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Abstract Bionic self‐cleaning coatings have exhibited scaling inhibition for their low surface free energy. The key issue is focused on the long‐term anti‐scaling performance for the hydrophobicity failure after scaled. Inspired by “grass‐to‐stone” phenomenon, we reported a polymer coating (WCA = 120°, WSA = 14°) with the water contact angle of its 720 h‐scaled surface increased to 135°and scaling reduced by 90–95%. The nucleation and growth of CaCO3 at “coating‐crystal” interface are investigated, and a physical model for self‐healing film interface inhibiting scaling is innovatively proposed, as an important step toward designing long‐term anti‐scaling coating for engineering application.

Abstract Icephobic material is of great importance in power transportation, communication, aerospace, and so on. Bionic lotus superhydrophobic surfaces show good application prospects in anti‐icing by repelling impacting droplets. However, the boundary (criterion) between droplet bounce and deposition on superhydrophobic surface under cold freezing rain is unclear. Here, from the view of statistics, the boundary and internal heat transfer mechanism of the droplet bounce, pinning, and three kinds of deposition including icing at later, early retraction, and spread. are clarified Droplet viscosity increase reduces droplet contact with surface and inhibited splash at high We. Surfaces with temperature above −20.6 °C showed 100% droplet bounce after impact on We = 64.7, and the probability of water adhesion and ice nucleation decreases to ≈0%, resulting in completely anti‐icing. Droplet bounce transition mainly ascribe to the decrease retraction driven force caused by interface freezing and transition temperature increases approximately linearly from −25.9 to −21.1 °C within 21.6 < We < 75.5. Ice nuclei brought by condensation in humid environment (60–100 RH%) further cause droplet eccentric retraction and transition temperature increases to −6 to −10 °C. The fundamental understanding of droplet behaviors on supercooled superhydrophobic surface is beneficial for icephobic surfaces applications.

As a low-carbon cementitious material, the application of fly ash based geopolymer in ground improvement has attracted more and more attention. However, the engineering characteristics of the soil stabilized by alkali activated cementitious material under the freezing-thawing extreme climate conditions are not clear. It is necessary to further study the strength, deformation characteristics and their influencing factors of the improved soil under the freezing-thawing cycle. Several laboratory tests are carried out to investigate the effects of the ratio of silicon to aluminum in raw material (Si/Al), modulus of alkali-activator and alkali solution concentration on the unconfined compressive strength (UCS) and the freezing-thawing resistance of fly ash based geopolymer stabilized soil, and the corresponding micro mechanism. The results show that (1) the UCS of geopolymer stabilized soil decreases with the increasing alkali-activator modulus and the decreasing alkali solution concentration, while increases with the Si/Al value in the range of 1.15 to 1.35, and the unconfined compressive strength of 28 d geopolymer stabilized soil can reach 8.98 MPa. (2) When the Si/Al value changes from 1.25 to 1.35 and the alkali solution concentration is within the range of 5.42 to 22.78 mol/L, the 28 d geopolymer stabilized soil can resist more than one (up to 6) freezing-thawing cycle. (3) The best performance of the freezing-thawing resistance of fly ash based geopolymer stabilized soil is mainly related to large number of Si-rich aluminosilicate gel generated by polymerization, while the highest compressive strength is related to the amount of Al-rich aluminosilicate gel generated by polymerization. The research results will provide technical reference for the mix design of soil stabilization with fly ash based geopolymer, and promote the application of alkali activated cementitious material in ground improvement.

Abstract Droplet bouncing on special wettability surface is common and important in daily life and engineering applications (anti‐icing and drag reduction, etc.). However, there are few studies on the multiple droplets impact and there is a lack of systematic research on the interaction of oscillation and bounce. Here, the impact and oscillation of multiple droplets on the porous superhydrophobic bionic lotus surface are studied by a high‐speed camera system. On the bionic lotus surface (Surf‐1), an impacting droplet can merge another larger sessile droplet and bounce off. Comparing with single droplet impact, it is suggested that multiple droplets impact make more efficient use of the air cushion on the micrometer‐nanometer‐scale binary structure (MNBS) and show the self‐cleaning performance of Surf‐1 better. Moreover, with the theory for damped harmonic oscillators, it is found that Surf‐1 can prolong the oscillation of droplets (last >250 ms) and slow down the attenuation of energy. The energy can be efficiently recycled to the bounce by shortening the droplet impact interval (ti). The fundamental understanding of multiple droplets impact and the reclamation of oscillating energy are beneficial for scientific design of new surface and engineering applications.

Background: Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. Methods: The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12–1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26–1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99–1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11–1.27) and mortality (HR 1.37. 95% CI 1.29–1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19–2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. Conclusions: PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. Funding: This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People’s Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

Abstract Background Emerging evidence suggests that Rho GTPases play a crucial role in tumorigenesis and metastasis, but their involvement in the tumor microenvironment (TME) and prognosis of hepatocellular carcinoma (HCC) is not well understood. Methods We aim to develop a tumor prognosis prediction system called the Rho GTPases-related gene score (RGPRG score) using Rho GTPase signaling genes and further bioinformatic analyses. Results Our work found that HCC patients with a high RGPRG score had significantly worse survival and increased immunosuppressive cell fractions compared to those with a low RGPRG score. Single-cell cohort analysis revealed an immune-active TME in patients with a low RGPRG score, with strengthened communication from T/NK cells to other cells through MIF signaling networks. Targeting these alterations in TME, the patients with high RGPRG score have worse immunotherapeutic outcomes and decreased survival time in the immunotherapy cohort. Moreover, the RGPRG score was found to be correlated with survival in 27 other cancers. In vitro experiments confirmed that knockdown of the key Rho GTPase-signaling biomarker SFN significantly inhibited HCC cell proliferation, invasion, and migration. Conclusions This study provides new insight into the TME features and clinical use of Rho GTPase gene pattern at the bulk-seq and single-cell level, which may contribute to guiding personalized treatment and improving clinical outcome in HCC.

Abstract Background In the post-pandemic era, a wide range of COVID-19 sequelae is of growing health concern. However, the risks of digestive diseases in long COVID have not been comprehensively understood. To investigate the long-term risk of digestive diseases among COVID patients. Methods In this large-scale retrospective cohort study with up to 2.6 years follow-up (median follow-up: 0.7 years), the COVID-19 group (n = 112,311), the contemporary comparison group (n = 359,671) and the historical comparison group (n = 370,979) predated the COVID-19 outbreak were built using UK Biobank database. Each digestive outcome was defined as the diagnosis 30 days or more after the onset of COVID-19 infection or the index date. Hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. Results Compared with the contemporary comparison group, patients with previous COVID-19 infection had higher risks of digestive diseases, including gastrointestinal (GI) dysfunction (HR 1.38 (95% CI 1.26 to 1.51)); peptic ulcer disease (HR 1.23 (1.00 to 1.52)); gastroesophageal reflux disease (GERD) (HR 1.41 (1.30 to 1.53)); gallbladder disease (HR 1.21 (1.06 to 1.38)); severe liver disease (HR 1.35 (1.03 to 1.76)); non-alcoholic liver disease (HR 1.27 (1.09 to 1.47)); and pancreatic disease (HR 1.36 (1.11 to 1.66)). The risks of GERD were increased stepwise with the severity of the acute phase of COVID-19 infection. Even after 1-year follow-up, GERD (HR 1.64 (1.30 to 2.07)) and GI dysfunction (HR 1.35 (1.04 to 1.75)) continued to pose risks to COVID-19 patients. Compared to those with one SARS-CoV-2 infection, reinfected patients were at a higher risk of pancreatic diseases (HR 2.57 (1.23 to 5.38)). The results were consistent when the historical cohort was used as the comparison group. Conclusions Our study provides insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing digestive diseases. The risks exhibited a stepwise escalation with the severity of COVID-19, were noted in cases of reinfection, and persisted even after 1-year follow-up. This highlights the need to understand the varying risks of digestive outcomes in COVID-19 patients over time, particularly those who experienced reinfection, and develop appropriate follow-up strategies.

Background: Activation of the Hedgehog signaling pathway is linked to the initiation and development of human hepatocellular carcinoma (HCC). However, its impact on clinical outcomes and the HCC microenvironment remains unclear. Methods: We performed comprehensive analyses of Hedgehog pathway genes in a large cohort of HCC patients. Specifically, we utilized univariate Cox regression analysis to identify Hedgehog genes linked to overall survival, and the LASSO algorithm was used to construct a Hedgehog-related gene pattern. We subsequently examined the correlation between the Hedgehog pattern and the HCC microenvironment employing the CIBERSORT and ssGSEA algorithms. Furthermore, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the anti-PD-L1 treatment dataset (IMvigor210) are used to evaluate the clinical response of the Hedgehog pattern in predicting immune checkpoint inhibitors. Results: We found that the Hedgehog activation score (HHAS), a prognostic score based on 11 Hedgehog genes, was significantly associated with HCC patient survival. Patients exhibiting high HHAS experienced markedly reduced survival rates compared to those with low HHAS, and HHAS emerged as an independent prognostic factor for HCC. Functional enrichment analysis unveiled the association of the HHAS phenotype with functions related to the immune system, and further investigation demonstrated that HCC patients exhibiting low HHAS displayed elevated levels of anti-tumor immune activation in CD8+ T cells, while high HHAS were linked to immune escape phenotypes and increased infiltration of immune suppressive cells. In addition, in the Immune Checkpoint Inhibitor (ICI) cohort of IMvigor210, patients with higher HHAS had worse ICI treatment outcomes and shortened survival time, indicating that the HHAS is a useful indicator for predicting patient response to immunotherapy. Conclusions: In summary, our study offers valuable insights for advancing research on Hedgehog and its impact on tumor immunity, which provides an opportunity to optimize prognosis and immune therapy for HCC.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders affecting the digestive tract, including ulcerative colitis and Crohn’s disease. Ruscogenin, a prominent steroidal sapogenin present in radix ophiopogon japonicus, has shown a protective effect on attenuating the inflammatory response associated with inflammatory diseases, but the efficacy of ruscogenin in IBD remains unclear. The aim of this study is to explore the effect of ruscogenin on intestinal barrier dysfunction and inflammatory responses as well as the underlying mechanism in ulcerative colitis. A dextran sulfate sodium salt (DSS)-induced C57BL/6 mouse colitis model was employed for the in vivo studies, while in vitro experiments were performed in THP-1 cells and human intestinal epithelial cells involved in inducing inflammatory responses and pyroptosis using LPS/nigericin. The results indicated that ruscogenin treatment attenuated the symptoms of ulcerative colitis, reduced the release of inflammatory cytokines and the expression of pyroptosis-associated proteins, and restored the integrity of the intestinal epithelial barrier in colon tissue in mice. Moreover, ruscogenin inhibited LPS/nigericin-induced pyroptosis in THP-1 cells. Mechanically, ruscogenin inhibited NLRP3 inflammasome activation and canonical pyroptosis, at least in part, through the suppression of the TLR4/NF-κB signaling pathway. These findings might provide new insights and a solid foundation for further exploration into the therapeutic potential of ruscogenin in the treatment of IBD.

Abstract Background Glioblastoma multiforme (GBM) is one of the most malignant tumors in brain with high morbidity and mortality. Mitophagy plays a significant role in carcinogenesis, metastasis, and invasion. In our study, we aim to construct a mitophagy-related risk model to predict prognosis in GBM. Methods RNA-seq data combined with clinical information were downloaded from TCGA. The 4-gene risk model and nomograph was then constructed and validated in external cohort. Evaluation of immune infiltration, functional enrichment and tumor microenvironment (TME) were then performed. Result A mitophagy-related risk model was established and patients in TCGA and CGGA were classified into low-risk and high-risk groups. In both cohorts, patients in low-risk group had improved survival, while high-risk group had poor prognosis. Also, the risk model was identified as an independent factor for predicting overall survival via Cox regression. Furthermore, a prognostic nomogram including mitophagy signatures was established with excellent predictive performance. In addition, the risk model was closely associated with regulation of immune infiltration as well as TME. Conclusion In conclusion, our study constructed a mitophagy-related risk model, which can be utilized for the clinical prognostic prediction in GBM.

Aim: It is to be elucidated the risk-predictive role of differentially expressed fatty acid metabolism related genes (DE-FRGs) in dilated cardiomyopathy (DCM) and myocardial infarction. Materials & methods: Four gene enrichment analyses defined DE-FRGs’ biological functions and pathways. Three strategies were applied to identify risk biomarkers and construct a nomogram. The 4-DE-FRG correlation with immune cell infiltration, drugs, and ceRNA was explored. Results: DE-FRGs were enriched in lipid metabolism. A risk nomogram was established by ACSL1, ALDH2, CYP27A1 and PPARA, demonstrating a good ability for DCM and myocardial infarction prediction. PPARA was positively correlated with adaptive immunocytes. Thirty-five drugs are candidate therapeutic targets. Conclusion: A nomogram and new biological targets for early diagnosis and treatment of DCM and myocardial infarction were provided.

IntroductionCrohn’s disease is characterized of dysregulated inflammatory and immune reactions. The role of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in Crohn’s disease remains largely unknown.MethodsThe microarray-based transcriptomic data and corresponding clinical information of GSE100833 and GSE16879 were obtained from the Gene Expression Omnibus (GEO) database. Identification of in the NLRP3 inflammasome-related genes and construction of LASSO regression model. Immune landscape analysis was evaluated with ssGSEA. Classification of Crohn’s-disease samples based on NLRP3 inflammasome-related genes with ConsensusClusterPlus. Functional enrichment analysis, gene set variation analysis (GSVA) and drug-gene interaction network.ResultsThe expressions of NLRP3 inflammasome-related genes were increased in diseased tissues, and higher expressions of NLRP3 inflammasome-related genes were correlated with generally enhanced immune cell infiltration, immune-related pathways and human leukocyte antigen (HLA)-gene expressions. The gene-based signature showed well performance in the diagnosis of Crohn’s disease. Moreover, consensus clustering identified two Crohn’s disease clusters based on NLRP3 inflammasome-related genes, and cluster 2 was with higher expressions of the genes. Cluster 2 demonstrated upregulated activities of immune environment in Crohn’s disease. Furthermore, four key hub genes were identified and potential drugs were explored for the treatment of Crohn’s disease.ConclusionsOur findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn’s disease from transcriptomic aspects. These findings provide in silico insights into the diagnosis and treatment of Crohn’s disease and might assist in the clinical decision-making process.

ObjectiveEnergy metabolism plays a crucial role in the improvement of heart dysfunction as well as the development of heart failure (HF). The current study is designed to identify energy metabolism-related diagnostic biomarkers for predicting the risk of HF due to myocardial infarction.MethodsTranscriptome sequencing data of HF patients and non-heart failure (NF) people (GSE66360 and GSE59867) were obtained from gene expression omnibus (GEO) database. Energy metabolism-related differentially expressed genes (DEGs) were screened between HF and NF samples. The subtyping consistency analysis was performed to enable the samples to be grouped. The immune infiltration level among subtypes was assessed by single sample gene set enrichment analysis (ssGSEA). Random forest algorithm (RF) and support vector machine (SVM) were applied to identify diagnostic biomarkers, and the receiver operating characteristic curves (ROC) was plotted to validate the accuracy. Predictive nomogram was constructed and validated based on the result of the RF. Drug screening and gene-miRNA network were analyzed to predict the energy metabolism-related drugs and potential molecular mechanism.ResultsA total of 22 energy metabolism-related DEGs were identified between HF and NF patients. The clustering analysis showed that HF patients could be classified into two subtypes based on the energy metabolism-related genes, and functional analyses demonstrated that the identified DEGs among two clusters were mainly involved in immune response regulating signaling pathway and lipid and atherosclerosis. ssGSEA analysis revealed that there were significant differences in the infiltration levels of immune cells between two subtypes of HF patients. Random-forest and support vector machine algorithm eventually identified ten diagnostic markers (MEF2D, RXRA, PPARA, FOXO1, PPARD, PPP3CB, MAPK14, CREB1, MEF2A, PRMT1) for risk prediction of HF patients, and the proposed nomogram resulted in good predictive performance (GSE66360, AUC = 0.91; GSE59867, AUC = 0.84) and the clinical usefulness in HF patients. More importantly, 10 drugs and 15 miRNA were predicted as drug target and hub miRNA that associated with energy metabolism-related genes, providing further information on clinical HF treatment.ConclusionThis study identified ten energy metabolism-related diagnostic markers using random forest algorithm, which may help optimize risk stratification and clinical treatment in HF patients.

Abstract Necrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.

Necrotizing enterocolitis (NEC) is one of the most prevalent neonatal gastrointestinal disorders. Despite ongoing breakthroughs in its treatment and prevention, the incidence and mortality associated with NEC remain high. New therapeutic approaches, such as breast milk composition administration, stem cell therapy, immunotherapy, and fecal microbiota transplantation (FMT) have recently evolved the prevention and the treatment of NEC. This study investigated the most recent advances in NEC therapeutic approaches and discussed their applicability to bring new insight to NEC treatment.

Mitophagy is a conserved cellular process that plays a vital role in maintaining cellular homeostasis by selectively removing dysfunctional mitochondria. Notwithstanding that growing evidence suggests that mitophagy is implicated in pancreatic tumorigenesis, the effect of mitophagy-related genes on pancreatic cancer (PC) prognosis and therapeutic response remains largely unknown. In this study, we sought to construct a mitophagy-related gene signature and assessed its ability to predict the survival, immune activity, mutation status, and chemotherapy response of PC patients. During the screening process, we identified three mitophagy-related genes (PRKN, SRC, VDAC1) from The Cancer Genome Atlas (TCGA) cohort and a 3-gene signature was established. The prognostic model was validated using an International Cancer Genome Consortium (ICGC) cohort and two Gene Expression Omnibus (GEO) cohorts. According to the median risk score, PC patients were divided into high and low-risk groups, and the high-risk group correlated with worse survival in the four cohorts. The risk score was then identified as an independent prognostic predictor, and a predictive nomogram was constructed to guide clinical decision-making. Remarkably, enhanced immunosuppressive levels and higher mutation rates were observed in patients from the high-risk group, which may account for their poor survival. Furthermore, we found that high-risk patients were more sensitive to paclitaxel and erlotinib. In conclusion, a mitophagy-related gene signature is a novel prognostic model that can be used as a predictive indicator and allows prognostic stratification of PC patients.

Background: Emerging evidence has proven that ferroptosis plays an important role in the development of acute myeloid leukemia (AML), whereas the exact role of ferroptosis-associated genes in AML patients’ prognosis remained unclear.Materials and Methods: Gene expression profiles and corresponding clinical information of AML cases were obtained from the TCGA (TCGA-LAML), GEO (GSE71014), and TARGET databases (TARGET-AML). Patients in the TCGA cohort were well-grouped into two clusters based on ferroptosis-related genes, and differentially expressed genes were screened between the two clusters. Univariate Cox and LASSO regression analyses were applied to select prognosis-related genes for the construction of a prognostic risk-scoring model. Survival analysis was analyzed by Kaplan–Meier and receiver operator characteristic curves. Furthermore, we explored the correlation of the prognostic risk-scoring model with immune infiltration and chemotherapy response. Risk gene expression level was detected by quantitative reverse transcription polymerase chain reaction.Results: Eighteen signature genes, including ZSCAN4, ASTN1, CCL23, DLL3, EFNB3, FAM155B, FOXL1, HMX2, HRASLS, LGALS1, LHX6, MXRA5, PCDHB12, PRINS, TMEM56, TWIST1, ZFPM2, and ZNF560, were developed to construct a prognostic risk-scoring model. AML patients could be grouped into high- and low-risk groups, and low-risk patients showed better survival than high-risk patients. Area under the curve values of 1, 3, and 5 years were 0.81, 0.827, and 0.786 in the training set, respectively, indicating a good predictive efficacy. In addition, age and risk score were the independent prognostic factors after univariate and multivariate Cox regression analyses. A nomogram containing clinical factors and prognostic risk-scoring model was constructed to better estimate individual survival. Further analyses demonstrated that risk score was associated with the immune infiltration and response to chemotherapy. Our experiment data revealed that LGALS1 and TMEM56 showed notably decreased expression in AML samples than that of the normal samples.Conclusion: Our study shows that the prognostic risk-scoring model and key risk gene may provide potential prognostic biomarkers and therapeutic option for AML patients.

Summary: Rho guanosine triphosphatase (GTPases), as molecular switches, have been identified to be dysregulated and involved in the pathogenesis of various rheumatic diseases, mainly including rheumatoid arthritis, osteoarthritis, systemic sclerosis, and systemic lupus erythematosus. Downstream pathways involving multiple types of cells, such as fibroblasts, chondrocytes, synoviocytes, and immunocytes are mediated by activated Rho GTPases to promote pathogenesis. Targeted therapy via inhibitors of Rho GTPases has been implicated in the treatment of rheumatic diseases, demonstrating promising effects. In this review, the effects of Rho GTPases in the pathogenesis of rheumatic diseases are summarized, and the Rho GTPase-mediated pathways are elucidated. Therapeutic strategies using Rho GTPase inhibitors in rheumatic diseases are also discussed to provide insights for further exploration of targeted therapy in preclinical studies and clinical practice. Future directions on studies of Rho GTPases in rheumatic diseases based on current understandings are provided.

Ulcerative colitis is a chronic inflammatory bowel disorder that is hard to cure once diagnosed. Bisdemethoxycurcumin has shown positive effects on inflammatory diseases. However, the underlying bioactive interaction between bisdemethoxycurcumin and ulcerative colitis is unclear. The objective of this study was to determine the core target and potential mechanism of action of bisdemethoxycurcumin as a therapy for ulcerative colitis. The public databases were used to identify potential targets for bisdemethoxycurcumin and ulcerative colitis. To investigate the potential mechanisms, the protein-protein interaction network, gene ontology analysis, and Kyoto encyclopedia of genes and genomes analysis have been carried out. Subsequently, experimental verification was conducted to confirm the findings. A total of 132 intersecting genes of bisdemethoxycurcumin, as well as ulcerative coli-tis-related targets, were obtained. SRC, EGFR, AKT1, and PIK3R1 were the targets of highest potential, and the PI3K/Akt and MAPK pathways may be essential for the treatment of ulcerative colitis by bisdemethoxycurcumin. Molecular docking demonstrated that bisdemethoxycurcumin combined well with SRC, EGFR, PIK3R1, and AKT1. Moreover, the in vitro experiments suggested that bisdemethoxycurcumin might reduce LPS-induced pro-inflammatory cytokines levels in RAW264.7 cells by suppressing PI3K/Akt and MAPK pathways. Our study provided a comprehensive overview of the potential targets and molecular mechanism of bisdemethoxycurcumin against ulcerative colitis. Furthermore, it also provided a theoretical basis for the clinical treatment of ulcerative colitis, as well as compelling evidence for further study on the mechanism of bisdemethoxycurcumin in the treatment of ulcerative colitis.

Esophageal adenocarcinoma (EAC) is a highly malignant type of digestive tract cancers with a poor prognosis despite therapeutic advances. Pyroptosis is an inflammatory form of programmed cell death, whereas the role of pyroptosis in EAC remains largely unknown. Herein, we identified a pyroptosis-related five-gene signature that was significantly correlated with the survival of EAC patients in The Cancer Genome Atlas (TCGA) cohort and an independent validation dataset. In addition, a nomogram based on the signature was constructed with novel prognostic values. Moreover, the downregulation of GSDMB within the signature is notably correlated with enhanced DNA methylation. The pyroptosis-related signature might be related to the immune response and regulation of the tumor microenvironment. Several inhibitors including GDC-0879 and PD-0325901 are promising in reversing the altered differentially expressed genes in high-risk patients. Our findings provide insights into the involvement of pyroptosis in EAC progression and are promising in the risk assessment as well as the prognosis for EAC patients in clinical practice.

Ethnopharmacological relevance: Two types of traditional Chinese formulas of botanical drugs are prescribed for treating perimenopausal syndrome (PMS), a disorder in middle-aged women during their transition to menopause. One is for treating PMS as kidney deficiency (KD) due to senescence and declining reproductive functions, and the other is for treating it as liver qi stagnation (LQS) in association with stress and anxiety. Despite the time-tested prescriptions, an objective attestation to the effectiveness of the traditional Chinese treatment of PMS is still to be established and the associated molecular mechanism is still to be investigated.Materials and methods: A model for PMS was generated from perimenopausal rats with chronic restraint stress (CRS). The effectiveness of traditional Chinese formulas of botanical drugs and a combination of two of the formulas was evaluated based on 1H NMR plasma metabolomic, as well as behavioral and physiological, indicators. To investigate whether the formulas contained ligands that could compensate for the declining level of estrogen, the primary cause of PMS, the ligand-based NMR technique of saturation transfer difference (STD) was employed to detect possible interacting molecules to estrogen receptors in the decoction.Results: Each prescription of the classical Chinese formula moderately attenuated the metabolomic state of the disease model. The best treatment strategy however was to combine two traditional Chinese formulas, each for a different etiology, to adjust the metabolomic state of the disease model to that of rats at a much younger age. In addition, this attenuation of the metabolomics of the disease model was by neither upregulating the estrogen level nor supplementing an estrogenic compound.Conclusion: Treatment of PMS with a traditional Chinese formula of botanical drugs targeting one of the two causes separately could ameliorate the disorder moderately. However, the best outcome was to treat the two causes simultaneously with a decoction that combined ingredients from two traditional prescriptions. The data also implicated a new paradigm for phytotherapy of PMS as the prescribed decoctions contained no interacting compound to modulate the activity of estrogen receptors, in contrast to the treatment strategy of hormone replacement therapy.

Background: Emerging data have suggested colorectal cancer (CRC) often coexists with cardiovascular diseases, but whether cardiovascular risk factors play a role in CRC remains unclear. We performed a systematic review and meta-analysis to better illustrate the associations between cardiovascular risk factors and CRC. Methods: We searched EMBASE, MEDLINE and Web of Science databases from inception up to June 14, 2020. Prospective cohort studies were included if they evaluated the association between at least one of cardiovascular risk factors and CRC incidence, containing sufficient data to obtain relative risk (RR) and 95% confidence interval (CI). We performed separate meta-analyses for each cardiovascular risk factor using random-effect model. PROSPERO registration number: CRD42020175537. Findings: Data from 84 studies, reporting 52, 348, 827 individuals and 384, 973 incident cases were included in the analysis. Overall, the risk of CRC was 1.31(95% CI, 1.21–1.42) for obesity, 1.14 (95% CI, 1.09–1.20) for per 5 kg/m2 increase in body mass index, 1.18 (95% CI, 1.14–1.23) for former smoker, 1.20 (95% CI, 1.11–1.30) for current smoker, 1.25 (95% CI, 1.16–1.35) for diabetes, 1.07 (95% CI, 1.02–1.12) for hypertension. The summary RRs of CRC for the highest versus lowest quartiles of total cholesterol, triglyceride, low-density lipoprotein were 1.12 (95% CI, 1.03–1.22), 1.18 (95% CI, 1.04–1.35), 0.85 (95% CI, 0.62–1.17) respectively and the pooled RR for the lowest versus highest quartile of high-density lipoprotein was 1.14 (95% CI, 1.02–1.28). Interpretation: Unfavorable cardiovascular risk factors are associated with increased risk of CRC, which may provide novel insight into the screening strategies of CRC in patient with these risk factors.

Background: Acute myocardial infarction (AMI) is a common cardiovascular disease that has a high mortality. Pyroptosis is a programmed cell death mediated by inflammasome. It remains to be clarified on the expression pattern and risk predictive role of pyroptosis-related genes in AMI. Methods: The gene expression data were extracted from the Gene Expression Omnibus (GEO), and pyroptosis-related genes were obtained from published articles. Pyroptosis-related differential expressed genes were selected between normal and AMI samples and then we explored their immune infiltration level using CIBERSORT. Univariate Cox and LASSO regression were applied to establish a classifier based on pyroptosis-related genes. ROC analysis was utilized to evaluate the classifier. Results: In this study, we obtained 20 pyroptosis-related genes which showed differential expression in AMI and normal samples. Among the differential expressed genes, GZMB was significantly positively associated with activated NK cells (R = 0.71, p < 0.01), while NLRP3 exhibited a negative correlation with resting NK cells (R = –0.66, p < 0.01). 9 genes (NLRP9, GSDMD, CASP8, AIM2, GPX4, NOD1, NOD2, SCAF11, GSDME) were eventually identified as a predictive risk classifier for AMI patients. With the classifier, patients at high and low risk could be discriminated. Further external validation showed the high accuracy of the classifier (AUC = 0.75). Conclusions: Pyroptosis-related genes are closely related to immune infiltration in AMI, and a 9-gene classifier has good performance in predicting the risk of AMI with high accuracy, which could provide a new way for targeted treatment in AMI.