Pantoprazole suppresses carcinogenesis and growth of hepatocellular carcinoma by inhibiting glycolysis and Na+/H+ exchange.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The prevention and therapy for this deadly disease remain a global medical challenge. In this study, we investigated the effect of pantoprazole (PPZ) on the carcinogenesis and growth of HCC. Both diethylnitrosamine (DEN) plus CCl4-induced and DEN plus high fat diet (HFD)-induced HCC models in mice were established. Cytokines and cell proliferation-associated gene in the liver tissues of mice and HCC cells were analyzed. Cellular glycolysis and Na+/H+ exchange activity were measured. The preventive administration of pantoprazole (PPZ) at a clinically relevant low dose markedly suppressed HCC carcinogenesis in both DEN plus CCl4-induced and HFD-induced murine HCC models, whereas the therapeutic administration of PPZ at the dose suppressed the growth of HCC. In the liver tissues of PPZ-treated mice, inflammatory cytokines, IL1, CXCL1, CXCL5, CXCL9, CXCL10, CCL2, CCL5, CCL6, CCL7, CCL20, and CCL22, were reduced. The administration of CXCL1, CXCL5, CCL2, or CCL20 all reversed PPZ-suppressed DEN plus CCL4-induced HCC carcinogenesis in mice. PPZ inhibited the expressions of CCNA2, CCNB2, CCNE2, CDC25C, CDCA5, CDK1, CDK2, TOP2A, TTK, AURKA, and BIRC5 in HCC cells. Further results showed that PPZ reduced the production of these inflammatory cytokines and the expression of these cell proliferation-associated genes through the inhibition of glycolysis and Na+/H+ exchange. In conclusion, PPZ suppresses the carcinogenesis and growth of HCC, which is related to inhibiting the production of inflammatory cytokines and the expression of cell proliferation-associated genes in the liver through the inhibition of glycolysis and Na+/H+ exchange.

Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/ß-catenin signaling.

Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.

Thermally Evaporated Blue Quasi-Two-Dimensional Perovskite Light-Emitting Diodes via Low-Dimensional Phase Distribution Arrangement.

Perovskite light-emitting diodes (PeLEDs) have shown great potential in the display domain due to their wide color gamut, narrow emission, and low cost. In current PeLEDs manufacturing methods, thermal evaporation shows great competitiveness with its advantages of easy patterning, production line compatibility, and solvent-free processability. However, the development of thermally evaporated blue PeLEDs is limited by their low radiative recombination rate and high defect density. Herein, we report high-performance thermally evaporated blue PeLEDs by in situ introduction of ammonium cations. We confirm that phenethylammonium (PEA+) has lower adsorption energy, which significantly reduces the low-n phases in a quasi-2D perovskite film. The energy transfer rate is also promoted by the PEA+ addition. As a result, we fabricate blue PeLEDs with an external quantum efficiency of 1.56% by thermal evaporation. The strategy of arranging phase distribution could benefit the industrialization of full-color PeLEDs.

L-GrAFT7 has High Accuracy in Predicting Early Allograft Failure after Liver Transplantation: A Multicenter Cohort Study in China.

Background and Aims: Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking. Methods: A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers. L-GrAFT (L-GrAFT7 and L-GrAFT10) was compared with existing models: the Early Allograft Failure Simplified Estimation (EASE) score, the model of early allograft function (MEAF), and the Early Allograft Dysfunction (EAD) model. Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group. Results: L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival, significantly superior to MEAF [area under the curve (AUC=0.78, p=0.044)] and EAD (AUC=0.78, p=0.006), while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE (AUC=0.84, p>0.05). Furthermore, L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index (DRI) cases (AUC=0.83 vs. MEAF, p=0.007 vs. EAD, p=0.014) and recipients of donors after cardiac death (AUC=0.92 vs. EAD, p<0.001). Through multivariate analysis, pretransplant bilirubin level, units of packed red blood cells, and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group. Conclusions: The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort, indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Insight into the High Mobility and Stability of In2 O3 :H Film.

Wide bandgap semiconductors, particularly In2 O3 :Sn (ITO), are widely used as transparent conductive electrodes in optoelectronic devices. Nevertheless, due to the strohave beenng scattering probability of high-concentration oxygen vacancy (VO ) defects, the mobility of ITO is always lower than 40 cm2  V-1  s-1 . Recently, hydrogen-doped In2 O3 (In2 O3 :H) films have been proven to have high mobility (>100 cm2  V-1  s-1 ), but the origin of this high mobility is still unclear. Herein, a high-resolution electron microscope and theoretical calculations are employed to investigate the atomic-scale mechanisms behind the high carrier mobility in In2 O3 :H films. It is found that VO can cause strong lattice distortion and large carrier scattering probability, resulting in low carrier mobility. Furthermore, hydrogen doping can simultaneously reduce the concentration of VO , which accounts for high carrier mobility. The thermal stability and acid-base corrosion mechanism of the In2 O3 :H film are investigated and found that hydrogen overflows from the film at high temperatures (>250 °C), while acidic or alkaline environments can cause damage to the In2 O3 grains themselves. Overall, this work provides insights into the essential reasons for high carrier mobility in In2 O3 :H and presents a new research approach to the doping and stability mechanisms of transparent conductive oxides.

All-Thermally Evaporated Blue Perovskite Light-Emitting Diodes for Active Matrix Displays.

With the rapid progress of perovskite light-emitting diodes (PeLEDs), the large-scale fabrication of active matrix PeLED displays (AM-PeLEDs) is gaining increasing attention. However, the integration of high-resolution PeLED arrays with thin-film transistor backplanes remains a significant challenge for conventional spin-coating techniques. Here, the demonstration of large-area, blue-emitting AM-PeLEDs are demonstrated using a vacuum deposition technique, which is regarded as the most effective route for organic light-emitting diode displays. By the introduction of an in situ passivation strategy, the defects-related nonradiative recombination is largely suppressed, which leads to an improved photoluminescence quantum yield of vapor-deposited blue-emitting perovskites. The as-prepared blue PeLEDs exhibit a peak external quantum efficiency of 2.47% with pure-blue emission at 475 nm, which represents state-of-the-art performance for vapor-deposited pure-blue PeLEDs. Benefiting from the excellent uniformity and compatibility of thermal evaporation, the 6.67-inch blue-emitting AM-PeLED display with a high resolution of 394 pixels per inch is successfully demonstrated. The demonstration of blue-emitting AM-PeLED display represents a crucial step toward full-color perovskite display technology.

The S100 calcium-binding protein A6 plays a crucial role in hepatic steatosis by mediating lipophagy.

BACKGROUND: S100 calcium-binding protein A6 (S100A6) is a calcium-binding protein that is involved in a variety of cellular processes, such as proliferation, apoptosis, and the cellular response to various stress stimuli. However, its role in NAFLD and associated metabolic diseases remains uncertain. METHODS AND RESULTS: In this study, we revealed a new function and mechanism of S100A6 in NAFLD. S100A6 expression was upregulated in human and mouse livers with hepatic steatosis, and the depletion of hepatic S100A6 remarkably inhibited lipid accumulation, insulin resistance, inflammation, and obesity in a high-fat, high-cholesterol (HFHC) diet-induced murine hepatic steatosis model. In vitro mechanistic investigations showed that the depletion of S100A6 in hepatocytes restored lipophagy, suggesting S100A6 inhibition could alleviate HFHC-induced NAFLD. Moreover, S100A6 liver-specific ablation mediated by AAV9 alleviated NAFLD in obese mice. CONCLUSIONS: Our study demonstrates that S100A6 functions as a positive regulator of NAFLD, targeting the S100A6-lipophagy axis may be a promising treatment option for NAFLD and associated metabolic diseases.

A potential tumor marker: Chaperonin containing TCP­1 controls the development of malignant tumors (Review).

Due to concealment, high invasiveness and a lack of indicators, malignant tumors have emerged as one of the deadliest diseases worldwide and their incidence is rising yearly. Research has revealed that the chaperonin family member, chaperonin containing TCP­1 (CCT), serves a crucial role in malignant tumors. CCT is involved in the growth of numerous malignant tumors such as lung cancer, breast cancer, hepatocellular carcinoma and colorectal cancer and assists the folding of a number of proteins linked to cancer, such as KRAS, p53 and STAT3. According to clinical data, CCT is highly expressed in a range of tumor cells and is associated with poor patient prognosis. In addition, through controlling the cell cycle or interacting with other proteins (including YAP1, HoXB2 and SMAD2), CCT has an effect on the proliferation, invasion and migration of cancer cells. As a result, it is possible that CCT will become a new tumor marker or therapeutic target, which will provide some guidance for early tumor screening or late tumor prognosis. In the present review, the molecular properties of CCT are introduced, alongside a summary of its interactions with other cancer­related proteins and a discussion of its function in common malignant tumors. It is expected that the present review will offer fresh approaches to the treatment of cancer.

Relationship between histone demethylase LSD family and development and prognosis of gastric cancer.

Objective: to elucidate the correlation between histone demethylase and gastric cancer. Research object: histone demethylase and gastric cancer. Results: As one of the important regulatory mechanisms in molecular biology and epigenetics, histone modification plays an important role in gastric cancer including downstream gene expression regulation and epigenetics effect. Both histone methyltransferase and histone demethylases are involved in the formation and maintaining different of histone methylation status, which in turn through a variety of vital molecules and signaling pathways involved in the recognition of histone methylation modification caused by the downstream biological process, eventually participate in the regulation of chromatin function, and with a variety of important physiological activities, especially closely related to the occurrence of gastric cancer and embryonic development. Conclusion: This paper intends to review the research progress in this field from the aspects of histone methylation modification and the protein structure, catalytic mechanism and biological function of the important histone demethylases LSD1 and LSD2, in order to provide the theoretical reference for further understanding and exploration of histone demethylases in development and prognosis of gastric cancer.

Gastric immune homeostasis imbalance: An important factor in the development of gastric mucosal diseases.

The gastric mucosal immune system is a unique immune organ independent of systemic immunity that not only maintains nutrient absorption but also plays a role in resisting the external environment. Gastric mucosal immune disorder leads to a series of gastric mucosal diseases, including autoimmune gastritis (AIG)-related diseases, Helicobacter pylori (H. pylori)-induced diseases, and various types of gastric cancer (GC). Therefore, understanding the role of gastric mucosal immune homeostasis in gastric mucosal protection and the relationship between mucosal immunity and gastric mucosal diseases is very important. This review focuses on the protective effect of gastric mucosal immune homeostasis on the gastric mucosa, as well as multiple gastric mucosal diseases caused by gastric immune disorders. We hope to offer new prospects for the prevention and treatment of gastric mucosal diseases.

The mechanisms of gastric mucosal injury: focus on initial chief cell loss as a key target.

Diffuse gastric mucosal injury is a chronic injury with altered cell differentiation, including spasmolytic polypeptide expression metaplasia (SPEM) and intestinal metaplasia (IM), which are considered precancerous lesions of gastric cancer (GC). Previously, most studies have focused on how parietal cell loss causes SPEM through transdifferentiation of chief cells. In theory, alteration or loss of chief cells seems to be a secondary phenomenon due to initial partial cell loss. However, whether initial chief cell loss causes SPEM needs to be further investigated. Currently, increasing evidence shows that initial chief cell loss is sufficient to induce gastric mucosal injury, including SPEM and IM, and ultimately lead to GC. Therefore, we summarized the two main types of models that explain the development of gastric mucosal injury due to initial chief cell loss. We hope to provide a novel perspective for the prevention and treatment of diffuse gastric mucosal injury.

Assessment and spatial partitioning of ecosystem services importance in Giant Panda National Park: To provide targeted ecological protection.

Giant Panda National Park is crucial for China's ecological security strategic pattern known as "two screens and three belts." The importance assessment and classification of ecosystem services in giant panda national parks has an important guiding role in the protection of giant panda national park ecosystems. In this study, we examined four indicators of habitat quality: carbon storage, water conservation, and soil and water conservation. Combined with data analysis were used to evaluate and classify the importance of ecosystem services in the study area. The results showed that: (1) the overall habitat quality index in the study area was relatively high, and the index was generally greater than 0.5. The total carbon storage was 60.5 × 106 t, and the highest carbon storage in the region was 16.9533 t. The area with the highest water conservation reached 715.275 mm. The total soil conservation was 2555.7 × 107 t. (2) From the perspective of spatial characteristics, the habitat quality in the study area presented a spatial distribution pattern of high-low from west to east. The carbon storage presented a spatial distribution pattern of high-low from east to west. The soil conservation presented a spatial pattern of decreasing from west to east, and the water conservation increased from west to east. (3) We divided the research into four levels of importance: The area of general importance in the study site accounted for 1017.58 km2 and was distributed in the northwest of the study site. The moderately important areas were distributed in the east of the study site, with an area of 1142.40 km2. The highly important areas were distributed in the west of the study site, totaling 2647.84 km2. Extremely important areas were distributed in the middle, with an area of 1451.32 km2. (4) The grid cell scale of the study area was used as the dataset to determine the weighting. This makes the weighting more objective and ensures that the spatial distribution of areas with different degrees of importance will be more accurate.

A novel method for cliff vegetation estimation based on the unmanned aerial vehicle 3D modeling.

The cliff ecosystem is one of the least human-disturbed ecosystems in nature, and its inaccessible and often extreme habitats are home to many ancient and unique plant species. Because of the harshness of cliff habitats, their high elevation, steepness of slopes, and inaccessibility to humans, surveying cliffs is incredibly challenging. Comprehensive and systematic information on cliff vegetation cover is not unavailable but obtaining such information on these cliffs is fundamentally important and of high priority for environmentalists. Traditional coverage survey methods-such as large-area normalized difference vegetation index (NDVI) statistics and small-area quadratic sampling surveys-are not suitable for cliffs that are close to vertical. This paper presents a semi-automatic systematic investigation and a three-dimensional reconstruction of karst cliffs for vegetation cover evaluation. High-resolution imagery with structure from motion (SFM) was captured by a smart unmanned aerial vehicle (UAV). Using approximately 13,000 records retrieved from high-resolution images of 16 cliffs in the karst region Guilin, China, 16 models of cliffs were reconstructed. The results show that this optimized UAV photogrammetry method greatly improves modeling efficiency and the vegetation cover from the bottom to the top of cliffs is high-low-high, and very few cliffs have high-low cover at the top. This study highlights the unique vegetation cover of karst cliffs, which warrants further research on the use of SFM to retrieve cliff vegetation cover at large and global scales.

Gastric alarmin release: A warning signal in the development of gastric mucosal diseases.

Alarmins exist outside cells and are early warning signals to the immune system; as such, alarmin receptors are widely distributed on various immune cells. Alarmins, proinflammatory molecular patterns associated with tissue damage, are usually released into the extracellular space, where they induce immune responses and participate in the damage and repair processes of mucosal diseases.In the stomach, gastric alarmin release has been shown to be involved in gastric mucosal inflammation, antibacterial defense, adaptive immunity, and wound healing; moreover, this release causes damage and results in the development of gastric mucosal diseases, including various types of gastritis, ulcers, and gastric cancer. Therefore, it is necessary to understand the role of alarmins in gastric mucosal diseases. This review focuses on the contribution of alarmins, including IL33, HMGB1, defensins and cathelicidins, to the gastric mucosal barrier and their role in gastric mucosal diseases. Here, we offer a new perspective on the prevention and treatment of gastric mucosal diseases.

Case report: New subtype of gastric adenocarcinoma arising from an H. pylori infection-negative stomach: Foveolar epithelium and mucous neck cell-mixed type adenocarcinoma.

The characteristics of Helicobacter pylori (H. pylori) infection-negative gastric cancer have not been well documented because of its rarity, despite several types of H. pylori infection-negative gastric cancers being reported. In this report, we describe a case of early gastric cancer that developed without H. pylori infection with characteristic magnifying narrow-band imaging and novel histological findings. The difficulty in making an accurate diagnosis and differential diagnosis is highlighted, with the goal of providing more clinical experience for the diagnosis of H. pylori infection-negative gastric cancer.

Lentinan enhances the antitumor effects of Delta-like 1 via neutrophils.

BACKGROUND: Selective activation of Delta-like 1 (DLL1)-Notch signaling is a new approach to activate CD8+ T cell and suppress tumor growth, while the efficacy remains modest. Lentinan (LNT) is a clinically used immunomodulation agent. Thus, we hypothesized that LNT could improve the efficacy of DLL1. METHODS: The effects of LNT combined with DLL1 on tumor growth were evaluated by growth curve and tumor weight in EO771 breast and LAP0297 lung tumor models. The impacts on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR. Neutrophil depletion was used to investigate the mechanism of the combination therapy on tumor growth. The data sets were compared using unpaired student's t-test or ordinary one-way ANOVA. RESULTS:  LNT treatments additively improved the antitumor effects of DLL1 in EO771 breast tumor growth. Remarkably, LNT treatments synergistically enhanced the suppression of DLL1 on LAP0297 lung tumor growth, resulting in tumor regression. Mechanically, the combination of LNT and DLL1 interventions not only promoted the accumulation and activation of CD8+ T cells, but also increased intratumoral CD45+CD11b+Ly6G+ neutrophils. Reduced neutrophils by anti-Gr1 antibody administrations reversed the improved antitumor effects by LNT treatments in LAP0297 lung tumor. These results suggest that LNT treatments improve the inhibition of DLL1 on tumor growth via neutrophils. CONCLUSIONS: Our findings indicates that LNT and DLL1 may induce synergistical antitumor immunity via simultaneous modulating lymphoid and myeloid cell populations regardless of the type of tumor, providing a potential new strategy to potentiate cancer immunotherapy.

Prognostic value of absolute lymphocyte count in patients with advanced esophageal cancer treated with immunotherapy: a retrospective analysis.

Background: Immunotherapy has become the standard of treatment for recurrent metastatic esophageal cancer (EC), and the value of efficacy predictive markers represented by programmed death-ligand 1 (PD-L1) is limited. The purpose of this study is to analyze the prognostic value of peripheral blood absolute lymphocyte count (ALC) at baseline in patients with recurrent metastatic EC treated with immunotherapy, and to further investigate the relationship between the minimal ALC value (Min ALC) and radiotherapy (RT) parameters. Methods: The main inclusion criteria were: histologically or imaging confirmed recurrent or metastatic EC; complete routine blood test data. A total of 105 patients were included in a single-center institution, 65 of whom had previously received RT. The optimal cut-off value for baseline lymphopenia was determined by the receiver operating characteristic (ROC) curve. The prognostic value of baseline phase lymphopenia for immunotherapy were determined by cox regression analysis and the associated factors affecting lymphopenia were explored by logistic regression analysis. Results: The cut-off value for baseline ALC predicting 1-year overall survival (OS) was 625 cells/µL. The OS was significantly lower in the lymphopenia group (ALC ≤625 cells/µL) than in the non-lymphopenia group (ALC >625 cells/µL) (median OS: 6 vs. 12 months, P=0.002). Multivariate analysis showed that pre-immunotherapy lymphopenia was an important factor influencing patient prognosis [hazard ratio (HR): 1.771, 95% confidence interval (CI): 1.051-2.985; P=0.032)] (adjusted for clinical factors including sex, age, tumor location, histology, degree of differentiation, distant metastasis, use of RT). Patients with a previous grade 4 (G4) Min ALC during RT were more likely to develop pre-immunotherapy lymphopenia following diagnosis of recurrent metastasis [odds ratio (OR): 10.809, 95% CI: 2.185-53.471; P=0.004]. Planning target volume (PTV) volume greater than 521.2 cm3 (OR: 19.981, 95% CI: 1.372-290.985; P=0.028) was an independent risk factor affecting the G4 Min ALC during RT. Conclusions: Lymphopenia is associated with a poorer immunotherapy prognosis in patients with recurrent metastatic EC and those with previous G4 Min ALC after RT. RT-related parameters, especially irradiation volume, can significantly affect lymphocyte counts.

SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice and aggressive gastric cancer in humans.

BACKGROUND: Solute carrier family 26 member (SLC26A9) is a Cl- uniporter with very high expression levels in the gastric mucosa. Here, we describe morphological and molecular alterations in gastric mucosa of slc26a9-/- mice and in selective parietal cell-deleted slc26a9fl/fl/Atp4b-Cre mice and correlate SLC26A9 expression levels with morphological and clinical parameters in a cohort of gastric cancer (GC) patients. METHODS: The expression patterns of genes related to transport and enzymatic function, proliferation, apoptosis, inflammation, barrier integrity, metaplasia and neoplasia development were studied by immunohistochemistry (IHC), quantitative RT-PCR, in situ hybridization and RNA microarray analysis. SLC26A9 expression and cellular/clinical phenotypes were studied in primary human GC tissues and GC cell lines. RESULTS: We found that both complete and parietal cell-selective Slc26a9 deletion in mice caused spontaneous development of gastric premalignant and malignant lesions. Dysregulated differentiation of gastric stem cells in an inflammatory environment, activated Wnt signaling, cellular hyperproliferation, apoptosis inhibition and metaplasia were observed. Analysis of human gastric precancerous and cancerous tissues revealed that SLC26A9 expression progressively decreased from atrophic gastritis to GC, and that downregulation of SLC26A9 was correlated with patient survival. Exogenous expression of SLC26A9 in GC cells induced upregulation of the Cl-/HCO3- exchanger AE2, G2/M cell cycle arrest and apoptosis and suppressed their proliferation, migration and invasion. CONCLUSIONS: Our data indicate that SLC26A9 deletion in parietal cells is sufficient to trigger gastric metaplasia and the development of neoplastic lesions. In addition, we found that SLC26A9 expression decreases during human gastric carcinogenesis, and that exogenous SLC26A9 expression in GC cells reduces their malignant behavior.

The source of the fat significantly affects the results of high-fat diet intervention.

High-fat diet (HFD) is widely used in animal models of many diseases, it helps to understand the pathogenic mechanism of related diseases. Several dietary fats were commonly used in HFD, such as corn oil, peanut oil, soybean oil, sunflower oil, and lard. However, it was reported that different dietary fat could have completely different effects on physiological indicators and the gut microbiome, and the sources of dietary fat used in high-fat diet research have not been comprehensively compared. In this research, we conduct comparative experiments on various sources of dietary fats to test their different effects during the high-fat diet intervention. We investigated the effects of twelve common dietary fats in high-fat diet intervention of mice, body/liver weight changes, four blood lipid indices, and gut microbiome were analyzed. Our results showed that the source of dietary fat used in high-fat diet significantly affects the changes of body/liver weight and triglyceride (TRIG) in the blood. Furthermore, the intervention of canola oil increased the alpha diversity of gut microbiota, and lard has decreased diversity compared with the control group. The composition of saturated fatty acid (SFA) in fat has the most significant effects on the gut microbiome. All dietary fats treatments have an increasing Firmicutes abundance and a reduced Bacteroidetes abundance in gut microbiome, while the canola oil has a slight variation compared to other intervention groups, and the lard group has the largest changes. This study showed that different types of dietary fat have different effects on the body indicators and intestinal microbiota of mice, and canola oil produced less disturbance than other types of dietary fats in high-fat diet.