Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer.

BACKGROUND: Although cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application. Additionally, triptolide (TP) was confirmed to possess a superior killing effect on cisplatin-resistant cell lines, partially through inhibiting the mTOR pathway. Even so, the clinical applications of TP are restricted by serious systemic toxicity and weak water solubility. RESULTS: Herein, whether the combined application of miR497 and TP could further overcome OC chemoresistance by synergically suppressing the mTOR signaling pathway was investigated. Bioinspired hybrid nanoparticles formed by the fusion of CD47-expressing tumor exosomes and cRGD-modified liposomes (miR497/TP-HENPs) were prepared to codeliver miR497 and TP. In vitro results indicated that the nanoparticles were efficiently taken up by tumor cells, thus significantly enhancing tumor cell apoptosis. Similarly, the hybrid nanoparticles were effectively enriched in the tumor areas and exerted significant anticancer activity without any negative effects in vivo. Mechanistically, they promoted dephosphorylation of the overactivated PI3K/AKT/mTOR signaling pathway, boosted reactive oxygen species (ROS) generation and upregulated the polarization of macrophages from M2 to M1 macrophages. CONCLUSION: Overall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.

Comparison of Energy Consumption of Osmotically Assisted Reverse Osmosis and Low-Salt-Rejection Reverse Osmosis for Brine Management.

Minimum and zero liquid discharge (MLD/ZLD) are emerging brine management strategies that attract heightened attention. Although conventional reverse osmosis (RO) can improve the energy efficiency of MLD/ZLD processes, its application is limited by the maximum hydraulic pressure (ΔPmax) that can be applied in current membrane modules. To overcome such limitation, novel RO-based technologies, including osmotically assisted RO (OARO) and low-salt-rejection RO (LSRRO), have been proposed. Herein, we utilize process modeling to systematically compare the energy consumption of OARO and LSRRO for MLD/ZLD applications. Our modeling results show that the specific energy consumption (SEC) of LSRRO is lower (by up to ∼30%) than that of OARO for concentrating moderately saline feed waters (<∼35,000 mg/L TDS) to meet MLD/ZLD goals, whereas the SEC of OARO is lower (by up to ∼40%) than that of LSSRO for concentrating higher salinity feed waters (>∼70,000 mg/L TDS). However, by implementing more stages and/or an elevated ΔPmax, LSRRO has the potential to outperform OARO energetically for treating high-salinity feed waters. Notably, the SEC of both OARO and LSRRO could be 50% lower than that of mechanical vapor compressor, the commonly used brine concentrator in MLD/ZLD applications. We conclude with a discussion on the practicability of OARO and LSRRO based on membrane module availability and capital cost, suggesting that LSRRO could potentially be more feasible than OARO.

Evaluation of the Therapeutic Effect of Bi-Maxillary Osteotomy Using the Stress Distribution on the Temporomandibular Joint When Doing Anterior Teeth Occlusion.

The purpose of this study was to investigate how sagittal split ramus osteotomy (SSRO) and Le Fort 1 osteotomy affected the stress distribution of the temporomandibular joint (TMJ) during an anterior teeth bite using the three-dimensional (3D) finite element (FE) method. Fourteen orthognathic surgery patients were examined with mandibular prognathism, facial asymmetry, and mandibular retraction. They underwent Le Fort 1 osteotomy in conjunction with SSRO. In addition, ten asymptomatic subjects were recruited as the control group. The 3D models of the mandible, disc, and maxilla were reconstructed according to cone-beam computed tomography (CBCT). Contact was used to simulate the interaction of the disc-condyle, disc-temporal bone, and upper-lower dentition. Muscle forces and boundary conditions corresponding to the anterior occlusions were applied on the models. The stresses on the articular disc and condyle in the pre-operative group were significantly higher than normal. The contact stress and minimum principal stress in TMJ for patients with temporomandibular disorder (TMD) were abnormally higher. The peak stresses of the TMJ of the patients under anterior occlusions decreased after bimaxillary osteotomy. No postoperative TMD symptoms were found. Maxillofacial deformity led to excessive stress on the TMJ. Bimaxillary osteotomy can partially improve the stress distributions of the TMJ and relieve the symptoms of TMD.

Multifunctional Irrigation-Assisted Vacuum Drainage versus Traditional Drainage in the Treatment of Odontogenic Deep Fascial Infection: A Retrospective Cohort Study.

PURPOSE: Odontogenic deep fascial space infection in the head and neck is a common potentially fatal clinical problem. Traditional drainage method is considered laborious and gravity-dependent. In this study, we aimed to evaluate the clinical effect of a modified multifunctional irrigation-assisted vacuum drainage (MIVD) by comparing it with the traditional drainage method in the treatment of odontogenic deep fascial infection. PATIENTS AND METHODS: Patients diagnosed with odontogenic deep fascial space infection in the Second Affiliated Hospital, Zhejiang University School of Medicine, China between March 2018 and March 2021 were studied. We divided the patients into two groups based on the drainage method they received: patients with the MIVD device were included in the MIVD group, patients with traditional drainage were included in the traditional group. Data were collected retrospectively including baseline characteristics and treatment outcome variables. RESULTS: A total of 65 patients were included. All the patients were eventually cured. There were no significant differences in age, gender, diabetes, end stage renal disease, autoimmune diseases, other systemic diseases, tobacco use, number of the infected spaces, preoperative white blood cell count and C-reactive protein between the two groups. The number and frequency of manual irrigation by clinicians (MIC), time required for white blood cell count to return to normal levels (TWBC), time required for C-reactive protein to return to normal levels (TCRP), the length of hospitalization and the length and total cost of antibiotics use were significantly less in the MIVD group. There was no significant difference in the cost of hospitalization between the 2 groups. CONCLUSION: The MIVD device significantly reduced the number and frequency of MIC, TWBC, TCRP, the length of hospitalization and the length and total cost of antibiotics use in comparison with the traditional drainage method. It provided a favorable treatment method for patients with odontogenic deep fascial space infection in the head and neck.

Exploring the essential factors of performance improvement in sludge membrane bioreactor technology coupled with symbiotic algae.

In this study, a coupled system of algal-sludge and membrane bioreactor (AS-MBR) was established for fouling control, and meanwhile the performance of wastewater treatment was enhanced. Results indicated that the AS-MBR increased the COD, NH4+-N, TN and PO43- -P removal efficiencies from 91.7% to 95.9%, 90.8%-96.9%, 22.0% to 34.3% and 18.4%-32.6%, respectively. Further analysis suggested that in the AS-MBR, the total specific oxygen utilization rate (SOUR), the SOUR of ammonia oxidizing bacteria and the SOUR of nitrite oxidizing bacteria were 26.6%, 58.5% and 52.4% higher than the control, respectively, indicating the improvement of microbial activities in AS-MBR. Additionally, the membrane fouling rates in the AS-MBR were 52.6% and 32.2% lower than the control in the slow and rapid fouling processes, respectively. A further mechanism investigation demonstrated that the concentrations of extracellular polymeric substance (EPS) were decreased by 19.8% and 22.1% in the mixed liquid and the fouling layer, respectively, after the inoculation of algae, which was expected to have a positive effect on the higher permeability and longer operation cycle of the membrane in the AS-MBR. More regular floc morphology was observed for the fouling layer on the membrane of AS-MBR, with the polysaccharides and proteins forming large clusters and channels in the fouling layer that likely decreased the filtration resistance. Consequently, high-throughput sequencing analysis revealed that the microbial community in the AS-MBR had higher abundances of bacteria and algae related to nutrients and organic matters degradation, which was beneficial for the improvement of wastewater treatment and alleviation of membrane fouling.

Effect of sagittal split ramus osteotomy on morphologic parameters of temporomandibular joint in patients with mandibular prognathism.

The purpose of this study was to evaluate the change in three-dimensional morphology and clinical symptoms of temporomandibular joint (TMJ) in class III dentofacial deformity patients postoperatively for 6 months after sagittal split ramus osteotomy (SSRO).Seventeen patients with skeletal Class III malocclusion and 10 asymptomatic volunteers (classified as Control group) were recruited for the study and underwent cone-beam computed tomography scanning. The geometries of the maxilla and mandible were reconstructed using MIMICS (Materialise, Leuven, Belgium). The morphologic measurements of the patients' TMJs were done before surgery and at 6-month follow-up - named as Pre and Post groups, respectively.The joint spaces (medial joint space, superior joint space, lateral joint space, anterior joint space, and posterior joint space) of the Control group were significantly greater than those of the Pre and Post groups (P < .05), and SSRO did not significantly change the TMJ morphology parameters. Five patients were found to have preoperative temporomandibular disorder (TMD) symptoms, and 3 of them were relieved at 6 months after surgery. Postoperative TMD symptom was observed in 1 patient without preoperative TMD symptom.SSRO did not markedly alter the TMJ morphology of the patients with mandibular prognathism. The effects of SSRO on TMD symptoms should be related to the type of deformity.

Polytetrafluoroethylene (PTFE) hollow fiber AnMBR performance in the treatment of organic wastewater with varying salinity and membrane cleaning behavior.

PTFE hollow fiber anaerobic membrane bio-reactor (AnMBR) performance was investigated in the treatment of organic wastewater, with varying salinity and PTFE membrane cleaning behavior. The AnMBR was operated for 226 days, with a total and biological COD removal efficiency of 97.2% and 89.9% respectively, at a NaCl concentration of 35 g L-1. A high number of Proteobacteria (38.2%) and Bacteroidetes (25.9%) were present in the system, with an increase in membrane fouling rate from 1.88 × 1011 to 2.63 × 1011 m-1 d-1 with higher salinity. The effects of soluble microbial products (SMP), extracellular polymeric substances (EPS), low molecular-weight (LMW) carbohydrates, sludge particle size and inorganic element accumulation, were evaluated on membrane fouling. Flux recovery of fouled PTFE membranes reached 91.6% with offline cleaning. Overall, results indicate that PTFE hollow fiber AnMBR provides a promising method for the treatment of saline organic wastewater.

A photoresponsive soft interface reversibly controls wettability and cell adhesion by conformational changes in a spiropyran-conjugated amphiphilic block copolymer.

The functionalities of soft interfaces including cell adhesion can be enhanced by dynamic conversion of polymer properties and movement via external stimuli. Light is a superior stimulus, and various surfaces modified with photoreactive molecules have been prepared. However, in most of these studies, the surface properties are irreversibly changed due to photo-degradation, and reversible adhesion and collection of cells is not feasible. In this study, we developed a photoresponsive polymer soft interface that was able to spatiotemporally control wettability, cell adhesion, and detachment in a reversible manner. Spiropyran molecules were introduced into the hydrophobic block of an amphiphilic diblock copolymer consisting of poly(methyl methacrylate) and polyethylene glycol, and the monomer unit numbers of these components were optimized. The copolymer was immobilized on a glass substrate as a nanofilm. With alternating irradiation using UV and visible light, the surface exhibited reversible changes in hydrophobicity and hydrophilicity, and the direction of change was opposite to the polarity change in photo-isomerization of spiropyran. We also achieved photo-control of effective cell adhesion and detachment with sequential irradiation with UV and visible light. These remarkable functions could be ascribed to conformational changes triggered by photo-isomerization of spiropyran. This photoresponsive polymer soft interface may have applications as a powerful tool in biological studies by facilitating sequential changes in wettability and bioaffinity. STATEMENT OF SIGNIFICANCE: We developed a photoresponsive polymer soft interface, which was able to spatiotemporally control wettability and cell adhesion/detachment in a reversible manner, by introducing spiropyran into the hydrophobic block of an amphiphilic diblock copolymer. With alternating irradiation using UV and visible light, the surface exhibited unique reversible wettability changes; the direction of hydrophobicity and hydrophilicity change was opposite to the polarity change in spiropyran photo-isomerization. Light-dependent reversible control of spatiotemporal cell adhesion and detachment was also achieved with sequential UV (adhesion) and visible light irradiation (detachment). Cell detachment using noncytotoxic visible light was realized for the first time. Cell-patterning capability stably lasted for 25days. This photoresponsive surface could be applied to fabrication of engineered tissues comprised of several cellular species.

[Construction of a High Efficiency Anaerobic Digestion System for Vinegar Residue].

The model of high solid anaerobic digestion was used by improving the degree of homogeneity of the reaction system and biogas slurry reflux to gradually increase the material load. The vinegar residue-efficient anaerobic digestion system was successfully constructed without pretreatment.The optimum anaerobic digestibility was observed when the material loading of the reaction system reached 6.15 g·(L·d)-1, when the amount of biogas produced per unit of dry material was 396 mL·g-1, and the amount of methane produced per unit of dry material was 211 mL·g-1. The degradation rate of hemicellulose reached 63.66%, which was the main reason for the improvement of anaerobic digestion performance. The degradation rates of cellulose and lignin were 21.46% and 24.43%, respectively. The lower degradation efficiency was mainly due to the complicated degradation of the benzene ring structure in lignin and hindered hydrolysis of cellulose, which had a shielding effect on cellulose degradation.

Long-term investigation of a novel electrochemical membrane bioreactor for low-strength municipal wastewater treatment.

A novel and cost-effective electrochemical membrane bioreactor (EMBR) was proposed for low-strength wastewater treatment. In this system, influent organic matter could act as electron donor in the anode chamber and then denitrification was driven on the cathodes. During 270 days of operation, a positive and time-lag correlation was found between temperature and exoelectrogenesis process. At lower temperatures (<10∼15 °C), power production in the EMBR was negligible and therefore the integration did not improve the reactor performance. With the rebound of water temperatures over 15∼20 °C, efficient redox reactions were achieved in the EMBR, which subsequently resulted in sludge reduction (27.3% lower than the control MBR) and membrane fouling alleviation. Due to the capture of electrons that were then used at the cathode to drive the denitrification process, the total nitrogen removal efficiency of the EMBR averaged 78.2% at high temperatures, despite the decrease of organic loading rate of the feed for heterotrophic denitrification. Pyrosequencing revealed that the denitrifiers of Denitratisoma, Ottowia, Sulfuritalea and Thiobacillus were notably enriched in the cathode biofilm of the EMBR at high temperatures, and 6.05% of the sequences in the activated sludge were assigned into the denitrification related phylotypes, which was 65% higher compared to that of the control MBR. The enrichment of versatile nitrate/nitrite reducers could be conducive to the autotrophic and heterotrophic denitrification processes. Energy balance analysis also indicated that the total energy consumption of the EMBR was decreased by 20% compared to that of the CMBR (0.386 kWh/m(3) wastewater). Overall, the obtained results clearly demonstrate that this novel EMBR is capable of providing superior effluent quality, alleviating membrane fouling and incorporating into existing treatment facilities for improving the sustainability of wastewater treatment.