Liposomal Nanodrug Based on Norcantharidin Derivative for Increased in Vivo Activity.

To address the limitations of norcantharidin (NCTD) in clinical applications, including restricted tumor accumulation and intense irritation, we have developed a new derivative of NCTD with (S)-1-benzyl-3-pyrrolidinol, which can be actively loaded into liposomes to achieve drug encapsulation and sustained release properties by using pH gradient loading technique. Cytotoxicity tests against cancer cell lines (Hepa 1-6 and 4 T1 cells) have demonstrated that this derivative exhibits comparable activity to NCTD in vitro. The NCTD derivative can be efficiently loaded into liposomes with high encapsulation efficiency (98.7%) and high drug loading (32.86%). Tolerability and antitumor efficacy studies showed that the liposomal NCTD derivative was well tolerated at intravenous injection doses of 3 folds higher than the parent drug solution, while significantly improved anticancer activity in vivo was achieved. This liposomal nanodrug could become a potent and safe NCTD formulation alternative for cancer therapy.

Mesoporous cellulose nanofibers-interlaced PEDOT:PSS hybrids for chemiresistive ammonia detection.

Chemiresistive ammonia (NH3) detection at room temperature is highly desired due to the unique merits of easy miniaturization, low cost, and minor energy consumption especially for portable and wearable electronics. In this regard, poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) has sparked considerable attention due to the benign room-temperature conductivity and environmental stability, but it is undesirably impeded by limited sensitivity and sluggish reaction kinetics. To overcome these, we incorporated cellulose nanofibers (CNF) into PEDOT:PSS via a facile blending. The constituent-optimized composite sensor displayed sensitive (sensitivity of ∼7.46%/ppm in the range of 0.2-3 ppm), selective, and stable NH3 sensing at 25 °C at 55% RH, with higher response and less baseline drift than pure PEDOT:PSS counterparts. Additionally, the response/recovery times (4.9 s/5.2 s toward 1 ppm NH3) ranked the best cases of conducting polymers based NH3 sensors. The humidity involved more than twofold response enhancement indicated a huge potential in exhaled breath monitoring. Furthermore, we observed an excellent flexible NH3-sensing performance with bending-tolerant features. This work provides an alternative strategy for trace NH3 sensing with low power consumption, superfast reaction, and high sensitivity.

An agar-polyvinyl alcohol hydrogel loaded with tannic acid with efficient hemostatic and antibacterial capacity for wound dressing.

Rapid hemostasis, antibacterial effect and promotion of wound healing are the most important functions that wound dressings need to have. In this work, we designed and prepared a hydrogel with antibacterial effect, hemostatic ability and wound healing promotion using agar, polyvinyl alcohol (PVA) and tannic acid (TA). We performed a series of tests to characterize the structure and properties of AGAR@PVA-TA hydrogels. The results showed that the AGAR@PVA-TA hydrogels had good mechanical properties and excellent antibacterial ability as well as good hemocompatibility. The cytotoxicity results showed that the AGAR@PVA-TA hydrogels had good cytocompatibility. And the TA loaded hydrogels also presented some good performances in animal studies. In the liver hemostasis model, the AGAR@PVA-TA hydrogel showed good hemostatic ability. Also, the AGAR@PVA-TA hydrogel was able to promote wound healing in an S. aureus-infected rat wound model. More importantly, our research results demonstrated that compared to other polyphenols (such as proanthocyanidins), TA could better improve the mechanical properties, antibacterial ability and rapid hemostasis of hydrogels, which illustrated the uniqueness of TA. Therefore, the TA loaded hydrogel (AGAR@PVA-TA hydrogel) has the potential to be applied as a wound dressing.

Emission Characteristics and Health Risks of Volatile Organic Compounds (VOCs) Measured in a Typical Recycled Rubber Plant in China.

The continued development of the automotive industry has led to a rapid increase in the amount of waste rubber tires, the problem of "black pollution" has become more serious but is often ignored. In this study, the emission characteristics, health risks, and environmental effects of volatile organic compounds (VOCs) from a typical, recycled rubber plant were studied. A total of 15 samples were collected by summa canisters, and 100 VOC species were detected by the GC/MS-FID system. In this study, the total VOCs (TVOCs) concentration ranged from 1000 ± 99 to 19,700 ± 19,000 µg/m3, aromatics and alkanes were the predominant components, and m/p-xylene (14.63 ± 4.07%-48.87 ± 3.20%) could be possibly regarded as a VOCs emission marker. We also found that specific similarities and differences in VOCs emission characteristics in each process were affected by raw materials, production conditions, and process equipment. The assessment of health risks showed that devulcanizing and cooling had both non-carcinogenic and carcinogenic risks, yarding had carcinogenic risks, and open training and refining had potential carcinogenic risks. Moreover, m/p-xylene and benzene were the main non-carcinogenic species, while benzene, ethylbenzene, and carbon tetrachloride were the dominant risk compounds. In the evaluation results of LOH, m/p-xylene (25.26-67.87%) was identified as the most key individual species and should be prioritized for control. In conclusion, the research results will provide the necessary reference to standardize the measurement method of the VOCs source component spectrum and build a localized source component spectrum.

A promising potential candidate for vascular replacement materials with anti-inflammatory action, good hemocompatibility and endotheliocyte-cytocompatibility: phytic acid-fixed amniotic membrane.

Due to its excellent biocompatibility and anti-inflammatory activity, amniotic membrane (AM) has attracted much attention from scholars. However, its clinical application in vascular reconstruction was limited for poor processability, rapid biodegradation, and insufficient hemocompatibility. A naturally extracted substance with good cytocompatibility, phytic acid (PA), which can quickly form strong and stable hydrogen bonds on the tissue surface, was used to crosslink decellularized AM (DAM) to prepare a novel vascular replacement material. The results showed that PA-fixed AM had excellent mechanical strength and resistance to enzymatic degradation as well as appropriate surface hydrophilicity. Among all samples, 2% PA-fixed specimen showed excellent human umbilical vein endothelial cells (HUVECs)-cytocompatibility and hemocompatibility. It could also stimulate the secretion of vascular endothelial growth factor and endothelin-1 from seeded HUVECs, indicating that PA might promote neovascularization after implantation of PA-fixed specimens. Also, 2% PA-fixed specimen could inhibit the secretion of tumor necrosis factor-αfrom co-cultured macrophages, thus might reduce the inflammatory response after sample implantation. Finally, the results ofex vivoblood test andin vivoexperiments confirmed our deduction that PA might promote neovascularization after implantation. All the results indicated that prepared PA-fixed DAM could be considered as a promising small-diameter vascular replacement material.

A novel bone cement screw system combined with vertebroplasty for the treatment of Kummell disease with bone deficiency at the vertebral anterior border: A minimum 3-year follow-up study.

OBJECTIVES: When vertebroplasty is used to treat Kummell disease with bone deficiency at the vertebral anterior border, bone cement displacement often occurs intraoperatively or postoperatively. We designed and used a new bone cement screw system to avoid this serious complication. The purpose of this study was to evaluate the safety and effectiveness of this novel operation method through more than 3 years of follow-up. PATIENTS AND METHODS: From January 2014 to August 2016, 27 patients suffering from single-segment Kummell disease with bone deficiency at the vertebral anterior border were treated by vertebroplasty combined with a novel bone cement screw. Bone cement was released into the diseased vertebrae through the screw to fully fill the intravertebral vacuum cleft. Screw fixation of bone cement can avoid intraoperatively or postoperatively displacement. All patients received surgery involving a unilateral technique, and only one screw was implanted in each patient. The clinical efficacy was evaluated using Odom's criteria and statistical analysis of the vertebral body index (VBI), vertebral body angle (VBA), bisegmental Cobb angle (BCA), visual analogue scale (VAS), Oswestry disability index (ODI), and the results of the MOS 36-item short form health survey (SF-36). RESULTS: The operation was completed successfully in 27 cases. The average operation time was 49.63 ± 10.82 min, and the average volume of cement injected was 4.70 ± 0.87 mL. The patients' preoperative VBI, VBA, BCA, VAS and ODI scores were 43.11 ± 5.94, 21.04 ± 2.55, 45.00 ± 6.26, 7.59 ± 0.84, and 79.85 ± 7.58, respectively. The postoperative measurements were 78.70 ± 2.55, 12.70 ± 2.11, 26.11 ± 4.73, 3.22 ± 0.93 and 50.04 ± 9.28, respectively. At the last follow-up, the measurements were 78.04 ± 2.30, 13.15 ± 2.38, 27.07 ± 4.87, 2.04 ± 0.65, and 22.85 ± 5.06, respectively. There was a significant difference between the preoperative and postoperative data, as well as the preoperative and the last follow-up data (P < 0.05). Comparing the results of SF-36 before operation and at the last follow-up revealed significant differences in physical function, role-physical, body pain, vitality, and social function (P < 0.05). However, there were no significant differences in general health, emotional function and mental health. Finally, 26 patients (96.3 %) had good to excellent clinical outcomes according to Odom's criteria. CONCLUSIONS: This 3-year follow-up study shows that the novel bone cement screw system combined with vertebroplasty has a good short and medium-term therapeutic effect in patients with Kummell disease and bone deficiency at the vertebral anterior border, while its long-term efficacy is subject to further studies.

shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) is one of the most important animal pathogens in the world. FMDV naturally infects swine, cattle, and other cloven-hoofed animals. FMD is not adequately controlled by vaccination. An alternative strategy is to develop swine that are genetically resistant to infection. Here, we generated FMDV-specific shRNA transgenic cells targeting either nonstructural protein 2B or polymerase 3D of FMDV. The shRNA-positive transgenic cells displayed significantly lower viral production than that of the control cells after infection with FMDV (P < 0.05). Twenty-three transgenic cloned swine (TGCS) and nine non-transgenic cloned swine (Non-TGCS) were produced by somatic cell nuclear transfer (SCNT). In the FMDV challenge study, one TGCS was completely protected, no clinical signs, no viremia and no viral RNA in the tissues, no non-structural antibody response, another one TGCS swine recovered after showing clinical signs for two days, whereas all of the normal control swine (NS) and Non-TGCS developed typical clinical signs, viremia and viral RNA was determined in the tissues, the non-structural antibody was determined, and one Non-TGCS swine died. The viral RNA load in the blood and tissues of the TGCS was reduced in both challenge doses. These results indicated that the TGCS displayed resistance to the FMDV infection. Immune cells, including CD3+, CD4+, CD8+, CD21+, and CD172+ cells, and the production of IFN-γ were analyzed, there were no significant differences observed between the TGCS and NS or Non-TGCS, suggesting that the FMDV resistance may be mainly derived from the RNAi-based antiviral pathway. Our work provides a foundation for a breeding approach to preventing infectious disease in swine.

Homogeneously alloyed nanoparticles of immiscible Ag-Cu with ultrahigh antibacterial activity.

Immiscible bimetallic Ag-Cu system has been synthesized by the pulsed plasma in liquid method with a graph of one pulse duration. Herein, by combining X-ray power diffraction, K-edge X-ray absorption near edge structure and high-resolution transmission electron microscopy, our results indicate that homogeneously alloyed Ag-Cu nanoparticles (Ag-Cu NAs) have the average diameter about 2.1 nm, composed by 48.5 at% Ag and 51.5 at% Cu with chemical analysis and the estimated lattice parameter was 3.873 Å. The antibacterial property of Ag-Cu NAs was detected against E. coli and S. aureus strains according to the colony formed abilities of bacteria on agar plates covered with the nanoparticles. With very short incubation period, Ag-Cu NAs completely inhibited the E. coli and S. aureus growth at an ultralow concentration. The mechanism of antibacterial property of Ag-Cu NAs was performed by the inductively coupled plasma-atomic emission spectrometry and the plane wave pseudopotential method implemented in the CASTEP package based on the density functional theory. The Ag+ dissolution is correlated with antibacterial activity for Ag-Cu NAs-assisted antibacterial treatment. These findings obtained revealed that our Ag-Cu NAs could be served as a containing material of numerous bacteria-free products in order to avoid their bacterial contamination.

Novel biodegradable HSAM nanoparticle for drug delivery.

The systemic pharmacological treatment of disease is limited by severe toxicity to normal organs/tissue. Therefore, various delivery vehicles have been designed to carry therapeutic drugs to their target tissues. We designed a novel vehicle formed by the interaction of biotins in a DNA (polymer) with avidins (crosslink), resulting in a porous particle. This self-assembled (HSAM) nanoparticle vehicle has been tested in our laboratory both in vitro and in vivo for its ability to carry doxorubicin, a widely used anticancer drug with a high toxicity to normal organs. Doxorubicin binds to the nanoparticle by intercalating into the DNA strands that are later degraded by nucleases released from cancer cells. Our results showed that 1.1 microg of HSAM DNA can carry 1 microg of doxorubicin, and the doxorubicin-bound HSAM nanoparticle can still be degraded by nucleases (BAL-31 and DNase I). The HSAM nanoparticle carrying doxorubicin can efficiently inhibit cancer cell growth in vitro and in a murine model. Furthermore, this nanoparticle is able to deliver up to 180 ng/mg of doxorubicin to the target tumor tissue, which is 15-fold above the systemic toxicity dose (12 mg/kg). These results suggest that the HSAM nanoparticle is both biocompatible and biodegradable, making it a valuable vehicle for drug delivery in cancer treatment.