Dual action photosensitive platinum(II) anticancer prodrugs with photoreleasable azide ligands

The synthesis, characterisation and properties of novel photosensitive Pt(II) complexes [Pt(terpyridine)(N3)]CF3SO3 (1b∙CF3SO3) and [Pt(N^C^N)(N3)] (2b) containing photoreleasable azide ligands with potential as dual photochemotherapeutic and photodynamic therapeutic agents are reported. Their X-ray crystal structures show distorted square-planar Pt(II) coordination geometry with π-stacking between adjacent planar Pt units. These complexes intercalate into DNA with similar binding ability as their chlorido analogues and generate singlet oxygen upon irradiation with blue light (420 nm). Photoactivation of azido complexes leads to the release of the azide ligands and the formation of new platinum species. These properties appear to be favourable for potential dual-action photoactive prodrugs

Extension of the Wu-Jing equation of state (EOS) for highly porous materials: thermoelectron based theoretical model

A thermodynamic equation of state (EOS) for thermoelectrons is derived which is appropriate for investigating the thermodynamic variations along isobaric paths. By using this EOS and the Wu-Jing (W-J) model, an extended Hugoniot EOS model is developed which can predict the compression behavior of highly porous materials. Theoretical relationships for the shock temperature, bulk sound velocity, and the isentrope are developed. This method has the advantage of being able to model the behavior of porous metals over the full range of applicability of pressure and porosity, whereas methods proposed in the past have been limited in their applicability.Comment: 18 pages, 1 figure, appeared at J. Appl. Phys. 92, 5924 (2002

EPIC TTS Models: Empirical Pruning Investigations Characterizing Text-To-Speech Models

Neural models are known to be over-parameterized, and recent work has shown that sparse text-to-speech (TTS) models can outperform dense models. Although a plethora of sparse methods has been proposed for other domains, such methods have rarely been applied in TTS. In this work, we seek to answer the question: what are the characteristics of selected sparse techniques on the performance and model complexity? We compare a Tacotron2 baseline and the results of applying five techniques. We then evaluate the performance via the factors of naturalness, intelligibility and prosody, while reporting model size and training time. Complementary to prior research, we find that pruning before or during training can achieve similar performance to pruning after training and can be trained much faster, while removing entire neurons degrades performance much more than removing parameters. To our best knowledge, this is the first work that compares sparsity paradigms in text-to-speech synthesis

Application of MET Technique after Upper Limb Dysfunction after Breast Cancer Surgery

Object: Explore the application and actual effect of MET (Muscle Energy) technology after breast cancer surgery with upper limb dysfunction. Methods: Taking 40 female breast cancer patients who underwent surgical treatment in our hospital from September 2017 to June 2019 as the research objects, all of them successfully completed modified radical mastectomy for breast cancer. According to different nursing methods, the patients were randomly divided into two groups. The experiment There were 20 cases in each group and the control group. The control group was given routine functional recovery exercise intervention after the operation, and the experimental group added MET technology to the base of the control group. One month after the operation, the functional recovery of the affected limbs of the two groups of patients was effectively assessed. The upper limb dysfunction of the two groups was compared by statistical methods, and the shoulder joint range of motion (ROM) was used for performance. Results: Through early functional recovery training and MET technology, 19 cases of ROM in the experimental group showed compliance (95%), compared with only 14 cases (70%) in the control group. The difference in upper limb dysfunction between the two groups is very obvious with statistical significance (P<0.05). Conclusions: Early functional recovery training combined with muscle energy technology can promote the recovery of upper limb dysfunction after breast cancer surgery faster and better, which is conducive to the recovery of patients as soon as possible and improve the quality of life

Axial functionalisation of photoactive diazido platinum(iv) anticancer complexes

Mono-axial functionalised octahedral diazido Pt(IV) complexes trans,trans,trans-[Pt(py)2(N3)2(OR1)(OR2)] (OR1 = OH and OR2 = anticancer agent coumarin-3 carboxylate (cou, 2a), pyruvate dehydrogenase kinase (PDK) inhibitors 4-phenylbutyrate (PhB, 2b) or dichloroacetate (DCA, 2c)), and their di-axial functionalised analogues with OR1 = DCA and OR2 = cou (3a), PhB (3b), or DCA (3c) have been synthesised and characterised, including the X-ray crystal structures of complexes 2a, 3a, 3b and 3c. These complexes exhibit dark stability and have the potential to generate cytotoxic Pt(II) species and free radicals selectively in cancer cells when irradiated. Mono-functionalised complexes 2a–2c showed higher aqueous solubility and more negative reduction potentials. Mono- and di-functionalised complexes displayed higher photocytotoxicity with blue light (1 h, 465 nm, 4.8 mW cm−2) than the parent dihydroxido complex 1 (OR1 = OR2 = OH) in A2780 human ovarian (IC50 0.9–2.9 μM for 2a–2c; 0.11–0.39 μM for 3a–3c) and A549 human lung cancer cells (5.4–7.8 μM for 2a–2c; 1.2–2.6 μM for 3a–3c) with satisfactory dark stability. Notably, no apparent dark cytotoxicity was observed in healthy lung MRC-5 fibroblasts for all complexes (IC50 > 20 μM). Significantly higher platinum cellular accumulation and photo-generated ROS levels were observed for the di-functionalised complexes compared with their mono-functionalised analogues when cancer cells were treated under the same concentrations

Biotinylated photoactive Pt(IV) anticancer complexes

Novel biotinylated diazido-Pt(IV) complexes exhibit high visible light photocytotoxicity while being stable in the dark. Photocytotoxicity and cellular accumulation of all-trans-[Pt(py)2(N3)2(biotin)(OH)] (2a) were enhanced significantly when bound to avidin; irradiation induced dramatic cellular morphological changes in human ovarian cancer cells treated with 2a

Unexpected photoactivation pathways in a folate-receptor-targeted trans-diazido Pt(iv) anticancer pro-drug

A conjugate between a photoactive trans-diazido Pt(IV) pro-drug, trans,trans,trans-[Pt(N3)2(OH)2(py)2], and folic acid has been synthesized and fully characterized by high resolution ESI-MS, NMR and UV-vis spectroscopy. Photoactivation of the Pt-folate conjugate with visible light confirmed the generation of cytotoxic Pt(II) species capable of binding to guanine nucleobases. Importantly, photoreduction of the Pt(IV) complex triggered the photodecomposition of the folate vector into a p-aminobenzoate-containing fragment and several pterin derivatives, including 6-formylpterin. Besides exhibiting high dark stability in physiologicallike conditions, the Pt-folate conjugate was ca. 2× more photocytotoxic towards MCF-7 breast cancer cell line than its parent Pt(IV) complex with a high photoselectivity index (PI > 6.9). The higher photocytotoxicity of the conjugate may be a consequence of its higher cellular accumulation and of the generation of a set of different cytotoxic species, including Pt(II) photoproducts and several pterin derivatives, which are known to generate ROS