Metformin suppresses gastric cancer progression by disrupting the STAT1-PRMT1 axis.

Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.

KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations.

BACKGROUND: Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion. Triggering senescence is now considered to benefit multiple cancer therapies. Furthermore, senescence-based "one-two punch" therapy was validated in clinical trials. Therefore, we hypothesized that screening epigenetic modulators might help identify a novel vulnerability to trigger senescence in gastric cancer harboring TP53 mutations. RESULTS: We developed a novel efficient approach to identify senescence inducers by sequentially treating cells with drug candidates and senolytic agents. Based on this, we demonstrated that QC6352 (a selective KDM4C inhibitor) efficiently triggered cellular senescence in gastric cancer harboring TP53 mutations. More importantly, the "one-two punch' therapy consisting of QC6352 and SSK1 eliminates tumor cells harboring TP53 mutations. This finding highlights a potential therapeutic strategy for the aggressive subgroup of gastric cancer. Besides, the functions of QC6352 were totally unknown. We demonstrated that QC6352 might possess far more powerful anti-tumor capacities compared to the traditional genotoxic drugs, 5-Fu and Oxaliplatin. CONCLUSIONS: This initial investigation to identify a senescence inducer revealed that QC6352 triggers senescence in gastric cancer cells harboring TP53 mutations by regulating the SP1/CDK2 axis through suppressing KDM4C. QC6352 and senolytic agent-SSK1 represent a novel 'one-two punch' therapeutic strategy for the more malignant gastric cancer subtypes.

A simple and efficient transfer method for fabricating stretchable AgNW patterns on PDMS using carboxylated cellulose nanofibers as a sacrificial layer.

Silver nanowire (AgNW) networks are one of the most promising materials of transparent electrodes in flexible applications. However, they still face challenges in fabricating AgNW transparent conductive films (TCFs) with excellent comprehensive performance on stretchable substrates. In this work, we developed an efficient and simple water-assisted method to completely transfer AgNW films from glass to polydimethylsiloxane (PDMS). Carboxylated cellulose nanofibers (CNF-C) are introduced between the AgNW network and glass as a sacrificial layer, which is dissolved in water in the transfer process, releasing the AgNW network on the PDMS. The transferred AgNW networks show an increase of sheet resistance less than 30% and a slight decrease of transmittance. The stretchable AgNW TCFs exhibited good opto-electrical performance with a figure of merit of about 200, low surface roughness, good film uniformity, long-term stability, electrical stability and mechanical performance. Two patterning approaches based on the transfer method were proposed and fine stretchable AgNW patterns with a linewidth of 200 µm were fabricated. The fabricated stretchable AgNW patterns were used in flexible wires, a film heater and sensors as a demonstration.

Facile Transfer of a Transparent Silver Nanowire Pattern to a Soft Substrate Using Graphene Oxide as a Double-Sided Adhesion-Tuning Layer.

Silver nanowires (AgNWs) have been employed in various optoelectronic devices as transparent electrodes. However, it remains a great challenge to facilely pattern silver nanowires to realize desirable soft skin devices. Here, we develop an intact transfer method via a double-layered adhesion regulator of graphene oxide (GO) enabling complete transfer of a silver nanowire pattern from a tough substrate onto soft polydimethylsiloxane (PDMS) and flexible polyethylene (PE). We achieve positive and negative patterns simultaneously when selectively transferring silver nanowire patterns. The resulting patterned AgNW electrodes have uniform conductivity and long-term stability. The underlying mechanism of the clean transfer is thoroughly investigated via transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). GO plays a role in reducing the adhesion of AgNW to the donor tough substrate and enhancing adhesion of AgNW to the target soft substrate simultaneously. Finally, we demonstrate the utility of the patterned electrodes as transparent sensors detecting body motion. This work offers an effective solution to the challenging patterning problem of silver nanowires on a hydrophobic soft substrate, which is compatible with the soft component in emerging smart skin or wearable electronics.

Facile preparation of cellulose nanofibrils (CNFs) with a high yield and excellent dispersibility via succinic acid hydrolysis and NaClO2 oxidation.

An efficient and low-cost approach to preparing CNFs with succinic acid hydrolysis and NaClO2 oxidation is explored. High-temperature-short-time hydrolysis can depolymerize the cellulose, whereas the dispersibility of the CNFs is hugely enhanced by NaClO2 oxidation under alkaline condition. The degradation of cellulose in succinic acid hydrolysis follows first-order reaction kinetics and is severely influenced by the hydrolysis temperature, moreover, the molecular chains of the cellulose are seriously cracked under the optimized condition. The NaClO2 oxidation greatly improves the zeta potential (-36.2 mV) and the dispersibility of the CNFs. The obtained CNFs have an ultimate yield of 94.6%, and the diameter distribution is mainly within 20-40 nm. In addition, some amount of carboxyl groups in the cellulose will be instead of the hydroxyl groups, and the crystallinity of the CNFs is significantly increased.

Person-Environment Fit and Employee Creativity: The Moderating Role of Multicultural Experience.

Previous research has demonstrated the positive effects of congruent personal and environmental characteristics on creativity. None of them, however, has tested the formal theory of person-environment fit for predicting creativity in the context of multicultural experiences. This study examined the effects of two versions of person-environment fit (Demands-abilities fit and Needs-supplies fit) on employee creativity in China, taking into account the moderating role of multicultural experiences. The results, based on the data of East Asian Social Survey in the Chinese General Social Survey (CGSS) in 2015, showed employees with demands-abilities fit have lower creativity than those with demands-abilities misfit; nevertheless, the demands-abilities fit creates a growing impact on employee creativity with increasing multicultural experience. Additionally, the higher the needs-supplies fit, the stronger the employee creativity; and, the needs-supplies fit creates a growing impact on employee creativity with increasing multicultural experience. It shows that different versions of person-environment fit have different effects on employee creativity and multicultural experience moderated the effects of person-environment fit on employee creativity. Implications for research and practice are discussed.

Removable Large-Area Ultrasmooth Silver Nanowire Transparent Composite Electrode.

In this work, a composite silver nanowire (AgNW) transparent electrode that is large-area ultrasmooth without conductivity or transmittance scarifice, removable but with good resistance to both water and organic solvent, is reported. Via a simple low-temperature solution process without complicated transfer steps or additional pressure pressing, a new kind of AgNWs composite with biocompatible and patternable chitosan polymer complex demonstrates a quite low root-mean-square roughness ∼7 nm at a largest reported scan size of 50 µm × 50 µm, which is among the best flat surface. After long-term exposure to both water and organic solvent, it still shows strong adhesion, unchanged transparency, and no obvious conductivity reduction, suggesting a good stability staying on the substrate. Meanwhile, the polymer and silver nanowire in the composite electrode can be damaged via the same process through concentrated acid or base etching to leave off the substrate, allowing a simple patterning technology. Besides, the imported insulating polymer does not lower down the opto-electrical performance, and a high figure of merit close to 300 is obtained for the composite electrode, significantly outperforming the optoelectronic performance of indium-tin oxide (ITO) coated plastics (∼100) and comparable to ITO-coated glass. It shows great advantage to replace ITO as a promising transparent electrode.