Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance ...of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r1 relaxivity (13.17 mM s–1), acceptable cytocompatibility, and targeting specificity to αvβ3 integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.
The development of a powerful nanoplatform to realize the simultaneous therapy and diagnosis of cancer using a similar element for theranostics remains a critical challenge. Herein, we report such a ...theranostic nanoplatform based on pyridine (Pyr)-functionalized generation 5 (G5) poly(amidoamine) dendrimers complexed with copper(II) (Cu(II)) for radiotherapy-enhanced T 1-weighted magnetic resonance (MR) imaging and the synergistic radio-chemotherapy of both tumors and tumor metastasis. In this study, amine-terminated G5 dendrimers were covalently linked with 2-pyridinecarboxylic acid, acetylated to neutralize their remaining terminal amines, and complexed with Cu(II) through both the internal tertiary amines and the surface Pyr groups to form the G5.NHAc-Pyr/Cu(II) complexes. We show that the complexes are able to inhibit the proliferation of different cancer cell lines with half-maximal inhibitory concentrations ranging from 4 to 10 μM and induce significant cancer cell apoptosis. Due to the presence of Cu(II), the G5.NHAc-Pyr/Cu(II) complexes display an r 1 relaxivity of 0.7024 mM–1 s–1, enabling effective in vivo MR imaging of tumor xenografts and lung metastatic nodules. Further, under radiotherapy (RT) conditions, the tumor MR imaging sensitivity can be significantly enhanced, and the G5.NHAc-Pyr/Cu(II) complexes enable the enhanced chemotherapy of both a xenografted tumor model and a blood-vessel metastasis model. With the demonstrated theranostic potential of the dendrimer-Cu(II) nanocomplexes without additional agents or elements for RT-enhanced MR imaging and chemotherapy of tumor and tumor metastasis, this novel Cu(II)-based nanohybrids may hold great promise for the theranostics of different cancer types and metastases.
The traditional surgical technique for esophageal cancer is mainly open esophagectomy. With the innovation of surgical instruments, it is necessary to re-optimize the minimally invasive surgery. ...Therefore, single-port thoracoscopic minimally invasive esophagectomy (SPTE) is an important direction of development. This study retrospectively analyzed 202 patients with esophageal squamous cell carcinoma undergoing SPTE. Surgical variables and postoperative complications were further evaluated. All procedures were performed using SPTE. The number of patients who received R0 resection was 201 (99.5%). The total number of resected lymph nodes during the whole operation was on average 32.01 ± 12.15, and the mean number of positive lymph nodes was 1.56 ± 2.51. In 170 cases (84.2%), intraoperative blood loss did not exceed 100 ml (ml), while 1 case had postoperative bleeding. Only 1 patient (0.5%) required reoperation after surgery. Postoperative complications included 42 cases of pneumonia (20.8%), 9 cases of anastomotic leak (4.5%), 7 cases of pleural effusion (3.8%), and 1 case (0.5%) of both pleural hemorrhage and acute gastrointestinal hemorrhagic ulcer. Besides, we also recorded the time to remove the drain tube, which averaged 9.13 ± 5.31 days. In our study, we confirmed that the application of SPTE in clinical practice is feasible, and that the postoperative complications are at a low level.
Recently, there is a rising interest in perceiving image aesthetics. The existing works deal with image aesthetics as a classification or regression problem. To extend the cognition from rating to ...reasoning, a deeper understanding of aesthetics should be based on revealing why a high- or low-aesthetic score should be assigned to an image. From such a point of view, the authors propose a model referred to as Neural Aesthetic Image Reviewer, which can not only give an aesthetic score for an image, but also generate a textual description explaining why the image leads to a plausible rating score. Specifically, they propose three models based on shared aesthetically semantic layers and task-specific embedding layers at a high level for performance improvement on different tasks. To facilitate researches on this problem, they collect the AVA-Reviews dataset, which contains 52,118 images and 312,708 comments in total. Through multi-task learning, the proposed models can rate aesthetic images as well as produce comments in an end-to-end manner. It is confirmed that the proposed models outperform the baselines according to the performance evaluation on the AVA-Reviews dataset. Moreover, they demonstrate experimentally that the authors’ model can generate textual reviews related to aesthetics, which are consistent with human perception.
Chinese calligraphic images have important historical and artistic value, but natural weathering and man-made decay severely damage these works, thus image denoising is an important topic to be ...addressed. Traditional denoising methods still leave room for improvement. In this paper, image denoising is modeled as generation of clean image by using GAN (Goodfellow I et al. Advances in Neural Information Processing Systems 2672–2680,
2014
) with an embedment of residual dense blocks (Zhang Y et al. The IEEE Conference on Computer Vision and Pattern Recognition (CVPR),
2018
) that was formerly used for super resolution reconstruction. Meanwhile, a new type of noise is defined to simulate the real noise, and is used for compensation of unpaired data in the training set for GAN. The new structure, used with some preprocessing and training methods, yield satisfactory results compared to known denoising methods.
To address the shortcomings of the recently proposed Fick's Law Algorithm, which is prone to local convergence and poor convergence efficiency, we propose a multi-strategy improved Fick's Law ...Algorithm (FLAS). The method combines multiple effective strategies, including differential mutation strategy, Gaussian local mutation strategy, interweaving-based comprehensive learning strategy, and seagull update strategy. First, the differential variation strategy is added in the search phase to increase the randomness and expand the search degree of space. Second, by introducing the Gaussian local variation, the search diversity is increased, and the exploration capability and convergence efficiency are further improved. Further, a comprehensive learning strategy that simultaneously updates multiple individual parameters is introduced to improve search diversity and shorten the running time. Finally, the stability of the update is improved by adding a global search mechanism to balance the distribution of molecules on both sides during seagull updates. To test the competitiveness of the algorithms, the exploration and exploitation capability of the proposed FLAS is validated on 23 benchmark functions, and CEC2020 tests. FLAS is compared with other algorithms in seven engineering optimizations such as a reducer, three-bar truss, gear transmission system, piston rod optimization, gas transmission compressor, pressure vessel, and stepped cone pulley. The experimental results verify that FLAS can effectively optimize conventional engineering optimization problems. Finally, the engineering applicability of the FLAS algorithm is further highlighted by analyzing the results of parameter estimation for the solar PV model.
Amplifying “eat me signal” during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary “eat me ...signal” for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe2+) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H2O2 concentration would induce hydroxyl radical (·OH) and oxygen (O2) generation through Fenton reaction by Fe2+. DOX and ATP would be released from the amplifier, which could induce ICD effect and “ICD adjuvant” to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.
Inspired by the indispensable role of adenosine triphosphate (ATP) in immunogenic cell death (ICD) cascade, a novel ICD amplifier (PADO-Fe) was developed for chemotherapy-sensitized immunotherapy. Display omitted
Intelligent optimization algorithms (IOA) refer to a kind of algorithm that is used to solve optimization problems by imitating the survival and evolution process of natural creatures or physical ...phenomena as the algorithm principle. The well-known intelligent optimization algorithms include genetic algorithm, particle swarm optimization, simulated annealing algorithm, etc. Intelligent optimization algorithm is a heuristic method, which is widely used in solving optimization problems and provides some new ideas for solving some practical problems. With the advan-cement of science and technology and the increase in the complexity of application scenarios, traditional intelligent optimization algorithms can no longer satisfy optimization problems in terms of solving effects and accuracy. Therefore, new and more efficient intelligent optimization algorithms are constantly being proposed. Several new intelligent optimization algorithms have been proposed at home and abroad in recent years, such as butterfly optim
Mitochondrial-targeting therapy was considered to be a promising approach for the efficient treatment of cancer while positive charge induced nonspecific cytotoxicity severely limits its application. ...To overcome this drawback, a novel mitochondria targeted conjugate triphenylphosphine-docetaxel (TD) has been synthesized successfully and incorporated it into liposomes (EPSLP/TD), which possessed excellent pH-sensitive characteristic, EphA 10 mediated active targetability as well as mitochondria-targeting capability. EPSLP/TD was characterized to have a small particle size, high-encapsulation efficiency and excellent pH-sensitive characteristic. Compared with DTX-loaded liposomes (EPSLP/DTX), EPSLP/TD possessed higher cytotoxicity against MCF-7 cell line. Mitochondrial-targeting assay demonstrated mitochondria-targeting moiety triphenylphosphine (TPP) could efficiently deliver DTX to mitochondria. Western immunoblotting assay indicated that EPSLP/TD could efficiently deliver antitumor drug to mitochondria and induce cell apoptosis via mitochondria-mediated apoptosis pathway. In vivo antitumor study demonstrated EPSLP/TD owed excellent in vivo antitumor activity. Histological assay demonstrated EPSLP/TD showed strongly apoptosis inducing effect, anti-proliferation effect and anti-angiogenesis effect. This work investigated the potential of hierarchical targeting pH-sensitive liposomes is a suitable carrier to activate mitochondria-mediated apoptosis pathway for cancer therapy.
Cancer stem-like cells (CSLCs) have been considered to be one of the main problems in tumor treatment owing to high tumorigenicity and chemotherapy resistance. In this study, we synthesized a novel ...mitochondria-target derivate, triphentlphosphonium-resveratrol (TPP-Res), and simultaneously encapsulated it with doxorubicin (Dox) in pH-sensitive liposomes (PSL (Dox/TPP-Res)), to reverse chemotherapeutic resistance of CSLCs. PSL (Dox/TPP-Res) was approximately 165 nm in size with high encapsulation efficiency for both Dox and TPP-Res. Cytotoxicity assay showed that the optimal synergistic effect was the drug ratio of 1:1 for TPP-Res and Dox. Cellular uptake and intracellular trafficking assay indicated that PSL (Dox/TPP-Res) could release drugs in acidic endosomes, followed by mitochondrial targeting of TPP-Res and nucleus transports for Dox. The mechanisms for reversing the resistance in CSLCs were mainly attributed to a synergistic effect for reduction of mitochondrial membrane potential, activation of caspase cascade reaction, reduction of ATP level and suppression of the Wnt/β-catenin pathway. Further, in vivo assay results demonstrated that the constructed liposomes could efficiently accumulate in the tumor region and possess excellent antineoplastic activity in an orthotopic xenograft tumor model with no evident systemic toxicity. The above experimental results determined that PSL (Dox/TPP-Res) provides a new method for the treatment of heterogenecity tumors.
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