"Two-Stage Rocket-Propelled" Strategy Boosting Theranostic Efficacy with Mitochondria-Specific Type I-II Photosensitizers.

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

A Hyperspectral Image Classification Method Based on the Nonlocal Attention Mechanism of a Multiscale Convolutional Neural Network.

Recently, convolution neural networks have been widely used in hyperspectral image classification and have achieved excellent performance. However, the fixed convolution kernel receptive field often leads to incomplete feature extraction, and the high redundancy of spectral information leads to difficulties in spectral feature extraction. To solve these problems, we propose a nonlocal attention mechanism of a 2D-3D hybrid CNN (2-3D-NL CNN), which includes an inception block and a nonlocal attention module. The inception block uses convolution kernels of different sizes to equip the network with multiscale receptive fields to extract the multiscale spatial features of ground objects. The nonlocal attention module enables the network to obtain a more comprehensive receptive field in the spatial and spectral dimensions while suppressing the information redundancy of the spectral dimension, making the extraction of spectral features easier. Experiments on two hyperspectral datasets, Pavia University and Salians, validate the effectiveness of the inception block and the nonlocal attention module. The results show that our model achieves an overall classification accuracy of 99.81% and 99.42% on the two datasets, respectively, which is higher than the accuracy of the existing model.

High Light Intensity Triggered Abscisic Acid Biosynthesis Mediates Anthocyanin Accumulation in Young Leaves of Tea Plant (Camellia sinensis).

There is increasing interest in the production and consumption of tea (Camellia sinensis L.) processed from purple-leaved cultivar due to their high anthocyanin content and health benefits. However, how and why seasonal changes affect anthocyanin accumulation in young tea leaves still remains obscured. In this study, anthocyanin and abscisic acid (ABA) contents in young leaves of Zifuxing 1 (ZFX1), a cultivar with new shoots turning to purple in Wuyi Mountain, a key tea production region in China, were monitored over four seasons. Young leaves produced in September were highly purplish, which was accompanied with higher anthocyanin and ABA contents. Among the environmental factors, the light intensity in particular was closely correlated with anthocyanin and ABA contents. A shade experiment also indicated that anthocyanin content significantly decreased after 168 h growth under 75% shade, but ABA treatment under the shade conditions sustained anthocyanin content. To confirm the involvement of ABA in the modulation of anthocyanin accumulation, anthocyanin, carotenoids, chlorophyll, ABA, jasmonic acid (JA), and salicylic acid (SA) in the young leaves of four cultivars, including ZFX1, Zijuan (ZJ), wherein leaves are completely purple, Rougui (RG) and Fudingdabaicha (FDDB) wherein leaves are green, were analyzed, and antioxidant activities of the leaf extracts were tested. Results showed that ABA, not other tested hormones, was significantly correlated with anthocyanin accumulation in the purple-leaved cultivars. Cultivars with higher anthocyanin contents exhibited higher antioxidant activities. Subsequently, ZFX1 plants were grown under full sun and treated with ABA and fluridone (Flu), an ABA inhibitor. ABA treatment elevated anthocyanin level but decreased chlorophyll contents. The reverse was true to those treated with Flu. To pursue a better understanding of ABA involvement in anthocyanin accumulation, RNA-Seq was used to analyze transcript differences among ABA- or Flu-treated and untreated ZFX1 plants. Results indicated that the differentially expressed genes in ABA or Flu treatment were mainly ABA signal sensing and metabolism-related genes, anthocyanin accumulation-related genes, light-responsive genes, and key regulatory MYB transcription factors. Taking all the results into account, a model for anthocyanin accumulation in ZFX1 cultivar was proposed: high light intensity caused reactive oxygen stress, which triggered the biosynthesis of ABA; ABA interactions with transcription factors, such as MYB-enhanced anthocyanin biosynthesis limited chlorophyll and carotenoid accumulation; and transport of anthocyanin to vacuoles resulting in the young leaves of ZFX1 with purplish coloration. Further research is warranted to test this model.

Donor-Acceptor-Acceptor-Conjugated Dual-State Emissive Acrylonitriles: Investigating the Effect of Acceptor Unit Order and Biological Imaging.

The effect of acceptor unit order on the photophysical properties of two distinct donor-acceptor-acceptor conjugated fluorescent acrylonitriles, TPA-AN-PhBT and TPA-BT-ANPh, was systematically investigated. Compared with faintly emissive TPA-AN-PhBT in solution, TPA-BT-ANPh showed strong red-shifted fluorescence. TPA-AN-PhBT and TPA-BT-ANPh exhibited enhanced green and deep red emissions with remarkable fluorescence quantum yields up to 44% in the solid state. In addition, TPA-BT-ANPh possessed stronger two-photon absorption than TPA-AN-PhBT. Furthermore, these biocompatible dyes served as excellent fluorescent markers for specific lipid droplet imaging.

Metabolite Profiling of 14 Wuyi Rock Tea Cultivars Using UPLC-QTOF MS and UPLC-QqQ MS Combined with Chemometrics.

Wuyi Rock tea, well-recognized for rich flavor and long-lasting fragrance, is a premium subcategory of oolong tea mainly produced in Wuyi Mountain and nearby regions of China. The quality of tea is mainly determined by the chemical constituents in the tea leaves. However, this remains underexplored for Wuyi Rock tea cultivars. In this study, we investigated the leaf metabolite profiles of 14 major Wuyi Rock tea cultivars grown in the same producing region using UPLC-QTOF MS and UPLC-QqQ MS with data processing via principal component analysis and cluster analysis. Relative quantitation of 49 major metabolites including flavan-3-ols, proanthocyanidins, flavonol glycosides, flavone glycosides, flavonone glycosides, phenolic acid derivatives, hydrolysable tannins, alkaloids and amino acids revealed clear variations between tea cultivars. In particular, catechins, kaempferol and quercetin derivatives were key metabolites responsible for cultivar discrimination. Information on the varietal differences in the levels of bioactive/functional metabolites, such as methylated catechins, flavonol glycosides and theanine, offers valuable insights to further explore the nutritional values and sensory qualities of Wuyi Rock tea. It also provides potential markers for tea plant fingerprinting and cultivar identification.

Preclinical qualification of a new multi-antigen candidate vaccine for metastatic melanoma.

New therapies are urgently required for the treatment of patients with melanoma. Here we describe the generation and preclinical evaluation of 3 new recombinant ALVAC(2) poxviruses vCP2264, vCP2291, and vCP2292 for their ability to induce the desired cellular immune responses against the encoded melanoma-associated antigens. This was done either in HLA-A2/K transgenic mice or using in vitro antigen-presentation studies. These studies demonstrated that the vaccine was able to induce HLA-A*0201-restricted T-cell responses against gp100 and NY-ESO-1, detectable directly ex vivo, in HLA-A2/K-transgenic mice. The in vitro antigen presentation studies, in the absence of appropriate animal models, demonstrated that target cells infected with the vaccine construct were lysed by MAGE-1, MAGE-3 or MART-1 peptide-specific T cells. These data indicate that ALVAC(2)-encoded melanoma-associated antigens can be properly processed and presented to induce antigen-specific cytotoxic T-cell responses. To enhance the immunogenicity of the melanoma antigens, a TRIad of COstimulatory Molecules (TRICOM) were also cloned into all 3 vectors. Increased in vitro proliferation and IFN-γ production was observed with all ALVAC(2) poxviruses encoding TRICOM, confirming the immune-enhancing effect of the ALVAC-encoded TRICOM. These studies demonstrated that all components of the vaccine were functionally active and provide a rationale for moving this candidate vaccine to the clinic.