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Flexible conductive elastomers play a pivotal role in biosensing, electronic skin, and wearable devices. However, fabricating self-healing conductive elastomers with superior mechanical properties remains a formidable challenge. Here, we introduce a simple strategy for the preparation of a flexible elastomer that integrates stretchability, conductivity, and self-healing capabilities. Initially, the self-healing lipoic acid (LA) and conductive deep eutectic solvents (DES) are thermally initiated ring-opening copolymerized, yielding a linear copolymer P(LA-DES). This polymer is then integrated with linear polyurethane by intermolecular hydrogen bonds, followed by the incorporation of Fe3+ions to form a dynamic cross-linked network containing disulfide bonds, hydrogen bonds, and metal coordination. This supramolecular cross-linked elastomer not only exhibits remarkable mechanical and conductive properties but also demonstrates stable and reliable signal response capabilities when used as a strain sensor. The elastomer possesses a tensile strength of 4.63 MPa and an elongation at break of 893%, with an electrical conductivity of up to 2.67 × 10–4S·m–1. Moreover, it achieves a healing efficiency exceeding 90% when subjected to 80 °C for healing for 24 h. Additionally, the elastomer-based strain sensor is capable of sensitively detecting human joint motion, underscoring its potential for applications in the realm of flexible wearable devices and health monitoring.

Lenvatinib is a multiple receptor tyrosine kinases inhibitor (TKI) authorized for first-line treatment of hepatocellular carcinoma (HCC). However, Lenvatinib resistance is common in HCC clinical treatment, highlighting the urgent need to understand mechanisms of resistance. Here, we identified Golgi membrane protein 1 (GOLM1), a type II transmembrane protein originally located in the Golgi apparatus, as a novel regulator of Lenvatinib resistance. We found GOLM1 was overexpressed in Lenvatinib resistant human HCC cell lines, blood and HCC samples. Additionally, GOLM1 overexpression contributes to Lenvatinib resistance and HCC progression in vitro and in vivo. Mechanistically, GOLM1 upregulates CSN5 expression through EGFR-STAT3 pathway. Reversely, CSN5 deubiquitinates and stabilizes GOLM1 protein by inhibiting ubiquitin-proteasome pathway of GOLM1. Furthermore, clinical specimens of HCC showed a positive correlation between the activation of the GOLM1-EGFR-STAT3-CSN5 axis. Finally, GOLM1 knockdown was found to act in synergy with Lenvatinib in subcutaneous and orthotopic mouse model. Overall, these findings identify a mechanism of resistance to Lenvatinib treatment for HCC, highlight an effective predictive biomarker of Lenvatinib response in HCC and show that targeting GOLM1 may improve the clinical benefit of Lenvatinib.

Cumulative studies have established the significance of transfer RNA-derived small RNA (tsRNA) in tumorigenesis and progression. Nevertheless, its function and mechanism in pancreatic cancer metastasis remain largely unclear. Here, we screened and identified tiRNA-Val-CAC-2 as highly expressed in pancreatic cancer metastasis samples by tsRNA sequencing. We also observed elevated levels of tiRNA-Val-CAC-2 in the serum of pancreatic cancer patients who developed metastasis, and patients with high levels of tiRNA-Val-CAC-2 exhibited a worse prognosis. Additionally, knockdown of tiRNA-Val-CAC-2 inhibited the metastasis of pancreatic cancer in vivo and in vitro, while overexpression of tiRNA-Val-CAC-2 promoted the metastasis of pancreatic cancer. Mechanically, we discovered that tiRNA-Val-CAC-2 interacts with FUBP1, leading to enhanced stability of FUBP1 protein and increased FUBP1 enrichment in the c-MYCpromoter region, thereby boosting the transcription of c-MYC. Of note, rescue experiments confirmed that tiRNA-Val-CAC-2 could influence pancreatic cancer metastasis viaFUBP1-mediated c-MYCtranscription. These findings highlight a potential novel mechanism underlying pancreatic cancer metastasis, and suggest that both tiRNA-Val-CAC-2 and FUBP1 could serve as promising prognostic biomarkers and potential therapeutic targets for pancreatic cancer.

Nitrogen is a limiting nutrient for degraders function in hydrocarbon-contaminated environments. Biological nitrogen fixation by diazotrophs is a natural solution for supplying bioavailable nitrogen. Here, we determined whether the diazotroph Azotobacter chroococcumHN can provide nitrogen to the polycyclic aromatic hydrocarbon-degrading bacterium Paracoccus aminovoransHPD-2 and further explored the synergistic interactions that facilitate pyrene degradation in nitrogen-deprived environments. We found that A. chroococcumHN and P. aminovoransHPD-2 grew and degraded pyrene more quickly in co-culture than in monoculture. Surface-enhanced Raman spectroscopy combined with 15N stable isotope probing (SERS?-?15N SIP) demonstrated that A. chroococcumHN provided nitrogen to P. aminovoransHPD-2. Metabolite analysis and feeding experiments confirmed that cross-feeding occurred between A. chroococcumHN and P. aminovoransHPD-2 during pyrene degradation. Transcriptomic and metabolomic analyses further revealed that co-culture significantly upregulated key pathways such as nitrogen fixation, aromatic compound degradation, protein export, and the TCA cycle in A. chroococcumHN and quorum sensing, aromatic compound degradation and ABC transporters in P. aminovoransHPD-2. Phenotypic and fluorescence in situ hybridization (FISH) assays demonstrated that A. chroococcumHN produced large amounts of biofilm and was located at the bottom of the biofilm in co-culture, whereas P. aminovoransHPD-2 attached to the surface layer and formed a bridge-like structure with A. chroococcumHN. This study demonstrates that distinct syntrophic interactions occur between A. chroococcumHN and P. aminovoransHPD-2 and provides support for their combined use in organic pollutant degradation in nitrogen-deprived environments.

Nitrogen is a limiting nutrient for degraders function in hydrocarbon-contaminated environments. Biological nitrogen fixation by diazotrophs is a natural solution for supplying bioavailable nitrogen. Here, we determined whether the diazotroph Azotobacter chroococcumHN can provide nitrogen to the polycyclic aromatic hydrocarbon-degrading bacterium Paracoccus aminovoransHPD-2 and further explored the synergistic interactions that facilitate pyrene degradation in nitrogen-deprived environments. We found that A. chroococcumHN and P. aminovoransHPD-2 grew and degraded pyrene more quickly in co-culture than in monoculture. Surface-enhanced Raman spectroscopy combined with 15N stable isotope probing (SERS − 15N SIP) demonstrated that A. chroococcumHN provided nitrogen to P. aminovoransHPD-2. Metabolite analysis and feeding experiments confirmed that cross-feeding occurred between A. chroococcumHN and P. aminovoransHPD-2 during pyrene degradation. Transcriptomic and metabolomic analyses further revealed that co-culture significantly upregulated key pathways such as nitrogen fixation, aromatic compound degradation, protein export, and the TCA cycle in A. chroococcumHN and quorum sensing, aromatic compound degradation and ABC transporters in P. aminovoransHPD-2. Phenotypic and fluorescence in situ hybridization (FISH) assays demonstrated that A. chroococcumHN produced large amounts of biofilm and was located at the bottom of the biofilm in co-culture, whereas P. aminovoransHPD-2 attached to the surface layer and formed a bridge-like structure with A. chroococcumHN. This study demonstrates that distinct syntrophic interactions occur between A. chroococcumHN and P. aminovoransHPD-2 and provides support for their combined use in organic pollutant degradation in nitrogen-deprived environments.

Microbial oxidizers of trace gases such as hydrogen (H2) and carbon monoxide (CO) are widely distributed in soil microbial communities and play a vital role in modulating biogeochemical cycles. However, the contribution of trace gas oxidizers to soil carbon fixation and the driving environmental factors remain unclear, especially on large scales. Here, we utilized biogeochemical and genome-resolved metagenomic profiling, assisted by machine learning analysis, to estimate the contributions of trace gas oxidizers to soil carbon fixation and to predict the key environmental factors driving this process in soils from five distinct ecosystems. The results showed that phylogenetically and physiologically diverse H2and CO oxidizers and chemosynthetic carbon-fixing microbes are present in the soil in different terrestrial ecosystems. The large-scale variations in soil carbon fixation were highly positively correlated with both the abundance and the activity of H2and CO oxidizers (p< 0.05–0.001). Furthermore, soil pH and moisture-induced shifts in the abundance of H2and CO oxidizers partially explained the variation in soil carbon fixation (55%). The contributions of trace gas oxidizers to soil carbon fixation in the different terrestrial ecosystems were estimated to range from 1.1% to 35.0%. The estimated rate of trace gas carbon fixation varied from 0.04 to 1.56 mg kg–1d–1. These findings reveal that atmospheric trace gas oxidizers may contribute to soil carbon fixation driven by key soil environmental factors, highlighting the non-negligible contribution of these microbes to terrestrial carbon cycling.

The development of induced pluripotent stem cell (iPSC) technology has inspired a series of methods to manipulate cell fate and has provided novel insight into the profound molecular events underlying the development of diseases. Reprogramming somatic cells into iPSCs has been intensively investigated. However, few studies have investigated the reprogramming of malignant cells and its potential application. Herein, we review the recent progress of iPSCs derived from malignant cells, and highlight tumor iPSCs applications on cancer research which mainly focus on mesenchymal-epithelial transition, genetic and epigenetic change, diseases model construction, drug screening and tumor pathway study.

As one of the main failure modes, embedded cracks occur in beam structures due to periodic loads. Hence it is useful to investigate the dynamic characteristics of a beam structure with an embedded crack for early crack detection and diagnosis. A new four-beam model with local flexibilities at crack tips is developed to investigate the transverse vibration of a cantilever beam with an embedded horizontal crack; two separate beam segments are used to model the crack region to allow opening of crack surfaces. Each beam segment is considered as an Euler-Bernoulli beam. The governing equations and the matching and boundary conditions of the four-beam model are derived using Hamilton’s principle. The natural frequencies and mode shapes of the four-beam model are calculated using the transfer matrix method. The effects of the crack length, depth, and location on the first three natural frequencies and mode shapes of the cracked cantilever beam are investigated. A continuous wavelet transform method is used to analyze the mode shapes of the cracked cantilever beam. It is shown that sudden changes in spatial variations of the wavelet coefficients of the mode shapes can be used to identify the length and location of an embedded horizontal crack. The first three natural frequencies and mode shapes of a cantilever beam with an embedded crack from the finite element method and an experimental investigation are used to validate the proposed model. Local deformations in the vicinity of the crack tips can be described by the proposed four-beam model, which cannot be captured by previous methods.

Miller-Fisher syndrome (MFS) is characterized by classical triad of ophthalmoplegia, ataxia and areflexia. The involvement of cerebral white matter in MFS is very rare. We report a typical MFS patient whose brain MRI showed unilateral and extensive involvement in cerebral white matter. We also found mild pleocytosis and raised protein concentration in cerebrospinal fluid. Deficits resolved completely after treatment with intravenous immunoglobulins. Subsequent brain MRI shows cavity formation in involved white matter.

Solid pseudopapillary tumor of the pancreas is a rare neoplasm with low malignant potential, which affects predominantly young females. Only approximately 10 to 15 cases of solid pseudopapillary tumors (SPTs) are malignant. We present the case of a 57-year-old woman who developed malignant SPT of the pancreas. Meanwhile, a literature review was carried out. Some clinicopathological features and strategies of management of malignant SPT are presented. In general, surgical removal of the tumor even in case of metastases or recurrence offers an excellent prognosis. Chemotherapy and radiotherapy should be taken into consideration in patients with unresectable tumor.

Integrin αvβ3 receptor is expressed on several types of cancer cells, including pancreatic cancer cells, and plays an important role in tumor growth and metastasis. The ability to target the integrin αvβ3 receptor on cancer cells increases the efficacy of targeted therapy and reduces the side effects. The aim of this study is to develop a novel arginine-glycine-aspartic acid (RGD) peptide-conjugated albumin nanoparticle to enhance the intracellular uptake of anticancer drug into the pancreatic cancer cells through receptor-mediated endocytosis. In cellular uptake studies, the fluorescent signal of RGD-conjugated BSANPs in BxPC3 cells was higher than that of BSANPs without RGD conjugation as determined by fluorescence spectrophotometer. We also found that BSANPs bound to BxPC3 cells in a time- and concentration-dependent manner. The uptake of RGD-conjugated BSANPs by pancreatic cancer cells was inhibited by an excess amount of free RGD peptide, indicating that the binding and/or uptake were mediated by the αvβ3 receptor. Furthermore, the nanoparticles were found to be located close to the nuclei by using laser scanning confocal microscopy. Besides, no significant in vitro cytotoxicity was observed as measured with MTT assay. Both in vitro and in vivo antitumor efficacy was improved by targeting gemcitabine-loaded nanoparticles to BxPC-3 cells using RGD peptides. Therefore, the RGD-conjugated BSANPs hold great potential as an effective drug delivery system to deliver therapeutic agents to pancreatic cancer.

Al2O3–TiO2composite oxide nanocrystals with different Al2O3/TiO2ratios (1/4, 2/3, 3/2, and 4/1) were prepared by the poly(ethylene glycol) (PEG) sol–gel method. The preparation process was monitored by thermogravimetric analysis and differential scanning calorimetry (TGA–DSC). Nanocrystal particles of these composite oxides obtained at various heat-treating temperatures (400–1100°C) were characterized in terms of morphology, size, specific surface area, composition, and structure by transmission electron microscopy (TEM), BET specific surface area analysis, and X-ray powder diffractometry (XRD). Nanoparticles of Al2O3–TiO2with grain sizes in the range 1–150 nm and specific surface areas of 4.3–136 m2/g could be obtained under different conditions. The morphology of the particles changed from spherical to cubic with increasing heat-treatment temperature. Anatase was stabilized in these composite nanomaterials and the mechanism was discussed. The change of the particles specific surface areas with increase of the Al2O3/TiO2ratio was researched. The Al2O3–TiO2composite oxide nanocrystals could catalyze the polymerization of maleic anhydride and may provide a route to obtain a product without rings at the end groups.