Selenium inhibits ferroptosis in ulcerative colitis through the induction of Nrf2/Gpx4.

BACKGROUND AND AIM: Selenium, an essential micronutrient for human and has been reported to have a protective effect in ulcerative colitis (UC). However, the role of selenium in UC is unclear. Our aim was to investigate the mechanism of action of selenium in UC. METHODS: Serum selenium levels were measured in UC patients and healthy controls. In addition, the effect of sodium selenite supplementation on experimental colitis in mice treated with dextran sulfate sodium (DSS) was investigated. The effect of sodium selenite on IECs ferroptosis was evaluated by observing the cell mortality, intracellular ferrous content, lipid reactive oxygen species and mitochondrial membrane damage in DSS-treated Caco2 cells. In addition, glutathione peroxidase 4 (Gpx4) and nuclear factor erythroid 2-like 2 (Nrf2) were detected in Caco2 cells and mouse intestines to explore their mechanisms. RESULTS: The serum selenium content of UC patients was lower than that of healthy subjects. In addition, serum selenium levels were negatively correlated with disease activity. The in vivo results showed that selenium treatment could improve colitis induced by DSS and inhibit IECs ferroptosis. The in vitro results further showed that selenium inhibited the ferroptosis of Caco-2 cells induced by DSS. Nrf2/Gpx4 was up-regulated after selenium supplementation in vivo and in vitro. CONCLUSIONS: Serum selenium level is associated with IECs ferroptosis in UC patients. Selenium can relieve DSS-induced colitis and inhibit IECs ferroptosis by up-regulating the expression of Nrf2/Gpx4.

Establishment of Prognostic Nomogram for Male Breast Cancer Patients: A Surveillance, Epidemiology and End Results Database Analysis.

BACKGROUND: Male breast cancer (MBC) represents a rare subtype of breast cancer, with limited prognostic factor studies available. The purpose of this research was to develop a unique nomogram for predicting MBC patient overall survival (OS) and breast cancer-specific survival (BCSS). METHODS: From 2010 to 2020, clinical characteristics of male breast cancer patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Following univariate and multivariate analyses, nomograms for OS and BCSS were created. Kaplan-Meier plots were further generated to illustrate the relationship between independent risk variables and survival. The nomogram's ability to discriminate was measured by employing the area under a time-dependent receiver operating characteristic curve (AUC) and calibration curves. Additionally, when the nomogram was used to direct clinical practice, we also used decision curve analysis (DCA) to evaluate the clinical usefulness and net clinical benefits. RESULTS: A total of 2143 patients were included in this research. Univariate and multivariate analysis showed that age, grade, surgery, chemotherapy status, brain metastasis status, subtype, marital status, race, and AJCC-T, AJCC-N, and AJCC-M stages were significantly correlated with OS. Lung metastasis, age, marital status, grade, surgery, and AJCC-T, AJCC-N, and AJCC-M stages were significantly correlated with BCSS. By comprising these variables, a predictive nomogram was constructed in the SEER cohort. Then, it could be validated well in the validation cohort by receiver operating characteristics (ROCs) curve and calibration plot. Furthermore, the nomogram demonstrated better decision curve analysis (DCA) results, indicating the ability to forecast survival probability with greater accuracy. CONCLUSION: We created and validated a unique nomogram that can assist clinicians in identifying MBC patients at high risk and forecasting their OS/BCSS.

Cancer cell membrane-camouflaged paclitaxel/PLGA nanoparticles for targeted therapy against lung cancer.

Paclitaxel (PTX) is a first-line drug for the treatment of lung cancer, but its targeting and therapeutic effect are unsatisfactory. Herein, lung cancer cell (A549) membrane biomimetic PTX-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (AM@PTX-NPs) were constructed to eliminate the shortcomings of PTX. The AM@PTX-NPs were successfully prepared with a high drug loading efficiency (10.90±0.06 %). Moreover, transmission electron microscopy, SDS-PAGE, and western blotting proved that AM@PTX-NPs were spherical nanoparticles camouflaged by the A549 cell membrane. Both in vitro and in vivo assays revealed that the AM@PTX-NPs displayed outstanding targeting capacity due to A549 membrane modification. The cytotoxicity experiment showed that the developed biomimetic formulation was able to effectively reduce the proliferation of A549 cells. Moreover, AM@PTX-NPs exhibited a significant tumor growth inhibition rate (73.00 %) with good safety in the tumor-bearing mice, which was higher than that of the PTX-NPs without A549 membrane coating (37.39 %). Overall, the constructed bioinspired vector could provide a novel platform for the PTX delivery and demonstrated a promising strategy for the targeted cancer treatment.

Ultrastable Organic Anode Enabled by Electrochemically Active MXene Binder toward Advanced Potassium Ion Storage.

Conjugated carbonyl compounds are regarded as promising organic anode materials for potassium ion batteries (PIBs) due to their rich redox sites, excellent reversibility, and structural tunability, but their low electrical conductivity and severe solubility in organic electrolytes have substantially restricted their practical application. Herein, 2D MXene is utilized as an electrochemically active binder to fabricate perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) electrodes for high-performance PIBs. MXene, coupled with Super-P particles, served as a binder and conductive matrix to facilitate rapid ion and electron transport, restrain the solubility of PTCDA, promote potassium adsorption, and alleviate the volume expansion of PTCDA during potassiation. Consequently, the PTCDA electrode bonded by the MXene/Super-P system delivers excellent potassium storage performance in terms of a high capacity of 462 mAh g-1 at 50 mA g-1, superior rate capability of 116.3 mAh g-1 at 2000 mA g-1, and stable cycle performance over 3000 cycles with a low capacity decay rate of ∼0.0033% per cycle. When configured with the PTCDA@450 cathode, an all-PTCDA potassium ion full cell delivers a maximum energy density of 179.5 Wh kg-1, indicating the superiority of MXene as an electrochemically active binder to promote the practical application of organic anodes for PIBs.

Biomimetic platelet-like nanoparticles enhance targeted hepatocellular carcinoma therapy.

Curcumin (CUR) is a promising natural product for hepatocellular carcinoma (HCC) therapy. However, its clinical application has been limited by some issues such as rapid clearance and inadequate tumor accumulation. To address these drawbacks, we developed platelet membrane-coated CUR-loaded PLGA nanoparticles (PCPNPs). In this work, due to the bioinspired strategy, the PCPNPs exhibited immune evasion, prolonged circulation, and improved accumulation at tumor sites compared to the traditional CUR formulation. The superior tumor targeting of PCPNPs was likely due to the interactions between platelet P-selectin and tumoral CD44. Furthermore, both in vitro and in vivo assays revealed that the PCPNPs showed outstanding anticancer efficacy without obvious toxicity. Therefore, PCPNPs represent a biosafe and promising anti-tumor strategy, overcoming the limitations associated with CUR. These findings not only contribute to the advancement of natural compound nano-formulation but also open new avenues for targeted cancer treatment.

A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.

Recombinant adeno-associated virus (rAAV)-based gene therapy is entering clinical and commercial stages at an unprecedented pace. Triple transfection of HEK293 cells is currently the most widely used platform for rAAV manufacturing. Here, we develop low-cis triple transfection that decreases transgene plasmid use by 10- to 100-fold and overcomes several major limitations associated with standard triple transfection. This new method improves packaging of yield-inhibiting transgenes by up to 10-fold, and generates rAAV batches with reduced plasmid backbone contamination that otherwise cannot be eliminated in downstream processing. When tested in mice and compared with rAAV produced by standard triple transfection, low-cis rAAV shows comparable or superior potency and results in diminished plasmid backbone DNA and RNA persistence in tissue. Mechanistically, low-cis triple transfection relies on the extensive replication of transgene cassette (i.e., inverted terminal repeat-flanked vector DNA) in HEK293 cells during production phase. This cost-effective method can be easily implemented and is widely applicable to producing rAAV of high quantity, purity, and potency.

A sensitive fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies to detect the H1N1 virus.

We propose a sensitive H1N1 virus fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies. Products are generated via the hybridization of single-stranded DNA (ssDNA) probes containing T7 promoter and crRNA templates to a target RNA sequence using SplintR ligase. This generates large crRNA quantities in the presence of T7 RNA polymerase. At such crRNA quantities, ternary Cas13a, crRNA, and activator complexes are successfully constructed and activate Cas13a to enhance fluorescence signal outputs. The biosensor sensitively and specifically monitored H1N1 viral RNA levels down to 3.23 pM and showed good linearity when H1N1 RNA concentrations were 100 pM-1 µM. Biosensor specificity was also excellent. Importantly, our biosensor may be used to detect other viral RNAs by altering the sequences of the two probe junctions, with potential applications for the clinical diagnosis of viruses and other biomedical studies.

Enhanced cellular therapy: revolutionizing adoptive cellular therapy.

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy.

Knowledge mapping of application of image-guided surgery in prostate cancer: a bibliometric analysis (2013-2023).

BACKGROUND: Image-guided surgery (IGS) refers to surgery navigated by medical imaging technology, helping doctors better clarify tumor boundaries, identify metastatic lymph nodes and preserve surrounding healthy tissue function. Recent studies have provided expectable momentum of the application of IGS in prostate cancer (PCa). The authors aim to comprehensively construct a bibliometric analysis of the application of IGS in PCa. METHOD: The authors searched publications related to application of IGS in PCa from 2013 to 2023 on the web of science core collection (WoSCC) databases. VOSviewer, CiteSpace, and R package 'bibliometrix' were used for bibliometric analysis. RESULTS: Two thousand three eighty-nine articles from 75 countries and 2883 institutions led by the United States were included. The number of publications related to the application of IGS in PCa kept high in the last decade. Johns Hopkins University is the top research institutions. Journal of Nuclear Medicine has the highest popularity as the selection of journal and co-cited journal. Pomper Martin G. had published the most paper. Ali Afshar-Oromieh was co-cited most frequently. The clinical efficacy of PSMA-PET/CT in PCa diagnosis and treatment are main topics in this research field, with emerging focuses on the use of fluorescence imaging guidance technology in PCa. 'PSMA' and 'PET/CT' are the main keywords as long-term research hotspots. CONCLUSION: This study is the first bibliometric analysis of researches on application of IGS in PCa with three recognized bibliometric software, providing an objective description and comprehensive guidance for the future relevant investigations.

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.

BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.

High-Performance Sulfurized Polyacrylonitrile Cathode by Using MXene as a Conductive and Catalytic Binder for Room-Temperature Na/S Batteries.

Sulfurized polyacrylonitrile (PAN@S) is a promising cathode material for room-temperature Na/S batteries but suffers from low conductivity and insufficient electrochemical activity, resulting in unsatisfactory actual capacity and rate performance. Herein, Ti3C2Tx MXene nanosheets are used as a conductive and catalytic binder to establish the PAN@S electrode, wherein MXene constructs a highly conductive framework for fast charge transport and provides high catalytic effect to improve the active material utilization and accelerate the redox kinetics significantly. Therefore, the PAN@S electrode bonded by MXene shows an electronic conductivity of 5.05 S cm-1, 4 orders of magnitude higher than the conventional electrodes bonded by the insulative polymer binders, and much decreased activation energy barrier and resistance. Consequently, the PAN@S electrode displays superior performance in terms of high capacity (697.3 mAh g-1 at 200 mA g-1), unparalleled rate capability (189.0 mAh g-1 at 20 A g-1), and excellent high-rate cycling performance (a capacity decay rate of ∼0.04% per cycle during 1000 cycles at 5 A g-1). This work provides a high-performance electrode for room-temperature Na/S batteries and shows the promising potential of conductive and catalytic MXene binders in boosting the performance of active materials.

Nonylphenol and its derivatives: Environmental distribution, treatment strategy, management and future perspectives.

In recent years, emerging pollutants, including nonylphenol (NP) and nonylphenol ethoxylate (NPE), have become a prominent topic. These substances are also classified as persistent organic pollutants. NP significantly affects the hormone secretion of organisms and exhibits neurotoxicity, which can affect the human hippocampus. Therefore, various countries are paying increased attention to NP regulation. NPEs are precursors of NPs and are widely used in the manufacture of various detergents and lubricants. NPEs can easily decompose into NPs, which possess strong biological and environmental toxicity. This review primarily addresses the distribution, toxicity mechanisms and performance, degradation technologies, management policies, and green alternative reagents of NPs and NPEs. Traditional treatment measures have been unable to completely remove NP from wastewater. With the progressively tightening management and regulatory policies, identifying proficient and convenient treatment methods and a sustainable substitute reagent with comparable product effectiveness is crucial.

Structural basis for antibody recognition of the proximal MUC16 ectodomain.

BACKGROUND: Mucin 16 (MUC16) overexpression is linked with cancer progression, metastasis, and therapy resistance in high grade serous ovarian cancer and other malignancies. The cleavage of MUC16 forms independent bimodular fragments, the shed tandem repeat sequence which circulates as a protein bearing the ovarian cancer biomarker (CA125) and a proximal membrane-bound component which is critical in MUC16 oncogenic behavior. A humanized, high affinity antibody targeting the proximal ectodomain represents a potential therapeutic agent against MUC16 with lower antigenic potential and restricted human tissue expression. RESULTS: Here, we demonstrate the potential therapeutic versatility of the humanized antibody as a monoclonal antibody, antibody drug conjugate, and chimeric antigen receptor. We report the crystal structures of 4H11-scFv, derived from an antibody specifically targeting the MUC16 C-terminal region, alone and in complex with a 26-amino acid MUC16 segment resolved at 2.36 Å and 2.47 Å resolution, respectively. The scFv forms a robust interaction with an epitope consisting of two consecutive ß-turns and a ß-hairpin stabilized by 2 hydrogen bonds. The VH-VL interface within the 4H11-scFv is stabilized through an intricate network of 11 hydrogen bonds and a cation-π interaction. CONCLUSIONS: Together, our studies offer insight into antibody-MUC16 ectodomain interaction and advance our ability to design agents with potentially improved therapeutic properties over anti-CA125 moiety antibodies.

Interfacial Engineering and Coupling of MXene/Reduced Graphene Oxide/C3 N4 Aerogel with Optimized d-Band Center as a Free-Standing Sulfur Carrier for High-Performance Li-S Batteries.

To overcome the shuttle effect and improve the energy density of Li-S batteries, developing free-standing sulfur carriers with high capture and catalytic effect towards polysulfides is an effective strategy. Herein, a MXene/reduced graphene oxide/C3 N4 aerogel (MG/C3 N4 ) with three-dimensional architecture prepared through low-temperature hydrothermal approach followed by thermal treatment is used as sulfur carrier for free-standing cathode of Li-S batteries. In the MG/C3 N4 , MXene and rGO construct a highly conductive framework, and the MXene nanosheets offer chemical capture and catalytic activity towards lithium polysulfides, in favor of good cycling stability. The introduction of g-C3 N4 further enhances the reactivity of C-Ti-N at the hetero-interface by engineering the electronic state of Ti atoms, leading to the optimized metal d-band for expediting the multistep conversion of sulfur electrochemistry. Therefore, the free-standing sulfur cathode with MG/C3 N4 carrier achieves excellent performance with a capacity of 1315.6 mAh g-1 at 0.2 C and a capacity retention of 97.5% after 100 cycles as well as superior rate capability with 1167.4 mAh g-1 at 2 C. Even at a high sulfur loading of 4.92 mg cm-2 , the cathode remains 940.3 mAh g-1 (4.62 mAh cm-2 ) after 200 cycles, indicating its promising potential for achieving high-performance Li-S batteries.

Microplastics could alter invasive plant community performance and the dominance of Amaranthus palmeri.

The increase in alien plant invasions poses a major threat to global biodiversity and ecosystem stability. However, the presence of microplastics (MPs) as an environmental stressor could impact the interactions between invasive and native species in an invasive plant community. Nevertheless, the community alterations and underlying mechanisms resulting from these interactions remain unclear. Herein, we systematically investigated the impacts of polyethylene (PE) and polypropylene (PP) on invasive plant communities invaded by Amaranthus palmeri through soil seed bank. The results illustrated that MPs markedly declined community height and biomass, and altered community structure, low-dose MPs could prominently increase community invasion resistance, but reduced community stability. The niche width and niche overlap of A. palmeri and S. viridis declined when exposed to high-dose MPs, but MPs elicited a significant rise in the niche width of S. salsa. PP had the potential to reduce the diversity of invasive plant community. Structural equation model revealed that PP addition could change soil total phosphorus content, thereby leading to a reduction of the community stability. Our study helps to fill the knowledge gap regarding the effects of MPs on invasive plant communities and provide new perspectives for invasive plant management.

Chattonella marina blooms in a trophic gradient system: Interaction with environmental drivers.

For coastal eutrophication, lots of studies focused on the influence from environmental factors, especially nitrogen and phosphorus, on algae blooms. The interaction between algae and environmental factors has been often ignored. Using Chattonella marina, a dominant species in marine algal blooms, we established a trophic gradient system that simulated C. marina blooms at three trophic levels: eutrophic, mesotrophic, and oligotrophic, and examined the life history patterns of C. marina and the interactions with environmental factors. Increased trophic levels influenced the growth potential of C. marina, while its unique cyst reproduction allowed it to thrive in nutrient-limited environments. Adequate nutrients caused changes in dissolved oxygen (DO) and pH led by C. marina, with the carbonate system playing a crucial role in regulating pH under nutrient-limited conditions. Limiting the growth of C. marina in areas with low nutrient by manipulating reactive silicate (SiO32-) availability may prove effective. Nitrate (NO3-) was the preferred nutrient for C. marina when its concentration exceeded that of ammonium (NH4+). Phosphorus played a crucial role in the growth and proliferation of C. marina, especially when other nutrients were scarce. The findings of this study may provide valuable insights into the effective management and prevention of algae blooms.

Bose Condensation of Upper-Branch Exciton-Polaritons in a Transferable Microcavity.

Exciton-polaritons are composite quasiparticles that result from the coupling of excitonic transitions and optical modes. They have been extensively studied because of their quantum phenomena and potential applications in unconventional coherent light sources and all-optical control elements. In this work, we report the observation of Bose-Einstein condensation of the upper polariton branch in a transferable WS2 monolayer microcavity. Near the condensation threshold, we observe a nonlinear increase in upper polariton intensity accompanied by a decrease in line width and an increase in temporal coherence, all of which are hallmarks of Bose-Einstein condensation. Simulations show that this condensation occurs within a specific particle density range, depending on the excitonic properties and pumping conditions. The manifestation of upper polariton condensation unlocks new possibilities for studying the condensate competition while linking it to practical realizations in polaritonic lasers. Our findings contribute to the understanding of bosonic systems and offer potential for the development of polaritonic devices.

Corneal metabolic biomarkers for moderate and high myopia in human.

This study aimed to identify the corneal metabolic biomarkers for moderate and high myopia in human. We enrolled 221 eyes from 221 subjects with myopia to perform the femtosecond laser small incision lenticule extraction (SMILE) surgery. Among these, 71 eyes of 71 subjects were enrolled in the low myopic group, 75 eyes of 75 subjects in the moderate myopic group and 75 eyes of 75 subjects in the high myopic group. The untargeted metabolomics analysis was performed to analyze the corneal tissues extracted during the SMILE surgery using an ultra-high-performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight (Q-TOF) mass spectrometry (MS). The one-way analysis of variance (ANOVA) was used to identify the different metabolites among the three myopic groups, the orthogonal partial least-squares discriminant analysis (OPLS-DA) model was used to reveal the different metabolites between moderate myopia and low myopia, and between high myopia and low myopia. The Venn gram was used to find the overlapped metabolites of the three datasets of the different metabolites. The stepwise multiple linear regression analysis was used to determine the metabolic molecules associated with manifest refractive spherical equivalents (MRSE). The Receiver Operating Characteristics (ROC) analysis was performed to reveal the corneal biomarkers for moderate and high myopia. The hub biomarker was further selected by the networks among different metabolites created by the Cytoscape software. A total of 1594 metabolites were identified in myopic corneas. 321 metabolites were different among the three myopic groups, 106 metabolites were different between high myopic corneas and low myopic corneas, 104 metabolites were different between moderate myopic corneas and low myopic corneas, and 30 metabolic molecules overlapped among the three datasets. The multivariate linear regression analysis revealed the myopic degree was significantly influenced by the corneal levels of azelaic acid, arginine-proline (Arg-Pro), 1-stearoyl-2-myristoyl-sn-glycero-3-phosphocholine, and hypoxanthine. The ROC curve analysis showed that azelaic acid, Arg-Pro and hypoxanthine were effective in discriminating low myopia from moderate to high myopia with the area under the curve (AUC) values as 0.982, 0.991 and 0.982 for azelaic acid, Arg-Pro and hypoxanthine respectively. The network analysis suggested that Arg-Pro had the maximum connections among these three biomarkers. Thus, this study identified azelaic acid, Arg-Pro and hypoxanthine as corneal biomarkers to discriminate low myopia from moderate to high myopia, with Arg-Pro serving as the hub biomarker for moderate and high myopia.

Establishment of a novel indicator of pyroptosis regulated gene transcription level and its application in pan-cancer.

Pyroptosis is a type of programmed cell death and plays a dual role in distinct cancers. It is elusive to evaluate the activation level of pyroptosis and to appraise the involvement of pyroptosis in the occurrence and development of diverse tumors. Accordingly, we herein established an indicator to evaluate pyroptosis related gene transcription levels based on the expression level of genes involved in pyroptosis and tried to elaborated on the association between pyroptosis and tumors across diverse tumor types. We found that pyroptosis related gene transcription levels could predict the prognosis of patients, which could act as either a favorable or a dreadful factor in diverse cancers. According to signaling pathway analyses we observed that pyroptosis played a significant role in immune regulation and tumorigenesis and had strong links with other forms of cell death. We also performed analysis on the crosstalk between pyroptosis and immune status and further investigated the predictive potential of pyroptosis level for the efficacy of immunotherapy. Lastly, we manifested that pyroptosis status could serve as a biomarker to the efficacy of chemotherapy across various cancers. In summary, this study established a quantitative indicator to evaluate pyroptosis related gene transcription levels, systematically explored the role of pyroptosis in pan-cancer. These results could provide potential research directions targeting pyroptosis, and highlighted that pyroptosis may be used to develop a novel strategy for the treatment of cancer.