill their mission of chronic sensing. Biodegradation is highly anticipated while biodegradable chemical sensors are rare due to concerns about the leakage of harmful active molecules after degradation, such as ionophores. Here, we introduce a novel biodegradable fiber calcium ion sensor, wherein ionophores are covalently bonded with bioinert nanoparticles to replace the classical ion-selective membrane. The fiber sensor demonstrates comparable sensing performance to classical ion sensors and good flexibility. It can monitor the fluctuations of Ca2+ in a four-day lifespan in vivo, and biodegrade in four weeks. Benefiting from the stable bonding between ionophores and nanoparticles, the biodegradable sensor exhibited a good biocompatibility after degradation. Moreover, our approach of bonding active molecules on bioinert nanoparticles can serve as an effective methodology for minimizing health concerns about biodegradable chemical sensors. This article is protected by copyright. All rights reserved.

High-performing fiber electrodes based on a gold-shelled silver nanowire framework for bioelectronics.

Flexible fiber electrodes offer new opportunities for bioelectronics and are reliable in vivo applications, high flexibility, high electrical conductivity, and satisfactory biocompatibility are typically required. Herein, we present an all-metal flexible and biocompatible fiber electrode based on a metal nanowire hybrid strategy, i.e., silver nanowires were assembled on a freestanding framework, and further to render them inert, they were plated with a gold nanoshell. Our fiber electrodes exhibited a low modulus of ∼75 MPa and electrical conductivity up to ∼4.8 × 106 S m-1. They can resist chemical erosion with negligible leakage of biotoxic silver ions in the physiological environment, thus ensuring satisfactory biocompatibility. Finally, we demonstrated the hybrid fiber as a neural electrode that stimulated the sciatic nerve of a mouse, proving its potential for applications in bioelectronics.

High-Performance Thermoelectric Fibers from Metal-Backboned Polymers for Body-Temperature Wearable Power Devices.

Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric composite fiber. It demonstrated a power factor of 719.48 µW ⋅m-1 K-2, which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the composite fiber further showed simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.

A novel radiomics nomogram based on T2-sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) images for predicting cochlear and vestibular endolymphatic hydrops in Meniere's disease patients.

OBJECTIVES: To construct and validate a radiomics nomogram based on T2-sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) images for predicting cochlear and vestibular endolymphatic hydrops (EH) in Meniere's disease patients. METHODS: A total of 156 patients (312 affected ears) with bilateral definite Meniere's disease who underwent delayed enhancement MRI scans were enrolled in this study. All ears of the patients were divided into a training set (n = 218) and an internal validation set (n = 94). A radiomics nomogram was constructed from radiomics features extracted from the T2-SPACE images, and a radiomics score was calculated. Performance of the radiomics nomogram was assessed using receiver operating characteristics analysis. RESULTS: Five features were selected for the construction of the cochlear radiomics nomogram, and seven features for the vestibular radiomics nomogram. The radiomics nomograms exhibited robust performance in differentiating between EH-positive and EH-negative statuses in both training and validation cohorts, with the area under the receiver operating characteristics curve values for cochlear and vestibular radiomic nomograms being 0.703 and 0.728 in the training set, and 0.718 and 0.701 in the validation set, respectively. CONCLUSION: The novel radiomics nomograms based on T2-SPACE images were successfully constructed to predict cochlear and vestibular EH in Meniere's disease. The models showed a solid and superior performance and may play an important role in the EH prediction. CLINICAL RELEVANCE STATEMENT: We constructed a novel radiomics nomogram, which can be a very useful tool for predicting cochlear and vestibular endolymphatic hydrops in Meniere's disease patients. KEY POINTS: • This is the first T2-SPACE-based nomogram to predict cochlear and vestibular endolymphatic hydrops. • The nomogram is of great value to patients who are unable to undergo delayed enhancement MRI scans.

Unraveling nitrogen loss in paddy soils: A study of anaerobic nitrogen transformation in response to various irrigation practice.

Soil nitrogen (N) transformation processes, encompassing denitrification, anaerobic ammonium oxidation (anammox), and anaerobic ammonium oxidation coupled with iron reduction (Feammox), constitute the primary mechanisms of soil dinitrogen (N2) loss. Despite the significance of these processes, there is a notable gap in research regarding the assessment of managed fertilization and irrigation impacts on anaerobic N transformations in paddy soil, crucial for achieving sustainable soil fertility management. This study addressed the gap by investigating the contributions of soil denitrification, anammox, and Feammox to N2 loss in paddy soil across varying soil depths, employing different fertilization and irrigation practices by utilizing N stable isotope technique for comprehensive insights. The results showed that anaerobic N transformation processes decreased with increasing soil depth under alternate wetting and drying (AWD) irrigation, but increased with the increasing soil depth under conventional continuous flooding (CF) irrigation. The denitrification and anammox rates varied from 0.41 to 2.12 mg N kg-1 d-1 and 0.062-0.394 mg N kg-1 d-1, respectively, which accounted for 84.3-88.1% and 11.8-15.7% of the total soil N2 loss. Significant correlations were found among denitrification rate and anammox rate (r = 0.986, p < 0.01), Fe (Ⅲ) reduction rate and denitrification rate (r = 0.527, p < 0.05), and Fe(Ⅲ) reduction rate and anammox rate (r = 0.622, p < 0.05). Moreover, nitrogen loss was more pronounced in the surface layer of the paddy soil compared to the deep layer. The study revealed that denitrification predominantly contributed to N loss in the surface soil, while Feammox emerged as a significant N loss pathway at depths ranging from 20 to 40 cm, accounting for up to 26.1% of the N loss. It was concluded that fertilization, irrigation, and soil depth significantly influenced anaerobic N transformation processes. In addition, the CF irrigation practice is best option to reduce N loss under managed fertilization. Furthermore, the role of microbial communities and their response to varying soil depths, fertilization practices, and irrigation methods could enhance our understanding on nitrogen loss pathways should be explored in future study.

Emerging mechanisms and implications of cGAS-STING signaling in cancer immunotherapy strategies.

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment. Within this landscape, the innate immune system, a critical sentinel protecting against tumor incursion, is a key player. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway has been found to be a linchpin of innate immunity: activation of this signaling pathway orchestrates the production of type I interferon (IFN-α/ß), thus fostering the maturation, differentiation, and mobilization of immune effectors in the tumor microenvironment. Furthermore, STING activation facilitates the release and presentation of tumor antigens, and therefore is an attractive target for cancer immunotherapy. Current strategies to activate the STING pathway, including use of pharmacological agonists, have made substantial advancements, particularly when combined with immune checkpoint inhibitors. These approaches have shown promise in preclinical and clinical settings, by enhancing patient survival rates. This review describes the evolving understanding of the cGAS-STING pathway's involvement in tumor biology and therapy. Moreover, this review explores classical and non-classical STING agonists, providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies. Despite challenges and complexities, the cGAS-STING pathway, a promising avenue for enhancing cancer treatment efficacy, has the potential to revolutionize patient outcomes.

A Fiber Sensor for Long-Term Monitoring of Extracellular Potassium Ion Fluctuations in Chronic Neuropsychiatric Diseases.

The extracellular potassium ion concentration in the brain exerts a significant influence on cellular excitability and intercellular communication. Perturbations in the extracellular potassium ion level are closely correlated with various chronic neuropsychiatric disorders including depression. However, a critical gap persists in performing real-time and long-term monitoring of extracellular potassium ions, which is necessary for comprehensive profiling of chronic neuropsychiatric diseases. Here, a fiber potassium ion sensor (FKS) that consists of a soft conductive fiber with a rough surface and a hydrophobic-treated transduction layer interfaced with a potassium ion-selective membrane is found to solve this problem. The FKS demonstrates stable interfaces between its distinct functional layers in an aqueous environment, conferring an exceptional stability of 6 months in vivo, in stark contrast to previous reports with working durations from hours to days. Upon implantation into the mouse brain, the FKS enables effective monitoring of extracellular potassium ion dynamics under diverse physiological states including anesthesia, forced swimming, and tail suspension. Using this FKS, tracking of extracellular potassium ion fluctuations that align with behaviors associated with the progression of depression over months is achieved, demonstrating its usability in studying chronic neuropsychiatric disorders from a new biochemical perspective.

Reinforcing the immunogenic cell death to enhance cancer immunotherapy efficacy.

Immunogenic cell death (ICD) has been a revolutionary modality in cancer treatment since it kills primary tumors and prevents recurrent malignancy simultaneously. ICD represents a particular form of cancer cell death accompanied by production of damage-associated molecular patterns (DAMPs) that can be recognized by pattern recognition receptors (PRRs), which enhances infiltration of effector T cells and potentiates antitumor immune responses. Various treatment methods can elicit ICD involving chemo- and radio-therapy, phototherapy and nanotechnology to efficiently convert dead cancer cells into vaccines and trigger the antigen-specific immune responses. Nevertheless, the efficacy of ICD-induced therapies is restrained due to low accumulation in the tumor sites and damage of normal tissues. Thus, researchers have been devoted to overcoming these problems with novel materials and strategies. In this review, current knowledge on different ICD modalities, various ICD inducers, development and application of novel ICD-inducing strategies are summarized. Moreover, the prospects and challenges are briefly outlined to provide reference for future design of novel immunotherapy based on ICD effect.

Automated Prediction of Early Recurrence in Advanced Sinonasal Squamous Cell Carcinoma With Deep Learning and Multi-parametric MRI-based Radiomics Nomogram.

RATIONALE AND OBJECTIVES: Preoperative prediction of the recurrence risk in patients with advanced sinonasal squamous cell carcinoma (SNSCC) is critical for individualized treatment. To evaluate the predictive ability of radiomics signature (RS) based on deep learning and multiparametric MRI for the risk of 2-year recurrence in advanced SNSCC. MATERIALS AND METHODS: Preoperative MRI datasets were retrospectively collected from 265 SNSCC patients (145 recurrences) who underwent preoperative MRI, including T2-weighted (T2W), contrast-enhanced T1-weighted (T1c) sequences and diffusion-weighted (DW). All patients were divided into 165 training cohort and 70 test cohort. A deep learning segmentation model based on VB-Net was used to segment regions of interest (ROIs) for preoperative MRI and radiomics features were extracted from automatically segmented ROIs. Least absolute shrinkage and selection operator (LASSO) and logistic regression (LR) were applied for feature selection and radiomics score construction. Combined with meaningful clinicopathological predictors, a nomogram was developed and its performance was evaluated. In addition, X-title software was used to divide patients into high-risk or low-risk early relapse (ER) subgroups. Recurrence-free survival probability (RFS) was assessed for each subgroup. RESULTS: The radiomics score, T stage, histological grade and Ki-67 predictors were independent predictors. The segmentation models of T2WI, T1c, and apparent diffusion coefficient (ADC) sequences achieved Dice coefficients of 0.720, 0.727, and 0.756, respectively, in the test cohort. RS-T2, RS-T1c and RS-ADC were derived from single-parameter MRI. RS-Combined (combined with T2WI, T1c, and ADC features) was derived from multiparametric MRI and reached area under curve (AUC) and accuracy of 0.854 (0.749-0.927) and 74.3% (0.624-0.840), respectively, in the test cohort. The calibration curve and decision curve analysis (DCA) illustrate its value in clinical practice. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (p < 0.001). CONCLUSION: Automated nomograms based on multi-sequence MRI help to predict ER in SNSCC patients preoperatively.

Cancer-associated fibroblasts-derived FMO2 as a biomarker of macrophage infiltration and prognosis in epithelial ovarian cancer.

OBJECTIVE: Recent molecular profiling revealed that cancer-associated fibroblasts (CAFs) are essential for matrix remodeling and tumor progression. Our study aimed to investigate the role of flavin-containing monooxygenase 2 (FMO2) in epithelial ovarian cancer (EOC) as a novel CAF-derived prognostic biomarker. METHODS: Primary fibroblasts were isolated from EOC samples. Microdissection and single-cell RNA sequencing (scRNA-seq) datasets (including TCGA, GSE9891, GSE63885, GSE118828 and GSE178913) were retrieved to determine the expression profiles. Gene set enrichment analysis (GSEA) was used to explore the correlation between FMO2 and stromal activation as well as immune infiltration. The predictive value of FMO2 and combined macrophage infiltration level was verified in an independent EOC cohort (n = 113). RESULTS: We demonstrated that FMO2 was upregulated in tumor stroma and correlated with fibroblast activation. Besides, FMO2 had the predictive power for worse clinical outcome of EOC patients. In the mesenchymal subtype of EOC, the FMO2-defined signature revealed that FMO2 contributed to infiltration of tumor-infiltrating lymphocytes. Moreover, we confirmed the positive correlation between FMO2 and CD163+ cell infiltration level in EOC tissues, and showed that combination of FMO2 expression with CD163+ cell infiltration level in the tumor stroma could predict poor overall survival (HR = 3.63, 95% CI = 1.93-6.84, p = 0.0008). Additionally, FMO2 also predicted the prognosis of patients with ovarian cancer based on the expression of immune checkpoints (such as PD-L1 and PD1). CONCLUSION: Our results address the tumor-supporting role of FMO2 in EOC and its association with immune components, and it might be a prospective target for stroma-oriented therapies against EOC.

Apparent Diffusion Coefficient-Based Radiomic Nomogram in Sinonasal Squamous Cell Carcinoma: A Preliminary Study on Histological Grade Evaluation.

PURPOSE: The aim of the study was to develop and validate a nomogram model combining radiomic features and clinical characteristics to preoperatively differentiate between low- and high-grade sinonasal squamous cell carcinomas. MATERIAL AND METHODS: A total of 174 patients who underwent diffusion-weighted imaging were included in this study. The patients were allocated to the training and testing cohorts randomly at a ratio of 6:4. The least absolute shrinkage and selection operator regression was applied for feature selection and radiomic signature (radscore) construction. Multivariable logistic regression analysis was applied to identify independent predictors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), the calibration curve, decision curve analysis, and the clinical impact curve. RESULTS: The radscore included 9 selected radiomic features. The radscore and clinical stage were independent predictors. The nomogram showed better performance (training cohort: AUC, 0.92; 95% confidence interval, 0.85-0.96; testing cohort: AUC, 0.91; 95% CI, 0.82-0.97) than either the radscore or the clinical stage in both the training and test cohorts ( P < 0.050). The nomogram demonstrated good calibration and clinical usefulness. CONCLUSIONS: The apparent diffusion coefficient-based radiomic nomogram model could be useful in differentiating between low- and high-grade sinonasal squamous cell carcinomas.

A Clinical-Radiomics Nomogram Based on the Apparent Diffusion Coefficient (ADC) for Individualized Prediction of the Risk of Early Relapse in Advanced Sinonasal Squamous Cell Carcinoma: A 2-Year Follow-Up Study.

Purpose: To develop and validate a nomogram model combining radiomic features and clinical characteristics to preoperatively predict the risk of early relapse (ER) in advanced sinonasal squamous cell carcinomas (SNSCCs). Methods: A total of 152 SNSCC patients (clinical stage III-IV) who underwent diffusion-weighted imaging (DWI) were included in this study. The training cohort included 106 patients assessed at the headquarters of our hospital using MR scanner 1. The testing cohort included 46 patients assessed at the branch of our hospital using MR scanner 2. Least absolute shrinkage and selection operator (LASSO) regression was applied for feature selection and radiomic signature (radscore) construction. Multivariable logistic regression analysis was applied to identify independent predictors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA). Furthermore, the patients were classified into high- or low-risk ER subgroups according to the optimal cutoff value of the nomogram using X-tile. The recurrence-free survival probability (RFS) of each subgroup was assessed. Results: ER was noted in 69 patients. The radscore included 8 selected radiomic features. The radscore, T stage and surgical margin were independent predictors. The nomogram showed better performance (AUC = 0.92) than either the radscore or the clinical factors in the training cohort (P < 0.050). In the testing cohort, the nomogram showed better performance (AUC = 0.92) than the clinical factors (P = 0.016) and tended to show better performance than the radscore (P = 0.177). The nomogram demonstrated good calibration and clinical utility. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (P < 0.001). Conclusions: The ADC-based radiomic nomogram model is potentially useful in predicting the risk of ER in advanced SNSCCs.

The Immunological Contribution of a Novel Metabolism-Related Signature to the Prognosis and Anti-Tumor Immunity in Cervical Cancer.

Cervical cancer is the most frequently diagnosed malignancy in the female reproductive system. Conventional stratification of patients based on clinicopathological characters has gradually been outpaced by a molecular profiling strategy. Our study aimed to identify a reliable metabolism-related predictive signature for the prognosis and anti-tumor immunity in cervical cancer. In this study, we extracted five metabolism-related hub genes, including ALOX12B, CA9, FAR2, F5 and TDO2, for the establishment of the risk score model. The Kaplan-Meier curve suggested that patients with a high-risk score apparently had a worse prognosis in the cervical cancer training cohort (TCGA, n = 304, p < 0.0001), validation cohort (GSE44001, n = 300, p = 0.0059) and pan-cancer cohorts (including nine TCGA tumors). Using a gene set enrichment analysis (GSEA), we observed that the model was correlated with various immune-regulation-related pathways. Furthermore, pan-cancer cohorts and immunohistochemical analysis showed that the infiltration of tumor infiltrating lymphocytes (TILs) was lower in the high-score group. Additionally, the model could also predict the prognosis of patients with cervical cancer based on the expression of immune checkpoints (ICPs) in both the discovery and validation cohorts. Our study established and validated a metabolism-related prognostic model, which might improve the accuracy of predicting the clinical outcome of patients with cervical cancer and provide guidance for personalized treatment.

Differences in Glycerolipid Response of Chlamydomonas reinhardtii Starchless Mutant to High Light and Nitrogen Deprivation Stress Under Three Carbon Supply Regimes.

Carbon source serves as a crucial factor for microalgal lipid biosynthesis. The supplied exogenous inorganic or organic carbon affects lipid accumulation in microalgae under stress conditions. However, the impacts of different carbon availability on glycerolipid metabolism, triacylglycerol (TAG) metabolism in particular, still remain elusive in microalgae. Chlamydomonas starchless mutant BAFJ5 has emerged as a model system to study TAG metabolism, due to its property of hyper-accumulating TAG. In this study, the glycerolipidomic response of the starchless BAFJ5 to high light and nitrogen-deprived (HL-N) stress was deciphered in detail to distinguish glycerolipid metabolism under three carbon supply regimes. The results revealed that the autotrophically and mixotrophically grown BAFJ5 cells aerated with air containing 2% CO2 presented similar changes in growth, photosynthetic activity, biochemical components, and glycerolipid metabolism under HL-N conditions. But the mixotrophically grown BAFJ5 aerated with air containing 0.04% CO2 exhibited more superior accumulation in TAG, which was esterified with a significantly higher proportion of C18:1n9 and prominently the lower proportions of polyunsaturated fatty acids. In addition, these cells increased the relative levels of C18:2n6 in the membrane lipids, i.e., monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), in priority, and decreased that of C18:3n3 and C18:4n3 in the betaine lipid, N,N,N-trimethylhomoserine diacylglycerol (DGTS), subsequently, to adapt to the HL-N stress conditions, compared to the cells under the other two conditions. Thus, it was suggested that C. reinhardtii starchless mutant appeared to present distinct metabolism for TAG biosynthesis involving membrane lipid remodeling under distinct carbon supply regimes. This study provides insights into how the different carbon supply regimes affect lipid metabolism in Chlamydomonas starchless cells, which will benefit the optimized production of storage lipids in microalgae.

Emerging role of RNA sensors in tumor microenvironment and immunotherapy.

RNA sensors detect foreign and endogenous RNAs to protect the host by initiating innate and adaptive immune response. In tumor microenvironment (TME), activation of RNA sensors induces tumor-inhibitory cytotoxic T lymphocyte responses and inhibits the activity of immunosuppressive cells though stimulating type I IFN signaling pathway. These characteristics allow RNA sensors to be prospective targets in tumor immunotherapy. Therefore, a comprehensive understanding of the roles of RNA sensors in TME could provide new insight into the antitumor immunotherapy. Moreover, RNA sensors could be prominent triggering targets to synergize with immunotherapies. In this review, we highlight the diverse mechanisms of RNA sensors in cancer immunity and their emerging contributions in cancer immunotherapy, including monotherapy with RNA sensor agonists, as well as combination with chemotherapy, radiotherapy, immune checkpoint blockade or cancer vaccine.

Achieving Partial Nitrification-Anammox Process Dependent on Microalgal-Bacterial Consortia in a Photosequencing Batch Reactor.

Partial nitrification coupled with anammox (PN/A) process is an energy-efficient approach for nitrogen removal from low C/N wastewater. In this study, PN/A was achieved with optimal oxygen supply from a green microalga, Chlorella sorokiniana. The PN process was first initiated within 35 days, and the following algae-intensified PN then reached the steady state within the next 32 days. The dissolved oxygen (DO) concentration was gradually maintained at 0.6 mg L-1 via adjusting the photoperiod to 6-h light/18-h dark cycles, when the accumulation ratio of NO2 --N and the removal ratio of NH4 +-N were both more than 90%. The nitrogen removal capability of anammox was acclimated via elevating the individual effluent NH4 +-N and NO2 --N levels from 100 to 200, to 300 mg L-1. After acclimation, the removal rates of NH4 +-N and total nitrogen (TN) reached more than 70 and 80%, respectively, and almost all the NO2 --N was removed. Then, the algae-intensified PN/A, algammox biofilm system, was successfully started up. When the NH4 +-N level increased from 100 to 300 mg L-1, the TN removal varied between 78 and 82%. In the photosequencing bioreactor, C. sorokiniana, ammonia-oxidizing bacteria (AOB), and anammox coexisted with an illumination of 200 µmol m-2 s-1 and a 6-h light/18-h dark cycles. The DO levels ranged between 0.4 and 0.5 mg L-1. In addition, the microbial community analysis by Illumina MiSeq sequencing showed that the dominant functional bacteria in the algae-intensified PN/A reactors included Nitrosomonas (AOB) and Candidatus Brocadia (anammox), while Nitrospira and Nitrobacter (nitrite oxidizing bacteria), together with Denitratisoma (denitrifier) were largely inhibited. Further studies are required to optimize the microalgal-bacterial consortia system to achieve superior nitrogen removal rates under controllable conditions.

Cell pyroptosis in health and inflammatory diseases.

Inflammation is a defense mechanism that can protect the host against microbe invasion. A proper inflammatory response can maintain homeostasis, but continuous inflammation can cause many chronic inflammatory diseases. To properly treat inflammatory disorders, the molecular mechanisms underlying the development of inflammation need to be fully elucidated. Pyroptosis is an inflammation-related cell death program, that is different from other types of cell death. Pyroptosis plays crucial roles in host defense against infections through the release of proinflammatory cytokines and cell lysis. Accumulating evidence indicates that pyroptosis is associated with inflammatory diseases, such as arthritis, pneumonia, and colonitis. Furthermore, pyroptosis is also closely involved in cancers that develop as a result of inflammation, such as liver cancer, esophageal cancer, pancreatic cancer, and colon cancer. Here, we review the function and mechanism of pyroptosis in inflammatory disease development and provide a comprehensive description of the potential role of pyroptosis in inflammatory diseases.

Increased co-expression of MEST and BRCA1 is associated with worse prognosis and immune infiltration in ovarian cancer.

OBJECTIVE: The crosstalk between tumor microenvironment (TME) and cancer cells plays a critical role in the occurrence and development of ovarian cancer. Imprinted gene MEST is a tumor-promoting factor that modulates several carcinogenic signaling pathways. This study aimed to investigate the expression pattern of MEST and its association with immune cell infiltration. METHODS: The transcriptome data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database was utilized, and the expression and immune characteristics of MEST were verified by immunohistochemistry of ovarian cancer specimens. Kaplan-Meier Plotter was used to assess the prognostic value in patients with ovarian cancer. RESULTS: We found that high expression of MEST was associated with diminished immune cell infiltration and worse prognosis of ovarian cancer patients in independent cohorts. There was a positive correlation between MEST and BRCA1 expression. The MESThighBRCA1high ovarian cancer group was correlated with lower infiltration of CD4+ cells, CD57+ cells, CD68+ cells and MPO+ cells, had worse overall survival (OS) in TCGA (HR = 1.57, p = 0.0004) and GSE27651 (HR = 4.27, p = 0.0002) cohorts, and predicted poor progress free survival (PFS) in GSE9891 (HR = 1.76, p = 0.0098) and GSE15622 (HR = 4.80, p = 0.0121) cohorts. Moreover, the expression of PD-L1 predicted unfavorable OS (HR = 2.48, p = 0.0415) and PFS (HR = 2.36, p = 0.0215) in MESTlowBRCA1low ovarian cancer group in GSE9891 cohort. CONCLUSION: These findings suggest that the co-expression of MEST and BRCA1 may be an ideal combination for predicting the prognosis and response to immunotherapy in patients with ovarian cancer.

High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer.

Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is frequently lost in breast cancer samples and is considered as a tumor suppressor. The roles and mechanisms of PAMR1 in other types of cancers are still unclear. In our present study, we identified PAMR1 as an invasion-related regulator in cervical cancer. Public database and immunohistochemical (IHC) analysis showed that the expression level of PAMR1 in cervical cancer tissues was lower than that in normal cervix tissues and was negatively related to clinicopathologic features. The high expression of PAMR1 also predicted a better prognosis of cervical cancer patients. CCK8, Transwell, and wound-healing assays demonstrated that knockdown of PAMR1 facilitated the proliferation, migration, and invasion of cervical cancer cells. Additionally, gene set enrichment analysis (GSEA) showed a variety of cancer-related pathways potentially activated or suppressed by PAMR1. Moreover, we verified that PAMR1 inhibited MYC target and mTORC1 signaling pathways. In conclusion, our study revealed the suppressor role of PAMR1 in cervical cancer, providing a new insight into the molecular mechanism of cervical cancer progression.

Dysregulated tumor-associated macrophages in carcinogenesis, progression and targeted therapy of gynecological and breast cancers.

Gynecological and breast cancers are a group of heterogeneous malignant tumors. Although existing treatment strategies have ameliorated the clinical outcomes of patients, the overall survival rate of advanced diseases remains unsatisfactory. Increasing evidence has indicated that the development and prognosis of tumors are closely related to the tumor microenvironment (TME), which restricts the immune response and provokes malignant progression. Tumor-associated macrophages (TAMs) are the main component of TME and act as a key regulator in tumor metastasis, immunosuppression and therapeutic resistance. Several preclinical trials have studied potential drugs that target TAMs to achieve potent anticancer therapy. This review focuses on the various functions of TAMs and how they influence the carcinogenesis of gynecological and breast cancers through regulating cancer cell proliferation, tumor angiogenesis and tumor-related immunosuppression. Besides, we also discuss the potential application of disabling TAMs signaling as a part of cancer therapeutic strategies, as well as CAR macrophages, TAMs-based vaccines and TAMs nanobiotechnology. These research advances support that targeting TAMs combined with conventional therapy might be used as effective therapeutics for gynecological and breast cancers in the future.