Causal association among glaucoma, cerebral cortical structures, and Alzheimer's disease: insights from genetic correlation and Mendelian randomization.

Glaucoma and Alzheimer's disease are critical degenerative neuropathies with global impact. Previous studies have indicated that glaucomatous damage could extend beyond ocular structures, leading to brain alterations potentially associated with Alzheimer's disease risk. This study aimed to explore the causal associations among glaucoma, brain alterations, and Alzheimer's disease. We conducted a comprehensive investigation into the genetic correlation and causality between glaucoma, glaucoma endophenotypes, cerebral cortical surficial area and thickness, and Alzheimer's disease (including late-onset Alzheimer's disease, cognitive performance, and reaction time) using linkage disequilibrium score regression and Mendelian randomization. This study showed suggestive genetic correlations between glaucoma, cortical structures, and Alzheimer's disease. The genetically predicted all-caused glaucoma was nominally associated with a decreased risk of Alzheimer's disease (OR = 0.96, 95% CI: 0.93-0.99, P = 0.013). We found evidence for suggestive causality between glaucoma (endophenotypes) and 20 cortical regions and between 29 cortical regions and Alzheimer's disease (endophenotypes). Four cortical regions were causally associated with cognitive performance or reaction time at a significant threshold (P < 6.2E-04). Thirteen shared cortical regions between glaucoma (endophenotypes) and Alzheimer's disease (endophenotypes) were identified. Our findings complex causal relationships among glaucoma, cerebral cortical structures, and Alzheimer's disease. More studies are required to clarify the mediation effect of cortical alterations in the relationship between glaucoma and Alzheimer's disease.

RNA-binding protein SYNCRIP contributes to neuropathic pain through stabilising CCR2 expression in primary sensory neurones.

BACKGROUND: Nerve injury-induced changes in gene expression in the dorsal root ganglion (DRG) contribute to the genesis of neuropathic pain. SYNCRIP, an RNA-binding protein, is critical for the stabilisation of gene expression. Whether SYNCRIP participates in nerve injury-induced alterations in DRG gene expression and nociceptive hypersensitivity is unknown. METHODS: The expression and distribution of SYNCRIP in mouse DRG after chronic constriction injury (CCI) of the unilateral sciatic nerve were assessed. Effect of microinjection of Syncrip small interfering RNA into the ipsilateral L3 and L4 DRGs on the CCI-induced upregulation of chemokine (C-C motif) receptor 2 (CCR2) and nociceptive hypersensitivity were examined. Additionally, effects of microinjection of adeno-associated virus 5 expressing full length Syncrip mRNA (AAV5-Syncrip) on basal DRG CCR2 expression and nociceptive thresholds were observed. RESULTS: SYNCRIP is expressed predominantly in DRG neurones, where it co-exists with CCR2. Levels of Syncrip mRNA and SYNCRIP protein in injured DRG increased time-dependently on days 3-14 after CCI. Blocking this increase through microinjection of Syncrip small interfering RNA into injured DRG attenuated CCI-induced upregulation of DRG CCR2 and development and maintenance of nociceptive hypersensitivities. Mimicking this increase through DRG microinjection of AAV5-Syncrip elevated CCR2 expression in microinjected DRGs, enhanced the responses to mechanical, heat, and cold stimuli, and induced ongoing pain in naive mice. Mechanistically, SYNCRIP bound to 3-UTR of Ccr2 mRNA and stabilised its expression in DRG neurones. CONCLUSIONS: SYNCRIP contributes to the induction and maintenance of neuropathic pain likely through stabilising expression of CCR2 in injured DRG. SYNCRIP may be a potential target for treating this disorder.

Association of dietary fiber intake with epileptic seizures in U.S. adults: A Population-base study of 13,277 participants.

OBJECTIVE: Epilepsy, a neurological disorder, is identified by the presence of recurrent seizures. We aimed to detect dietary fiber intake and its association with epilepsy prevalence in U.S. adults. METHODS: This cross-sectional study obtained data from the 2013-2018 National Health and Nutrition Examination Survey database. Univariate and multivariate logistic regression models were employed to estimate the association between dietary fiber intake and epilepsy prevalence. The restricted cubic spline (RCS) model was also applied to investigate the dose-response relationships between dietary fiber intake and epileptic seizure events(ESEs). RESULTS: Our final sample included 13,277 NHANES participants, with the average prevalence of ESEs being 1.09 % (145/13277). After adjusting for all confounding factors, the third quartile of dietary fiber intake levels remained significantly associated with a decreased risk of ESEs[odds ratios (OR) 0.54,95 % confidence interval (CI) 0.33-0.88, P = 0.014)] compared to the first quartile. Higher fiber intake indicated a stable negative association with ESEs in the multivariate logistic regression analysis, weighted generalized additive model. A nonlinear dose-response relationship was observed between dietary fiber intake levels and decreased ESEs risk (P for overall=0.017, P for nonlinear=0.155). Interaction tests showed no significant effect of demographic and disease status on the association between dietary fiber intake and ESEs. CONCLUSION: In this cross-sectional study, people with a high dietary fiber intake were at a reduced risk of ESEs. However, further prospective studies are needed to investigate the effect of dietary fiber intake in epilepsy events and to determine causality.

A class of geranylquinol-derived polycyclic meroterpenoids from Arnebia euchroma against heart failure by reducing excessive autophagy and apoptosis in cardiomyocytes.

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.

Mendelian randomization implicates causal association between epigenetic age acceleration and age-related eye diseases or glaucoma endophenotypes.

BACKGROUND: Age-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes. METHODS: Instrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates. RESULTS: The results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E-04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (ß = -0.190 year, 95% CI -0.374 to -0.008, P = 0.041). The EEA of HannumAge (ß = -0.85 µm, 95% CI -1.57 to -0.14, P = 0.019) and HorvathAge (ß = -0.63 µm, 95% CI -1.18 to -0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (ß = 0.06 µm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P < 0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P < 0.05). CONCLUSION: The present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs.

Acousto-Drag Photovoltaic Effect by Piezoelectric Integration of Two-Dimensional Semiconductors.

Light-to-electricity conversion is crucial for energy harvesting and photodetection, requiring efficient electron-hole pair separation to prevent recombination. Traditional junction-based mechanisms using built-in electric fields fail in nonbarrier regions. Homogeneous material harvesting under a photovoltaic effect is appealing but is only realized in noncentrosymmetric systems via a bulk photovoltaic effect. Here we report the realization of a photovoltaic effect by employing surface acoustic waves (SAWs) to generate zero-bias photocurrent in the conventional layered semiconductor MoSe2. SAWs induce periodic modulation to electronic bands and drag the photoexcited pairs toward the traveling direction. The photocurrent is extracted from a local barrier. The separation of generation and extraction processes suppresses recombination and yields a large nonlocal photoresponse. We distinguish the acousto-electric drag and electron-hole pair separation effect by fabricating devices of different configurations. The acousto-drag photovoltaic effect, enabled by piezoelectric integration, offers an efficient light-to-electricity conversion method, independent of semiconductor crystal symmetry.

Analysis of Chemical Oxygen Demand in Barrel Finishing Based on Reusing Water Resource of Grinding Fluid.

To explore the sustainable development of grinding fluid in barrel finishing, the idea of water resource reuse in grinding fluid has been proposed. The influence of the graphene oxide (GO) and the sodium dodecyl benzene sulfonate (SDBS) as main components in the grinding fluid on the chemical oxygen demand (COD) was analyzed. Repreparing new grinding fluids by utilizing the water resources in grinding fluid after finishing will not cause a sharp increase in COD value. GO which absorbs SDBS can be taken away from grinding fluid by physical separation. It will decrease the COD value of grinding fluid. However, SDBS exists in the form of colloids in the grinding fluid and cannot be removed through physical separation, which also affects the COD value. Based on water quality indicators (the COD, pH, total hardness, metal aluminum, anionic surfactants, and total dissolved solids), the water quality index (WQI) of the reusing grinding fluid after finishing by the physical separation is significantly reduced. It indicates that reusing water resources in grinding fluid is a feasible way to reuse grinding fluid.

Recent progress on triterpenoid derivatives and their anticancer potential.

Cancer poses a significant global public health challenge, with commonly used adjuvant or neoadjuvant chemotherapy often leading to adverse side effects and drug resistance. Therefore, advancing cancer treatment necessitates the ongoing development of novel anticancer agents with diverse structures and mechanisms of action. Natural products remain crucial in the process of drug discovery, serving as a primary source for pharmaceutical leads and therapeutic advancements. Triterpenoids are particularly compelling due to their complex structures and wide array of biological activities. Recent research has demonstrated that naturally occurring triterpenes and their derivatives have the potential to serve as promising candidates for new drug development. This review aims to comprehensively explore the anticancer properties of triterpenoids and their synthetic analogs, with a focus on recent advancements. Various aspects, such as synthesis, phytochemistry, and molecular simulation for structure-activity relationship analyses, are summarized. It is anticipated that triterpenoid derivatives will emerge as notable anticancer agents following further investigation into their mechanisms of action and in vivo studies.

Effect of testosterone replacement therapy on lower urinary tract symptoms: A systematic review and network meta-analysis.

OBJECTIVE: In this study, we aimed to perform a network meta-analysis (NMA) to investigate the effects of different testosterone replacement therapy (TRT) administration routes on lower urinary tract symptoms (LUTS) in aging men with late-onset hypogonadism (LOH). METHODS: A systematic search of PubMed, Embase, The Cochrane Library, CNKI, WanFang Data, and VIP was conducted to identify randomized controlled trials (RCTs) reporting data on International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) level, or prostate volume. NMA was performed, and subgroup analysis was conducted to assess the impact of TRT duration on outcomes. RESULTS: A total of 21 RCTs involving 2453 participants were included. For pairwise meta-analysis, p values for TRT delivered by transdermal, intramuscular, and oral routes were as follows: IPSS: 0.93, 0.20, and 0.76; PSA level: 0.20, 0.27, and 0.98; prostate volume: 0.18, 0.04, and 0.16. There were no significant differences in IPSS, PSA level, or prostate volume between TRT routes. In subgroup analysis, long-term intramuscular TRT significantly decreased IPSS (p = 0.03), short-term transdermal TRT increased PSA levels (p < 0.001), and short-term intramuscular TRT increased the prostate volume (p = 0.04). Other forms of TRT showed no significant change in IPSS, PSA level, and prostate volume compared with the placebo. Indirect comparison of the three administration routes demonstrated no significant differences in IPSS, PSA level, and prostate volume. Nevertheless, surface under the cumulative ranking curve analysis indicated that intramuscular TRT had an 83% probability of being the best method for decreasing IPSS. CONCLUSIONS: The results demonstrate that TRT does not worsen LUTS regardless of the administration route. Intramuscular TRT may be the preferred treatment for aging men with LOH and LUTS. Intramuscular TRT may be the preferred treatment for men with LOH and LUTS. Further research is warranted to validate these findings and optimize TRT management strategies.

Two new cucurbitane-type triterpenoid saponins from the fruit of Citrullus colocynthis.

Two new cucurbitane-type triterpenoid saponins, 2,20ß,22ß-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-ß-D-glucopyranoside (1), 2,20ß,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-ß-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 µM against paracetamol-induced HepG2 cell damage.

The predictive value of estimated pulse wave velocity (ePWV) combined with BMI for newly diagnosed diabetes.

PURPOSE: Estimated pulse wave velocity (ePWV) and body mass index (BMI) are significant predictors of new-onset diabetes. This study aims to evaluate the impact and predictive value of combining ePWV and BMI on the incidence of new-onset diabetes. METHODS: A secondary analysis was conducted on a cohort study by Rich Healthcare (China), involving 211,833 eligible participants. Logistic regression analysis identified factors influencing diabetes occurrence, while ROC curve analysis assessed the predictive value of ePWV, BMI, and their combination for new-onset diabetes. RESULTS: Over a mean follow-up period of 3.12 years, 3,000 men (1.41%) and 1,174 women (0.55%) were diagnosed with diabetes. Logistic regression revealed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and family history of diabetes are high-risk factors for new-onset diabetes. The combination of ePWV and BMI provided a higher area under the ROC curve (0.822) compared to ePWV or BMI alone. CONCLUSION: Elevated levels of ePWV and BMI are independent risk factors for new-onset diabetes. Combining these measures enhances predictive accuracy compared to using either indicator alone.

Comprehensive analysis and experimental verification reveal the molecular characteristics of EGLN3 in pan-cancer and its relationship with the proliferation and apoptosis of lung cancer.

Background: Egl-9 family hypoxia-inducible factor 3 (EGLN3) is involved in the regulation of tumor microenvironment and tumor progression. However, its biological function and clinical significance in various cancers remain unclear. Methods: RNA-seq, immunofluorescence, and single-cell sequencing were used to investigate the expression landscape of EGLN3 in pan-cancer. The TISCH2 and CancerSEA databases were used for single-cell function analysis of EGLN3 in tumors. TIMER2.0 database was used to explain the relationship between EGLN3 expression and immune cell infiltration. In addition, the LinkedOmics database was used to perform KEGG enrichment analysis of EGLN3 in pan-cancer. siRNA was used to silence gene expression. CCK8, transwell migration assay, flow cytometry analysis, RT-PCR, and western blotting were used to explore biological function of EGLN3. Results: The results showed that EGLN3 was highly expressed in a variety of tumors, and was mainly localized to the cytosol. EGLN3 expression is associated with immunoinfiltration of a variety of immune cells, including macrophages in the tumor immune microenvironment and tumor-associated fibroblasts. Functional experiments revealed that EGLN3 knockdown could inhibit cell proliferation, migration, and promote cell apoptosis. In addition, we found that Bax expression was up-regulated and Bcl-2 expression was down-regulated in the si-EGLN3 group. Taken together, as a potential oncogene, EGLN3 is involved in the regulation of tumor malignant process, especially tumor cell apoptosis. Conclusion: We comprehensively investigated the expression pattern, single-cell function, immune infiltration level and regulated signaling pathway of EGLN3 in pan-cancer. We found that EGLN3 is an important hypoxia and immune-related gene that may serve as a potential target for tumor immunotherapy.

Glycnsisitin A: A promising bicyclic peptide against heart failure that facilitates TFRC-mediated uptake of iron in cardiomyocytes.

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A-C (1-3), with distinctive C-C and C-O-C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

Cellular senescence mediates retinal ganglion cell survival regulation post-optic nerve crush injury.

Traumatic optic neuropathy refers to optic nerve (ON) injury by trauma, including explosion and traffic accident. Retinal ganglion cell (RGC) death is the critical pathological cause of irreversible visual impairment and blindness in ON injury. We previously investigated the patterns of 11 modes of cell death in mouse retina post-ON injury. Here we aimed to identify additional signalling pathways regulating RGC survival in rodents post-ON injury. RNA sequencing analysis identified the upregulation of inflammation and cellular senescence-related genes in retina post-ON injury, which were confirmed by immunoblotting and immunofluorescence analyses. Increased expression of senescence-associated ß-galactosidase (SA-ßgal) in RGCs and activation of microglia were also found. Transforming growth factor-ß receptor type II inhibitor (LY2109761) treatment suppressed p15Ink4b and p21Cip1 protein and SA-ßgal expression and promoted RGC survival post-ON injury with decreasing the expression of cell death markers in retina. Consistently, senolytics (dasatinib and quercetin) treatments can promote RGC survival and alleviate the reduction of ganglion cell complex thickness and pattern electroretinography activity post-ON injury with reducing SA-ßgal, p15Ink4b, p21Cip1, microglial activation and cell death marker expression. In summary, this study revealed the activation of cellular senescence in rodent retina post-ON injury and contribute to RGC survival regulation. Targeting cellular senescence can promote RGC survival after ON injury, suggesting a potential treatment strategy for traumatic optic neuropathy.

Studies of Anticancer Activities In Vitro and In Vivo for Butyltin(IV)-Iridium(III) Imidazole-Phenanthroline Complexes with Aggregation-Induced Emission Properties.

Organotin(IV) and iridium(III) complexes have shown good application potential in the field of anticancer; however, the aggregation-caused quenching (ACQ) effect induced by high concentration or dose has limited the research on their targeting and anticancer mechanism. Then, a series of aggregation-induced emission (AIE)-activated butyltin(IV)-iridium(III) imidazole-phenanthroline complexes were prepared in this study. Complexes exhibited significant fluorescence improvement in the aggregated state because of the restricted intramolecular rotation (RIR), accompanied by an absolute fluorescence quantum yield of up to 29.2% (IrSn9). Complexes demonstrated potential in vitro antiproliferative and antimigration activity against A549 cells, following a lysosomal-mitochondrial apoptotic pathway. Nude mouse models further confirmed that complexes had favorable in vivo antitumor and antimigration activity in comparison to cisplatin. Therefore, butyltin(IV)-iridium(III) imidazole-phenanthroline complexes possess the potential as potential substitutes for platinum-based drugs.

ESRRG-controlled downregulation of KCNN1 in primary sensory neurons is required for neuropathic pain.

Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.

Memristive switching in the surface of a charge-density-wave topological semimetal.

Owing to the outstanding properties provided by nontrivial band topology, topological phases of matter are considered as a promising platform towards low-dissipation electronics, efficient spin-charge conversion, and topological quantum computation. Achieving ferroelectricity in topological materials enables the non-volatile control of the quantum states, which could greatly facilitate topological electronic research. However, ferroelectricity is generally incompatible with systems featuring metallicity due to the screening effect of free carriers. In this study, we report the observation of memristive switching based on the ferroelectric surface state of a topological semimetal (TaSe4)2I. We find that the surface state of (TaSe4)2I presents out-of-plane ferroelectric polarization due to surface reconstruction. With the combination of ferroelectric surface and charge-density-wave-gapped bulk states, an electric-switchable barrier height can be achieved in (TaSe4)2I-metal contact. By employing a multi-terminal-grounding design, we manage to construct a prototype ferroelectric memristor based on (TaSe4)2I with on/off ratio up to 103, endurance over 103 cycles, and good retention characteristics. The origin of the ferroelectric surface state is further investigated by first-principles calculations, which reveal an interplay between ferroelectricity and band topology. The emergence of ferroelectricity in (TaSe4)2I not only demonstrates it as a rare but essential case of ferroelectric topological materials, but also opens new routes towards the implementation of topological materials in functional electronic devices.

Three new flavonoids from the roots of Sophora tonkinensis.

Three new flavonoids including two isoflavanones sophortones A and B (1 and 2), and one chalcone sophortone C (3) were isolated from the roots of Sophora tonkinensis. Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Prognostic role of MUCIN family and its relationship with immune characteristics and tumor biology in diffuse-type gastric cancer.

The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor prognosis in different carcinomas. Diffuse-type gastric cancer (DGC) has long been associated with genomic stability and unfavorable clinical outcomes. To investigate further, we obtained clinical information and the RNA-seq data of the TCGA-STAD cohort. Through the use of unsupervised clustering methods and GSEA, we identified two distinct clusters, characterized by higher and lower expression of MUC2 and MUC20, denoted as cluster 1 and cluster 2, respectively. Subsequently, employing CIBERSORT, it was determined that cluster 2 exhibited a higher tumor mutation burden (TMB) and a greater abundance of CD8+ T cells and activated CD4+ memory T cells, in addition to immune checkpoints (ICPs). On the other hand, cluster 1 showed a lower TIDE score estimation, indicating a higher probability of tumor immune escape. Furthermore, overexpression of MUC15 and MUC20 was confirmed through qPCR and Western blotting, and their specific roles in mediating the epithelial-mesenchymal transition (EMT) process of GC cells (SNU484 and Hs746t) were validated via CCK-8 assay and wound healing assay in vitro. These findings highlight the potential prognostic value of MUC20 and offer insights into the prospects of immunotherapy for DGC by targeting MUC20.