A biocompatible pure organic porous nanocage for enhanced photodynamic therapy.

Porphyrin-based photosensitizers have been widely utilized in photodynamic therapy (PDT), but they suffer from deteriorating fluorescence and reactive oxygen species (ROS) due to their close π-π stacking. Herein, a biocompatible pure organic porphyrin nanocage (Py-Cage) with enhanced both type I and type II ROS generation is reported for PDT. The porphyrin skeleton within the Py-Cage is spatially separated by four biphenyls to avoid the close π-π stacking within the nanocage. The Py-Cage showed a large cavity and high porosity with a Brunauer-Emmett-Teller surface area of over 300 m2 g-1, facilitating a close contact between the Py-Cage and oxygen, as well as the fast release of ROS to the surrounding microenvironment. The Py-Cage shows superb ROS generation performance over its precursors and commercial ones such as Chlorin E6 and Rose Bengal. Intriguingly, the cationic π-conjugated Py-Cage also shows promising type I ROS (superoxide and hydroxyl radicals) generation that is more promising for hypoxic tumor treatment. Both in vitro cell and in vivo animal experiments further confirm the excellent antitumor activity of the Py-Cage. As compared to conventional metal coordination approaches to improve PDT efficacy of porphyrin derivatives, the pure organic porous Py-Cage demonstrates excellent biocompatibility, which is further verified in both mice and rats. This work of an organic porous nanocage shall provide a new paradigm for the design of novel, biocompatible and effective photosensitizers for PDT.

NIR light-driven pure organic Janus-like nanoparticles for thermophoresis-enhanced photothermal therapy.

Photothermal therapy (PTT) represents a promising noninvasive tumor therapeutic modality, but the current strategies for enhancing photothermal effect have been mainly based on promoting thermal relaxation or suppressing radiative dissipation process of excited energy, leaving little room for further improvement in photothermal effect. Herein, as a proof of concept, we report the thermophoresis-enhanced photothermal effect with pure organic Janus-like nanoparticles (Janus-like NPs) for PTT. The Janus-like NPs are eccentrically loaded with compactly J-aggregated photothermal molecules (DMA-BDTO), which show red-shifted absorption wavelength and inhibited radiative decay as compared to individual molecules. Under NIR irradiation, the asymmetric heat generation at particle surface endows Janus-like NPs the active thermophoresis, which further increases collisions and converts kinetic energy into thermal energy, and Janus-like NPs exhibit significantly elevated temperature as compared to conventional NPs with homogenously distributed DMA-BDTO. Both in vitro and in vivo results confirm such thermophoresis-enhanced photothermal effect for improved PTT. Our new strategy of thermophoresis-enhanced photothermal effect shall open new insights for improving photothermal-related tumor therapy.

Pure Organic AIE Nanoscintillator for X-ray Mediated Type I and Type II Photodynamic Therapy.

X-ray induced photodynamic therapy (X-PDT) circumvents the poor penetration depth of conventional PDT with minimal radio-resistance generation. However, conventional X-PDT typically requires inorganic scintillators as energy transducers to excite neighboring photosensitizers (PSs) to generate reactive oxygen species (ROS). Herein, a pure organic aggregation-induced emission (AIE) nanoscintillator (TBDCR NPs) that can massively generate both type I and type II ROS under direct X-ray irradiation is reported for hypoxia-tolerant X-PDT. Heteroatoms are introduced to enhance X-ray harvesting and ROS generation ability, and AIE-active TBDCR exhibits aggregation-enhanced ROS especially less oxygen-dependent hydroxyl radical (HO•- , type I) generation ability. TBDCR NPs with a distinctive PEG crystalline shell to provide a rigid intraparticle microenvironment show further enhanced ROS generation. Intriguingly, TBDCR NPs show bright near-infrared fluorescence and massive singlet oxygen and HO•- generation under direct X-ray irradiation, which demonstrate excellent antitumor X-PDT performance both in vitro and in vivo. To the best of knowledge, this is the first pure organic PS capable of generating both 1 O2 and radicals (HO•- ) in response to direct X-ray irradiation, which shall provide new insights for designing organic scintillators with excellent X-ray harvesting and predominant free radical generation for efficient X-PDT.

Synchronous Design of Membrane Material and Process for Pre-Combustion CO2 Capture: A Superstructure Method Integrating Membrane Type Selection.

Membrane separation technology for CO2 capture in pre-combustion has the advantages of easy operation, minimal land use and no pollution and is considered a reliable alternative to traditional technology. However, previous studies only focused on the H2-selective membrane (HM) or CO2-selective membrane (CM), paying little attention to the combination of different membranes. Therefore, it is hopeful to find the optimal process by considering the potential combination of H2-selective and CO2-selective membranes. For the CO2 capture process in pre-combustion, this paper presents an optimization model based on the superstructure method to determine the best membrane process. In the superstructure model, both CO2-selective and H2-selective commercial membranes are considered. In addition, the changes in optimal membrane performance and capture cost are studied when the selectivity and permeability of membrane change synchronously based on the Robeson upper bound. The results show that when the CO2 purity is 96% and the CO2 recovery rate is 90%, the combination of different membrane types achieves better results. The optimal process is the two-stage membrane process with recycling, using the combination of CM and HM in all situations, which has obvious economic advantages compared with the Selexol process. Under the condition of 96% CO2 purity and 90% CO2 recovery, the CO2 capture cost can be reduced to 11.75$/t CO2 by optimizing the process structure, operating parameters, and performance of membranes.

Albumin Paclitaxel Combined with Intrapleural Infusion of Bevacizumab + Lobaplatin for the Second-Line Treatment of Patients with Non-Squamous Non-Small Cell Lung Cancer.

Objective: To investigate the clinical efficacy and safety of albumin paclitaxel combined with intrapleural bevacizumab + lobaplatin for patients with non-squamous non-small cell lung cancer (NS-NSCLC) with malignant pleural effusion (MPE) and analyze prognostic factors. Methods: A total of 126 NS-NSCLC patients were included in the study. Control group with 64 cases received intrapleural infusion of lobaplatin + intravenous albumin paclitaxel, and treatment group with 62 cases received additional intrapleural bevacizumab perfusion. Analysis was performed by collecting data about MPE, progression-free survival (PFS), overall survival (OS), and scores of quality of life. Results: In the treatment and control groups, objective response rate (ORR) was 51.6% and 31.3% (χ 2 = 5.39, P=0.02), and disease control rate (DCR) was 91.9% and 71.9% (χ 2 = 8.49, P=0.004), respectively. The main adverse reactions (≥grade 3) in the treatment group were thrombocytopenia, peripheral neurotoxicity, proteinuria, neutropenia, and nausea/vomiting, and in the control group, they were weakness, nausea/vomiting, anemia, and peripheral neurotoxicity. In the control and treatment groups, the median PFS was 6.2 (95% confidence interval (CI): 5.86-6.56) and 5.1 (95% CI: 4.956-5.191), and the median OS was 14.4 (95% CI: 12.681-16.113) and 10.6 months (95% CI: 8.759-12.391). The score of quality of life for treated patients was significantly higher than those before treatment and the control group, and the parameters included general health status (GH), role physical (RP), body pain (BP), social function (SF), and vitality (VT); pH, CD4+/CD8+ values, and vascular endothelial growth factor (VEGF) in the pleural effusion significantly affected the PFS and OS (P < 0.05). Bevacizumab administration in patients with bloody pleural effusion did not increase the risk of pleural hemorrhage. Conclusion: The combination of albumin paclitaxel and intrapleural bevacizumab + lobaplatin is effective and may reverse the adverse events in patients with NS-NSCLC and MPE. The change of CD4+/CD8+ ratio before and after treatment is an independent and prognostic factor for patients with NS-NSCLC and MPE.

Heart Rate Variability-Based Subjective Physical Fatigue Assessment.

Accurate assessment of physical fatigue is crucial to preventing physical injury caused by excessive exercise, overtraining during daily exercise and professional sports training. However, as a subjective feeling of an individual, physical fatigue is difficult for others to objectively evaluate. Heart rate variability (HRV), which is derived from electrocardiograms (ECG) and controlled by the autonomic nervous system, has been demonstrated to be a promising indicator for physical fatigue estimation. In this paper, we propose a novel method for the automatic and objective classification of physical fatigue based on HRV. First, a total of 24 HRV features were calculated. Then, a feature selection method was proposed to remove useless features that have a low correlation with physical fatigue and redundant features that have a high correlation with the selected features. After feature selection, the best 11 features were selected and were finally used for physical fatigue classifying. Four machine learning algorithms were trained to classify fatigue using the selected features. The experimental results indicate that the model trained using the selected 11 features could classify physical fatigue with high accuracy. More importantly, these selected features could provide important information regarding the identification of physical fatigue.

Deep Multi-Branch Two-Stage Regression Network for Accurate Energy Expenditure Estimation With ECG and IMU Data.

OBJECTIVE: Energy Expenditure (EE) estimation plays an important role in objectively evaluating physical activity and its impact on human health. EE during activity can be affected by many factors, including activity intensity, individual physical and physiological characteristics, environment, etc. However, current studies only use very limited information, such as heart rate and step count, to estimate EE, which leads to a low estimation accuracy. METHODS: In this study, we proposed a deep multi-branch two-stage regression network (DMTRN) to effectively fuse a variety of related information including motion information, physiological characteristics, and human physical information, which significantly improved the EE estimation accuracy. The proposed DMTRN consists of two main modules: a multi-branch convolutional neural network module which is used to extract multi-scale context features from electrocardiogram (ECG) and inertial measurement unit (IMU) data, and a two-stage regression module which aggregated the extracted multi-scale context features containing the physiological and motion information and the anthropometric features to accurately estimate EE. RESULTS: Experiments performed on 33 participants show that our proposed method is more accurate and the average root mean square error (RMSE) is reduced by 22.8% compared with previous works. CONCLUSION: The EE estimation accuracy was improved by the proposed DMTRN model with a well-designed network structure and new input signal ECG. SIGNIFICANCE: This study verified that ECG was much more effective than HR for EE estimation and cast light on EE estimation using the deep learning method.

Clinical efficacy evaluation and prevention of adverse reactions in a randomized trial of a combination of three drugs in the treatment of cancerous pudendal neuralgia.

BACKGROUND: To explore the clinical efficacy, safety, and prevention of major adverse reactions of the non-steroidal anti-inflammatory drug celecoxib combined with OxyContin and Pregabalin in the treatment of cancerous pudendal neuralgia. METHODS: A total of 51 patients presenting with pelvic malignancies with cancerous pudendal neuralgia were selected, and random number table method was used to allocate them to either the experimental group (n=27) or control group (n=24). The control group was treated with OxyContin combined with Pregabalin, and the experimental group was treated with Celecoxib on the basis of the control group. RESULTS: At 24 hours after treatment, the clinical effective rate of the experimental group was 92.6%, which was significantly higher than the 66.7% of the control group (P<0.05). The numerical rating scale (NRS) scores of the 2 groups of participants on the 7th and 14th days after treatment were lower than before treatment (P<0.05), and the NRS scores of the participants in the experimental group had decreased more significantly. At the same time, the average daily consumption of OxyContin on the 7th and 14th day of the experimental group was lower than that of the control group (P<0.05). Compared with the control group, the incidence of constipation and dysuria in the experimental group was significantly reduced (P<0.05). Co-occurring in both groups during treatment, 10 participants with urinary dysfunction were treated with tamsulosin hydrochloride sustained-release capsules, no urinary retention occurred, catheterization was avoided, tamsulosin hydrochloride sustained-release capsules could be stopped after 1 week, and urination was smooth (P<0.05). After treatment, the quality of life of the 2 groups of participants had improved compared to before treatment, and the improvement was more significant in the experimental group. CONCLUSIONS: When treating patients with cancerous pudendal neuralgia with OxyContin and Pregabalin, the addition of celecoxib has a significant effect, which can effectively improve the patient's pain, improve their quality of life to a certain extent, and reduce the consumption of OxyContin. Lowering the dose of OxyContin reduces the occurrence of adverse reactions related to the drug, especially the incidence of constipation and urinary retention. Tamsulosin hydrochloride sustained-release capsules can effectively relieve urinary disorders caused by OxyContin. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046045.