Metabolic enzymes have an indispensable role in metabolic reprogramming, and their aberrant expression or activity has been associated with chemosensitivity. Hence, targeting metabolic enzymes remains an attractive approach for treating tumors. However, the influence and regulation of cysteine desulfurase (NFS1), a rate-limiting enzyme in iron–sulfur (Fe–S) cluster biogenesis, in colorectal cancer (CRC) remain elusive. Here, using an in vivo metabolic enzyme gene-based clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 library screen, we revealed that loss of NFS1 significantly enhanced the sensitivity of CRC cells to oxaliplatin. In vitro and in vivo results showed that NFS1 deficiency synergizing with oxaliplatin triggered PANoptosis (apoptosis, necroptosis, pyroptosis, and ferroptosis) by increasing the intracellular levels of reactive oxygen species (ROS). Furthermore, oxaliplatin-based oxidative stress enhanced the phosphorylation level of serine residues of NFS1, which prevented PANoptosis in an S293 phosphorylation-dependent manner during oxaliplatin treatment. In addition, high expression of NFS1, transcriptionally regulated by MYC, was found in tumor tissues and was associated with poor survival and hyposensitivity to chemotherapy in patients with CRC. Overall, the findings of this study provided insights into the underlying mechanisms of NFS1 in oxaliplatin sensitivity and identified NFS1 inhibition as a promising strategy for improving the outcome of platinum-based chemotherapy in the treatment of CRC.

Nerve guide conduits (NGCs) with geometric design have shown significant advantages in guidance of nerve reinnervation across the defect of injured peripheral nerves. It is realized that intraluminal fillers with distinctive structure can effectively provide an inner guidance for sprouting of axons and improve the permeability of NGC. In this work, a poly(lactic‐co‐glycolic acid) (PLGA) NGC is prepared containing intraluminal sponge fillers (labeled as ISF‐NGC) and used for reconstruction of a rat sciatic nerve with a 10 mm gap. For comparison, the same procedure is applied to a single hollow PLGA NGC (labeled as H‐NGC) and an autologous nerve. As evidenced by significantly improved nerve morphology and function, the ISF‐NGC achieves a superior nerve repair effect over H‐NGC, which is comparable to autologous nerve grafting. It is likely that the H‐NGC only provides a protected tunnel for nerve fiber regrowth and axonal extension, while ISF‐NGC offers an extracellular matrix‐mimetic architecture as autograft to provide contact guidance for nerve reinnervation. This newly developed ISF‐NGC is a promising candidate to aid nerve reinnervation across longer gaps commonly encountered in clinical cases.

Carbodiimide cross-linked silk fibroin (SF)/sodium alginate (SA) composite hydrogels with superior stability and tunable properties are developed by varying preparation parameters. SF/SA blend ratio modulation allows to achieve composite hydrogel gelation times of 18-65 min, and rheological analysis shows that the speed of gel formation, the hydrogel network's density, and the hydrogels' compressive properties are closely related to the blend ratio. The G′ of different hydrogels varies substantially from 28 to 413 Pa, and the hydrogel with higher SF content has a greater stiffness. The composite hydrogels present appropriate porosity of 76.63-85.09% and pore size of 316-603 μm. Hydrogel stability improves significantly after cross-linking, and substantial swelling occurs due to the hydrophilicity of SA. The 7/3 and 6/4 SF/SA hydrogels are more resistant to degradation in PBS, and cytotoxicity testing confirmed their biocompatibility. For release studies in vitro, two model compounds are used as drug models, tetracycline hydrochloride, and bovine serum albumin (BSA). Different ratios of SF/SA have a greater influence on the release of BSA. This study provides a practical preparation method for flexible SF/SA composite hydrogels, which can help design hydrogels with specific physicochemical properties for different applications, especially drug delivery.

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Realizing high-efficiency solar evaporation has great potential for purification of sewage and seawater desalination. However, continuous water supply, solar energy conversion, and thermal management must be further studied to improve water evaporation. In this research, inspired by the Amazon water lily, an interfacial water-trapping tridimensional structure solar evaporator was developed to achieve continuous supply of water from the water-trapping layer and three-dimensional heat distribution management. First, an artificial photothermal membrane with poly­(N-phenylglycine) (PNPG) was conveniently prepared by vacuum filtration. Then, combined with the three-dimensional heat distribution management design and the water-trapping layer for continuous supply of water, more optimized energy utilization and efficient interface heating were realized. Besides, because the novel nanoscale PNPG has excellent light capture performance and the absorbed solar energy can be concentrated in the water-trapping layer, the solar evaporation is more effective, showing higher energy efficiency (93.5%) and higher evaporation rate (1.72 kg m–2 h–1) under 1 sun. A special structure is designed to minimize energy loss and better regulate the connection between water evaporation, solar energy conversion, and thermal regulation. According to the results, these bioinspired solar evaporators can provide new ideas for designing high-efficiency solar evaporator structures and provide new opportunities for practical applications.

In this study, in order to obtain hydrogels with good properties for sustained release of hydrophobic drugs or for tissue engineering, poly(vinyl alcohol) (PVA)/silk fibroin (SF) semi-interpenetrating (semi-IPN) hydrogels with varied ratios of PVA/SF were enzymatically cross-linked using horseradish peroxidase. A vial inversion test determined approximate gelation times of PVA/SF hydrogels ranging from 5 to 10 min.The hydrogels with varied ratios showed differences in pore size and morphology. Mass loss rate of hydrogels increased from 15% to 58% with increasing PVA concentration. Stable hydrogels with PVA/SF at 0.5 : 1 w/w showed the best swelling ratio values in distilled water (7.36). FTIR analysis revealed that silk fibroin in these hydrogels exhibited the coexistence of amorphous and silk I crystalline structures and the SF and PVA molecules interacted with each other well. The mechanical properties of the composite hydrogels were controlled by the SF content. From the cell viability results, it was found that the hydrogels exerted very low cytotoxicity. Paeonol was chosen as the hydrophobic drug model for release studies from the hydrogels. Paeonol can be uniformly loaded into the composite hydrogels using the emulsifying property of PVA and paeonol release from the hydrogels was dependent on the PVA/SF ratio.This study applied a novel type of enzymatically crosslinked semi-IPN hydrogel that may have potential applications in drug delivery. Fig. 6 (a) The morphologies of cells growing in the extracted media of different samples after 3 days culture, using 33342 and PI fluorescent dyes. Scale bars, 50 mm. (b) The cell viability assessed by MTT assay after 1, 3 and 5 days exposure to hydrogel extract media. 41080 | RSC Adv., 2019, 9, 41074-41082 This journal isFig. 7 Cumulative release of paeonol from PVA/SF hydrogels over a period of 48 hours.This journal is

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