Identification of cancer-associated fibroblast-related Ectodysplasin-A as a novel indicator for prognosis and immune response in gastric cancer.

Studies have indicated cancer-associated fibroblasts (CAFs) could have a significant impact in gastric cancer (GC) progression and chemotherapy resistance. However, the gene related to cancer fibroblasts that can be used as biomarkers to judge the occurrence of gastric cancer has not been fully explored. Based on two Gene Expression Omnibus (GEO) datasets, we focus on differentially expressed genes which may act as CAFs markers related to GC. Through COX regression, LASSO regression and Kaplan-Meier survival analysis, we discovered three upregulated genes (GLT8D2, GNAS and EDA) associated with poor GC patients' survival. By single-cell analysis and nomogram, we found that EDA may affect fibroblast production and disease prognosis in GC patients. EDA expression showed a positive correlation with 5-Fluorouracil IC50 values. Immunohistochemistry (IHC) and real time PCR indicated elevated EDA levels in GC tissues and cells. Enrichment analysis revealed that EDA was closely linked to immune system regulation. IHC and single-cell analysis indicated that EDA gene was associated with cancer fibroblasts marker FGF12 and influence cell interferon-gamma response, which may play a role in regulating immune-related characteristics. In summary, we concluded that EDA may be used as a new therapeutic CAFs marker for GC.

Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression.

The functional heterogeneity and ecological niche of prostate cancer stem cells (PCSCs), which are major drivers of prostate cancer development and treatment resistance, have attracted considerable research attention. Cancer-associated fibroblasts (CAFs), which are crucial components of the tumor microenvironment (TME), substantially affect PCSC stemness. Additionally, CAFs promote PCSC growth and survival by releasing signaling molecules and modifying the surrounding environment. Conversely, PCSCs may affect the characteristics and behavior of CAFs by producing various molecules. This crosstalk mechanism is potentially crucial for prostate cancer progression and the development of treatment resistance. Using organoids to model the TME enables an in-depth study of CAF-PCSC interactions, providing a valuable preclinical tool to accurately evaluate potential target genes and design novel treatment strategies for prostate cancer. The objective of this review is to discuss the current research on the multilevel and multitarget regulatory mechanisms underlying CAF-PCSC interactions and crosstalk, aiming to inform therapeutic approaches that address challenges in prostate cancer treatment.

EZH2-H3K27me3-Mediated Epigenetic Silencing of DKK1 Induces Nucleus Pulposus Cell Pyroptosis in Intervertebral Disc Degeneration by Activating NLRP3 and NAIP/NLRC4.

Nucleus pulposus (NP) cell pyroptosis is crucial for intervertebral disc degeneration (IDD). However, the precise mechanisms underlying pyroptosis in IDD remain elusive. Therefore, this study aimed to investigate how dickkopf-1 (DKK1) influences NP cell pyroptosis and delineate the regulatory mechanisms of IDD. Behavioral tests and histological examinations were conducted in rat IDD models to assess the effect of DKK1 on the structure and function of intervertebral discs. Detected pyroptosis levels using Hoechst 33,342/propidium iodide (PI) double staining, and determined pyroptosis-related protein expression via western blotting. The cellular mechanisms of DKK1 in pyroptosis were explored in interleukin (IL)-1ß-induced NP cells transfected with or without DKK1 overexpression plasmids (oe-DKK1). In addition, IL-1ß-treated NP cells transfected with sh-EZH2 and/or sh-DKK1 were utilized to clarify the interplay between the enhancer of zeste homologue 2 (EZH2) and DKK1 in pyroptosis. Additionally, the epigenetic regulation of DKK1 by EZH2 was explored in NP cells treated with the EZH2 inhibitors GSK126/DZNep. DKK1 expression decreased in IDD rats. Transfection with oe-DKK1 reduced pro-inflammatory factors and extracellular matrix markers in IDD rats. In IL-1ß-induced NP cells, DKK1 overexpression suppressed pyroptosis and inhibited the NLRP3 and NAIP/NLRC4 inflammasome activation. EZH2 knockdown increased DKK1 expression and reduced pyroptosis-related proteins. Conversely, DKK1 downregulation reversed the inhibitory effects of EZH2 knockdown on pyroptosis. Furthermore, EZH2 suppressed DKK1 expression via H3K27 methylation at the DKK1 promoter. EZH2 negatively regulates DKK1 expression via H3K27me3 methylation, promoting NP cell pyroptosis in IDD patients. This regulatory effect involves the activation of NLRP3 and NAIP/NLRC4 inflammasomes.

Mechanism of N2O formation in catalytic after-treatment systems of ammonia/hydrogen-fuelled engines.

The combustion processes and catalytic after-treatment of ammonia/hydrogen-fueled engines, including NOx storage and reduction (NSR) and noble-metal selective catalytic reduction (SCR), can produce the byproduct N2O, a potent greenhouse gas that weakens the zero-carbon attribute of these fuels. Currently, the mechanism of N2O formation on DeNOx catalysts remains unclear due to limited research on catalytic after-treatment for such engines and the complexity of surface catalytic reactions. To elucidate the formation of N2O on the DeNOx catalysts of ammonia/hydrogen fuel engines, the impact factors on N2O formation on platinum catalysts (typical catalysts in NSR and noble-metal SCR) were investigated using first-principles molecular dynamics (FPMD). By employing the blue-moon ensemble enhanced sampling method and the slow-growth approach for free energy surface exploration, together with density functional theory (DFT) for electronic structure analysis, a linear relationship between the spin splitting of the d states of Pt clusters and N2O formation energy barriers was revealed, along with the increased structural sensitivity of Pt clusters with fewer atoms. It is highlighted that the energy barrier for N2O formation is determined by the matching degree of energy levels between molecules and surfaces. These findings provide atomic-scale insights into N2O formation on DeNOx catalysts for ammonia/hydrogen-fueled engines, facilitating N2O emission control for carbon-free engines.

Understanding the relationship between HCV infection and progression of kidney disease.

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

MFAP2 induces epithelial-mesenchymal transformation of osteosarcoma cells by activating the Notch1 pathway.

Background: Osteosarcoma (OS) is a malignancy originating from mesenchymal tissue. Microfibril-associated protein 2 (MFAP2) plays a crucial role in cancer, notably promoting epithelial-mesenchymal transition (EMT). However, its involvement in OS remains unexplored. Methods: MFAP2 was silenced in U2OS cells using shRNA targeting MFAP2 (sh-MFAP2) and validated by quantitative real-time polymerase chain reaction (qRT-PCR). We extracted gene chip data of MFAP2 from multiple databases (GSE28424, GSE42572, and GSE126209). Correlation analyses between MFAP2 and the Notch1 pathway identified through the gene set variation analysis (GSVA) enrichment analysis were conducted using the Pearson correlation method. Cellular behaviors (viability, migration, and invasion) were assessed via the Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays. EMT markers (N-cadherin, vimentin, and ß-catenin) and Notch1 levels were examined by western blotting and qRT-PCR. Cell morphology was observed microscopically to evaluate EMT. Finally, the role of MFAP2 in OS was validated through a xenograft tumor model. Results: OS cell lines exhibited higher MFAP2 mRNA expression than normal osteoblasts. MFAP2 knockdown in U2OS cells significantly reduced viability, migration, and invasion, along with downregulation of N-cadherin and vimentin, as well as upregulation of ß-catenin. MFAP2 significantly correlated with the Notch1 pathway in OS and its knockdown inhibited Notch1 protein expression. Furthermore, Notch1 activation reversed the inhibitory effects of MFAP2 knockdown on the malignant characteristic of U2OS cells. Additionally, MFAP2 knockdown inhibited tumor growth, expression levels of EMT markers, and Notch1 expression in OS tumor tissues. Conclusions: Our study revealed that MFAP2 was an upstream regulator of the Notch1 signaling pathway to promote EMT in OS. These findings suggested MFAP2 as a potential OS therapy target.

Impact and pathway of halogens on atmospheric oxidants in coastal city clusters in the Yangtze River Delta region in China.

Halogens (chlorine, bromine, and iodine) are known to profoundly influence atmospheric oxidants (hydroxyl radical (OH), hydroperoxyl radical (HO2), ozone (O3), and nitrate radical (NO3)) in the troposphere and subsequently affecting air quality. However, their impact on atmospheric oxidation and air pollution in coastal areas in China is poorly characterized. In this study, we use the WRF-CMAQ (Weather Research and Forecasting-Community Multiscale Air Quality) model with full halogen chemistry and process analysis to assess the influences and pathways of halogens on atmospheric oxidants in the Yangtze River Delta (YRD) region, a typical coastal city cluster in China. Halogens cause the annual OH radical increase by up to 16.4% and NO3 decrease by up to 45.3%. O3 increases by 2.0% in the YRD but decreases by 3.3% in marine environment. Halogen induced changes in atmospheric oxidants lead to a general increase of atmospheric oxidation capacity by 5.1% (maximum 48.4%). The production rate of OH (POH) in the YRD is enhanced by anthropogenic chlorine through both increased HO2 pathway and hypohalous acid photolysis pathway, while POH over ocean is enhanced by oceanic halogens through converting HO2 into hypohalous acid. Anthropogenic chlorine enhances both O3 and NO3 production (PNO3) rates through influencing their precursors while oceanic halogens reduce PNO3 and directly destroy ozone. Iodine contributed most (on average of 91% in oceanic halogens) in reducing production rates of oxidants. Thus, halogen emissions and potential effects of halogens on air quality need to be considered in air quality policies and regulations in the YRD region.

Clotrimazole inhibits growth of multiple myeloma cells in vitro via G0/G1 arrest and mitochondrial apoptosis.

Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ's effects on MM are unclear. We investigated CTZ's effect on MM cell proliferation and apoptosis induction mechanisms. CTZ's effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Mechanism and treatment of secondary glaucoma after corneal transplantation: a review.

Corneal transplantation is a common treatment for corneal diseases. Secondary glaucoma after corneal transplantation is the second leading cause of failure of keratoplasty. This article reviews the mechanism and treatment of secondary glaucoma after corneal transplantation.

SIDERITE: Unveiling hidden siderophore diversity in the chemical space through digital exploration.

In this work, we introduced a siderophore information database (SIDERTE), a digitized siderophore information database containing 649 unique structures. Leveraging this digitalized data set, we gained a systematic overview of siderophores by their clustering patterns in the chemical space. Building upon this, we developed a functional group-based method for predicting new iron-binding molecules with experimental validation. Expanding our approach to the collection of open natural products (COCONUT) database, we predicted a staggering 3199 siderophore candidates, showcasing remarkable structure diversity that is largely unexplored. Our study provides a valuable resource for accelerating the discovery of novel iron-binding molecules and advancing our understanding of siderophores.

Plant-Derived Exosomes as Novel Nanotherapeutics Contrive Glycolysis Reprogramming-Mediated Angiogenesis for Diabetic Ulcer Healing.

Reversal of endothelial cell (EC) dysfunction under high-glucose (HG) conditions to achieve angiogenesis has remained a big challenge in diabetic ulcers. Herein, exosomes derived from medicinal plant ginseng (GExos) were shown as excellent nanotherapeutics with biomimetic cell membrane-like structures to be able to efficiently transfer the encapsulated active substances to ECs, resulting in a marked reprogramming of glycolysis by up-regulating anaerobic glycolysis and down-regulating oxidative stress, which further restore the proliferation, migration, and tubule formation abilities of ECs under HG conditions. In vivo, GExos enhance the angiogenesis and nascent vessel network reconstruction in full-thickness diabetic complicated skin ulcer wounds in mice with high biosafety. GExos were shown as promising nanotherapeutics in stimulating glycolysis reprogramming-mediated angiogenesis in diabetic ulcers, possessing wide application potential for reversing hyperglycemic dysangiogenesis and stimulating vascular regeneration.

A novel higher performance nomogram based on explainable machine learning for predicting mortality risk in stroke patients within 30 days based on clinical features on the first day ICU admission.

BACKGROUND: This study aimed to develop a higher performance nomogram based on explainable machine learning methods, and to predict the risk of death of stroke patients within 30 days based on clinical characteristics on the first day of intensive care units (ICU) admission. METHODS: Data relating to stroke patients were extracted from the Medical Information Marketplace of the Intensive Care (MIMIC) IV and III database. The LightGBM machine learning approach together with Shapely additive explanations (termed as explain machine learning, EML) was used to select clinical features and define cut-off points for the selected features. These selected features and cut-off points were then evaluated using the Cox proportional hazards regression model and Kaplan-Meier survival curves. Finally, logistic regression-based nomograms for predicting 30-day mortality of stroke patients were constructed using original variables and variables dichotomized by cut-off points, respectively. The performance of two nomograms were evaluated in overall and individual dimension. RESULTS: A total of 2982 stroke patients and 64 clinical features were included, and the 30-day mortality rate was 23.6% in the MIMIC-IV datasets. 10 variables ("sofa (sepsis-related organ failure assessment)", "minimum glucose", "maximum sodium", "age", "mean spo2 (blood oxygen saturation)", "maximum temperature", "maximum heart rate", "minimum bun (blood urea nitrogen)", "minimum wbc (white blood cells)" and "charlson comorbidity index") and respective cut-off points were defined from the EML. In the Cox proportional hazards regression model (Cox regression) and Kaplan-Meier survival curves, after grouping stroke patients according to the cut-off point of each variable, patients belonging to the high-risk subgroup were associated with higher 30-day mortality than those in the low-risk subgroup. The evaluation of nomograms found that the EML-based nomogram not only outperformed the conventional nomogram in NIR (net reclassification index), brier score and clinical net benefits in overall dimension, but also significant improved in individual dimension especially for low "maximum temperature" patients. CONCLUSIONS: The 10 selected first-day ICU admission clinical features require greater attention for stroke patients. And the nomogram based on explainable machine learning will have greater clinical application.

The investigation of quenching conditions for the analysis of total organic halogen, aliphatic and aromatic halogenated disinfection byproducts formed from chlor(am)ination.

Total organic halogen (TOX) is used to describe total amount of halogenated DBPs. Typically, once a chlor(am)inated water sample is collected, it is necessary to add a quenching agent to quench the residual disinfectant so that further reactions to form more DBPs during the holding time can be prevented. In this study, we evaluated the effects of four quenching agents: ammonium chloride (NH4Cl), ascorbic acid, sodium sulfite (Na2SO3), and sodium thiosulfate (Na2S2O3) on the decomposition of TOX, aliphatic and aromatic halogenated DBPs under various quenching conditions (quenching time, pH, quenching ratio, temperature). The results showed that ascorbic acid had the least impact on TOX. Ascorbic acid appeared to be the most suitable quenching agent for aliphatic halogenated DBPs, especially since it could preserve more haloacetonitriles than other quenching agents. Both ascorbic acid and Na2SO3 could be used for the analysis of aromatic halogenated DBPs. The lower pH (pH 6.0), not excessive quenching agents and lower temperature (4 ºC) were all conducive to the preservation of TOX and halogenated DBPs. Importantly, unknown TOX (UTOX) also contained significantly toxic components. It was also found that addition of quenching agents might lead to underestimation of UTOX by researchers. SYNOPSIS: The quenching agents and quenching conditions for the analysis of total organic halogen, aliphatic and aromatic halogenated DBPs formed from chlor(am)ination were investigated.

Disrupting redox homeostasis for tumor therapy based on PDT/chemo/ferroptosis therapeutic hybrid liposomes.

Synergistic photodynamic therapy (PDT) with other therapeutic modalities can enhance the therapeutic efficacy of tumor treatment and reduce the adverse effects associated with drug leakage and off-target accumulation. However, shaping combined strategies for synergistic therapy remains challenging. Herein, we developed versatile hybrid liposomes self-assembled from Ce6-lipid conjugates and loaded with the chemo drug doxorubicin (DOX) and ferroptosis inducer Fe3O4 nanoparticles for synergistic PDT/chemo/ferroptosis therapy. Abundant ROS are generated by PDT upon 650 nm light irradiation, Fe3O4-mediated Fenton reaction, and DOX-induced apoptosis. Furthermore, amplifying oxidative stress in cancer cells to disrupt cellular redox homeostasis could accelerate tumor cell death through oxidative damage to lipids, proteins, and DNA. Overall, this work highlights liposome-based therapeutic nanoformulations, thus offering a breakthrough redox homeostasis-based synergistic PDT/chemo/ferroptosis therapy for lung cancer.

IDENTIFICATION OF A NOVEL SEPSIS PROGNOSIS MODEL: BASED ON TRANSCRIPTOME AND PROTEOME ANALYSIS.

ABSTRACT: Sepsis is a highly prevalent and deadly disease. Currently, there is a lack of ideal biomarker prognostis models for sepsis. We attempt to construct a model capable of predicting the prognosis of sepsis patients by integrating transcriptomic and proteomic data. Through analysis of proteomic and transcriptomic data, we identified 25 differentially expressed genes (DEGs). Single-factor Cox-Lasso regression analysis identified 16 DEGs (overall survival-DEGs) associated with patient prognosis. Through multifactor Cox-Lasso regression analysis, a prognostic model based on these 16 genes was constructed. Kaplan-Meier survival analysis and receiver operating characteristic curve analysis were used to further validate the high stability and good predictive ability of this prognostic model with internal and external data. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of overall survival-DEGs and differentially expressed genes between high and low-risk groups based on the prognostic model revealed significant enrichment in immune-related pathways, particularly those associated with viral regulation.

Active shimming for a 25 T NMR superconducting magnet by spectrum convergence method.

In the design of ultrahigh field nuclear magnetic resonance (NMR) superconducting magnets, it typically requires a high homogeneous magnetic field in the diameter of spherical volume (DSV) to obtain high spectrum resolution. However, shimming technique presents challenges due to the magnet bore space limitations, as accurate measurement of magnetic field distribution is very difficult, especially for customized micro-bore magnets. In this study, we introduced an active shimming method that utilized iterative adjustment of shim coil currents to improve the magnetic field homogeneity based on the full width at half maximum (FWHM) of the spectrum. The proposed method can determine the optimal set of currents for shim coils, effectively enhancing spatial field homogeneity by converging the FWHM. Experimental validation on a 25 T NMR superconducting magnet demonstrated the efficacy of the proposed method. Specifically, the active shimming method improved the field homogeneity of a 10 mm DSV from 7.09 ppm to 2.27 ppm with only four shim coils, providing a superior magnetic field environment for solid NMR and further magnetic resonance imaging (MRI) experiment. Furthermore, the proposed method can be promoted to more customized micro-bore magnets that require high magnetic field homogeneity.

Ferroptosis and hepatocellular carcinoma: the emerging role of lncRNAs.

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma.

Antisymmetric planar Hall effect in rutile oxide films induced by the Lorentz force.

The conventional Hall effect is linearly proportional to the field component or magnetization component perpendicular to a film. Despite the increasing theoretical proposals on the Hall effect to the in-plane field or magnetization in various special systems induced by the Berry curvature, such an unconventional Hall effect has only been experimentally reported in Weyl semimetals and in a heterodimensional superlattice. Here, we report an unambiguous experimental observation of the antisymmetric planar Hall effect (APHE) with respect to the in-plane magnetic field in centrosymmetric rutile RuO2 and IrO2 single-crystal films. The measured Hall resistivity is found to be linearly proportional to the component of the applied in-plane magnetic field along a particular crystal axis and to be independent of the current direction or temperature. Both the experimental observations and theoretical calculations confirm that the APHE in rutile oxide films is induced by the Lorentz force. Our findings can be generalized to ferromagnetic materials for the discovery of anomalous Hall effects and quantum anomalous Hall effects induced by in-plane magnetization. In addition to significantly expanding knowledge of the Hall effect, this work opens the door to explore new members in the Hall effect family.

Multi role ChatGPT framework for transforming medical data analysis.

The application of ChatGPTin the medical field has sparked debate regarding its accuracy. To address this issue, we present a Multi-Role ChatGPT Framework (MRCF), designed to improve ChatGPT's performance in medical data analysis by optimizing prompt words, integrating real-world data, and implementing quality control protocols. Compared to the singular ChatGPT model, MRCF significantly outperforms traditional manual analysis in interpreting medical data, exhibiting fewer random errors, higher accuracy, and better identification of incorrect information. Notably, MRCF is over 600 times more time-efficient than conventional manual annotation methods and costs only one-tenth as much. Leveraging MRCF, we have established two user-friendly databases for efficient and straightforward drug repositioning analysis. This research not only enhances the accuracy and efficiency of ChatGPT in medical data science applications but also offers valuable insights for data analysis models across various professional domains.

A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives.

Background: Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, cell necrosis, and autophagy. Recent studies suggest its role in exacerbating or mitigating diseases by influencing metabolic and signaling pathways in conditions such as tumors and ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting a review of its research status and potential breakthroughs in understanding and treating these conditions. Summary: In acute kidney disease (AKI), ferroptosis has been confirmed in animal kidneys after being induced by various factors such as renal ischemia-reperfusion and cisplatin, and glutathione peroxidase 4 (GPX4) is linked with AKI. Ferroptosis is associated with renal fibrosis in chronic kidney disease (CKD), TGF-ß1 being crucial in this regard. In diabetic nephropathy (DN), high SLC7A11 and low nuclear receptor coactivator 4 (NCOA4) expressions are linked to disease progression. For polycystic kidney disease (PKD), ferroptosis promotes the disease by regulating ferroptosis in kidney tissue. Renal cell carcinoma (RCC) and lupus nephritis (LN) also have links to ferroptosis, with mtDNA and iron accumulation causing RCC and oxidative stress causing LN. Key Messages: Ferroptosis is a newly identified form of programmed cell death that is associated with various diseases. It targets metabolic and signaling pathways and has been linked to kidney diseases such as AKI, CKD, PKD, DN, LN, and clear cell RCC. Understanding its role in these diseases could lead to breakthroughs in their pathogenesis, etiology, and treatment.