High-efficiency large-bandgap material for polymer solar cells.

High-molecular-weight conjugated polymer HD-PDFC-DTBT with N-(2-hexyldecyl)-3,6-difluorocarbazole as the donor unit, 5,6-bis(octyloxy)benzothiadiazole as the acceptor unit, and thiophene as the spacer is synthesized by Suzuki polycondensation. HD-PDFC-DTBT shows a large bandgap of 1.96 eV and a high hole mobility of 0.16 cm(2) V(-1) s(-1) . HD-PDFC-DTBT:PC71 BM-based inverted polymer solar cells (PSCs) give a power conversion efficiency (PCE) of 7.39% with a Voc of 0.93 V, a Jsc of 14.11 mA cm(-2) , and an FF of 0.56.

Planar conjugated polymers containing 9,10-disubstituted phenanthrene units for efficient polymer solar cells.

Four novel conjugated polymers (P1-4) with 9,10-disubstituted phenanthrene (PhA) as the donor unit and 5,6-bis(octyloxy)benzothiadiazole as the acceptor unit are synthesized and characterized. These polymers are of medium bandgaps (2.0 eV), low-lying HOMO energy levels (below -5.3 eV), and high hole mobilities (in the range of 3.6 × 10(-3) to 0.02 cm(2) V(-1) s(-1) ). Bulk heterojunction (BHJ) polymer solar cells (PSCs) with P1-4:PC71 BM blends as the active layer and an alcohol-soluble fullerene derivative (FN-C60) as the interfacial layer between the active layer and cathode give the best power conversion efficiency (PCE) of 4.24%, indicating that 9,10-disubstituted PhA are potential donor materials for high-efficiency BHJ PSCs.

Cellulase-responsive hydroxypropyl cellulose-anchored hollow mesoporous silica carriers for pesticide delivery.

In this study, a cellulase-responsive controlled-release formulation (FPR-HMS-HPC) was developed by grafting hydroxypropyl cellulose (HPC) onto fipronil (FPR) loaded hollow mesoporous silica (HMS) nanoparticles via ester linkage. The FPR-HMS-HPC formulation was characterized using scanning and transmission electron microscopies, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The results indicated that FPR-HMS-HPC exhibited a high loading capacity of 10.0 % (w/w) and demonstrated favorable responsiveness to cellulase enzyme. Moreover, its insecticidal efficacy against Reticulitermes flaviceps surpassed that of an equivalent dose of FPR. Toxicology studies showed that the mortality and hatching rates of zebrafish exposed to FPR-HMS-HPC nanoparticles were reduced by >6.5 and 8.0 times, respectively. Thus, HPC-anchored HMS nanoparticles as insecticide delivery systems present a sustainable method for pest control significantly reducing harm to non-target organisms and the environment.

Anthracene-containing wide-band-gap conjugated polymers for high-open-circuit-voltage polymer solar cells.

The synthesis, characterization, and photophysical and photovoltaic properties of two anthracene-containing wide-band-gap donor and acceptor (D-A) alternating conjugated polymers (P1 and P2) are described. These two polymers absorb in the range of 300-600 nm with a band gap of about 2.12 eV. Polymer solar cells with P1:PC71 BM as the active layer demonstrate a power conversion efficiency (PCE) of 2.23% with a high Voc of 0.96 V, a Jsc of 4.4 mA cm(-2) , and a comparable fill factor (FF) of 0.53 under simulated solar illumination of AM 1.5 G (100 mW cm(-2) ). In addition, P2:PC71 BM blend-based solar cells exhibit a PCE of 1.42% with a comparable Voc of 0.89 V, a Jsc of 3.0 mA cm(-2) , and an FF of 0.53.

Dual delivery of BMP-2 and bFGF from a new nano-composite scaffold, loaded with vascular stents for large-size mandibular defect regeneration.

The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs), bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA). AlamarBlue assay and alkaline phosphatase (ALP) activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01). In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large bone defects in bone tissue engineering.

Surface grafting of sericin onto thermoplastic polyurethanes to improve cell adhesion and function.

Thermoplastic polyurethane (TPU) membrane has super physical-mechanical properties and biocompatibility, but the surface is inert and lack of active groups which limit its application in cell culture. Silk sericin (SS) can improve cell adhesion, proliferation, growth and metabolism. In this paper, SS was grafted onto the surface of TPU membrane by -NH2 bridge to build a high efficiency cell culture membrane. The FT-IR spectrum results indicated SS was grafted by chemical bond. According to the SEM and AFM results, we found that the grafting of SS reduced the water contact angle by 43.31% and increased the surface roughness by about four times. When TPU-SS was used for HepG2 cell culture, the cell adhesion rate of TPU-SS was significantly higher than that of the general TCPS cell culture plate, and the cell proliferation rate was close to that of TCPS. FDA/EB staining showed that HepG2 cells remained a better cellular growth behavior. HepG2 cells had higher cell vitality including the albumin secretion and the intracellular total protein synthesis. Grafting SS maintained the stability of cell and significantly decreased the cytotoxicity by decreased LDH release. In conclusion, SS grafting is beneficial to cell culture in vitro, and provides a key material for bioartificial liver culture system.

Photoinduced inverse vulcanization.

The inverse vulcanization (IV) of elemental sulfur to generate sulfur-rich functional polymers has attracted much recent attention. However, the harsh reaction conditions required, even with metal catalysts, constrains the range of feasible crosslinkers. We report here a photoinduced IV that enables reaction at ambient temperatures, greatly broadening the scope for both substrates and products. These conditions enable volatile and gaseous alkenes and alkynes to be used in IV, leading to sustainable alternatives for environmentally harmful plastics that were hitherto inaccessible. Density functional theory calculations reveal different energy barriers for thermal, catalytic and photoinduced IV processes. This protocol circumvents the long curing times that are common in IV, generates no H2S by-products, and produces high-molecular-weight polymers (up to 460,000 g mol-1) with almost 100% atom economy. This photoinduced IV strategy advances both the fundamental chemistry of IV and its potential industrial application to generate materials from waste feedstocks.

Molybdenum-catalyzed hydrogenolysis of herbaceous biomass: A procedure integrated lignin fragmentation and components fractionation.

In this work, a low-cost MoO2/C catalyst was prepared for the reductive catalytic fractionation (RCF) of various herbaceous biomass feedstocks (Miscanthus, Triarrhena, Floridulus, Sorghum stem and Corncob). Phenolic monomers from the hydrogenolysis of lignin component were obtained in up to 26.4 wt%, with high selectivity towards methyl coumarate (33%) and methyl ferulate (24%). The RCF left solid carbohydrate pulps with high retentions (up to 87%), which were suitable for enzymatic hydrolysis. The reaction conditions, including temperature, time, H2 pressure, and sawdust size were examined in terms of monophenols yield, selectivity, delignification and sugar retention. This study showed that MoO2/C could function as an excellent catalyst for lignin fragmentation as well as the fractionation of herbaceous biomass components.

[Observation of therapeutic effect on coronavirus disease 2019 with insomnia in treatment with baduanjin and auricular point sticking therapy].

OBJECTIVE: To compare the clinical therapeutic effect on coronavirus disease 2019 (COVID-19) with insomnia between the combined treatment of baduanjin and auricular point sticking therapy and the medication with oral estazolam on the base of the conventional treatment. METHODS: A total of 90 patients with COVID-19 accompanied with insomnia were randomly divided into an observation group (45 cases, 3 cases dropped off) and a control group (45 cases). In the observation group, baduanjin, a traditional Chinese fitness activity, was practiced everyday. Besides, auricular point sticking therapy was exerted at ear-shenmen (TF 4), subcortex (AT 4), heart (CO 15), occiput (AT 3), etc. These auricular points were pressed and kneaded three times a day, 30 s at each point each time, consecutively for 12 days. In the control group, estazolam tablets were prescribed for oral administration, 1 mg, once daily, consecutively for 12 days. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS) and the score of symptoms in traditional Chinese medicine (TCM) were observed in the two groups and the clinical therapeutic effect was evaluated. RESULTS: After treatment, the scores of every item and the total scores in PSQI were all reduced as compared with those before treatment in the two groups (P<0.01). The scores of sleep time and sleep efficiency in the observation group were lower than those in the control group after treatment (P<0.05). SAS scores and SDS scores in the observation group and SAS score in the control group after treatment were all reduced as compared with those before treatment (P<0.01), and SDS score in the observation group was lower than that in the control group (P<0.01). After treatment, in the observation group, the score of each of the symptoms of TCM, i.e. unsound sleep, irritability and hot temper, profuse sputum and sticky feeling in the mouth, bitter taste in the mouth and foul breath, abdominal distention and poor appetite, as well as lassitude was reduced as compared with that before treatment successively (P<0.01), and the scores aforementioned (excepted for the unsound sleep) in the observation group were all lower than the control group (P<0.05). The total effective rates were 83.3% (35/42) in the observation group and 84.4% (38/45) in the control group, without statistical difference in comparison (P>0.05). CONCLUSION: The combined treatment of baduanjin and auricular point sticking therapy improves sleep quality, the conditions of anxiety and depression and the symptoms in TCM for patients of COVID-19 with insomnia. The therapeutic effect of this combined treatment is better than the oral administration of estazolam.

Acidic tumor microenvironment-sensitive liposomes enhance colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the "soil" in the tumor microenvironment (TME). Accordingly, it would be a promising strategy to enhance the antitumor effect by killing both tumor cells and CAFs simultaneously. Herein, novel TME acid-responsive liposomes for co-delivery of IRI and 398 (IRI&398-s-LPs) were developed, in which the rapid release of both drugs could be triggered under acidic conditions. Notably, a CT-26/3T3 cell co-culture system was used to mimic the real TME both in vitro and in vivo. Cellular immunofluorescence revealed that IRI&398-s-LPs could efficiently decrease the activation of CAFs. In vitro cytotoxicity evaluation demonstrated that IRI&398-s-LPs exhibited higher cytotoxicity than the other liposomal formulations in the CT-26 and CT-26/3T3 cell co-culture system. In vivo NIRF imaging showed that the IRI&398-s-LPs could increase drug accumulation in the tumor sites. Furthermore, IRI&398-s-LPs not only presented superior in vivo anti-tumor activity in CT-26 bearing BALB/c mice, but also enhanced the effect in CT-26/3T3 cell bearing mice with decreased collagen and CAF biomarker expression. Furthermore, IRI&398-s-LPs also presented superior anti-metastatic efficiency in a lung metastasis model. These results indicated that this combinational strategy for eliminating both tumor cells and CAFs provides a new approach for cancer therapy, and the prepared TME-responsive liposomes for co-delivery of drugs hold promising clinical application prospects.

Co-Delivery of Curcumin and Capsaicin by Dual-Targeting Liposomes for Inhibition of aHSC-Induced Drug Resistance and Metastasis.

Recent research studies have shown that the low survival rate of liver cancer is due to drug resistance and metastasis. In the tumor microenvironment (TME), activated hepatic stellate cells (aHSCs) have been proven to favor the development of liver cancer. Hence, the combination therapy dual-targeting aHSCs and tumor cells might be an effective strategy for treatment of liver cancer. In this study, the novel multifunctional liposomes (CAPS-CUR/GA&Gal-Lip) were prepared for co-delivery of curcumin (CUR) and capsaicin (CAPS), in which glycyrrhetinic acid (GA) and galactose (Gal) were chosen as targeting ligands to modify the liposomes (Lip) for dual-targeting liver cancer. To mimic TME, a novel HSCs+HepG2 (human hepatoma cell line) cocultured model was established for the antitumor effect in vitro. The results showed that, compared to HepG2 cells alone, the cocultured model promoted drug resistance and migration by upregulating the expression of P-glycoprotein (P-gp) and Vimentin, which were effectively inhibited by CAPS-CUR/GA&Gal-Lip. The efficacy of the in vivo antitumor was evaluated by three mice models: subcutaneous H22 (mouse hepatoma cell line) tumor-bearing mice, H22+m-HSC (mouse hepatic stellate cell) tumor-bearing mice, and orthotopic H22 cells-bearing mice. The results showed that CAPS-CUR/GA&Gal-Lip exhibited lesser extracellular matrix (ECM) deposition, lesser tumor angiogenesis, and superior antitumor effect compared with the no- and/or Gal-modified Lip, which was attributed to the simultaneous blocking of the activation of HSCs and inhibition of the metastasis of tumor cells. The dual-targeting method using Lip is thus a potential strategy for liver cancer treatment.

Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer.

Canine acanthomatous ameloblastomas (CAA), analogs of human ameloblastoma, are oral tumors of odontogenic origin for which the genetic drivers have remained undefined. By whole-exome sequencing, we have now discovered recurrent HRAS and BRAF activating mutations, respectively, in 63% and 8% of CAA. Notably, cell lines derived from CAA with HRAS mutation exhibit marked sensitivity to MAP kinase (MAPK) pathway inhibitors, which constrain cell proliferation and drive ameloblast differentiation. Our findings newly identify a large-animal spontaneous cancer model to study the progression and treatment of RAS-driven cancer. More broadly, our study highlights the translational potential of canine cancer genome sequencing to benefit both humans and their companion animals.

Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone quantity in bone remodeling following injury in the same individuals, shown as increased cortical bone thickness, increased trabecular bone formation and accelerated bone defect repair. We find that the RANKL/OPG ratio and Wnt-3a expression are suppressed at the extracted alveolar sites in Zol-treated rats compared with those at the injured sites of peripheral bones. We also show that Zol-treated bone marrow stromal cell (BMSCs) derived from jaw and peripheral bones exhibit differences in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic and chondrogenic related marker genes, and in vivo bone formation capacity. Hopefully, this study will help us better understand the pathogenesis of BRONJ, and deepen the theoretical research.

Osteogenesis of rat mesenchymal stem cells and osteoblastic cells on strontium-doped nanohydroxyapatite-coated titanium surfaces.

PURPOSE: The aim of this study was to compare the promotion of osteogenesis in vitro on three types of titanium surfaces: a strontium-hydroxyapatite (Sr-HA)-coated surface, a nano-HA-coated surface, and an uncoated roughened surface. MATERIALS AND METHODS: Sr-HA and HA were placed on disks with a roughened titanium surface by electrochemical deposition. MC3T3-E1 preosteoblast cells and rat bone mesenchymal stem cells were cultured on the Sr-HA, HA-coated, and uncoated roughened disks, and cell adhesion, proliferation, viability, osteogenic differentiation, and formation of mineralized nodules were measured at various time points. RESULTS: The Sr-HA coating produced by a simple electrochemical deposition treatment evidently enhanced the attachment, spreading, alkaline phosphatase activity, and extracellular matrix calcium mineralization of mouse bone mesenchymal stem cells and MC3T3-E1 cells compared with an untreated roughened titanium surface and a nano-HA-coated surface. CONCLUSION: This study suggests that a Sr-doped nano-HA coating produced through electrochemical deposition improves the osteoconductivity of a microrough titanium surface.

Identification of recurrent SMO and BRAF mutations in ameloblastomas.

Here we report the discovery of oncogenic mutations in the Hedgehog and mitogen-activated protein kinase (MAPK) pathways in over 80% of ameloblastomas, locally destructive odontogenic tumors of the jaw, by genomic analysis of archival material. Mutations in SMO (encoding Smoothened, SMO) are common in ameloblastomas of the maxilla, whereas BRAF mutations are predominant in tumors of the mandible. We show that a frequently occurring SMO alteration encoding p.Leu412Phe is an activating mutation and that its effect on Hedgehog-pathway activity can be inhibited by arsenic trioxide (ATO), an anti-leukemia drug approved by the US Food and Drug Administration (FDA) that is currently in clinical trials for its Hedgehog-inhibitory activity. In a similar manner, ameloblastoma cells harboring an activating BRAF mutation encoding p.Val600Glu are sensitive to the BRAF inhibitor vemurafenib. Our findings establish a new paradigm for the diagnostic classification and treatment of ameloblastomas.

Enhancing the performance of polymer photovoltaic cells by using an alcohol soluble fullerene derivative as the interfacial layer.

Alcohol soluble fullerene derivative (FN-C60) has been synthesized and used as a cathode interfacial layer for high-efficiency polymer solar cells (PSCs). To examine the function of the FN-C60 interfacial layer, polymer solar cells were fabricated with blends of P3:PC71BM, HXS-1:PC71BM, PDFCDTBT:PC71BM, and PDPQTBT:PC71BM as the active layer. In comparison to the bare Al electrode, power conversion efficiencies (PCEs) of P3:PC71BM, HXS-1:PC71BM, PDFCDTBT:PC71BM, and PDPQTBT:PC71BM based PSCs were increased from 3.50 to 4.64%, 4.69 to 5.25%, 2.70 to 4.60%, and 1.52 to 2.29%, respectively, when FN-C60/Al was used as the electrode. Moreover, the overall photovoltaic performances of PSCs with the FN-C60/Al electrode were better than those of cells with LiF/Al electrode, indicating that FN-C60 is a potential interfacial layer material to replace LiF.

Subchronic safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis stimulating agent, after 5-week subcutaneous injection in Cynomolgus monkeys and Sprague-Dawley rats.

EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is coupled to polyethylene glycol (PEG) and designed to specifically bind and activate the erythropoietin (EPO) receptor to result in production of red blood cells. This study was designed to evaluate the potential subchronic toxicity of EPO-018B for Cynomolgus monkeys and Sprague-Dawley rats both at 0, 0.5, 5 and 50 mg/kg every week for 5 weeks, followed by 6-week recovery for rats and 12-week recovery for monkeys. The No Observed Adverse Effect Level (NOAEL) for rats and monkeys were both considered to be at least 0.5 mg/kg/day, the minimum toxic dose to be 5.0 mg/kg/day and the severe toxic dose to be more than 50.0 mg/kg/day. The toxicological effects included the exaggerated pharmacology and secondary sequelae that resulted from an erythropoiesis-stimulating agent treatment to healthy animals. Most treatment induced effects were reversible or showed ongoing recovery upon discontinuation of treatment. The anticipated patient population for EPO-018B treatment is targeted to be the anemia patients caused by chronic renal failure or chemotherapy against to cancer and is expected to have an ideal clinical application prospect.