Glycolysis-non-canonical glutamine dual-metabolism regulation nanodrug enhanced the phototherapy effect for pancreatic ductal adenocarcinoma treatment.

Clinical pancreatic ductal adenocarcinoma (PDAC) treatment is severely limited by lack of effective KRAS suppression strategies. To address this dilemma, a reactive oxygen species (ROS)-responsive and PDAC-targeted nanodrug named Z/B-PLS was constructed to confront KRAS through dual-blockade of its downstream PI3K/AKT/mTOR and RAF/MEK/ERK for enhanced PDAC treatment. Specifically, photosensitizer zinc phthalocyanine (ZnPc) and PI3K/mTOR inhibitor BEZ235 (BEZ) were co-loaded into PLS which was constructed by click chemistry conjugating MEK inhibitor selumetinib (SEL) to low molecular weight heparin with ROS-responsive oxalate bond. The BEZ and SEL blocked PI3K/AKT/mTOR and RAF/MEK/ERK respectively to remodel glycolysis and non-canonical glutamine metabolism. ZnPc mediated photodynamic therapy (PDT) could enhance drug release through ROS generation, further facilitating KRAS downstream dual-blockade to create treatment-promoting drug delivery-therapeutic positive feedback. Benefiting from this broad metabolic modulation cascade, the metabolic symbiosis between normoxic and hypoxic tumor cells was also cut off simultaneously and effective tumor vascular normalization effects could be achieved. As a result, PDT was dramatically promoted through glycolysis-non-canonical glutamine dual-metabolism regulation, achieving complete elimination of tumors in vivo. Above all, this study achieved effective multidimensional metabolic modulation based on integrated smart nanodrug delivery, helping overcome the therapeutic challenges posed by KRAS mutations of PDAC.

Grafting with an invasive Xanthium strumarium improves tolerance and phytoremediation of native congener X. sibiricum to cadmium/copper/nickel tailings.

Invasive plants could play an important role in the restoration of tailings, but their invasiveness limits their practical application. In this study, the phytoremediation potentials and invasive risks of an exotic invasive plant (Xanthium strumarium, LT), a native plant (X. sibiricum, CR), and combinations of inoculations (EG, with CR as the scion and LT as the rootstock; SG, with CR as both the scion and rootstock) were evaluated on Cd/Cu/Ni tailings. LT rootstock has a stronger nutrient and metal transport capacity, compared with CR. EG not only had higher biomass and Cd/Cu/Ni accumulation, but also abundant rhizosphere microbial communities. Hydroponic and common garden experiments showed that the growth and metal enrichment characteristics of EG are not inherited by plant offspring, which reduces the risk of the biological diffusion in the process of using exotic species. Transcriptome analysis shows that a large number of differentially-expressed genes in EG leaves and roots are involved in phenylpropanoid biosynthesis, secondary metabolite generation, and signal transduction. The genes induced in EG leaves, including cyclic nucleotide-gated ion channel, calcium-binding protein, and WRKY transcription factor, were found to be differentially expressed compared to CR. The genes induced in EG roots, included phenylalanine ammonia-lyase, cinnamoyl-CoA reductase, caffeoyl-CoA O-methyltransferase, and beta-glucosidase. We speculate that lignin and glucosinolates play an important role in the metal accumulation and transportation of EG. The results demonstrate that grafting with LT not only improved CR tolerance and accumulation of Cd, Cu, and Ni, but also created a beneficial microbial environment for plants in tailings. More importantly, grafting with LT did not enhance the invasiveness of CR. Our results provide an example of the safe use of invasive plants in the restoration of Cd/Cu/Ni tailings.

Automatic Classification Framework of Tongue Feature Based on Convolutional Neural Networks.

Tongue diagnosis is an important part of the diagnostic process in traditional Chinese medicine (TCM). It primarily relies on the expertise and experience of TCM practitioners in identifying tongue features, which are subjective and unstable. We proposed a tongue feature classification framework based on convolutional neural networks to reduce the differences in diagnoses among TCM practitioners. Initially, we used our self-designed instrument to capture 482 tongue photos and created 11 data sets based on different features. Then, the tongue segmentation task was completed using an upgraded facial landmark detection method and UNET. Finally, we used ResNet34 as the backbone to extract features from the tongue photos and classify them. Experimental results show that our framework has excellent results with an overall accuracy of over 86 percent and is particularly sensitive to the corresponding feature regions, and thus it could assist TCM practitioners in making more accurate diagnoses.

Phytoremediation potential of hybrids of the exotic plant Xanthium strumarium and its native congener Xanthium sibiricum for cadmium-contaminated soils.

Exotic plants could play an essential role in the restoration of heavy metal-contaminated soil. This study evaluated the tolerance of and extraction of cadmium (Cd) by ZCR (CR♀ × LT♂), hybrids of Xanthium strumarium (LT, exotic species) and X. sibiricum (CR, indigenous congener), and their parental species under different Cd treatments (0, 10, 40, and 80 mg·kg-1). The results showed that the hybrids had significantly improved tolerance to Cd. Under Cd stress, the biomass of ZCR increased by more than 50% on average compared with that of CR. Moreover, the hybrids showed a more remarkable ability to transport Cd from the root to the shoot. The Cd content of the shoots of ZCR increased by 128.33, 147.22, and 252.63% when treated with 10, 40, and 80 mg·kg-1 Cd, respectively. ZCR stored more than 70% of Cd in litter leaves, thereby reducing the toxic effects of Cd on photosynthesis and growth. The results showed that ZCR showed excellent Cd tolerance and enrichment in the presence of Cd. The hybrids of Xanthium strumarium and its native congener X. sibiricum may remediate soil Cd pollution.Novelty statementWith the changing world economy and increasing human activities, exotic plants have become a global issue of common concern to the international community. This study describes new findings on using hybrids of the exotic plant of Xanthium strumarium and its native congener Xanthium sibiricum for the restoration of cadmium-contaminated soils. Under Cd stress, the hybrids' biomass, tolerance, and ability to accumulate Cd were significantly higher than that of X. sibiricum, indicating that hybrids gained useful heavy metal extraction traits from X. strumarium.