Spherization indices measured by resting SPECT improve risk stratification in patients with ischemia with non-obstructive coronary artery disease (INOCA).

BACKGROUND: The prevalence of ischemia with non-obstructive coronary artery disease (INOCA) is substantial, but its risk stratification has been suboptimal. Resting SPECT myocardial perfusion imaging (MPI) could provide useful heart information including spherical indices. We aimed to evaluate the prognostic value of spherical indices in individuals with INOCA. RESULTS: During a median follow-up of 47.2 ± 20.8 months, 49 (17.2%) patients experienced major adverse cardiac events (MACE). Compared to those without MACE, those with MACE had a higher shape index (SI) (0.60 ± 0.07 vs. 0.58 ± 0.06; P = 0.028) and a lower E2 (eccentricity index calculated by the QPS) (0.81 ± 0.05 vs. 0.83 ± 0.04; P = 0.019). MACE event-free survival analysis revealed significant differences in the SI and E2 among all patients (all log-rank P < 0.01). Multivariate Cox analysis showed abnormal SI (HR: 2.73, 95% CI 1.44-5.18, P = 0.002) and E2 (HR: 1.94, 95% CI 1.08-3.48, P = 0.026) were both independent predictors for MACE when they were put into the same model, respectively. The incorporation of the SI into the baseline model demonstrated a significant improvement in the predictive accuracy for MACEs (P = 0.026), whereas E2 did not exhibit a similar improvement (P > 0.05). CONCLUSION: For patients with INOCA, spherical indices (especially the SI) were associated with long-term MACE, which could be a preferable indicator for risk stratification and prognostic prediction.

Phytic acid cross-linked and Hofmeister effect strengthened polyvinyl alcohol hydrogels for zinc ion storage.

It is a big challenge to retain the water and thus reduce the charge impedance for solid electrolytes used in flexible and wearable zinc ion batteries. Here, we propose novel phytic acid (PA) cross-linked polyvinyl alcohol (PVA) hydrogels as high-performanced solid electrolytes strengthened by the Hofmeister effect. In this approach, freeze-thawing followed by a salting-out procedure via anions to induce the Hofmeister effect can greatly improve the tensile strain and flexibility of the hydrogels. The PA addition dramatically enhances the ionic conductivity and increases the affinity between the electrolyte and zinc plate. Consequently, the PVA/PA hydrogels exhibit remarkable electrochemical performances with stable full-cell cycling in zinc ion storage and capability in inhibiting Zn dendrite growth.

A Novel Photosensitizer for Lipid Droplet-Location Photodynamic Therapy.

Lipid droplets (LDs), an extremely important cellular organelle, are responsible for the storage of neutral lipids in multiple biological processes, which could be a potential target site for photodynamic therapy (PDT) of cancer. Herein, a lipid droplet-targeted photosensitizer (BODSeI) is developed, allowing for fluorescence imaging-guided PDT. Owing to the location of lipid droplets, BODSeI demonstrates enhanced PDT efficiency with an extremely low IC50 value (around 125 nM). Besides, BODSeI shows good biocompatibility and high photostability. Therefore, BODSeI is promising for droplet-location PDT, which may trigger wide interest for exploring the pathway of lipid droplet-location PDT.

3,5-Anthryl-Bodipy dyad/triad: Preparation, effect of F-B-F induced conformation restriction on the photophysical properties, and application in triplet-triplet-annihilation upconversion.

We prepared a series of compact Bodipy-anthryl electron donor/acceptor triads and dyads by attaching anthryl moieties at the 3-,5-positions of the Bodipy core, with a novel conformation restriction approach, to study the spin-orbit charge transfer intersystem crossing (SOCT-ISC). The conformation restrictions are imposed by the BF2 unit of Bodipy without invoking the previously reported method with 1,7-dimethyl or 1,3-dimethyl groups. Our new approach shows a few advantages, including the stronger electron accepting ability of the methyl-free Bodipy core (reduction potential anodically shifted by +0.3 V vs the methylated Bodipy), red-shifted absorption (by 21 nm), and longer triplet state lifetime (372 µs vs 126 µs). The effects of the different mutual orientations of the electron donor and acceptor on ultraviolet-visible absorption, fluorescence, triplet state quantum yields, and lifetimes were studied. Triads with orthogonal geometries show higher singlet oxygen quantum yields (ΦΔ = 37%) than those with more coplanar geometries. Since the non-radiative decay for the S1 state is significant in the parent Bodipy chromophore (ΦF = 6.0%), we propose that in dyads/triads, the charge separation and recombination-induced ISC outcompete the non-radiative decay to the ground state, which is new in the study of SOCT-ISC. Density functional theory computation indicated a shallow torsion potential energy curve as compared to the meso-anthryl-Bodipy dyad analog, which may contribute a low triplet state quantum yield of the new dyads/triads. Triplet-triplet annihilation upconversion was performed with the electron donor/acceptor dyads as the triplet photosensitizer, with an upconversion quantum yield of 12.3%.

Mucin 17 inhibits the progression of human gastric cancer by limiting inflammatory responses through a MYH9-p53-RhoA regulatory feedback loop.

BACKGROUND: Mucins are key components of the mucosal barrier in the stomach that protects epithelia from carcinogenic effects of chronic inflammation. Analysis of The Cancer Genome Atlas database indicated that mucin-17 (MUC17) was more highly expressed in gastric cancer (GC) specimens, with favourable prognosis for patients. To explore the underlying mechanisms, we investigated the potential role of MUC17 in controlling chronic gastric inflammation. METHODS: We initially quantified the expression of MUC17 and inflammatory factor, as well as the association of MUC17 with survive in GC using immunohistochemistry. To establish how the inflammatory factors affect MUC17 expression, we explored luciferase reporter, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift (EMSA) assays. The role and mechanism that MUC17 plays in inflammation-induced cell proliferation was examined in AGS cells with reduced MUC17 expression and MKN45 cells overexpressing a truncated MUC17. RESULTS: We found MUC17 was induced by inflammatory cytokines in GC cells via CDX1upregulation. MUC17 thus inactivated NFκB to inhibit GC cell proliferation in response to pro-inflammatory cytokines. We also revealed that the function of MUC17 was dependent on its conserved epidermal growth factor domain and on downstream sequences to enable its interaction with myosin-9, resulting in a sustained regulatory feedback loop between myosin-9, p53, and RhoA, and then activation of p38 to negatively regulate the NFκB pathway in GC cells. This mechanism was also confirmed in vivo. CONCLUSIONS: Our study demonstrates MUC17 as a GC suppressor protein which has the therapeutic potential for human GC.

Whole-genome sequencing reveals novel tandem-duplication hotspots and a prognostic mutational signature in gastric cancer.

Genome-wide analysis of genomic signatures might reveal novel mechanisms for gastric cancer (GC) tumorigenesis. Here, we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as CCND1, ERBB2 and MYC. Specifically, we nominate a novel hotspot involving the super-enhancer of ZFP36L2 presents in approximately 10% GCs from different cohorts, the oncogenic role of which is further confirmed by experimental data. In addition, our data reveal a mutational signature, specifically occurring in noncoding region, significantly enriched in tumors with cadherin 1 mutations, and associated with poor prognoses. Collectively, our data suggest that TDs might serve as an important mechanism for cancer gene activation and provide a novel signature for stratification.

Epigenetic downregulation of MUC17 by H. pylori infection facilitates NF-κB-mediated expression of CEACAM1-3S in human gastric cancer.

BACKGROUND AND AIMS: Helicobacter pylori invades the mucosal barrier and infects the mucins of gastric epithelial cells. However, whether gastric carcinogenesis caused by H. pylori infection involves the membrane-bound mucins is unclear. This study explored the role of mucin 17 (MUC17) in gastric cancer (GC) associated with H. pylori infection. METHODS: The expression of MUC17 and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was examined in human GC cells and tissues with H. pylori infection. Gain- and loss-of-function assays were performed to assess the role of MUC17 in regulating CEACAM1 in H. pylori-infected GC cells. RESULTS: MUC17 was downregulated in H. pylori-infected GC cells and tissues in association with poor survival of GC patients. Downregulation of MUC17 was attributable to MUC17 promoter methylation mediated by DNA methyltransferase 1 (DNMT1) H. pylori-enhanced GC cell proliferation and colony formation associated with MUC17 downregulation. Gain- and loss-of-function assays showed that MUC17 inhibited the H. pylori-enhanced GC cell growth by preventing the translocation of H. pylori CagA into GC cells. Moreover, MUC17 downregulated the expression of CEACAM1 variant 3S (CEACAM1-3S) in GC cells and tissues with H. pylori infection. Additionally, MUC17 downregulated CEACAM1 promoter activity via attenuation of NF-κB activation in GC cells. CONCLUSIONS: MUC17 was epigenetically downregulated in GC with H. pylori infection. MUC17 inhibited H. pylori CagA translocation via attenuation of NF-κB-mediated expression of CEACAM1-3S in GC cells. Thus, MUC17 may serve as a valuable prognostic biomarker for H. pylori-associated GC.