A Ru-porphyrin metal-organic framework with Mn2+ paddlewheel nodes for the selective oxidation of C(sp3)-H bonds.

The activation and selective functionalization of inert C(sp3)-H bonds is fundamental for industrial applications and occupies a very important place in industry, but it remains a great challenge in current synthetic chemistry. In this paper, we report an approach for activating reactive tert-butyl peroxyl radicals by modifying Ru-porphyrin into metal-organic frameworks (MOFs) for the activation of inert C(sp3)-H bonds. Under mild conditions, the Ru-porphyrinyl MOF can activate the peroxyl radical, extracting a hydrogen atom from the inert C(sp3)-H bond. Mn2+ paddlewheels with unsaturated coordination sites were introduced into the MOF, and direct oxidative conversion using environmentally friendly oxygen provides a new pathway to activate the inert C(sp3)-H bond.

Enzymatic Activation and Continuous Electrochemical Production of Methane from Dilute CO2 Sources with a Self-Healing Capsule.

Converting dilute CO2 source into value-added chemicals and fuels is a promising route to reduce fossil fuel consumption and greenhouse gas emission, but integrating electrocatalysis with CO2 capture still faced marked challenges. Herein, we show that a self-healing metal-organic macrocycle functionalized as an electrochemical catalyst to selectively produce methane from flue gas and air with the lowest applied potential so far (0.06 V vs reversible hydrogen electrode, RHE) through an enzymatic activation fashion. The capsule emulates the enzyme' pocket to abstract one in situ-formed CO2-adduct molecule with the commercial amino alcohols, forming an easy-to-reduce substrate-involving clathrate to combine the CO2 capture with electroreduction for a thorough CO2 reduction. We find that the self-healing system exhibited enzymatic kinetics for the first time with the Michaelis-Menten mechanism in the electrochemical reduction of CO2 and maintained a methane Faraday efficiency (FE) of 74.24% with a selectivity of over 99% for continuous operation over 200 h. A consecutive working lab at 50 mA·cm-2, in an eleven-for-one (10 h working and 1 h healing) electrolysis manner, gives a methane turnover number (TON) of more than 10,000 within 100 h. The integrated electrolysis with CO2 capture facilitates the thorough reduction of flue gas (ca. 13.0% of CO2) and first time of air (ca. 400 ppm of CO2 to 42.7 mL CH4 from 1.0 m3 air). The new self-healing strategy of molecular electrocatalyst with an enzymatic activation manner and anodic shifting of the applied potentials provided a departure from the existing electrochemical catalytic techniques.

A Porphyrin-Faced Zn8L6 Cage for Selective Oxidation of C(sp3)-H Bonds and Sulfides.

Catalytic oxidation of benzyl C-H bonds and sulfides from fuel oils stands as an attractive proposition in the quest for clean energy, yet their simultaneous oxidation with a singular, economically friendly catalyst is not well established. In this work, the combination of a cobalt(II) porphyrin ligand with 2-pyridinecarboxaldehyde and ZnII yielded a Zn8L6 cage (Co cube). The three-dimensional conjugated structure effectively enhances energy transfer efficiency, enabling the Co cube to show a good ability to activate oxygen under light conditions for photooxidation. Moreover, this catalytic system demonstrates high selectivity for the photocatalytic oxidation of C(sp3)-H bonds and sulfides, employing the Co cube as a single component catalyst, molecular oxygen as the oxidant, and activating oxygen into 1O2 under mild reaction conditions. This provides significant insights for organic synthesis and future design of photocatalysts with complex molecular components.

Lignin-based emulsive liquid-liquid microextraction for detecting triazole fungicides in water, juice, vinegar, and alcoholic beverages via UHPLC-MS/MS.

A universal, green, and rapid lignin-based emulsive liquid-liquid microextraction (ELLME) method was established to detect nine triazole fungicides in water, juice, vinegar, and alcoholic beverages via UHPLC-MS/MS. By employing an environmentally friendly emulsifier (lignin), the proposed ELLME was compatible with more extractants, and not restricted to fatty acids. Due to the high amphiphilic properties and three-dimensional structure of lignin, the emulsion was quickly formed through several aspirate-dispense cycles of the green extractant (guaiacol) and lignin solution. And a micropipette was used for rapid microextraction. The limit of detection was 0.0002-0.0057 µg L-1. The extraction recoveries and relative standard deviation were 81.7%-102.0% and 0.9%-7.1%, respectively. Finally, three green metric tools were used to verify the greenness of the whole procedure. The proposed lignin-based ELLME successfully emulsified green solvents, indicating that emerging solvents may be excellent alternatives as extractants in ELLME for pesticide residue analysis in food samples.

Tumor angiogenesis and anti-angiogenic therapy.

ABSTRACT: Anti-angiogenic drugs (AADs), which mainly target the vascular endothelial growth factor-A signaling pathway, have become a therapeutic option for cancer patients for two decades. During this period, tremendous clinical experience of anti-angiogenic therapy has been acquired, new AADs have been developed, and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy. However, improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required. This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development. We revisit the history of concept initiation and AAD discovery, and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.

Modifying Parallel Excitations into One Framework for C(sp3)─H Bond Activation with Energy Combined More Than Two Photons.

Natural photosynthesis enzymes utilize energies of several photons for challenging oxidation of water, whereas artificial photo-catalysis typically involves only single-photon excitation. Herein, a multiphoton excitation strategy is reported that combines parallel photo-excitations with a photoinduced electron transfer process for the activation of C(sp3)─H bonds, including methane. The metal-organic framework Fe3-MOF is designed to consolidate 4,4',4″-nitrilotrisbenzoic units for the photoactivation of dioxygen and trinuclear iron clusters as the HAT precursor for photoactivating alkanes. Under visible light irradiation, the dyes and iron clusters absorbed parallel photons simultaneously to reach their excited states, respectively, generating 1O2 via energy transfer and chlorine radical via ligand-to-metal charge transfer. The further excitation of organic dyes leads to the reduction of 1O2 into O2 •- through a photoinduced electron transfer, guaranteeing an extra multiphoton oxygen activation manner. The chlorine radical abstracts a hydrogen atom from alkanes, generating the carbon radical for further oxidation transformation. Accordingly, the total oxidation conversion of alkane utilizing three photoexcitation processes combines the energies of more than two photons. This new platform synergistically combines a consecutive excited photoredox organic dye and a HAT catalyst to combine the energies of more than two photons, providing a promising multiphoton catalysis strategy under energy saving, and high efficiency.

A novel Cu(I)-based coordination polymer for efficient photocatalytic oxidation of C(sp3)-H bonds.

A novel coordination polymer CuCl-Pyhc was successfully synthesized, which can catalyze efficient and selective oxidation of C(sp3)-H bonds under mild conditions, exhibiting exceptional stability and remarkable recyclability. Furthermore, CuCl-Pyhc can mimic natural monooxygenases and activate oxygen into singlet oxygen (1O2).

A novel porphyrin MOF catalyst for efficient conversion of CO2 with propargyl amines.

The capture and conversion of carbon dioxide (CO2) into valuable chemical products under mild conditions is an important and challenging approach for contemporary industry. Carboxylic acid ligands are widely used in the development of functionalized metal organic framework materials due to their excellent stability. Herein, a novel mixed-metal organic framework Cu-TCPP(Fe) was assembled from iron-(Fe)-porphyrin ligands, which can efficiently catalyze the reaction of propargylic amines and CO2 to synthesize 2-oxazolidinones.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

Multi-frequency electromagnetic radiation induces anxiety in mice via inflammation in the cerebral cortex.

Modern life is filled with radiofrequency electromagnetic radiation (RF-EMR) in various frequency bands, while the health risks are not clear. In this study, mice were whole-body exposed to 0.9/1.5/2.65 GHz radiofrequency radiation at 4 W/kg for 2 h per day for 4 weeks to investigate the emotional effects. It was found that the mice showed anxiety but no severe depression. The ELISA results showed a significant decrease in amino acid neurotransmitters (GABA, DA, 5-HT), although acetylcholine (ACH) levels were not significantly altered. Furthermore, Western blot results showed that BDNF, TrkB, and CREB levels were increased in the cerebral cortex, while NF-κB levels were decreased. In addition, pro-inflammatory factors (IL-6, IL-1ß, TNF-α) were significantly elevated, and anti-inflammatory factors (IL-4, IL-10) tended to decrease. In conclusion, multi-frequency electromagnetic radiation induces an inflammatory response through the CREB-BDNF-TrkB and NF-κB pathways in the cerebral cortex and causes a decrease in excitatory neurotransmitters, which ultimately causes anxiety in mice.

Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells. Upon contact with tumor-experienced NK cells, monocytes and neutrophils displayed increased expression of MDSC-related suppressive factors along with increased capacities to suppress T cells. These changes were accompanied by impaired antigen presentation by monocytes and increased ER stress response by neutrophils. In a cohort of patients with sarcoma and breast cancer, the production of interleukin-6 (IL-6) by tumor-infiltrating NK cells correlated with S100A8/9 and arginase-1 expression by MDSCs. At the same time, NK cell-derived IL-6 was associated with tumors with higher major histocompatibility complex class I expression, which we further validated with b2m-knockout (KO) tumor mice models. Similarly in syngeneic wild-type and IL-6 KO mouse models, we then demonstrated that the accumulation of MDSCs was influenced by the presence of such regulatory NK cells. Inhibition of the IL-6/signal transducer and activator of transcription 3 (STAT3) axis alleviated suppression of T cell responses, resulting in reduced tumor growth and metastatic dissemination. Together, these results characterize a critical NK cell-mediated mechanism that drives the development of MDSCs during tumor immune escape.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. Results: The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. Conclusions: The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.

High-throughput semi-automated emulsive liquid-liquid microextraction for detecting SDHI fungicides in water, juice, and alcoholic beverage samples via UHPLC-MS/MS.

Herein, a High-Throughput Semi-automated Emulsive Liquid-Liquid Microextraction (HTSA-ELLME) method was developed to detect Succinate Dehydrogenase Inhibitor (SDHI) fungicides in food samples via UHPLC-MS/MS. The Oil-in-Water (O/W) emulsion comprising a hydrophobic extractant and water was dilutable with the aqueous sample solution. Upon injecting the primary emulsion into the sample solution, a secondary O/W emulsion was formed, allowing SDHI fungicides to be extracted. Subsequently, a NaCl-saturated solution was injected in the secondary O/W emulsion as a demulsifier to rapidly separate the extractant, eliminating the need for centrifugation. A 12-channel electronic micropipette was used to achieve a high-throughput semi-automation of the novel sample pretreatment. The linear range was 0.003-0.3 µg L-1 with R2 > 0.998. The limit of detection was 0.001 µg L-1. The HTSA-ELLME method successfully detected SDHI fungicides in water, juice, and alcoholic beverage samples, with recoveries and relative standard deviations of 82.6-106.9% and 0.8-5.8%, respectively. Unlike previously reported liquid-liquid microextraction approaches, the HTSA-ELLME method is the first to be both high-throughput and semi-automated and may aid in designing pesticide pretreatment processes in food samples.

Fatty Acid Oxidation Supports Lymph Node Metastasis of Cervical Cancer via Acetyl-CoA-Mediated Stemness.

Accumulating evidence indicates that metabolic reprogramming of cancer cells supports the energy and metabolic demands during tumor metastasis. However, the metabolic alterations underlying lymph node metastasis (LNM) of cervical cancer (CCa) have not been well recognized. In the present study, it is found that lymphatic metastatic CCa cells have reduced dependency on glucose and glycolysis but increased fatty acid oxidation (FAO). Inhibition of carnitine palmitoyl transferase 1A (CPT1A) significantly compromises palmitate-induced cell stemness. Mechanistically, FAO-derived acetyl-CoA enhances H3K27 acetylation (H3K27Ac) modification level in the promoter of stemness genes, increasing stemness and nodal metastasis in the lipid-rich nodal environment. Genetic and pharmacological loss of CPT1A function markedly suppresses the metastatic colonization of CCa cells in tumor-draining lymph nodes. Together, these findings propose an effective method of cancer therapy by targeting FAO in patients with CCa and lymph node metastasis.

Association of serum albumin with heart failure mortality with NYHA class IV in Chinese patients: Insights from PhysioNet database (version 1.3).

BACKGROUND: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. OBJECTIVES: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. METHODS: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. RESULTS: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. CONCLUSION: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.

Engineering NH2-Cu-NH2 Triple-atom Sites in Defective MOFs for Selective Overall Photoreduction of CO2 into CH3COCH3.

Selective photoreduction of CO2 to multicarbon products, is an important but challenging task, due to high CO2 activation barriers and insufficient catalytic sites for C-C coupling. Herein, a defect engineering strategy for incorporating copper sites into the connected nodes of defective metal-organic framework UiO-66-NH2 for selective overall photo-reduction of CO2 into acetone. The Cu2+ site in well-modified CuN2O2 units served as a trapping site to capture electrons via efficient electron-hole separation, forming the active Cu+ site for CO2 reduction. Two NH2 groups in CuN2O2 unit adsorb CO2 and cooperated with copper ion to functionalize as a triple atom catalytic site, each interacting with one CO2 molecule to strengthen the binding of *CO intermediate to the catalytic site. The deoxygenated *CO attached to the Cu site interacted with *CH3 fixed at one amino group to form the key intermediate CO*-CH3, which interacted with the third reduction intermediate on another amino group to produce acetone. Our photocatalyst realizes efficient overall CO2 reduction to C3 product acetone CH3COCH3 with an evolution rate of 70.9 µmol gcat -1 h-1 and a selectivity up to 97 % without any adducts, offering a promising avenue for designing triple-atomic sites to producing C3 product from photosynthesis with water.

Metaplastic regeneration in the mouse stomach requires a reactive oxygen species pathway.

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.

Interface fluid syndrome caused by the corneal perforation injury after small incision lenticule extraction: a case report.

BACKGROUND: To report a case of interface fluid syndrome (IFS) following traumatic corneal perforation repair after small incision lenticule extraction (SMILE). CASE PRESENTATION: A 23-year-old woman, with a past history of SMILE, was struck in the left eye with a barbecue prod and subsequently underwent corneal perforation repair at local hospital. Primary wound repaired with a single 10 - 0 nylon suture at the area of leakage. After the surgery, her best corrected visual acuity (BCVA) was 20/30. Four days later, she presented at our hospital with blurred vision, and interface fluid syndrome (IFS) was diagnosed. Intraoperative optical coherence tomography (iOCT) was used to guide the resuturing of the corneal perforation in the left eye, followed by anterior chamber gas injection. At the first postoperative month, the BCVA was 20/25. The corneal cap adhered closely to the stroma, the surface became smooth. CONCLUSIONS: This case illustrates that any corneal perforation following lamellar surgery, including SMILE, may lead to IFS. It is crucial to consider the depth of corneal perforation, and intraoperative optical coherence tomography (iOCT) plays a unique role in the repair procedure.

CircMAST1 inhibits cervical cancer progression by hindering the N4-acetylcytidine modification of YAP mRNA.

BACKGROUND: Cervical cancer (CCa) is the fourth most common cancer among females, with high incidence and mortality rates. Circular RNAs (circRNAs) are key regulators of various biological processes in cancer. However, the biological role of circRNAs in cervical cancer (CCa) remains largely unknown. This study aimed to elucidate the role of circMAST1 in CCa. METHODS: CircRNAs related to CCa progression were identified via a circRNA microarray. The relationship between circMAST1 levels and clinicopathological features of CCa was evaluated using the clinical specimens and data of 131 patients with CCa. In vivo and in vitro experiments, including xenograft animal models, cell proliferation assay, transwell assay, RNA pull-down assay, whole-transcriptome sequencing, RIP assay, and RNA-FISH, were performed to investigate the effects of circMAST1 on the malignant behavior of CCa. RESULTS: CircMAST1 was significantly downregulated in CCa tissues, and low expression of CircMAST1 was correlated with a poor prognosis. Moreover, our results demonstrated that circMAST1 inhibited tumor growth and lymph node metastasis of CCa. Mechanistically, circMAST1 competitively sequestered N-acetyltransferase 10 (NAT10) and hindered Yes-associated protein (YAP) mRNA ac4C modification to promote its degradation and inhibit tumor progression in CCa. CONCLUSIONS: CircMAST1 plays a major suppressive role in the tumor growth and metastasis of CCa. In particular, circMAST1 can serve as a potential biomarker and novel target for CCa.

Gastric intestinal metaplasia: progress and remaining challenges.

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.