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The compound 7-ethyl-10-hydroxy-camptothecin (SN38) is a broad-spectrum antitumor agent whose applications are greatly limited by its poor solubility. Therefore, irinotecan, the hydrophilic derived prodrug of SN38, has been developed as the commercial formulation Campto® for colorectal cancer. However, only 1% to 0.1% of irinotecan is converted to active SN38 in vivo, thus leading to unsatisfactory antitumor activity in clinical settings. Herein, we report a smart stimuli-responsive SN38 prodrug nanoassembly for efficient cancer therapy. First, SN38 was conjugated with an endogenous lipid, cholesterol (CST), via a redox dual-responsive disulfide bond (namely SN38-SS-CST). The prodrug self-assembled into uniform prodrug nanoassemblies with good colloidal stability and ultrahigh drug loading. SN38-SS-CST NPs released sufficient SN38 in the redox environments of tumor cells but remained intact in normal tissues. Finally, SN38-SS-CST NPs potently inhibited the growth of colon cancer without causing systemic toxicity, thus indicating their promise as a translational chemotherapeutic nanomedicine.

The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely “platesomes”, which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.

Wastewater treatment plants (WWTPs) are large-scale and nonlinear processes with tightly integrated operating units. The application of online optimization-based control strategies, such as model predictive control (MPC), to WWTPs generally faces high computational complexity. This paper proposes an event-triggered approach to address this issue. The model predictive controller updates information and solves the optimization problem only when the corresponding triggered logic is satisfied. The triggered logic sets the maximum allowable deviation for the tracking variables. Moreover, to ensure system performance, the design of the event-triggered logic incorporates the effluent quality. By obtaining the optimal sequence for the effluent quality within the receding horizon of the MPC, the cumulative deviation between the predicted and desired effluent quality is analyzed to evaluate the performance within that horizon. Based on these two conditions, the need for adjusting control actions is determined. Even if the maximum allowable range for the tracking variables in the triggered logic design is set unreasonably, the consideration of effluent quality factors in the triggered conditions ensures good performance. Simulation results demonstrate an average reduction in computational effort of 25.49% under different weather conditions while simultaneously ensuring minimal impact on the effluent quality and total cost index and compliance with effluent discharge regulations. Furthermore, this method can be combined with other approaches to guarantee effluent quality while further reducing computation time and complexity.

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

Indolizine derivatives have been reported for the treatment of numerous diseases. However, few studies were carried out for non-small cell lung cancer (NSCLC). We synthesized series of indolizine compounds. The results of MTT assay showed compound 8 (C8) markedly inhibited the proliferation of A549 cells, however, C8 (15, 30 μg/mL) had little cytotoxicity in other cell lines (SH-SY5Y, HepG2, and BEAS-2B cells), Hoechst staining and JC-1 staining showed that C8 induced changes in the nucleus morphology, increased the loss in mitochondrial membrane potential in A549 cells. The results of flow cytometry manifested that cell cycle of the cells was arrested in the G2 / M phase by C8, ROS levels and the proportion of apoptosis of cells increased. We performed western blotting analysis to detect the expression levels of apoptosis and cycle-related proteins. These results validated that the apoptosis of cells was triggered by endoplasmic reticulum stress (ERS) and the PI3K/Akt-mediated mitochondrial pathway collaboratively. Besides, the utilization of PI3K/Akt inhibitors and p53 inhibitors further proves the above argument and C8-induced cycle arrest of A549 cells is majorly regulated by p53. C8 induced the accumulation of ROS contents involved in mitochondrial damage. The proliferation of A549 cells was inhibited after treatment with the compound, which induced apoptosis and cycle arrest of cells. It is suggested that C8(dithiolation indolizine) is a potential candidate compound against non-small cell lung cancer.

Indolizine derivatives are a class of compounds with excellent biological activity. In this study, a series of indolizine derivatives, compound 1 (C1), compound 2 (C2), compound 3 (C3), and compound 4 (C4), were synthesized. 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) assay was used to evaluate their cytotoxicity against HepG2 (p53-wild), A549, and HeLa cell lines. HepG2 cells apoptosis induced by C3 was determined using Hoechst staining and acridine orange/ethidium bromide staining. Cells’ apoptotic ratio was measured by Annexin V–FITC/PI double staining. Changes in mitochondrial membrane potential and intracellular reactive oxygen species (ROS) in HepG2 cells after C3 treatment were determined. Immunofluorescence staining and Western blot analysis were carried out to detect p53 levels and analyze the apoptosis-associated proteins, respectively. Moreover, the cytotoxic activity of C3 was examined in two other hepatocellular carcinoma (HCC) cell lines with different p53 status including Huh-7 cells (p53-mutant) and Hep3B cells (p53-null). The results indicated that C3 showed stronger inhibition towards HepG2 cells than other cell lines. Fluorescent staining and flow cytometry analysis confirmed that C3 induced apoptosis of HepG2 cells. C3 could also increase intracellular ROS and cause a decrease in the mitochondrial membrane potential. C3 promoted p53 activation and increased p53 accumulation in nuclei. The expression of p53 and Bax was increased with the down-regulation of Bcl-2, which promoted the release of cytochrome c and caspase-3 activation. Collectively, the study demonstrated that C3 caused HepG2 cell apoptosis via the mitochondria p53 pathway. These results inspired us to further develop indolizine derivatives as potential potent inhibitors against liver cancer.

Split hydrogen direct injection (SHDI) has been proved capable of better efficiency and fewer emissions. Therefore, to investigate SHDI deeply, a numerical study on the effect of second injection timing was presented at a gasoline/hydrogen spark ignition (SI) engine with SHDI. With an excess air ratio of 1.5, five different second injection timings achieved five kinds of hydrogen mixture distribution (HMD), which was the main factor affecting the engine performances. With SHDI, since the HMD is manageable, the engine can achieve better efficiency and fewer emissions. When the second injection timing was 105° crank angle (CA) before top dead center (BTDC), the Pmax was the highest and the position of the Pmax was the earliest. Compared with the single hydrogen direct injection (HDI), the NOX, CO and HC emissions with SHDI were reduced by 20%, 40% and 72% respectively.

This study contributes to a method based on an aqueous solution of ammonia direct injection for NOx emissions control from internal combustion engines. Many previously published studies about deNOx technology are based on selective catalytic reduction (SCR), but only few deal with inner selective non-catalytic reduction (inner SNCR) technology, which is an intensive improvement of selective non-catalytic reduction (SNCR) applied in the in-cylinder purification procedure. Before numerical calculations were carried out, the computational fluid dynamic (CFD) simulation model was validated with steady-state experimental results. The main results revealed that with the increasing concentration of aqueous solution of ammonia, nitrogen oxides gradually decrease, and the largest decline of NOx is 65.1% with little loss of cylinder peak pressure. Unburned hydrocarbon (UHC) and carbon monoxide (CO) may increase using inner SNCR, and soot emissions show a decreased tendency. However, there is little change when ammonia content varies. Ulteriorly, refining the direct injection phase is of great help to inner SNCR technology to enhance the reduction of NOx and reduce NH3 oxidation and NH3 slipping.

American contemporary writer John Irving is one of the few famous for his unique artistic skills. He appreciates traditional novels and criticizes modern novels, and all of them embody metafiction skills in his creation. Through detailed analyses of his several representative works, the writer of this essay explores John Irving's perception of novel writing and elaborates his own writing practice including his repetitive narration of the same image. With the help of contemporary trauma theory, this paper also analyzes the recurring image of "Broken Arm" in his novels to restore the symptoms of the narrator's post-traumatic behavior so as to explore John Irving's outstanding artistic talent in narrative skills and characterization. [ABSTRACT FROM AUTHOR]

High-performance automated detection methods for epilepsy play a crucial role in clinical diagnostic support. To address the challenge of effectively extracting features from epileptic EEG signals, characterized by strong spontaneity and complexity, a novel feature extraction approach based on Window Kullback-Leibler Divergence (WKLD) is proposed, coupled with discrete wavelet analysis for EEG signal feature extraction. Then, a Residual Multidimensional Taylor Network (ResMTN) classifier is applied for epilepsy state classification. Experimental results demonstrate an accuracy of 98% in classifying EEG signals during seizure and interictal periods, with both specificity and sensitivity reaching 98.18%, outperforming existing widely-used feature extraction and classification methods.

Thermally activated delayed fluorescence (TADF) materials with high photoluminescence quantum yields and fast reverse intersystem crossing (RISC) capabilities are highly desirable for applications in high-efficiency organic light-emitting diodes. Herein, we report the synthesis as well as structural and photophysical properties of 5,9-diselena-13b-boranaphtho[3,2,1-de]anthracene (SeBSe) as a narrowband-emissive TADF material. The incorporation of two selenium atoms into the boron-fused pentacyclic π-core results in a small singlet–triplet energy gap (ΔEST) and thereby significant TADF properties. Moreover, theoretical calculations revealed a noticeable spin-orbit coupling enhancement between the singlet and triplet manifolds in SeBSe by virtue of the heavy-atom effect of selenium atoms. Consequently, SeBSe allows ultrafast spin-flip RISC with the rate constant surpassing 108 s−1, which far exceeds the corresponding fluorescence radiative decay rate (∼106 s−1), enabling an ideal singlet–triplet superimposed excited state.

Abstract Carbazole‐triazine dendrimers with a bulky terminal substituent were synthesized, and the thermally activated delayed fluorescence (TADF) property was investigated. Compared to unsubstituted carbazole dendrimers, dendrimers with bulky terminal substituents showed comparable to better photoluminescence quantum yields (PLQY) in neat films. Phenylfluorene (PF)‐substituted dendrimers showed the highest PLQY of 81%, a small ΔEst of 0.06 eV, and the fastest reverse intersystem crossing (RISC) rate of ∼1 × 105 s−1 compared to other dendrimers. Phosphorescence measurements of dendrimers and dendrons (fragments) indicate that the close proximity of the triplet energy of phenylfluorene‐substituted carbazole dendrons (3LE) to that of phenylfluorene‐substituted dendrimers (1CT, 3CT) contributes to RISC promotion and improves TADF efficiency. Terminal modification fine‐tunes the energy level and suppresses intermolecular interactions, and this study provides a guideline for designing efficient solution‐processable and non‐doped TADF materials.

Ground penetrating radar (GPR), as a non-destructive and rapid detection instrument, has been widely used for underground pipeline detection. However, as the interpretation of 3-dimensional GPR images is still manually performed, the process is inefficient. Aiming at solving the challenges of automatic recognition for underground pipelines, we propose a recognition method based on a deep learning algorithm, which uses 3-dimensional GPR images and the improved 3D depth-wise separable convolution block. In order to expand the number of samples in the dataset, we propose a data augmentation method based on three-dimensional matrix rotation and use a wavelet-based denoising method to filter out the direct wave interference. To prove the effectiveness and efficiency of our method, we compared the classification performance of the improved 3D depth-wise separable convolutional block with the traditional 3D convolutional block and the ordinary 3D depth-wise separable convolutional block under the same conditions. According to the experiment’s results, the number of parameters of the method we proposed is 66.9% less than that of the traditional 3D convolution method, while the classification performance is similar. Furthermore, compared with ordinary 3D depth-wise separable convolution, our method can significantly improve the classification and recognition ability of the neural network, while the number of calculations and the number of parameters remain almost the same. This study demonstrates the effectiveness of 3D-CNN in the field of GPR image interpretation. An improved 3D depth-wise separable convolutional block is also proposed. It greatly reduces the amount of calculation and parameters while ensuring classification performance. It is better than the existing algorithms in performance. At the same time, to obtain the position and direction of the pipeline, in this study, a conic fitting method using the Canny operator is proposed to locate the vertices of B-Scan images and record their horizontal and vertical coordinates. This method can estimate the direction of the pipeline and it lays the foundation for future work such as measuring the pipeline depth.

Exosomes, a subset of small extracellular vesicles, carry various nucleic acids, proteins, lipids, amino acids and metabolites. They function as a mode of intercellular communication and molecular transfer. Exosome cargo molecules, including small non-coding RNAs (sncRNAs), are involved in the immune response in various organisms. However, the role of exosome-derived sncRNAs in immune responses in molluscs remains unclear. Here, we aimed to reveal the sncRNAs involved in the immune response during grafting transplantation by the pearl oyster Pinctada fucata. Exosomes were successfully extracted from the P. fucata haemolymph during graft transplantation. Abundant microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) were simultaneously discovered in P. fucata exosomes by small RNA sequencing. The expression patterns of the miRNAs and piRNAs at the grafting and initial stages were not substantially different, but varied significantly between the initial and later stages. Target prediction and functional analysis indicate that these miRNAs and piRNAs are related to immune response upon grafting transplantation, whereas piRNAs may also be associated with transposon silencing by targeting with genome transposon elements. This work provides the basis for a functional understanding of exosome-derived sncRNAs and helps to gain further insight into the PIWI/piRNA pathway function outside of germline cells in molluscs.

Psoriasis is reported to be a common chronic immune-mediated skin disease characterized by abnormal keratinocytes and cell proliferation. Perilla leaves are rich in essential oils, fatty acids, and flavonoids, which are recognized for their antioxidant and anti-inflammatory effects. In this study, the alleviating effect of essential oil (PO) extracted from Perilla frutescens stems and leaves on imiquimod (IMQ) -induced psoriasis-like lesions in BALB/c mice were investigated. Results showed that PO ameliorated psoriasis-like lesions in vivo, reduced the expression of lymphocyte antigen 6 complex locus G6D (Ly-6G), which is a marker of neutrophil activation, and inhibited the expression of inflammatory factors interleukin 1 (IL-1), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). In addition, PO significantly decreased the expression of cytokines such as IL-6, IL-1, interleukin 23 (IL-23), interleukin 17 (IL-17), and nuclear factor kappa-B (NF-κB). Furthermore, the down-regulation of mRNA levels of psoriasis-related pro-inflammatory cytokines, such as IL-17, interleukin 22 (IL-22), IL-23, interferon-α (IFN-α), and Interferon-γ (IFN-γ) was observed with the treatment of PO. All results show a concentration dependence of PO, with low concentrations showing the best results. These results suggest that PO effectively alleviated psoriasis-like skin lesions and down-regulated inflammatory responses, which indicates that PO could potentially be used for further studies on inflammation-related skin diseases such as psoriasis and for the treatment of psoriasis such as psoriasis natural plant essential oil resources.

We demonstrate a discretely tunable multiwavelength visible laser through second harmonic generation (SHG) and sum frequency generation (SFG) of multiorder Stokes lasers generated from an external Raman laser oscillator. The Raman laser oscillator, driven by a 1064 nm laser with an energy of 120 mJ, is based on a cascade of Ba(NO3)2 and two axial orthogonal KGd(WO4)2 crystals. Through adjusting the angle of the SHG/SFG crystal, we obtain 16 visible wavelengths with a wide range from 579.5–658.4 nm. In addition, we investigate the output energy and conversion efficiency of the resulting laser with various phase-matching angles. We show that the maximum energy of the visible laser is 8.87 mJ with five wavelengths, and the corresponding total conversion efficiency is 7.4%. These experimental results demonstrate a practical and effective method of generating a discretely tunable multiwavelength visible laser.

Plasmon-enhanced photothermal and optomechanical effects on deforming and reshaping a gold nanoparticle (NP) are studied theoretically. A previous paper (Wang and Ding, ACS Nano 13, 32–37, 2019) has shown that a spherical gold nanoparticle (NP) irradiated by a tightly focused laser beam can be deformed into an elongated nanorod (NR) and even chopped in half (a dimer). The mechanism is supposed to be caused by photothermal heating for softening NP associated with optical traction for follow-up deformation. In this paper, our study focuses on deformation induced by Maxwell’s stress provided by a linearly polarized Gaussian beam upon the surface of a thermal-softened NP/NR. We use an elastic model to numerically calculate deformation according to optical traction and a viscoelastic model to theoretically estimate the following creep (elongation) as temperature nears the melting point. Our results indicate that a stretching traction at the two ends of the NP/NR causes elongation and a pinching traction at the middle causes a dent. Hence, a bigger NP can be elongated and then cut into two pieces (a dimer) at the dent due to the optomechanical effect. As the continuous heating process induces premelting of NPs, a quasi-liquid layer is formed first and then an outer liquid layer is induced due to reduction of surface energy, which was predicted by previous works of molecular dynamics simulation. Subsequently, we use the Young–Laplace model to investigate the surface tension effect on the following deformation. This study may provide an insight into utilizing the photothermal effect associated with optomechanical manipulation to tailor gold nanostructures.

The products quality and welfare of animals are closely related to the environment parameters in livestock buildings. A monitoring and control method of environment parameters in livestock buildings based on wireless sensor network is proposed in this paper. Temperature, humidity, light, carbon dioxide concentration, ammonia concentration, and hydrogen sulfide concentration can be monitored in real time by this method. The above six parameters will be adjusted and controlled through WLS algorithm and the minimizing deviation criteria. Compared with the traditional method, the high labor cost will be saved and energy consumption will be decreased. The experimental results show that this method can in real time monitor, effectively adjust, and control the environmental parameters in livestock buildings.