Synergistic Effects of Matrix Biophysical Properties on Gastric Cancer Cell Behavior via Integrin-Mediated Cell-ECM Interactions.

The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.

Boron nitride microfiber reinforced polyacrylic acid hydrogels with excellent self-adhesion, fast pH response, and strain sensitivity.

Hydrogels are widely utilized in the sensor field, but their inadequate adhesion presents a significant obstacle. Herein, a new multifunctional BNMFs/PAA composite hydrogel was prepared via the incorporation of one-dimensional porous boron nitride microfibers (BNMFs) and polyacrylic acid (PAA) hydrogels. BNMFs, as a reinforcing filler, play a very important role in enhancing the properties of the composite hydrogels. In particular, the porous micrometer structure plays a unique role in improving the adhesion properties of PAA hydrogels. The steric hindrance and the rich hydroxyl functional groups coming from BNMFs are key factors for the excellent adhesion of the composite hydrogels. The composite hydrogels show strong adhesion to various substrate materials. For iron plates and biological tissues, the adhesion energy can reach 1377 J m-2 and 317 J m-2, respectively. In addition, the developed BNMFs/PAA composite hydrogels exhibit excellent mechanical properties. The fracture strain of the composite hydrogels is increased by 2.4 times compared to pure PAA hydrogels. The hydrogen bonds formed between BNMFs and PAA are conducive to the mechanical properties of the BNMFs/PAA composite hydrogels. Meanwhile, BNMFs as fillers play a role in carrying and dissipating force. Furthermore, the BNMFs/PAA composite hydrogels have excellent strain and pH response characteristics. This is because the crosslinking network of the composite hydrogels becomes loose after the addition of BNMFs, resulting in rapid ion transport pathways. Therefore, the developed BNMFs/PAA composite hydrogels will have broad application prospects in the fields of motion monitoring, intelligent skin and biological adhesives.

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for primary sclerosing cholangitis.

BACKGROUND: Previous studies indicate that gut microbiota correlates to primary sclerosing cholangitis (PSC), but the causation is still unclear. We sought to reveal the causal relationship between gut microbiota and PSC with a bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: The large-scale genome-wide association study (GWAS) summary statistics and a bidirectional two-sample MR study were used to assess the causality between gut microbiota and PSC. Multiple sensitivity analyses were used to identify the robustness of our results. RESULTS: Three microbial taxa causally correlated to PSC. Genus Ruminococcaceae UCG002 (OR: 1.855, 95% CI: 1.068-3.220, P = 0.028) increased the risk of PSC. Class Betaproteobacteria (OR: 0.360, 95% CI: 0.171-0.758, P = 0.007), and genus Ruminiclostridium6 (OR: 0.474, 95% CI: 0.219-0.820, P = 0.011) had protective effects on PSC. In addition, we found the causal relationship of PSC with higher abundance of genus Dialister (beta: 0.059, 95% CI: 0.017-0.102, P = 0.006), genus Veillonella (beta: 0.065, 95% CI: 0.016-0.113, P = 0.009), class Melainabacteria (beta: 0.073, 95% CI: 0.012-0.133, P = 0.019), and order Gastranaerophilales (beta: 0.072, 95% CI: 0.011-0.113, P = 0.133). CONCLUSION: Our study reveals the causality between gut microbiota and PSC, providing new insights into the pathological mechanisms of PSC and facilitating the development of novel biomarkers and disease-modifying therapeutics for PSC from the perspective of gut microbiota.

A comprehensive Mendelian randomization study highlights the relationship between psychiatric disorders and non-tumor gastrointestinal diseases.

Objective: Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear. Methods: We explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results. Results: We found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320-2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291-2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295-1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008-1.078, p = 0.0157). Conclusion: Our study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

Exposure to tris (1,3-dichloro-2-propyl) phosphate affects the embryonic cardiac development of Oryzias melastigma.

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) is a growing concern and may be a potential risk to marine environmental health due to its widespread usage and distribution. However, the toxic effects of TDCPP on cardiac development in marine fish have not been reported. In this study, Oryzias melastigma embryos were exposed to TDCPP at doses of 0, 0.04, 0.4, 4 and 40 µg/L from early embryogenesis to 10 days postfertilization (dpf). Then, the heart rate and sinus venosus-bulbus arteriosus (SV-BA) distance of the exposed embryos were measured at 5, 6, 8 and 10 dpf. Furthermore, alterations in the mRNA levels of the genes encoding cyclooxygenase-2 (COX-2), bone morphogenetic protein 4 (BMP4), fibroblast growth factor 8 (FGF8), and GATA-binding protein 4 (GATA4) were evaluated at 5, 6, 8 and 10 dpf. We found that the heart rate significantly increased in all TDCPP exposure groups at 10 dpf. The SV-BA distance significantly decreased in all TDCPP exposure groups at all developmental stages (except for the 0.4 µg/L group at 5 dpf and the 4 µg/L group at 10 dpf). The mRNA expression of COX-2 was downregulated at 5 dpf, BMP4 was downregulated at 5 and 6 dpf, FGF8 was downregulated at 5, 6 and 8 dpf, GATA4 was downregulated at 8 dpf, and GATA4 was upregulated at 10 dpf. These results indicate that the changes in heart rate and SV-BA distance might be accompanied by disturbances in the four genes involved in cardiac development. Our findings will help to illustrate the possible cardiac toxic effects of marine fish exposed to TDCPP.

Engineered probiotic Escherichia coli elicits immediate and long-term protection against influenza A virus in mice.

Influenza virus infection remains a major global health problem and requires a universal vaccine with broad protection against different subtypes as well as a rapid-response vaccine to provide immediate protection in the event of an epidemic outbreak. Here, we show that intranasal administration of probiotic Escherichia coli Nissle 1917 activates innate immunity in the respiratory tract and provides immediate protection against influenza virus infection within 1 day. Based on this vehicle, a recombinant strain is engineered to express and secret five tandem repeats of the extracellular domain of matrix protein 2 from different influenza virus subtypes. Intranasal vaccination with this strain induces durable humoral and mucosal responses in the respiratory tract, and provides broad protection against the lethal challenge of divergent influenza viruses in female BALB/c mice. Our findings highlight a promising delivery platform for developing mucosal vaccines that provide immediate and sustained protection against respiratory pathogens.