USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis.

Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.

FXR controls duodenogastric reflux-induced gastric inflammation through negatively regulating ER stress-associated TNXIP/NLPR3 inflammasome.

Duodenogastric reflux (DGR) is closely associated with gastric inflammation and tumorigenesis; however, the precise mechanism is unclear. Hence, we aim to clarify this molecular mechanism and design an effective therapeutic strategy based on it. The present study found that DGR induced TXNIP/NLRP3 inflammasome activation and triggered pyroptosis in gastric mucosa in vitro and in vivo, in which endoplasmic reticulum (ER) stress via PERK/eIF2α/CHOP signaling was involved. Mechanistically, farnesoid X receptor (FXR) antagonized the DGR-induced PERK/eIF2α/CHOP pathway and reduced TXNIP and NLRP3 expression. Moreover, FXR suppressed NLRP3 inflammasome activation by physically interacting with NLRP3 and caspase-1. Administration of the FXR agonist OCA protected the gastric mucosa from DGR-induced barrier disruption and mucosal inflammation. In conclusion, our study demonstrates the involvement of TXNIP/NLRP3 inflammasome-mediated pyroptosis in DGR-induced gastric inflammation. FXR antagonizes gastric barrier disruption and mucosal inflammation induced by DGR. Restoration of FXR activity may be a therapeutic strategy for DGR-associated gastric tumorigenesis.

Eating behavior during pregnancy mediates the association between depression and diet quality--a new strategy for intervention in pregnancy.

Background: Depression can result in changes in eating behavior and decrease the quality of eating. It has been shown that maternal depression during pregnancy can result in malnutrition, which can have adverse effects on the pregnancy and the offspring. There is currently no clear association between depression and diet. Methods: Five hundred and forty-nine pregnant women recruited from Danyang Maternal and Child Health Hospital in Jiangsu Province participated in this study and were administered the Intuitive Eating Scale-2 (IES-2), Edinburgh Post-natal Depression Scale (EPDS), Pregnancy Stress Scale (PPS), Self-rating Anxiety Scale (SAS), and Dietary Guidelines Adherence Index for Pregnant Women during Pregnancy (CDGCI-PW). The nutritional software collected dietary records for three consecutive days in mid-pregnancy to calculate dietary intake and nutrients that support energy production. The mediation analyses were conducted using SPSS 24.0 macro PROCESS. Results: The relationship between depressive symptoms during pregnancy and diet quality was moderated primarily by two aspects of eating behavior, "Reliance on Hunger and Satiety Cues" (RHS) and "Body-Food Choice Congruence" (BFC). Depressive symptoms (EPDS scores) showed a negative correlation with RHS, BFC, and RHS, and BFC showed a positive correlation with diet quality, yielding a significant specific indirect effect. The multiple mediation model explained 14.7% of the variance in the diet quality. Conclusion: This study highlights the important role of eating behaviors during pregnancy in the relationship between depressive symptoms (EPDS scores) and diet quality, and provides preliminary evidence for feasible ways pregnant women with depressive symptoms can improve diet quality, promote maternal and child health, and reduce depression.

Triphenyl phosphate exposure impairs colorectal health by altering host immunity and colorectal microbiota.

Colorectal diseases such as colorectal cancer (CRC) and inflammatory bowel disease (IBD) have become one of the most common public health concerns worldwide due to the increasing incidence. Environmental factors are one of the important causes of colorectal diseases, as they can affect the intestinal barrier function, immune response and microbiota, causing intestinal inflammation and tumorigenesis. Triphenyl phosphate (TPHP), a widely used organophosphorus flame retardant that can leach and accumulate in various environmental media and biota, can enter the human intestine through drinking water and food. However, the effects of TPHP on colorectal health have not been well understood. In this study, we investigated the adverse influence of TPHP exposure on colorectal cells (in vitro assay) and C57BL/6 mice (in vivo assay), and further explored the potential mechanism underlying the association between TPHP and colorectal disease. We found that TPHP exposure inhibited cell viability, increased apoptosis and caused G1/S cycle arrest of colorectal cells. Moreover, TPHP exposure damaged colorectal tissue structure, changed immune-related gene expression in the colorectal transcriptome, and disrupted the composition of colorectal microbiota. Importantly, we found that TPHP exposure upregulated chemokine CXCL10, which was involved in colorectal diseases. Our study revealed that exposure to TPHP had significant impacts on colorectal health, which may possibly stem from alterations in host immunity and the structure of the colorectal microbial community.

Pyrolysis temperature matters: Biochar-derived dissolved organic matter modulates aging behavior and biotoxicity of microplastics.

Microplastics (MPs) have emerged as a novel and highly concerning contaminant that is ubiquitous in the aqueous environment. However, the aging of MPs induced by dissolved organic matter (DOM), especially biochar-derived dissolved organic matter (BDOM), and the biological toxicity after aging are not fully understood. In this study, the effects of biochar-derived BDOMs on the photoaging and biotoxicity of MPs were investigated at different pyrolysis temperatures using micro-scale polyethylene (PE) as an example. The results showed that the amount of ·OH generated by the BDOM/PE systems was related to the molecular composition and structure of BDOMs. High temperature BDOM7/9 with less lignin-like (34.33 % / 41.80 %) and more lipid (24.58 % / 19.88 %) content could produce more ·OH by itself, and its binding ability with PE was weaker due to its less hydrophobic components (SUVA260 = 0.10 / 0.11), which resulted in a weaker shading effect and less inhibition of the system, thus resulting in more ·OH production in the high temperature BDOM7/9/PE system. However, the involvement of BDOM, although favoring the long-term stable ·OH production of the system, did not significantly promote the photoaging of MPs. Furthermore, combined in vivo and in vitro biotoxicity studies of MPs showed that photoaging PE with the involvement of BDOM greatly improved systemic inflammation and tissue damage, as well as reactive oxygen species (ROS, such as ·OH and -OH)-induced cell death. For example, the addition of BDOM5/PE-light reduced the cell death of human lung, liver, and kidney cells from 54.70 %, 69.39 %, and 48.35 % to 22.78 %, 33.13 %, and 25.83 %, respectively, compared to the PE-light group. The results of this study contribute to an in-depth understanding of the environmental behavior of BDOM and MPs systems.

Effect of skipping breakfast on cardiovascular risk factors: a grade-assessed systematic review and meta-analysis of randomized controlled trials and prospective cohort studies.

Skipping breakfast is one of the most prevalent irregular eating habits. Several pieces of evidence have reported the association between breakfast omission and a higher risk of cardiovascular diseases. Numerous publications have focused on the impact of skipping breakfast on various cardiovascular risk factors. Therefore, the current systematic review and meta-analysis aimed to assess this impact, especially with regard to anthropometric measurements, serum lipid profiles, blood pressure, and glycemic control indicators. A comprehensive search was performed in PubMed, Web of Science, Embase, Scopus, and the Cochrane Central Register of Controlled Trials up to 1 April 2023. A total of 11 eligible trials were identified to evaluate the combined effects of skipping breakfast. Final integrated results demonstrated that breakfast omission significantly decreased the body weight (mean difference = -0.66, 95% CI: -1.09 to -0.24, p = 0.002, I2 = 0.0) and increased the level of serum low-density lipoprotein cholesterol (LDL-C) (mean difference = 9.89, 95% CI: 5.14 to 14.63, p = 0.000, I2 = 17.3). Subgroup analysis also revealed potential factors that may affect the outcomes, for example, the physiological condition of participants, duration, gender, and type of breakfast. In conclusion, skipping breakfast may reduce body weight while increasing the level of serum LDL-C at the same time. In view of the limited trials, further studies are needed to expound the role of breakfast omission in cardiovascular diseases.

Effects of green tea catechin on the blood pressure and lipids in overweight and obese population-a meta-analysis.

Background: Overweight and obesity as main health problems harm human beings worldwide. The number of people diagnosed with overweight and obese is gradually increasing. Green tea catechin has been reported to effectively help control body weight in overweight and obese population, and is protectively against the blood pressure and lipids in people with type 2 diabetes and metabolic syndrome. Methods: We retrieved 4 English databases (PubMed, Web of science, Cochrane, Scoups) from inception to April 20, 2023. Two reviewers independently determined eligibility, assessed the reporting quality of included studies, and extracted the data. Data were extracted from eleven studies. The results were presented with the weighted mean differences (WMDs), and the confidence intervals (CIs) was 95 %. The random-effects or fixed-effects model was applied according to the heterogeneity. The subgroup analysis was used to identify the source of heterogeneity. Publication bias was evaluated using funnel plots, Egger's test, and Begg's test. Results: Eleven randomized controlled trials (RCTs) inclusion studies were screened from 3072 literature articles, involving 613 overweight and obese patients. After combining all studies, it was found that in overweight and obese people green tea catechin could reduce waist circumference (WC) (pooled WMD = -1.37 cm, 95 % CI: -2.52 to -0.22 cm, p = 0.019), and triglyceride (TG) (pooled WMD = -0.18 mmol/L, 95 % CI: -0.35 to -0.02 mmol/L, p = 0.032), and increase high density lipoprotein cholesterol (HDL-c) (pooled WMD = 0.07 mmol/L, 95 % CI: 0.01-0.14 mmol/L, p = 0.031). Conclusion: Green tea catechin supplement effectively reduced WC and TG levels and improved HDL-c levels. However, it did not show the significant effect on the blood pressure in overweight and obese people. The present meta-analysis showed a moderate benefit of green tea catechin supplementation on lipid profiles in overweight and obese people.

A novel hydrangea-like magnetic composite Fe3O4@MnO2@ZIF-67 for efficient selective adsorption of Pd(II) from metallurgical wastewater.

The selective adsorption of palladium from wastewater is a feasible solution to solving palladium pollution and resource scarcity. Because traditional solvent extraction methods often involve the use of considerable amounts of organic solvents, research is focused on investigating adsorption techniques that can selectively remove palladium from wastewater. In this paper, the magnetic composite Fe3O4@MnO2@ZIF-67 was synthesized and its performance for the adsorption of Pd(II) in acidic water was investigated. Fe3O4@MnO2@ZIF-67 was characterized by various analytical methods such as TEM, SEM, EDS, BET, XRD, FTIR, zeta potential analysis, VSM, and TGA. The effects of palladium ion concentration, contact time, pH, and temperature on adsorption were evaluated. The kinetics were shown to follow the pseudo-second-order kinetic model and Elovich model, and the rate-limiting step was chemisorption. Thermodynamic studies showed that increasing the temperature promoted the adsorption of Pd(II), and the maximum uptake capacity of Fe3O4@MnO2@ZIF-67 for Pd(II) was 531.91 mg g-1. Interestingly, Fe3O4@MnO2@ZIF-67 exhibited superior selectivity for Pd(II) in the presence of Ir(IV), Pt(IV), and Rh(III). The adsorbent can be used repeatedly for selective adsorption of palladium. Even at the fifth cycle, the uptake rate of Pd(II) remained as high as 83.1%, and it showed a favorable adsorption capacity and selectivity for Pd(II) in real metallurgical wastewater. The adsorption mechanism was analyzed by SEM, FTIR, XRD, XPS, and DFT calculations, which indicated that electrostatic interactions and coordination with nitrogen-containing groups were involved. Fe3O4@MnO2@ZIF-67 is a promising adsorbent for the efficient adsorption and selective separation of palladium ions.

USP51 facilitates colorectal cancer stemness and chemoresistance by forming a positive feed-forward loop with HIF1A.

In the current study, we have shown that USP51 promotes colorectal cancer stemness and chemoresistance, and high expression of USP51 predicts survival disadvantage in colorectal cancer patients. Mechanically, USP51 directly binds to Elongin C (ELOC) and forms a larger functional complex with VHL E3 ligase (USP51/VHL/CUL2/ELOB/ELOC/RBX1) to regulate the ubiquitin-dependent proteasomal degradation of HIF1A. USP51 efficiently deubiquitinates HIF1A and activates hypoxia-induced gene transcription. Conversely, the activation of HIF1A under hypoxia transcriptionally upregulates the expression of USP51. Thus, USP51 and HIF1A form a positive feedback loop. Further, we found that the SUMOylation of ELOC at K32 inhibits its binding to USP51. SUMO-specific protease 1 (SENP1) mediates the deSUMOylation of ELOC, promoting the binding of USP51 to ELOC and facilitating the deubiquitination and stabilization of HIF1A by USP51. Importantly, USP51 plays a crucial role in promoting the HIF1A and SENP1-dependent proliferation, migration, stemness, and chemoresistance under hypoxia in colorectal cancer. Together, our data revealed that USP51 is an oncogene stabilizing the pro-survival protein HIF1A, offering a potential therapeutic target for colorectal cancer.

Self-triggered thermoelectric nanoheterojunction for cancer catalytic and immunotherapy.

The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.

A Prospective Long-Term Follow-Up Study: The Application of Circulating Tumor Cells Analysis to Guide Adjuvant Therapy in Stage II Colorectal Cancer.

BACKGROUND: The efficacy of circulating tumor cells (CTCs) in the selection of stage II colorectal cancer (CRC) patients for adjuvant chemotherapy remains inconclusive. OBJECTIVE: The aim of this study was to validate the necessity of adjuvant chemotherapy for stage II CRC patients with positive postoperative CTCs. METHODS: The clinicopathological features and overall survival (OS) of a cohort of 70 patients with confirmed CRC were collected and analyzed. RESULTS: The total rate of positive CTCs was 55.7%, while the average OS was 70.8 months and the OS rate was 75.7% (53/70). These 70 patients were divided into four subgroups, including a CTC-negative group with non-adjuvant chemotherapy (CHEMO-/CTC-) versus a CTC-positive group with non-adjuvant chemotherapy (CHEMO-/CTC+), CHEMO+/CTC- versus CHEMO+/CTC+, CHEMO-/CTC- versus CHEMO+/CTC-, and CHEMO+/CTC+ versus CHEMO-/CTC+; the total numbers in each subgroup were 25 versus 32, 6 versus 7, 25 versus 6, and 7 versus 32, respectively. The average OS of the CHEMO-/CTC- and CHEMO-/CTC+ groups was 82.0 and 68.1 months, respectively (p = 0.020); the average OS of the CHEMO+/CTC- and CHEMO+/CTC+ groups was 83.6 months and 76.4 months, respectively (p = 0.963); the average OS of the CHEMO-/CTC- and CHEMO+/CTC- groups was 82.0 months and 83.6 months, respectively (p = 0.999); and the average OS of the CHEMO+/CTC+ and CHEMO-/CTC+ groups was 76.4 months and 68.1 months, respectively (p = 0.247). CONCLUSIONS: Positive CTCs are a potential prognostic marker for stage II CRC.

3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis.

Colorectal cancer (CRC) remains a leading cause of cancer-related death worldwide. Cetuximab, in combination with chemotherapy, is effective for treating patients with wild-type KRAS/BRAF metastatic CRC (mCRC). However, intrinsic or acquired drug resistance often limits the use of cetuximab. In this study, we investigated the potential of co-treatment with 3-Bromopyruvate (3-BP) and cetuximab to overcome cetuximab resistance in CRC, both in vitro and in vivo. Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines with intrinsic cetuximab resistance (DLD-1 (KRASG13D/-) and HT29 (BRAFV600E)) and in a cetuximab-resistant cell line derived from Caco-2 with acquired resistance (Caco-2-CR). Further analysis revealed that co-treatment induced ferroptosis, autophagy, and apoptosis. Mechanistically, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1 (KRASG13D/-), HT29 (BRAFV600E), and Caco-2-CR cells. In conclusion, our findings suggest that co-treatment with 3-BP and cetuximab could be a promising strategy to overcome cetuximab resistance in human CRC.

A Magnetic Levitation System for Range/Sensitivity-Tunable Measurement of Density.

Magnetic levitation (MagLev) is a promising density-based analytical technique with numerous applications. Several MagLev structures with different levels of sensitivity and range have been studied. However, these MagLev structures can seldom satisfy the different performance requirements simultaneously, such as high sensitivity, wide measurement range, and easy operation, which have prevented them from being widely used. In this work, a tunable MagLev system was developed. It is confirmed by numerical simulation and experiments that this system possesses a high resolution down to 10-7 g/cm3 or even higher compared to the existing systems. Meanwhile, the resolution and range of this tunable system can be adjusted to meet different requirements of measurement. More importantly, this system can be operated simply and conveniently. This bundle of characteristics demonstrates that the novel tunable MagLev system could be handily applied in various density-based analyses on demand, which would greatly expand the ability of MagLev technology.

Identification and Evaluation of Hub Long Noncoding RNAs and mRNAs in High Fat Diet Induced Liver Steatosis.

Nonalcoholic fatty liver disease (NAFLD) is considered the most prevalent chronic liver disease, but the understanding of the mechanism of NAFLD is still limited. The aim of our study was to explore hub lncRNAs and mRNAs and pathological processes in high-fat diet (HFD)-induced and lycopene-intervened liver steatosis. We analyzed the gene profiles in the GSE146627 dataset from the Gene Expression Omnibus (GEO) database to identify differentially expressed lncRNAs and mRNAs, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for functional enrichment analysis. We found that the turquoise, blue, brown, yellow, green, and black modules were significantly correlated with NAFLD. Functional enrichment analysis revealed that some hub lncRNAs (Smarca2, Tacc1, Flywch1, and Mef2c) might be involved in the regulation of the inflammatory and metabolic pathways (such as TNF signaling, metabolic, mTOR signaling, MAPK signaling, and p53 signaling pathways) in NAFLD. The establishment of an NAFLD mouse model confirmed that lycopene supply attenuated hepatic steatosis in HFD-induced NAFLD. Our analysis revealed that the inflammatory and metabolic pathways may be crucially involved in the pathogenesis of NAFLD, and hub lncRNAs provide novel biomarkers, therapeutic ideas, and targets for NAFLD. Moreover, lycopene has the potential to be a phytochemical for the prevention of HFD-induced liver steatosis.

Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this study was to explore the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. We searched PubMed, Web of Science, Embase, and the Cochrane library from database inception to 30 April 2022. This meta-analysis included eight trials with 387 participants. We found that supplementation of n-3 PUFAs has no significant reduction in TC level (SMD = -0.02; 95% CI: -0.22 ~ 0.18, I2 = 23.7%) and LDL-c level in serum (SMD = 0.18; 95% CI: -0.18 ~ 0.53, I2 = 54.9%) of patients with metabolic syndrome. Moreover, we found no significant increase in serum high-density lipoprotein cholesterol level (SMD = 0.02; 95% CI: -0.21 ~ 0.25, I2 = 0%) in patients with metabolic syndrome after consuming n-3 PUFAs. In addition, we found that n-3 PUFAs can significantly decrease serum triglyceride levels (SMD= -0.39; 95% CI: -0.59 ~ -0.18, I2 = 17.2%), systolic blood pressure (SMD = -0.54; 95% CI: -0.86 ~ -0.22, I2 = 48.6%), and diastolic blood pressure (SMD = -0.56; 95% CI: -0.79 ~ 0.33, I2 = 14.0%) in patients with metabolic syndrome. The results from the sensitivity analysis confirmed that our results were robust. These findings suggest that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in metabolic syndrome. Given the quality of the included studies, further studies are still needed to verify our findings.

Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.

Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.

A novel chromatin regulator signature predicts the prognosis, clinical features and immunotherapy of colon cancer.

Aim: To elucidate the potential function and prognostic value of chromatin regulators (CRs) in colon cancer. Materials & methods: A comprehensive analysis of CR RNA expression data from public databases was conducted. Results: The authors successfully established and validated a 17 CR-based signature using public databases. Ten CRs of the signature were eventually verified at the protein level using the Human Protein Atlas database. Functional enrichment showed that CRs were significantly enriched in cancer-related pathways. This signature was remarkably relevant to immune cell infiltration, immune checkpoints, tumor immune dysfunction and exclusion (TIDE) score and drug sensitivity. Conclusion: The authors identified a novel, reliable prognostic signature for colon cancer. The study provided new insights into the function of CRs and has important clinical implications for immunotherapy for colon cancer.

Intestinal Gasdermins for regulation of inflammation and tumorigenesis.

Gasdermins (GSDMs) protein family express in intestinal epithelial cells or lamina propria immune cells, and play a nonnegligible function during gut homeostasis. With the gradually in-depth investigation of GSDMs protein family, the proteases that cleave GSDMA-E have been identified. Intestinal GSDMs-induced pyroptosis is demonstrated to play a crucial role in the removal of self-danger molecules and clearance of pathogenic organism infection by mediating inflammatory reaction and collapsing the protective niche for pathogens. Simultaneously, excessive pyroptosis leading to the release of cellular contents including inflammatory mediators into the extracellular environment, enhancing the mucosal immune response. GSDMs-driver pyroptosis also participates in a novel inflammatory cell death, PANoptosis, which makes a significant sense to the initiation and progression of gut diseases. Moreover, GSDMs are expressed in healthy intestinal tissue without obvious pyroptosis and inflammation, indicating the potential intrinsic physiological functions of GSDMs that independent of pyroptotic cell death during maintenance of intestinal homeostasis. This review provides an overview of the latest advances in the physiological and pathological properties of GSDMs, including its mediated pyroptosis, related PANoptosis, and inherent functions independent of pyroptosis, with a focus on their roles involved in intestinal inflammation and tumorigenesis.