Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study.

BACKGROUND: Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. METHODS: We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR-Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR-Egger intercept test, MR-PRESSO global test, and leave-one-out method. RESULT: Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9, Eubacterium oxidoreducens group, and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. CONCLUSION: Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.

Vimentin cage - A double-edged sword in host anti-infection defense.

Vimentin, a type III intermediate filament, reorganizes into what is termed the 'vimentin cage' in response to various pathogenic infections. This cage-like structure provides an envelope to key components of the pathogen's life cycle. In viral infections, the vimentin cage primarily serves as a scaffold and organizer for the replication factory, promoting viral replication. However, it also occasionally contributes to antiviral functions. For bacterial infections, the cage mainly supports bacterial proliferation in most observed cases. These consistent structural alterations in vimentin, induced by a range of viruses and bacteria, highlight the vimentin cage's crucial role. Pathogen-specific factors add complexity to this interaction. In this review, we provide a thorough overview of the functions and mechanisms of the vimentin cage and speculate on vimentin's potential as a novel target for anti-pathogen strategies.

UHMK1 aids colorectal cancer cell proliferation and chemoresistance through augmenting IL-6/STAT3 signaling.

UHMK1, a serine/threonine kinase with a U2AF homology motif, is implicated in RNA processing and protein phosphorylation. Increasing evidence has indicated its involvement in tumorigenesis. However, it remains to be elucidated whether UHMK1 plays a role in the development of colorectal cancer (CRC). Here, we demonstrated that UHMK1 was frequently upregulated in CRC samples compared with adjacent normal tissue and high expression of UHMK1 predicted poor outcomes. Knockdown of UHMK1 by siRNAs restrained CRC cell proliferation and increased oxaliplatin sensitivity, whereas overexpression of UHMK1 promoted CRC cell growth and oxaliplatin resistance, suggesting that UHMK1 plays important oncogenic roles in CRC. Mechanistically, we showed that UHMK1 had a significant effect on IL6/STAT3 signaling by interacting with STAT3. The interaction of UHMK1 with STAT3 enhanced STAT3 activity in regulating gene transcription. Furthermore, we found that STAT3 could in turn transcriptionally activate UHMK1 expression in CRC cells. The complementary experiments for cell growth and oxaliplatin resistance indicated the interdependent relationship between UHMK1 and STAT3. Thus, these collective findings uncovered a new UHMK1/STAT3 positive feedback regulatory loop contributing to CRC development and chemoresistance.

Interface cisplatin-crosslinked doxorubicin-loaded triblock copolymer micelles for synergistic cancer therapy.

Combination chemotherapy is an effective way to improve the therapeutic efficiency in anticancer treatment. Herein, we synthesized a novel amphiphilic triblock copolymer via a two-step ring-opening polymerization (ROP) followed by post-modification. Doxorubicin (DOX) was encapsulated into the copolymeric micelles through hydrophobic interactions, cisplatin (CDDP) was employed to in situ crosslink the interface of DOX-loaded micelles through Pt-carboxyl coordination interaction. The CDDP-mediated crosslinking improved the stability of the micelles and also reduced the release of DOX at physiological pH. After being taken up into the endosome/lysosome, the low environmental pH weakened the Pt-carboxyl coordination interactions, resulting in the destruction of the micelles and the release of CDDP and DOX. Moreover, these micelles loaded with dual drugs enabled a synergistic anticancer effect, showing promise as a potential drug delivery platform for cancer therapy.

Interface crosslinked mPEG-b-PAGE-b-PCL triblock copolymer micelles with high stability for anticancer drug delivery.

The stability of polymeric micelles is a key property for anticancer drug delivery. In this study, a novel amphiphilic triblock copolymer, methoxy poly(ethylene glycol)-b-poly(allyl glycidyl ether)-b-poly(ε-caprolactone) (mPEG-b-PAGE-b-PCL), with different hydrophobic lengths was designed and synthesized using the combination of two successive ring-opening polymerizations. The products were characterized using 1H NMR and gel permeation chromatography (GPC). The triblock copolymers could self-assemble into micelles to encapsulate doxorubicin (DOX). The diameter of the DOX-loaded micelles increased from 63 to 92 nm with increasing PCL block length in the copolymer composition. The interface of the mPEG-b-PAGE-b-PCL micelles was crosslinked by a thiol-ene reaction with 1,4-butanedithiol. The stability, drug release and in vitro cytotoxicity of the DOX-loaded micelles were studied. The results showed that the DOX-loaded micelles could be effectively endocytosed by cancer cells and have good antitumor efficacy. In addition, the crosslinked micelles (CLMs) had better tumor accumulation than the noncrosslinked micelles (NCLMs) after intravenous injection using the lipophilic dye DiR.

A new species of genus Agryllus Gorochov, 1994 from Yunnan, China (Orthoptera: Gryllidae: Gryllinae).

One new species, Agryllus apterus He sp. nov., is described from Yunnan, China. This new species is wingless, which is different from all other Agryllus species. The type specimens are deposited in Museum of Biology, East China Normal University (ECNU).