Nanozyme-Based Pump-free Microfluidic Chip for Colorectal Cancer Diagnosis via Circulating Cancer Stem Cell Detection.

Circulating cancer stem cells (CCSCs) are subpopulations of cancer cells with high tumorigenicity, chemoresistance, and metastatic potential, which are also major drivers of disease progression. Herein, to achieve the prediction of tumor diagnosis and progression in colorectal cancer (CRC), a new, automated, and portable lateral displacement patterned pump-free (LP) microfluidic chip (LP-chip) with the CoPt3 nanozyme was established for CCSC capture and detection in peripheral blood and feces samples ex vivo. In this design, CoPt3@HA probes with functions of magnetic separation and colorimetric signal transduction by peroxidase-mimicking activity were applied for the capture of CCSCs and signal output in clinical samples. The generated colors of polydopamine (PDA) were quantifiable through the smartphone APP and visualizable by the naked eye in the test line (T line) and control line (C line) of the LP-chip. In the optimal experimental conditions, the CCSC concentration was sensitive to change in the range 0-105 cells mL-1, with a detection limit of 3 cells mL-1 (S/N = 3). Preliminary studies of clinical samples suggest that the platform has the potential for prediction of colorectal cancer progression and poor prognosis. Overall, the LP-chip provides potential strategies for timely diagnosis, therapeutic monitoring, and recurrence prediction to improve home-based patient care.

Does bilateral Wilms' tumor involving the collecting system in children have a worse prognosis?

BACKGROUND: The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms' tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. METHODS: Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. RESULTS: Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). CONCLUSIONS: To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Cascaded nanozyme-based high-throughput microfluidic device integrating with glucometer and smartphone for point-of-care pheochromocytoma diagnosis.

The development of point-of-care (POC) diagnostics devices for circulating tumor cells (CTCs) detection plays an important role in the early diagnosis of pheochromocytoma (PCC), especially in a low-resource setting. To further realize the rapid, portable, and high-throughput detection of CTCs, an Au@CuMOF cascade enzyme-based microfluidic device for instant point-of-care detection of CTCs was constructed by combining a smartphone application and a commercial portable glucose meter (PGM). In this microfluidic system, DOTA and norepinephrine (NE) modified Au@CuMOF signal probes and Fe3O4@SiO2 capture probes were used for the dual recognition and capture of rare PCC-CTCs. Then, the targeted binding of the Au@CuMOF cascade nanozymes to the CTCs endowed the cellular complexes with multienzyme mimetic activities (i.e., glucose oxidase-like and peroxidase-like activity) to catalyze glucose reduction as signal output for colorimetric and personal glucose meter (PGM) dual-mode detection of CTCs. The developed method has a linear range of 4 to 105 cells mL-1 and a detection limit of 3 cells mL-1. This method allows the simultaneous detection of six samples and demonstrates good applicability for CTCs detection in whole blood samples. More importantly, the combination of PGM, smartphone app and array microfluidic chips enables the rapid, portable, and high-throughput diagnoses of PCC, and providing provide a convenient and reliable alternative to traditional liquid biopsy diagnosis of various cancers.

Carbon dot-based fluorescent probe for early diagnosis of pheochromocytoma through identification of circulating tumor cells.

Pheochromocytoma (PCC), as a rare neuroendocrine tumor, is often missed or misdiagnosed because of its atypical clinical manifestations. To realize the early accurate diagnosis of PCC, we have selected circulating tumor cells (CTCs) with more complete biological information as biomarkers and developed a simple and novel fluorescence cytosensor. Octreotide-2,2',2'',2'''- (1,4,7,10 -tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) modified magnetic Fe3O4 and signal amplification CDs@SiO2 nanospheres are prepared to capture and detect PCC-CTCs from peripheral blood via binding to the somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. During the detection process, the target cells were separated and enriched by magnetic capture probes (Fe3O4-DOTA), and then signal probes (CDs@SiO2-DOTA) could also specifically bound to target cells to form the sandwich-like structure for fluorescence signal output. The proposed fluorescence cytosensor has revealed good sensitivity and selectivity for quantitative analysis of PCC-CTCs in the concentration of 5-1000 cells mL-1 with a LOD of 2 cells mL-1. More importantly, designed fluorescence cytosensor has shown good reliability and stability in complex serum samples. This strategy provides a new way for detection of PCC-CTCs.

Treatment of bilateral Wilms' tumor in children: how to improve the application of nephron-sparing surgery.

PURPOSE: To summarize the experience of nephron-sparing surgery (NSS) for bilateral Wilms tumors (BWT) in children. METHODS: This study included children with BWT admitted to our hospital between January 2008 and June 2022. The details of the treatments and outcomes were analyzed. RESULTS: In all, 70 patients (39 males and 31 females) were enrolled, including 66 patients with synchronous tumors and 4 patients with metachronous tumors. The median age at diagnosis was 13 (3-75) months. Overall, 59 patients received preoperative chemotherapy and 45.8% (54/118) of the 118 sides of WT achieved a partial response (PR). Of the 70 patients, 48 (68.6%) underwent bilateral NSS and 22 (31.4%) underwent unilateral NSS and contralateral total nephrectomy. The proportion of bilateral NSS in the preoperative chemotherapy group was significantly higher than in the non-chemotherapy group (P = 0.031). Additionally, there were 26, 25, 14, and 5 cases of stage I, stage II, stage III, and stage IV, respectively. Among the 70 children, 16 had a recurrence, and 8 died. The 4 years EFS and OS were 67.9% and 89.3%, respectively. CONCLUSIONS: The long-term survival rates of patients with BWT improved. Hence, preoperative chemotherapy should be administered to enhance the use of NSS in BWT.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

Knowledge, attitude and application towards fast track surgery among operating room paramedics: a cross-sectional study.

BACKGROUND: Fast track surgery has shown its effectiveness to accelerate recovery and gained acceptance in many operations. However, data for paramedics using fast track surgery are limited in China. The aims of our study are to evaluate the knowledge, attitude and application status of fast track surgery in paramedics and to provide suggestions for the better application of fast track surgery. METHODS: Two Hundred Ninety-one operating room paramedics were investigated by simple random sampling from October 20 to December 20, 2019 time. A self-reported questionnaire was used to collect data with five dimensions: demographic data, cognitive level, knowledge, attitude and application of fast track surgery. Data were analyzed using qualitative and quantitative methods. RESULTS: 19.93% of participants never heard fast track surgery and only 3.32% of participants were very familiar with it. Gender (0.702, 95% CI 0.109-1.294), technical title (0.342, 95% CI 0.126-0.558) and awareness of the concept of fast track surgery (0.471, 95% CI 0.165-0.776) had a correlation with the knowledge level of paramedics towards fast track surgery. In terms of attitude towards fast track surgery, gender (- 1.944, 95% CI -3.830- -0.058), age (0.303, 95% CI 0.021-0.585) and knowledge score of fast track surgery (0.426, 95% CI 0.014-0.838) are related. Half of the paramedics believe the most difficult problem in the application of fast track surgery was the lack of multi-team communication and cooperation. CONCLUSION: The knowledge of fast track surgery among paramedics in Wuhan is poor, and some paramedics have a negative attitude towards it. As the attitude is positively correlated with the knowledge, it is necessary to improve the knowledge level of fast track surgery among paramedics in Wuhan.

A multicenter study on surgical procedure selection and risk factor analysis of postoperative complications after TIP and Duckett hypospadias repair.

BACKGROUND: Hypospadias is a common congenital malformation in pediatric urology with surgery being the only curative treatment. Although there are hundreds of surgical methods for hypospadias, no single method can treat all types, and there are still high rates of postoperative complications. We performed this study to investigate surgical procedure selection and perform risk factor analysis of postoperative complications in hypospadias repair. METHODS: Retrospective analysis was performed of complete clinical and follow-up data of children with hypospadias who were treated and followed up at 15 children's clinical centers in Mainland China from December 2018 to December 2019. Children were divided into groups according to Barcat classification and surgical methods in order to analyze the surgical choice for different types of hypospadias and the influencing factors of different surgical methods for complications. RESULTS: In total, 1011 patients were followed up for 26 months. According to Barcat classification, there were 248 cases of distal type hypospadias, 214 of intermediate, and 549 of proximal type. Transverse preputial island flap urethroplasty (Duckett) and tubularized incised plate urethroplasty (TIP) were performed in 375 (37.1%) and 336 cases (33.2%), respectively. The postoperative complication rate of distal hypospadias was 23.4% (15.8-57.1%), mid shaft 29.0% (22.7-40.0%), and proximal 43.7% (30.2-52.9%). Among the 375 patients in Duckett group, 192 had complications. Multivariate logistic analysis showed that the length of prepuce island flap (OR = 3.506, 95% CI: 2.258-5.442) was an independent risk factor for complications after Duckett operation (P < 0.001). In TIP group, there were 336 cases with 84 complications. Multivariate logistic analysis showed that the width of urethral plate after longitudinal resection (OR = 0.836, 95% CI: 0.742-0.942) and glans width (OR = 0.851, 95% CI: 0.749-0.965) were independent risk factors for postoperative complications after TIP (P = 0.003, P = 0.012). CONCLUSION: Several anatomical features play a role during the selection process among the different surgical approaches, including glans size, urethral plate width, and the meatal position. The width of the urethral plate and glans width were risk factors for postoperative complications after TIP. The length of prepuce island flap was a risk factor for complications after Duckett operation.

Role of m6A modification in female infertility and reproductive system diseases.

Gamete abnormalities and reproductive system tumors have become a dominant cause of infertility, troubling people globally. In recent years, increasing evidence emerged and found that N6-methyladenosine (m6A) played a leading role in reproduction. The biological effects of m6A modification are dynamically and reversibly regulated by methyltransferases (writers), WTAP, METTL3, METTL14 and KIAA1429, demethylases (erasers), FTO and ALKBH5, and m6A binding proteins (readers), including YTH domain. In this review, we highlight the change of m6A modification in abnormal oogenesis, female reproductive system diseases including reproductive system tumors, adenomyosis, endometriosis, premature ovarian failure and polycystic ovary syndrome. Moreover, we review some of the mechanisms and the specific modified genes that have been identified. Especially, with the underlying mechanisms being uncovered, m6A and its protein machineries are expected to be the markers and targets for the diagnosis and treatment of female reproductive dysfunction.

Cadmium exposure and the risk of GDM: evidence emerging from the systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) has become a global concern for its severe adverse effects on both mother and fetus. Recent epidemiological studies reported inconsistent results of the association between cadmium (Cd) exposure and GDM. Therefore, a systematic review and meta- analysis were performed. PubMed, Web of Science, Scopus, Embase, and SpringerLink were searched up to July 2021. Observational studies containing the adjusted relative risks between Cd exposure and GDM were included in the quantitative synthesis. The retrieval comprised 218 articles out of which 11 met our criteria and 9 were included in the meta-analysis, representing a total of 32,392 subjects (2881 GDM). In total, Cd exposure might increase the risk of GDM in some extent (OR = 1.21, 95% CI [0.89, 1.64]), even without statistical significance in high heterogeneity (Q = 28.45, p < 0.05, I2 = 71.9%). Filtering two outliers indicated by Galbraith plot yielded a similar risk (OR = 1.19, 95% CI [1.02, 1.39]) with statistical significance. However, the heterogeneity among studies was obviously reduced (Q = 11.75, p = 0.068, I2 = 48.9%). Additionally, biological specimen, study design, and diagnostic criteria contributed to the high heterogeneity according to the subgroup analysis. Since some important results do not deny that Cd exposure increases the risk of GDM, high-quality multi-centered large cohort studies are required in the future.

Kaempferol 3-O-(2G-glucosylrutinoside)-7-O-glucoside isolated from the flowers of Hosta plantaginea exerts anti-inflammatory activity via suppression of NF-κB, MAPKs and Akt pathways in RAW 264.7 cells.

Kaempferol 3-O-(2G-glucosylrutinoside)-7-O-glucoside (KGG) has isolated from Hosta plantaginea flowers and possessed an inhibitory effect on cyclooxygenase 2 (COX-2), could be effective in inhibiting inflammation. However, the anti-inflammatory activity and mechanism of KGG remain unknown. In this study, for the first time, the anti-inflammatory effect of KGG and its potential molecular mechanisms were explored in cells. KGG had no cytotoxicity at concentrations of 1.25, 2.5, 5, 10, 20, and 40 µM by Cell Counting kit-8 assay in RAW 264.7 cells. Besides, KGG concentration-dependently (1.25, 2.5, and 5 µM) inhibited secretions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Western blot showed that the phosphorylation of nuclear factor kappa-B (NF-κB) p65, inhibitor of NF-κB (IκB), p38 MAPK, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (Erk), and protein kinase B (Akt), together with inducible nitric oxide synthase (iNOS) and COX-2 were significantly attenuated by KGG (1.25, 2.5, and 5 µM) in a concentration-dependent relationship. Meanwhile, KGG remarkably enhanced the protein expression of IκB. Taken together, KGG may be one of bioactive phytochemicals from H. plantaginea flowers, and be an anti-inflammatory agent via inhibiting NF-κB, mitogen-activated protein kinases (MAPKs), and Akt signaling pathways.

Varicocele-Mediated Male Infertility: From the Perspective of Testicular Immunity and Inflammation.

Background: Varicocele (VC) is present in 35 - 40% of men with infertility. However, current surgical and antioxidant treatments are not completely effective. In addition to oxidative stress, it is likely that other factors such as testicular immune microenvironment disorder contribute to irreversible testicular. Evidence suggests that VC is associated with anti-sperm antibodies (ASAs), spermatogenesis and testosterone secretion abnormalities, and testicular cytokine production. Moreover, inhibition of inflammation can alleviate VC-mediated pathogenesis. The normal function of the testis depends on its immune tolerance mechanism. Testicular immune regulation is complex, and many infectious or non-infectious diseases may damage this precision system. Results: The testicular immune microenvironment is composed of common immune cells and other cells involved in testicular immunity. The former includes testicular macrophages, T cells, dendritic cells (DCs), and mast cells, whereas the latter include Leydig cells and Sertoli cells (SCs). In animal models and in patients with VC, most studies have revealed an abnormal increase in the levels of ASAs and pro-inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha in the seminal plasma, testicular tissue, and even peripheral blood. It is also involved in the activation of potential inflammatory pathways, such as the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing (NLRP)-3 pathway. Finally, the development of VC-mediated infertility (VMI) may be facilitated by abnormal permeability of proteins, such as claudin-11, that constitute the blood-testis barrier (BTB). Conclusions: The testicular immune response, including the production of ASAs and inflammatory factors, activation of inflammatory pathways, and destruction of the BTB may be involved in the pathogenesis of VMI it is necessary to further explore how patient outcomes can be improved through immunotherapy.

Plantanone C attenuates LPS-stimulated inflammation by inhibiting NF-κB/iNOS/COX-2/MAPKs/Akt pathways in RAW 264.7 macrophages.

The flowers of Hosta plantaginea (Lam.) Aschers are commonly used for the treatment of inflammatory diseases in traditional Chinese medicine with limited scientific evidence. Plantanone C (PC) is a new phytochemical isolated from H. plantaginea flowers; nevertheless, the anti-inflammatory effect remains unknown. Herein, we aimed to study the anti-inflammatory effects of PC and its underlying molecular mechanisms in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The cell viability of PC-treated RAW 264.7 macrophage was measured by the Cell Counting kit-8 (CCK-8) assay. The anti-inflammatory effect of PC was investigated by measuring the levels of inflammatory mediators and pro-inflammatory cytokines using the Griess reaction and enzyme-linked immunosorbent assay (ELISA). Furthermore, the mechanism of action of PC was evaluated by Western blot analysis. The results showed that PC was not cytotoxic at concentrations as high as 40 µM. Furthermore, PC potently suppressed LPS-stimulated overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6 in RAW 264.7 macrophages. Western blot demonstrated that PC remarkably suppressed the phosphorylation of nuclear factor kappa-B (NF-κB) p65, inhibitor of NF-κB (IκB), c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (Erk), p38, and protein kinase B (Akt), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in a concentration-dependent manner. Taken together, these findings suggest that PC exhibits anti-inflammatory effects by inhibiting NF-κB, iNOS, COX-2, mitogen-activated protein kinases (MAPKs), and Akt signaling pathways in RAW 264.7 macrophages.

Anti-inflammatory effect of phenylpropanoids from Dendropanax dentiger in TNF-α-induced MH7A cells via inhibition of NF-κB, Akt and JNK signaling pathways.

The root of Dendropanax dentiger (Harms) Merr. has been used for centuries as an empirical treatment for rheumatoid arthritis (RA) in China without scientific validation. In our recent study, nineteen phenylpropanoids (1-19) with cyclooxygenase-2 inhibitory activities from the ethanol extract of D. dentiger roots, indicated to have a potential anti-RA effect. This study, evaluated the anti-RA effect of 19 phenylpropanoids on tumor necrosis factor (TNF)-α induced inflammation in MH7A cells and clarified their underlying mechanisms. As a result, 16 compounds remarkably suppressed nitric oxide (NO) production at a concentration of 40 µM in TNF-α-induced MH7A cells. Among them, pinoresinol (12) and dendrocoumarin A (1) were the most effective substances, which showed significant inhibitory effect on NO production, with IC50 values of 6.25 ± 0.42 and 7.87 ± 0.67 µM, respectively. Furthermore, pinoresinol and dendrocoumarin A remarkably decreased the levels of interleukin (IL)-2, 6, 8, and interferon-gamma (IFN-γ), as well as prominently reduced the phosphorylation protein levels of nuclear factor kappa B (NF-κB) p65, I-kappa-B-alpha (IkBα), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) by Western blot analysis. Taken together, our findings suggest that pinoresinol and dendrocoumarin A may offer new and safe anti-RA candidates by inhibiting NF-kB, Akt and JNK signaling pathways.

Relationship between the honeydew of mealy bugs and the growth of Phlebopus portentosus.

BACKGROUND: Phlebopus portentosus and mealy bugs form a fungus-insect gall on the roots of host plants. The fungus and mealy bugs benefit mutually through the gall, which is the key link in the nutritional mechanism of P. portentosus. The cavity of the fungus-insect gall provides an ideal shelter for mealy bugs survival and reproduction, but how does P. portentosus benefit from this symbiotic relationship? METHODOLOGY AND RESULTS: Anatomical examination of fungus-insect galls revealed that one or more mealy bugs of different generations were living inside the galls. The mealy bug's mouthpart could penetrate through the mycelium layer of the inside of the gall and suck plant juice from the host plant root. Mealy bugs excreted honeydew inside or outside the galls. The results of both honeydew agar medium and quartz tests showed that the honeydew can attract and promote the mycelial growth of P. portentosus. A test of the relationship between the honeydew and the formation of the fungus-insect gall showed that honeydew promoted gall formation. CONCLUSIONS: All experimental results in this study show that the honeydew secreted by mealy bugs can attract and promote the mycelial growth of P. portentosus, forming a fungus-insect gall, because mealy bugs' honeydew is rich in amino acids and sugars.

Investigation on the Effect of Hyperbranched Polyester Grafted Graphene Oxide on the Crystallization Behaviors of ß-Nucleated Isotactic Polypropylene.

In this article, hyperbranched polyester grafted graphene oxide (GO) was successfully prepared. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) were performed for its characterizations. On the other hand, differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD) were also performed to study its influences on non-isothermal crystallization behaviors of ß-nucleated isotactic polypropylene (ß-iPP). The grafting ratios of hyperbranched polyester with different supermolecular structures were calculated to be 19.8-24.0 wt %, which increase with the degree of branching. The results showed that the grafting of hyperbranched polyester was advantageous in increasing the crystallization peak temperature Tp and decreasing the crystallization activation energy ΔE of ß-iPP/GO composites, which contributed to the iPP's crystallization process. Moreover, under all cooling rates (2, 5, 10, 20, 40 °C/min), crystallinities of ß-iPP/GO were greatly improved after being grafted with hyperbranched polyester, because of the increase of the relative contents of α-phase αc and the average α-crystal sizes.

Exploring the Effects of Stereo-Defect Distribution on Nonisothermal Crystallization and Melting Behavior of ß-Nucleated Isotactic Polypropylene/Graphene Oxide Composites.

In this work, using two isotactic polypropylene (iPP) resins with similar average isotacticity and molecular weight but different uniformities of stereo-defect distribution, the ß-nucleated iPP/graphene oxide (ß-iPP/GO) composites (NPP-A and NPP-B) were prepared to investigate the effect of stereo-defect distribution on the nonisothermal crystallization kinetics and polymorphic melting behavior of the composites by means of scanning electron microscopy, wide-angle X-ray diffraction, and differential scanning calorimetry. The results showed that more uniform stereo-defect distribution led to a slight increase of the crystallization rate and decrease of the crystallization activation energy E c. NPP-B with more uniform stereo-defect was more favorable for the formation of a large amount of ß-phase. Moreover, the role of the cooling rate was also discussed and it was found that the higher the cooling rate, the higher the ß-phase content and the smaller the crystalline sizes, meanwhile, the higher the amount of ß-phase with relatively lower thermal stability that will take part in ß-α recrystallization during the subsequent melting process. For ß-iPP/GO composites, although the cooling rate greatly influences the polymorphic behavior and crystalline structures of the composites, the uniformity of stereo-defect distribution was found to be the first factor determining the formation of the ß-phase.

EGF-modified mPEG-PLGA-PLL nanoparticle for delivering doxorubicin combined with Bcl-2 siRNA as a potential treatment strategy for lung cancer.

CONTEXT: Nanoparticles (NPs) have been widely used as carriers to deliver siRNA and chemotherapeutic agents. Bcl-2 siRNA has been widely used to induce cancer cell apoptosis, and doxorubicin (Dox) can destroy cancer cells by binding with cancer cell DNA. OBJECTIVE: To investigate the therapeutic effect on lung cancer of simultaneously delivering Dox and Bcl-2-siRNA using epidermal growth factor (EGF) modified monomethoxy (polyethylene glycol)-poly (D, L-lactide-co-glycolide)-poly(L-lysine) (mPEG-PLGA-PLL, PEAL) NPs (EGF-PEAL). METHODS: EGF-PEAL NPs were characterized with respect to size, zeta potential and morphology. Cytotoxicity and drug (or siRNA) loading capacity of EGF-PEAL NPs were analyzed. Cellular uptake, drug release profile, cell killing effects of Dox and Bcl-2-siRNA-loaded EGF-PEAL NPs were assessed. Biodistribution and therapeutic effects of Dox and Bcl-2-siRNA EGF-PEAL NPs were evaluated in H1299 tumor-bearing mice. RESULTS AND DISCUSSION: EGF-PEAL NPs or PEAL NPs had nearly negligible cytotoxicity toward H1299 cells. Dox and Bcl-2-siRNA gradually released from EGF-PEAL NPs and exhibited sustained release patterns. Dox and Bcl-2-siRNA-loaded NPs were taken up by cells and induced the apoptosis of H1299 cells more effectively than using Dox or Bcl-2 siRNA alone. With the intravenous injection of PEAL NPs into H1299 xenografted mice, we found that combination treatment suppressed lung cancer growth and reduced Bcl-2 expression in tumor tissue, and EGF-PEAL NPs concentrated in lung tumor much more than non-targeted PEAL NPs. CONCLUSION: We conclude that co-delivery of Dox and Bcl-2-siRNA by tumor-targeted EGF-PEAL NPs could significantly inhibit lung cancer growth.

[Preparation of a hyaluronic acid modified bovine serum albumin nanoparticle and its anti-tumor effect].

OBJECTIVE: To prepare hyaluronic acid modified bovine serum albumin nanoparticle, investigate the modification extent, the drug entrapment property and its anti-tumor effect. METHODS: Bovine serum albumin nanoparticles were prepared by desolvation method, then use hyaluronic acid to modify the surface of bovine serum albumin nanoparticle. The decrement of reactive amino groups on the surface of bovine serum albumin nanoparticles was applied to evaluate the modification extent of hyaluronic acid. Single factor was used to study the effects of several influencing factors in preparation on the modification extent of hyaluronic acid modified bovine serum albumin nanoparticles. The influence of pH on drug entrapment ratio as well as the drug entrapment property were studied. The inhibition rate of nanoparticle on HepG2 was evaluated with MTT asasay. RESULTS: The prepared hyaluronic acid modified bovine serum albumin nanoparticle had a average particle size of 396 nm, and Zeta potential of - 19.7 mV, the deceased ratio of surface reactive amino groups was 34.28%; hyaluronic acid modified mitoxantrone bovine serum albumin nanoparticles had a property of drug load ratio 11.13%, drug entrapment ratio 94.64% and 398 nm average particle size, Zeta potential - 17.9 mV, with a distinguished delayed drug release effect. A higher inhibition rate was observed for hyaluronic acid modified bovine serum albumin nanoparticle than that of mitoxantrone solution (P < 0.05). CONCLUSION: The preparation technique is stable which could be used to prepare hyaluronic acid modified bovine serum albumin nanoparticle, and the prepared nanoparticle has a higer anti-tumor effect than that of mitoxantrone solution.