Polymeric Nanocarriers Delivering Anticancer Agents for the Treatment of Chemoresistant Prostate Cancer and Lung Metastatic Melanoma

The aims of this thesis is to first develop novel combination chemotherapies of two anticancer agents and their appropriate drug delivery platforms to treat chemoresistant prostate cancer, and second develop a polymeric conjugate of a biodegradable polymer and novel tubulin destabilizer to treat lung metastatic melanoma. In Chapter 1, a general introduction of polymeric nanocarriers including polymeric micelles and polymer drug conjugates for cancer therapy was given. In Chapter 2, we described a combination therapy of paclitaxel (PTX) polymer conjugate and cyclopamine (CYP) polymer conjugate, which had the potential to treat chemoresistant prostate cancer. We first synthesized mPEG-b-PCC-g-PTX-g-DC (P-PTX) and mPEG-b-PCC-g-CYP-g-DC (P-CYP) polymer-drug conjugates, which they self-assembled into micelles. The combination of P-PTX and P-CYP alleviated PTX resistance and suppressed tumor colony formation. Further, combination therapy inhibited Hedgehog (Hh) signaling and upregulated tumor suppressor miRNAs. We established orthotopic prostate tumor in nude mice and there was significant tumor growth inhibition in the group treated with the combination therapy of P-PTX and P-CYP compared with monotherapy. In Chapter 3, we designed a novel microtubule destabilizer QW-296 and combined it with a newly synthesized Hh signaling inhibitor MDB5 to treat taxane-resistant prostate cancer. The combination of QW-296 and MDB5 exhibited stronger anticancer activity towards chemoresistant prostate cancer cells than single drug treatment, and the results revealed that they synergistically worked together via distinct but complementary mechanisms. To improve the translation and promote therapeutic efficacy of the two novel anticancer agents, we synthesized an amphiphilic copolymer mPEG-p(TMC-MBC) that could self-assemble into polymeric micelles and encapsulate two hydrophobic drugs with high drug loading. We established a model of orthotopic prostate tumor in nude mice to evaluate in vivo efficacy of QW-296, MDB5 and their combination. The results confirmed that combination of QW-296 and MDB5 in micelles showed maximum inhibition of tumor growth compared with monotherapy or combination therapy in co-solvent. In Chapter 4, we introduced a new microtubule destabilizer SMART-OH and its polymer-drug conjugate, methoxy-poly (ethylene glycol)-block-poly (2-methyl-2-carboxyl-propylene carbonate-graft-SMART-graft-dodecanol) (abbreviated as P-SMART). Similar to its parent drug, P-SMART showed significant anticancer activity against melanoma cells in cytotoxicity, colony formation, and cell invasion studies. In addition, P-SMART treatment led to cell cycle arrest at G2/M phase and cell accumulation in sub-G1 phase. We established a model of metastatic melanoma to the lung in C57/BL6 albino mice to determine in vivo efficacy of P-SMART and SMART-OH at the dose of 20 mg/kg. P-SMART treatment resulted in significant inhibition of tumor growth and prolonged mouse median survival. In the end, Chapter 5 summarized the featured results of this thesis and gave some suggestions for future studies

Comparative Metabolomic Analysis of Rapeseeds from Three Countries

Rapeseed is an important oilseed with proper fatty acid composition and abundant bioactive components. Canada and China are the two major rapeseed-producing countries all over the world. Meanwhile, Canada and Mongolia are major importers of rapeseed due to the great demand for rapeseed in China. To investigate the metabolites in rapeseeds from three countries, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics was employed to analyze rapeseeds from China, Canada, and Mongolia. As results, 67, 53, and 68 metabolites showed significant differences between Chinese and Canadian, Chinese and Mongolian, and Canadian and Mongolian rapeseeds, respectively. Differential metabolites were mainly distributed in the metabolic pathways including phenylpropanoid biosynthesis, flavone and flavonol biosynthesis, and ubiquinone and other terpenoid-quinone biosynthesis. Among the differential metabolites, contents of sinapate and sinapine were higher in Chinese rapeseeds, while the contents of brassicasterol, stigmasterol, and campestanol were higher in Canadian rapeseeds. These findings might provide insight into the metabolic characteristics of rapeseeds from three countries to guide processing and consumption of the products of rapeseed

PURE: passive multi-person identification via footstep for mobile service networks

Recently, passive behavioral biometric (e.g., gesture or footstep) acquired from wireless networks or mobile services have become promising complements to conventional user identification methods (e.g., face or fingerprint) under special situations, yet existing sensing technologies require lengthy measurement traces and cannot identify multiple users at the same time. To this end, we propose PURE as a passive multi-person identification system leveraging deep learning enabled footstep separation and recognition. PURE passively identifies a user by identifying the unique “footprints” in its footstep. Different from existing gait-enabled recognition systems incurring a long sensing delay to acquire many footsteps, PURE can recognize a person by as few as only one step, substantially cutting the identification latency. To make PURE adaptive to walking pace variations, environmental dynamics, and even unseen targets, we apply an adversarial learning technique to improve its domain generalisability and identification accuracy. Finally, PURE is robust against replay attack, enabled by the richness of footstep and spatial awareness. We implement a PURE prototype using commodity hardware and evaluate it in typical indoor settings. Evaluation results demonstrate a cross-domain identification accuracy of over 90%.This work was supported in part by the National Natural Science Foundation of China under Grant 6220011218 and in part by Hubei Natural Science Foundation under Grant 2022CFB034

Genotypic distribution and phylogenetic characterization of Enterocytozoon bieneusi in diarrheic chickens and pigs in multiple cities, China: potential zoonotic transmission.

This study investigated diarrheic broiler and layer chickens (60 days; n=64) for E. bieneusi genotypes in northeast China and evaluated the potential roles of chickens and pigs in zoonotic transmission of microsporidiosis. Two 45-day-old layer chickens in city Jixi, Heilongjiang province and one 23-day-old broiler chicken in city Songyuan, Jilin province were identified to harbor a human-pathogenic E. bieneusi genotype Henan-IV and a new genotype named CC-1, respectively, by nested PCR and sequence analysis of the ribosomal internal transcribed spacer (ITS). Eleven of 64 (17.2%) duodenal mucosal specimens from pigs in city Tianjin, city Tongliao of Inner Mongolia, cities Jilin and Songyuan of Jilin province, and cities Daqing, Harbin, and Suihua of Heilongjiang province, were positive for E. bieneusi, with the infection rates of weaned pigs (35%, 7/20) significantly higher than preweaned ones (3.6%, 1/28; P<0.05). Nucleotide sequences of the ITS were obtained from 6 pig specimens, belonging to 3 known genotypes CHN7, EbpC, and Henan-IV. That the previous reports have described the occurrence of genotypes EbpC and Henan-IV in humans and EbpC in wastewater in central China and the clustering of genotypes CC-1 and CHN7 into a major phylogenetic group of E. bieneusi genotypes with zoonotic potential indicated that chickens and pigs could be potential sources of human micorsporidiosis. To our knowledge, this is the first report describing the existence of zoonotic E. bieneusi genotypes in diarrheic chickens

Parathyroid hormone administration improves bone marrow microenvironment and partially rescues haematopoietic defects in Bmi1-null mice.

The epigenetic regulator Bmi1 is key in haematopoietic stem cells, and its inactivation leads to defects in haematopoiesis. Parathyroid hormone (PTH), an important modulator of bone homeostasis, also regulates haematopoiesis, so we asked whether PTH administration improves bone marrow microenvironment and rescues the haematopoietic defects in Bmi1-null mice. The mice were treated with PTH1-34 (containing the first 34 residues of mature PTH), an anabolic drug currently used for treating osteoporosis, and compared with the vehicle-treated Bmi1-/- and wild-type littermates in terms of skeletal and haematopoietic phenotypes. We found that the administration significantly increased all parameters related to osteoblastic bone formation and significantly reduced the adipocyte number and PPARγ expression. The bone marrow cellularity, numbers of haematopoietic progenitors and stem cells in the femur, and numbers of lymphocytes and other white blood cells in the peripheral blood all increased significantly when compared to vehicle-treated Bmi1-/- mice. Moreover, the number of Jagged1-positive cells and percentage of Notch intracellular domain-positive bone marrow cells and protein expression levels of Jagged1 and NICD in bone tissue were also increased in Bmi1-/- mice upon PTH1-34 administration,whereas the up-regulation of PTH on both Notch1 and Jagged1 gene expression was blocked by the Notch inhibitor DAPT administration. These results thus indicate that PTH administration activates the notch pathway and partially rescues haematopoietic defects in Bmi1-null mice, further suggesting that haematopoietic defects in the animals are not only a result of reduced self-renewal of haematopoietic stem cells but also due to impaired bone marrow microenvironment

Collaborative design between architecture and structure of large complex ice shell based on air-ribbed inflatable mold: A case of ice restaurant

In 2019, the ice restaurant at the 21st Harbin Ice and Snow World is one of the representative works of contemporary Chinese ice shell architecture. Through the summary of practical experience of the ice restaurant. The design thinking and practice method of coordination between architecture and structure of large complex ice shell are elaborated in detail. The logic and advantages of air-ribbed inflatable mold construction method, numerical simulation optimization process based on Grasshopper platform and structural performance calculation of ABAQUS platform are included. The feasibility of collaborative design method in the design of ice shell building is proved. It promotes the development of ice shell construction. On the basis, the future development direction is prospected

Evaluation and comparison of in vitro antioxidant activities of unsaponifiable fraction of 11 kinds of edible vegetable oils

The radical scavenging capabilities of the extracts from eleven edible vegetable oils were investigated by using 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH ), 2,2′‐azino‐bis‐3‐ ethylbenzothiazoline‐6‐sulfonic acid (ABTS ), and ferric reducing ability of plasma (FRAP ) assays. The results indicated that rapeseed oil and sesame oil showed higher radical scavenging abilities than other vegetable oils. When the radical scavenging capabilities of the extracts from virgin camellia oils and commercially available refined camellia oils were evaluated by FRAP assay, the results showed that the antioxidant capabilities of the former were higher than the latter. Therefore, it is recommended that moderate refining processes should be taken to minimize the loss of antioxidant components and people consume virgin oils or less processed edible vegetable oils for higher antioxidant activities

Comparative advantages of chemical compositions of specific edible vegetable oils

As important supplementary to major edible oils, comparative chemical advantages of minor edible oils decide their development and usage. In this study, chemical composition of 13 kinds of specific edible vegetable oils were investigated. The comparative advantages of chemical compositions of these edible oils were obtained as follows: (1) camellia, tiger nut and almond oil were rich in oleic acid, the contents of which accounted for 79.43%, 69.16% and 66.26%, respectively; (2) safflower oil contained the highest content of linoleic acid (76.69%), followed by grape seed (66.85%) and walnut oil (57.30%); (3) perilla seed, siritch, peony seed and herbaceous peony seed oil were rich in α-linolenic acid (59.61%, 43.74%, 40.83% and 30.84%, respectively); (4) the total phytosterol contents of these oils ranged from 91.46 mg/100 ​g (camellia oil) to 506.46 mg/100 ​g (siritch oil); and (5) The best source of tocopherols was sacha inchi oil (122.74 mg/100 ​g), followed by perilla seed oil (55.89 mg/100 ​g), peony seed oil (53.73 mg/100 ​g) and herbaceous peony seed oil (47.17 mg/100 ​g). The comparative advantages of these specific edible oils indicated that they possess the high potential nutritional values and health care functions

Convolutional Neural Network Defect Detection Algorithm for Wire Bonding X-ray Images

To address the challenges of complex backgrounds, small defect sizes, and diverse defect types in defect detection of wire bonding X-ray images, this paper proposes a convolutional-neural-network-based defect detection method called YOLO-CSS. This method designs a novel feature extraction network that effectively captures semantic features from different gradient information. It utilizes a self-adaptive weighted multi-scale feature fusion module called SMA which adaptively weights the contribution of detection results based on different scales of feature maps. Simultaneously, skip connections are employed at the bottleneck of the network to ensure the integrity of feature information. Experimental results demonstrate that on the wire bonding X-ray defect image dataset, the proposed algorithm achieves mAP 0.5 and mAP 0.5–0.95 values of 97.3% and 72.1%, respectively, surpassing the YOLO series algorithms. It also exhibits certain advantages in terms of model size and detection speed, effectively balancing detection accuracy and speed

Ultrasonic-Assisted Extraction of Flavonoids from Juglans mandshurica Maxim.: Artificial Intelligence-Based Optimization, Kinetics Estimation, and Antioxidant Potential

Ultrasonic-assisted extraction (UAE) of flavonoids (JMBF) from Juglans mandshurica Maxim., an important industrial crop in China, was investigated in the present study. To improve the extraction efficiency of JMBF, suitable UAE was proposed after optimization using a hybrid response surface methodology&ndash;artificial neural network&ndash;genetic algorithm approach (RSM&ndash;ANN&ndash;GA). The maximum extraction yield (6.28 mg&middot;g&minus;1) of JMBF was achieved using the following optimum UAE conditions: ethanol concentration, 62%; solid&ndash;liquid ratio, 1:20 g&middot;mL&minus;1; ultrasonic power, 228 W; extraction temperature, 60 &deg;C; extraction time, 40 min; total number of extractions, 1. Through the investigation of extraction kinetics, UAE offered a higher saturated concentration (Cs) for JMBF in comparison to traditional solvent extraction (TSE). Scanning electron microscopy (SEM) images showed that deeper holes were generated in J. mandshurica powder under the action of ultrasound, indicating that ultrasound significantly changed the structure of the plant materials to facilitate the dissolution of active substances. Extracts obtained using UAE and TSE were compared by Fourier-transform infrared spectroscopy analysis, the results of which revealed that the functional group of bioactive compounds in the extract was unaffected by the ultrasonication process. Moreover, JMBF was further shown to exhibit significant antioxidant properties in vitro. This study provides a basis for the application of JMBF as a natural antioxidant