Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity

Photodynamic therapy (PDT) is a promising therapeutic modality which uses a photosensitizer to capture visible light resulting in phototoxicity in the irradiated region. PDT has been used in a number of pathological indications, including tumor. A key desirable feature of the photosensitizer is the high phototoxicity on tumor cells but not on normal cells. In this study, we conjugate a gonadotropin-releasing hormone (GnRH) to a photosensitizer, Zinc phthalocyanine (ZnPc), in order to enhance its specificity to breast cancer, which over-expresses GnRH receptor. ZnPc has unique advantages over other photosensitizers, but is difficult to derivatize and purify as a single isomer. We previously developed a straight-forward way to synthesize mono-substituted β-carboxy-phthalocyanine zinc (ZnPc-COOH). Photophysical and photochemical parameters of this ZnPc-GnRH conjugate including fluorescence quantum yield (Фf), fluorescence decay time (τs) and singlet oxygen quantum yield (ФΔ) were evaluated and found comparable with that of ZnPc, indicating that addition of a GnRH peptide does not significantly alter the generation of singlet oxygen from ZnPc. Cellular uptakes and phototoxicities of this conjugate were tested and found significantly enhanced on human breast cancer cell lines overexpressing GnRH receptors (MDA-MB-231 and MCF-7 cells) compared to cells with low levels of GnRH receptors, such as human embryonic lung fibroblast (HELF) and human liver carcinoma (HepG2) cells. In addition, the cellular uptake of this conjugate toward MCF-7 cells were found clearly alleviated by a GnRH receptor blocker Cetrorelix, suggesting that the cellular uptake of this conjugate was GnRH receptor-mediated. Put together, these findings revealed that coupling ZnPc with GnRH analogue was an effective way to improve the selectivity of ZnPc towards tumors with over-expressed GnRH receptors

Gujin Dan is a Chinese medicine formulation that stimulates cell proliferation and differentiation by controlling multiple genes involved in MC3T3-E1 cells

Background: With the development of Traditional Chinese medicine (TCM) in recent years, the use of TCM in the treatment of osteoporosis has received much attention and research. Gujin Dan (GJD) is one of the representative Chinese medicine formulations that work synergistically with 19 herbs and has been used for decades to treat cervical spondylosis, lumbar disc herniation, osteoarthritis and osteoporosis. However, the exact molecular mechanism by which GJD is used to strengthen bones in the treatment of osteoporosis remains largely unknown. / Methods: In this study, an aqueous extract of GJD was prepared and its components were identified by high-performance liquid chromatography (HPLC). The effect of GJD aqueous extract on MC3T3-E1 cells was determined by Cell Counting Kit-8 (CCK-8) assay, alkaline phosphatase (ALP), and alizarin red S staining (ARS), combined with RNA sequencing (RNA-seq) and qRT-PCR. / Results: Our study showed that GJD significantly promoted the proliferation of MC3T3-E1 cells, as well as the synthesis and mineralisation of the extracellular matrix. GJD significantly increased the expression levels of genes that promote cell proliferation such as Adamts1, Mcam, Cyr61, Fos, Cebpd, Fosl2, Sirt1, Nipbl, Sema3c and Kcnq1ot1, up-regulated genes that inhibit apoptosis such as Gadd45a, Birc3, up-regulated genes that inhibit osteoclastogenesis such as Bcl6, Nfkbiz, Clcf1, Bcl3, Lgals3, Wisp1, Dusp1 and Fblim1, up-regulated genes that promote MC3T3-E1 cell differentiation such as Junb, Egr1, Klf10, Atf6, Malat1, Btg2, Sertad4, Zfyve16, Tet2, Creb5, Snai2, Fam46a, Calcrl and Pdzrn3. In addition, GJD mildly upregulated the expression levels of gene markers such as Atf4, Fn1, Usp7, Sox4, Col16a1, Spp1, Bmp1, Runx2, Bglap, Col12a1, and Alpl in osteoblasts. / Conclusions: Our results show that GJD promotes the differentiation and proliferation of MC3T3-E1 cells, inhibits osteoclast formation, and prevents osteoblast apoptosis. The present study significantly improves the current understanding of the molecular effects of GJD on MC3T3-E1 cells. This study also provides a new strategy for the further use of Chinese medicinal preparations against bone metabolism-related diseases

YOLOv4-Tiny-Based Coal Gangue Image Recognition and FPGA Implementation

Nowadays, most of the deep learning coal gangue identification methods need to be performed on high-performance CPU or GPU hardware devices, which are inconvenient to use in complex underground coal mine environments due to their high power consumption, huge size, and significant heat generation. Aiming to resolve these problems, this paper proposes a coal gangue identification method based on YOLOv4-tiny and deploys it on the low-power hardware platform FPGA. First, the YOLOv4-tiny model is well trained on the computer platform, and the computation of the model is reduced through the 16-bit fixed-point quantization and the integration of a BN layer and convolution layer. Second, convolution and pooling IP kernels are designed on the FPGA platform to accelerate the computation of convolution and pooling, in which three optimization methods, including input and output channel parallelism, pipeline, and ping-pong operation, are used. Finally, the FPGA hardware system design of the whole algorithm is completed. The experimental results of the self-made coal gangue data set indicate that the precision of the algorithm proposed in this paper for coal gangue recognition on the FPGA platform are slightly lower than those of CPU and GPU, and the mAP value is 96.56%; the recognition speed of each image is 0.376 s, which is between those of CPU and GPU; the hardware power consumption of the FPGA platform is only 2.86 W; and the energy efficiency ratio is 10.42 and 3.47 times that of CPU and GPU, respectively

Hierarchical Porous Carbon Derived from Sichuan Pepper for High-Performance Symmetric Supercapacitor with Decent Rate Capability and Cycling Stability

Hierarchical micro-mesoporous carbon (denoted as HPC-2 in this study) was synthesized by pre-carbonization of biomass Sichuan pepper followed by KOH activation. It possessed well-developed porosity with the specific surface area of 1823.1 m2 g−1 and pore volume of 0.906 cm3 g−1, and exhibited impressive supercapacitive behaviors. For example, the largest specific capacitance of HPC-2 was tested to be ca. 171 F g−1 in a three-electrode setup with outstanding rate capability and stable electrochemical property, whose capacitance retention was near 100% after cycling at rather a high current density of 40 A g−1 for up to 10,000 cycles. Furthermore, a two-electrode symmetric supercapacitor cell of HPC-2//HPC-2 was constructed, which delivered the maximum specific capacitance and energy density of ca. 30 F g−1 and 4.2 Wh kg−1, respectively, had prominent rate performance and cycling stability with negligible capacitance decay after repetitive charge/discharge at a high current density of 10 A g−1 for over 10,000 cycles. Such electrochemical properties of HPC-2 in both three- and two-electrode systems are superior or comparable to those of a great number of porous biomass carbon reported previously, hence making it a promising candidate for the development of high-performance energy storage devices

Permeability Experiment of Fractured Rock with Rough Surfaces under Different Stress Conditions

To investigate the permeability changes and the mechanisms of fractured rock under dynamic and static stresses produced by earthquakes, permeability experiments on fractured rock with rough surfaces under axial dynamic and static stresses were conducted on the MTS815 Rock Mechanics Testing System. Surface asperity was investigated by scanning the specimen surfaces before and after testing. The results show that the roughness of fracture surface has a great influence on the permeability when the axial displacement is not enough to cause the fracture rock to slip. Moreover, the rougher fracture surface leads to severer surface damage as indicated by the more gouge productions. The accumulation of gouge materials on larger roughness fracture surfaces causes a slow drop in permeability. The fracture surfaces experience larger degradations, but it has small weights of gouge materials on fracture surface after testing under axial dynamic stress. The reason is that the gouge material transport and mobilization tend to occur in process of dynamic loading. Therefore, the permeability drops of axial dynamic stress are larger than those of axial static stress

Permeability Evolution of Fractured Rock Subjected to Cyclic Axial Load Conditions

Permeability experiments on saw-cut fractured rock subjected to cyclic axial load conditions were conducted on the MTS815 rock mechanics testing system. The influence of the frequency and amplitude of cyclic axial forces on axial displacement and permeability evolution of fractured rock was experimentally investigated. Results show that the increasing frequency under the same amplitude of axial load leads to a reduction in axial displacement, but a drop followed by an increase in permeability, while the permeability values oscillated sharply under high amplitude of cyclic loads, which can be attributed to the production of gouge materials. Besides, the increase in axial displacement roughly contributed to the permeability reduction, and excessive amplitude of cyclic load posed limited boost to the permeability enhancement. By comparing with the quasistatic function, we found that it did not completely correspond to the trend of the permeability evolution subjected to cyclic axial forces, and sensitivity coefficients evolving with frequency and amplitude should be considered. A new function of the permeability evolution subjected to the amplitude and frequency of cyclic axial forces was derived and verified by the experimental data. This study suggests that small amplitude and high frequency of dynamic forces have the potential for enhancing the permeability of fracture and triggering the disaster of fractured rock

Experimental investigation and theoretical analysis of indentations on cuboid hard rock using a conical pick under uniaxial lateral stress

Abstract: Stress conditions are critical in deep hard rock mining and significantly influence hard rock cuttability. The peak cutting force (PCF), cutting work (CW), and specific energy (SE) can reflect rock cuttability and determine the feasibility and saving of mechanized mining to some extent. In this paper, the influence of uniaxial lateral stress on rock cuttability was investigated by an indentation experiment on cuboid rock using a conical pick, and a theoretical model was proposed to analyze the PCF and associated factors. The PCF, CW, and SE were used as indices to measure hard rock cuttability. The regression analyses show that rock cuttability presents as decreasing followed by increasing as uniaxial lateral stresses increases. The theoretical model was established by simplifying rock fragments into three-dimensional ellipse cones, and a formula was derived based on the elastic fracture mechanics theory. The error between the calculated and experimental values is 3.8%, which confirms the accuracy of the prediction formula. Finally, rock fragmentation by using conical picks was successfully applied on the field mining stope by inducing high geostresses to promote adjustments in stress and improve ore-rock cuttability. Highlights: (1)The influences of uniaxial lateral stress on rock cuttability have been investigated.(2)The peak cutting force, cutting work and specific energy can reflect the rock cuttability.(3)A new theoretical model has been proposed to analyze the peak cutting force.(4)The rock fragmentation using conical picks was successfully applied in deep hard rock mining. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG

Dipole field in nitrogen-enriched carbon nitride with external forces to boost the artificial photosynthesis of hydrogen peroxide

Abstract Artificial photosynthesis is a promising strategy for efficient hydrogen peroxide production, but the poor directional charge transfer from bulk to active sites restricts the overall photocatalytic efficiency. To address this, a new process of dipole field-driven spontaneous polarization in nitrogen-rich triazole-based carbon nitride (C3N5) to harness photogenerated charge kinetics for hydrogen peroxide production is constructed. Here, C3N5 achieves a hydrogen peroxide photosynthesis rate of 3809.5 µmol g−1 h−1 and a 2e− transfer selectivity of 92% under simulated sunlight and ultrasonic forces. This high performance is attributed to the introduction of rich nitrogen active sites of the triazole ring in C3N5, which brings a dipole field. This dipole field induces a spontaneous polarization field to accelerate a rapid directional electron transfer process to nitrogen active sites and therefore induces Pauling-type adsorption of oxygen through an indirect 2e− transfer pathway to form hydrogen peroxide. This innovative concept using a dipole field to harness the migration and transport of photogenerated carriers provides a new route to improve photosynthesis efficiency via structural engineering

Phototoxicity (□) (at a light dosage of 1.5 Jcm⁻²) and dark toxicity (▪) of ZnPc-GnRH conjugate at various concentrations after 12 hr incubation with MDA-MB-231 (a), MCF-7 (b), HELF (c), and HepG2 (d).

<p>Values represent the mean of four independent experiments; bars represent standard error of the mean (SEM).</p