The selective formation of nanomaterials in cancer cells and tumors holds great promise for cancer diagnostics and therapy. Until now, most strategies rely on a single trigger to control the formation of nanomaterials in situ . The combination of two or more triggers may provide for more sophisticated means of manipulation. In this study, we rationally designed a molecule ( Comp. 1 ) capable of responding to two enzymes, alkaline phosphatase (ALP), and reductase. Since the A549 lung cancer cell line showed elevated levels of extracellular ALP and intracellular reductase, we demonstrated that Comp. 1 responded in a stepwise fashion to those two enzymes and displayed a tandem molecular self-assembly behavior. The selective formation of nanofibers in the mitochondria of the lung cancer cells led to the disruption of the mitochondrial membrane, resulting in an increased level of reactive oxygen species (ROS) and the release of cytochrome C (Cyt C). ROS can react with proteins, resulting in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). This severe ER stress led to disruption of the ER, formation of vacuoles, and ultimately, apoptosis of the A549 cells. Therefore, Comp. 1 could selectively inhibit lung cancer cells in vitro and A549 xenograft tumors in vivo . Our study provides a novel strategy for the selective formation of nanomaterials in lung cancer cells, which is powerful and promising for the diagnosis and treatment of lung cancer.

Phenotypic transformation of macrophages plays important immune response roles in the occurrence, development and regression of periodontitis. Under inflammation or other environmental stimulation, mesenchymal stem cells (MSCs) exert immunomodulatory effects through their secretome. It has been found that secretome derived from lipopolysaccharide (LPS)-pretreated or three-dimensional (3D)-cultured MSCs significantly reduced inflammatory responses in inflammatory diseases, including periodontitis, by inducing M2 macrophage polarization. In this study, periodontal ligament stem cells (PDLSCs) pretreated with LPS were 3D cultured in hydrogel (termed SupraGel) for a certain period of time and the secretome was collected to explore its regulatory effects on macrophages. Expression changes of immune cytokines in the secretome were also examined to speculate on the regulatory mechanisms in macrophages. The results indicated that PDLSCs showed good viability in SupraGel and could be separated from the gel by adding PBS and centrifuging. The secretome derived from LPS-pretreated and/or 3D-cultured PDLSCs all inhibited the polarization of M1 macrophages, while the secretome derived from LPS-pretreated PDLSCs (regardless of 3D culture) had the ability to promote the polarization of M1 to M2 macrophages and the migration of macrophages. Cytokines involved in the production, migration and polarization of macrophages, as well as multiple growth factors, increased in the PDLSC-derived secretome after LPS pretreatment and/or 3D culture, which suggested that the secretome had the potential to regulate macrophages and promote tissue regeneration, and that it could be used in the treatment of inflammation-related diseases such as periodontitis in the future.

Although several synthetic hydrogels with defined stiffness have been developed to facilitate the proliferation and maintenance of human pluripotent stem cells (hPSCs), the influence of biochemical cues in lineage-specific differentiation and functional cluster formation has been rarely reported. Here, we present the application of Supragel, a supramolecular hydrogel formed by synthesized biotinylated peptides, for islet-like cluster differentiation. We observed that Supragel, with a peptide concentration of 5 mg/mL promoted spontaneous hPSCs formation into uniform clusters, which is mainly attributable to a supporting stiffness of ∼1.5 kPa as provided by the Supragel matrix. Supragel was also found to interact with the hPSCs and facilitate endodermal and subsequent insulin-secreting cell differentiation, partially through its components: the sequences of RGD and YIGSR that interacts with cell membrane molecules of integrin receptor. Compared to Matrigel and suspension culturing conditions, more efficient differentiation of the hPSCs was also observed at the stages 3 and 4, as well as the final stage toward generation of insulin-secreting cells. This could be explained by 1) suitable average size of the hPSCs clusters cultured on Supragel; 2) appropriate level of cell adhesive sites provided by Supragel during differentiation. It is worth noting that the Supragel culture system was more tolerance in terms of the initial seeding densities and less demanding, since a standard static cell culture condition was sufficient for the entire differentiation process. Our observations demonstrate a positive role of Supragel for hPSCs differentiation into islet-like cells, with additional potential in facilitating germ layer differentiation.

Dajue Temple, a representative ancient architectural heritage in North China, houses numerous lacquered wooden components of exceptional historical and artistic value. Prolonged environmental exposure causes severe dark discoloration and black spotting on lacquer surfaces, threatening their structural integrity. This first investigation into the damage identifies the spots as microbial in origin, with Cladosporium spp. as the primary agent driving deterioration and possessing wood-degrading capabilities. Antifungal tests show that thymol, clove essential oil, and nano-silver gel are all effective inhibitors. We proposed targeted, relic-friendly microbial control strategies tailored for ancient lacquered wooden components. These findings provided scientific guidance for the sustainable conservation and restoration of lacquered architectural elements in historic temples and comparable cultural heritage sites. In future work, environmental monitoring and the biocides’ compatibility should be involved, which will help to clarify microbe–environment interactions, enable early warning of biodeterioration risks and explore the wood-friendly biocides.

Dajue Temple, a representative ancient architectural heritage in North China, houses numerous lacquered wooden components of exceptional historical and artistic value. Despite their significance, this study is the first to investigate the severe dark discoloration and black spotting afflicting these lacquer surfaces—damage triggered by prolonged environmental exposure that endangers structural integrity and long-term conservation. To address this unstudied threat, we confirmed the microbial origin of black spots using ATP bioluminescence assays, then characterized microbial communities via culture-dependent methods and ITS sequencing—identifying Cladosporium spp. as the dominant biodeterio-gen driving lacquer deterioration. Functional assays on carboxymethylcellulose (CMC) and guaiacol-amended potato dextrose agar (PDA) media verified the wood-degrading potential of isolated Cladosporium spp. Antifungal susceptibility screening against ten agents demonstrates that thymol and clove essential oils achieved significant efficacy at 200 mg/mL, while nano silver gel also provided durable suppression. We proposed targeted, relic‑friendly microbial control strategies tailored for ancient lacquered wooden components. These findings provided scientific guidance for the sustainable conservation and restoration of lacquered architectural elements in historic temples and comparable cultural heritage sites. In future work, environmental monitoring should be involved, which will help to clarify microbe–environment interactions and enable early warning of biodeterioration risks.