Triggered Crosslinking of Main-Chain Enediyne Polyurethanes via Bergman Cyclization.

Crosslinking chemistries occupy an important position in polymer modification with a particular importance when triggered in response to external stimuli. Enediyne (EDY) moieties are used as functional entities in this work, known to undergo a pericyclic Bergman cyclization (BC) to induce a triggered crosslinking of polyurethanes (PU) via the intermediately formed diradicals. Diamino-EDYs, where the distance between the enyne-moieties is known to be critical to induce a BC, are placed repetitively as main-chain structural elements in isophorone-based PUs to induce reinforcement upon heating, compression, or stretching. A 7-day compression under room temperature results in a ≈69% activation of the BC, together with the observation of an increase in tensile strength by 62% after 25 stretching cycles. The occurrence of BC is further proven by the decreased exothermic values in differential scanning calorimetry, together with characteristic peaks of the formed benzene moieties via IR spectroscopy. Purely heat-induced crosslinking contributes to 191% of the maximum tensile strength in comparison to the virgin PU. The BC herein forms an excellent crosslinking strategy, triggered by heat or force in PU materials.

Aging Characteristics and Ecological Effects of Primary Microplastics in Cosmetic Products Under Different Aging Processes.

Microplastics are becoming an increasingly environmental concern, but only a few studies have focused on primary microplastics. Herein, four primary microplastics (Lapis, Jade, Topaz and White) commonly used in cosmetic products were selected to investigate the effects of sunlight, seawater, and soil aging on their environmental behaviors. After sunlight and seawater aging, the surfaces of all four microplastics developed breaks and cracks, with particle sizes decreased and specific surface areas increased. Topaz exhibited the most significant changes under sunlight and seawater aging and its maximum adsorption capacity of phenanthrene significantly increased by 22.50% and 47.86%, respectively. Under soil aging, amending with either White or Topaz changed the soil bacterial community composition and diversity, but they had less ecological impacts than polyvinyl chloride plastic. The results of this study provide vital information for understanding the aging characteristics, environmental behavior, and ecological effects of primary microplastics under natural aging processes.

A New Ester-Substituted Quinoxaline-Based Narrow Bandgap Polymer Donor for Organic Solar Cells.

The electron-deficient ester group substitution in the sidechain of the commonly used electron-withdrawing quinoxaline (Qx) unit is seldom studied, while ester-substituted Qx units possess easy syntheses and facile modulation of the polymer solubility, and the enhanced electron-withdrawing property of ester substituted Qx unit can theoretically broaden the optical absorption of the resulting polymers and improve the open circuit voltage in the corresponding organic solar cells (OSCs). In this work, a novel ester-substituted Qx-based narrow bandgap polymer (NBG) donor material PBDTT-EFQx, which exhibits an absorption edge of 790 nm (bandgap < 1.6 eV), is designed and synthesized. Results show that the OSCs composed of PBDTT-EFQx and PC71 BM present the highest power conversion efficiency (PCE) of 6.8%, compared to PCEs of 5.0% for PBDTT-EFQx:ITIC based devices and 4.1% for PBDTT-EFQx:N2200 based devices, respectively. Characterizations and analyses indicate that the PC71 BM-based OSCs have well-matched energy levels, better complementary light absorption, the highest and most balanced carrier mobilities, as well as the lowest degree of recombination losses, and therefore, leading to the highest PCE among the three types of OSCs. This work reveals that the ester-substituted quinoxaline unit is one of the potential building blocks for NBG polymer donors.

Cell-Penetrating Peptide Modified PEG-PLA Micelles for Efficient PTX Delivery.

On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects of drugs, cell-penetrating peptides have been used to functionalize the surface of polymer micelles endowed with the ability to target tumor tissues. Herein, we first synthesized functional polyethylene glycol-polylactic acid (PEG-PLA) tethered with maleimide at the PEG section of the block polymer, which was further conjugated with a specific peptide, the transactivating transcriptional activator (TAT), with an approved capacity of aiding translocation across the plasma membrane. Then, TAT-conjugated, paclitaxel-loaded nanoparticles were self-assembled into stable nanoparticles with a favorable size of 20 nm, and displayed a significantly increased cytotoxicity, due to their enhanced accumulation via peptide-mediated cellular association in human breast cancer cells (MCF-7) in vitro. But when further used in vivo, TAT-NP-PTX showed an acceleration of the drug's plasma clearance rate compared with NP-PTX, and therefore weakened its antitumor activities in the mice model, because of its positive charge, its elimination by the endoplasmic reticulum system more quickly, and its targeting effect on normal cells leading towards being more toxic. So further modification of TAT-NP-PTX to shield TAT peptide's positive charges may be a hot topic to overcome the present dilemma.

Nanoformulation of a Novel Pyrano[2,3-c] Pyrazole Heterocyclic Compound AMDPC Exhibits Anti-Cancer Activity via Blocking the Cell Cycle through a P53-Independent Pathway.

Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated as AMDPC). The IC50 of AMDPC against Bcap-37 breast cancer cells was 46.52 µg/mL. Then the hydrophobic AMDPC was encapsulated in PEG-PLGA block copolymers, and then self-assembled as polymeric micelle (mPEG-PLGA/AMDPC) to improve both physiochemical and release profiles. The effect of mPEG-PLGA/AMDPC on BCAP-37 cancer cells showed similar anti-tumor effects as AMDPC. Furthermore, the anti-tumor mechanism of mPEG-PLGA/AMDPC was investigated, which can probably be attributed to stimulating the expression of P21 gene and therefore protein production on BCAP-37 cells, and then blocked the cell cycle through the P53-independent pathway both in S phase and G2 phase. Thus, mPEG-PLGA/AMDPC is a promising therapeutic agent for cancer treatment, and further in vivo studies will be developed.

[Study on digital models of normal deciduous dentition in 189 children from Shanghai].

PURPOSE: To study the gender difference and the regulation of growth and development in normal deciduous dentition． METHODS: A total of 189 children with normal deciduous dentition aged 3 to 6 years in several kindergartens in Xuhui District in Shanghai were selected. The three-dimensional(3D) digital dental models were reconstructed by intraoral scanning. Geomagic Studio, a 3D reverse engineering software, was employed to extract the data, such as the dental arc perimeter of C(APC), the dental arc perimeter of E(APE), the dental arc length of C(LC), the dental arc length of E(LE), the dental arc width of C(C-C), the dental arc width of E(E-E), the mesiodistal width of the deciduous crown, the maxillary and mandibular space. SPSS 22.0 software package was used for data analysis. RESULTS: Parameters of deciduous dentition in boys were significantly elevated than in girls(P＜0.05). All the boys and girls were divided into 4 groups by age. In 3-year-old group, significant differences were observed in maxillary APC, C-C, E-E(P＜0.05) between boys and girls. In 4-year-old group, all boys' parameters were significantly greater than girls'(P＜0.05) except maxillary LC. In 5-year-old group, there were significant differences in all the parameters between boys and girl(P＜0.05) except maxillary APE and mandibular APC, LC, LE, C-C. No significant difference was observed in all the parameters except mandibular APE in 6-year old group. The significant difference between boys and girls were observed in the mesiodistal width of each deciduous crown except that of the maxillary lateral incisor and mandibular central incisor (P＜0.05). There were significant differences in maxillary LE and E-E among children of different ages(P＜0.05).The maxillary space was significantly greater than the mandibular space(P＜0.01). CONCLUSIONS: There was gender difference in children's normal deciduous dentition, especially when they were 4 years old.

Enhanced Transdermal Peptide-Modified Flexible Liposomes for Efficient Percutaneous Delivery of Chrysomycin A to Treat Subcutaneous Melanoma and Intradermal MRSA Infection.

Superficial skin diseases, including skin infections and tumors, are common healthcare burdens. In this study, the in vivo activity of chrysomycin A (CA) is explored, and a transdermal liposomal CA formulation is further constructed for the simultaneous treatment of cutaneous melanoma and cutaneous methicillin-resistant Staphylococcus aureus (MRSA) infection. The prepared liposomes (TD-LP-CA) display a strong antitumor effect with an IC50 value of less than 0.1 µm in B16-F10 cells, suppress the proliferation of MRSA with a minimum inhibitory concentration (MIC) of 1 µm, and eradicate established MRSA biofilms at 10× MIC in vitro. More importantly, TD-LP-CA shows enhanced stratum corneum (SC) penetration, reaching more than 500 µm beneath the skin's surface due to modification with the TD peptide, and demonstrates excellent subcutaneous tumor penetration after skin application in vivo. TD-LP-CA displays an excellent therapeutic effect against intradermal MRSA infection in mice after topical dermal administration, as well as a moderate inhibitory effect on subcutaneous melanoma with a 75% tumor inhibition rate. The liposomes prepared herein can be a promising carrier for transcutaneous CA transfer for the treatment of superficial diseases such as skin tumors and infections due to their ability to overcome the skin barrier.

Successful replantation of amputated facial tissues by supermicrosurgery.

BACKGROUND: Although replantation of amputated facial segments remains challenging in reconstructive surgery, it offers excellent aesthetic and functional outcomes. METHODS: From May 2004 to October 2019, 12 patients underwent replantation of amputated facial tissues by supermicrosurgery. The case details, such as the rationale for replantation, the operation method, and postoperative therapy, are described. Four cases are discussed to demonstrate the replantation of different facial parts. RESULTS: Facial tissue replantation was successful in all 12 patients without secondary surgery. The cases included the nose (1 patient), ears (8 patients), lips (2 patients), and one of the soft tissue segments surrounding the lower jaw. Venous congestion occurred in three patients who received a solitary arterial repair and were treated with bloodletting. All patients expressed satisfaction with the cosmetic and functional results at the final follow-up. CONCLUSIONS: Supermicrosurgical facial tissue replantation is a promising and effective procedure for providing patients with the best aesthetic and functional outcomes.

Improved paclitaxel delivery with PEG-b-PLA/zein nanoparticles prepared via flash nanoprecipitation.

Polymeric micelle is a promising vehicle to improve the bioavailability and clinical outcomes of paclitaxel (PTX) which has been proven effective in the treatment of a wide range of cancers. However, conventional PTX formulation with the amphiphilic PEG-b-PLA usually suffers from insufficient PTX loading, low stability of PTX-micelles, and rapid PTX release due to low compatibility between PTX and PLA, limiting its clinical application. In this study, a novel nanoparticle platform was developed to improve the stability of PTX-loaded nanoparticles (NPs) and the delivery efficacy of PTX by integrating the flash nanoprecipitation (FNP) technique and a combination of amphiphilic PEG-PLA and super hydrophobic zein. The incorporation of zein led to the formation of distinct hydrophobic interiors of NPs which enhanced the interaction between PTX and NPs, therefore improving the encapsulation efficiency of PTX and sustained drug release compared with PEG-PLA micelles without zein. In addition, FNP allowed facile fabrication of PTX-NPs with smaller sizes and higher stability. These PTX-NPs showed superior sustained release of PTX and good cancer cell-killing in vitro. Among them, PTX-5k-16k-1Z NPs exhibited excellent biosafety and anti-tumor efficacy in a xenograft tumor model in mice, suggesting great potential in the delivery of hydrophobic drugs for cancer therapy.

[Effects of Land-use Conversion on Soil Nitrification and NO & N2O Emissions in Tropical China Under Different Moisture Conditions].

Rain and heat conditions are abundant in tropical areas, and rubber and tea are widely planted in this region; the nitrification process produces nitrate content, which is not conducive to the maintenance of nitrogen nutrients, and has negative environmental effects (nitrogen oxide emissions). The characteristics of soil nitrification rate and nitrogen oxide emission under different land use patterns remain unclear. An incubation experiment was conducted under the 5 a (T5) and 15 a (T15) tea plantation soils and the nearby typical rubber plantation (XJ) soils in Baisha county of Hainan province under two moisture contents (50% WFPS-L and 80% WFPS-H) for 71 d at 25℃. The results showed that:① after the rubber plantation was converted to a tea plantation, the net nitrification and soil NO and N2O emissions were significantly reduced under high moisture content. The overall trend was in the order of XJH>T15H>T5H, and the values of soil net nitrification and NO and N2O emissions were as high as 4.2 mg·(kg·d)-1, 1.4 mg·kg-1, and 14.3 mg·kg-1 in the XJH treatment, respectively. Under the low moisture content, soil NO emissions in tea field soil were significantly reduced relative to those in rubber plantation soil, N2O emissions had no significant difference among different treatments, and net nitrification had no significant difference between the XJ and T15 treatments. There was a significant positive correlation between NO emissions and net nitrification rate (P<0.01). ② The net nitrification of XJH was higher than that of XJL, but the net nitrification values under different moisture contents in tea field soil was in contrast to that in rubber plantation soil. The NO emissions of XJ and T15 under different moisture contents were consistent with the trend of net nitrification, and the high nitrification promoted NO emissions, whereas NO emissions of T5 were not significantly affected by moisture content. The high moisture content treatment significantly promoted N2O emissions relative to those under the low moisture content treatment. The results showed that SOM, TN, pH, and moisture content were the key factors affecting soil net nitrification rate, NO, and N2O emissions. The conversion of the rubber plantation to a tea plantation significantly reduced the net nitrification rate and negative impact on the environment under high moisture content.

Nanostructured Shell-Layer Artificial Antibody with Fluorescence-Tagged Recognition Sites for the Trace Detection of Heavy Metal Ions by Self-Reporting Microsensor Arrays.

Herein, a strategy for a metal ion-imprinted artificial antibody with recognition sites tagged by fluorescein was carried out to construct the selective sites with a sensitive optical response signal to the specific metal ion. The synthesized silica nanoparticles were modified by the derivative residue group of 3-aminopropyltriethoxysilane conjugated with a 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) molecule through the hydrolysis and condensation reactions. The as-prepared silica nanoparticles were encapsulated by metal ion (Cu2+, Cd2+, Hg2+, and Pb2+)-imprinted polymers with nanostructured layers through the copolymerization of ethyl glycol dimethyl methacrylate (EGDMA) as a cross-linker, AIBN as an initiator, metal ions as template molecules, AA as a functional monomer, and acetonitrile as a solvent. The layers of molecular imprinted polymers (MIPs) with a core-shell structure removed template molecules by EDTA-2Na to retain the cavities and spatial sizes to match the imprinted metal ions. The microsensor arrays were achieved by the self-assembly technique of SiO2@MIP nanoparticles on the etched silicon wafer with regular dot arrays. The nanostructured-shell layers with fluorescence-tagged recognition sites rebound metal ions by the driving force of concentration difference demonstrates the high selective recognition and sensitive detection to heavy metal ions through the decline of fluorescence intensity. The LOD concentration for four metal ions is down to 10-9 mol·L-1. The method will provide biomimetic synthesis, analyte screen, and detection of highly dangerous materials in the environment for theoretical foundation and technological support.

Immunobiology of T Cells in Sjögren's Syndrome.

Sjögren's syndrome (SjS) is a systemic autoimmune disease marked by xerostomia (dry mouth), keratoconjunctivitis sicca (eye dryness), and other systematic disorders. Its pathogenesis involves an inflammatory process that is characterized by lymphocytic infiltration into exocrine glands and other tissues. Although the development of ectopic lymphoid tissue and overproduction of autoantibodies by hyperactive B cells suggest that they may promote SjS development, treatment directed towards them fails to induce significant laboratory or clinical improvement. T cells are overwhelming infiltrators in most phases of the disease, and the involvement of multiple T cell subsets of suggests the extraordinary complexity of SjS pathogenesis. The factors, including various cellular subtypes and molecules, regulate the activation and suppression of T cells. T cell activation induces inflammatory cell infiltration, B cell activation, tissue damage, and metabolic changes in SjS. Knowledge of the pathways that link these T cell subtypes and regulation of their activities are not completely understood. This review comprehensively summarizes the research progress and our understanding of T cells in SjS, including CD4+ T cells, CD8+ TRM cells, and innate T cells, to provide insights into for clinical treatment.

Tumor-targeting peptide functionalized PEG-PLA micelles for efficient drug delivery.

Because of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, block copolymer micelles are widely utilized for chemotherapy drug delivery. In order to further improve the anti-tumor ability and reduce unwanted side effects of drugs, tumor-targeting peptides were used to functionalize the surface of polymer micelles so that the micelles can target tumor tissues. Herein, we synthesized a kind of PEG-PLA that is maleimide-terminated and then conjugated with a specific peptide F3 which revealed specific capacity binding to nucleolin that is overexpressed on the surface of many tumor cells. Then, F3 conjugated, paclitaxel loaded nanoparticles (F3-NP-PTX) were prepared as stable micelles that displayed an enhanced accumulation via a peptide-mediated cellular association in human breast cancer cells (MCF-7). Furthermore, F3-NP-PTX showed a prominent anti-tumor efficacy compared with non-targeting nanoparticles (NP-PTX) both in vitro and in vivo, and showed great potential as an efficacious targeting drug delivery system for breast cancer treatment.

In vitro evaluation of a bone morphogenetic protein­2 nanometer hydroxyapatite collagen scaffold for bone regeneration.

Scaffold fabrication and biocompatibility are crucial for successful bone tissue engineering. Nanometer hydroxyapatite (nHAP) combined with collagen (COL) is frequently utilized as a suitable osseous scaffold material. Furthermore, growth factors, including bone morphogenetic protein­2 (BMP­2), are used to enhance the scaffold properties. The present study used blending and freeze­drying methods to develop a BMP­2­nHAP­COL scaffold. An ELISA was performed to determine the BMP­2 release rate from the scaffold. Flow cytometry was used to identify rat bone marrow­derived mesenchymal stem cells (BMSCs) prior to their combination with the scaffold. Scanning electron microscopy was used to observe the scaffold structure and BMSC morphology following seeding onto the scaffold. BMSCs were also used to assess the biological compatibility of the scaffold in vitro. BMP­2­nHAP­COL and nHAP­COL scaffolds were assessed alongside the appropriate control groups. Cells were counted to determine early cell adhesion. Cell Counting kit­8 and alkaline phosphatase assays were used to detect cell proliferation and differentiation, respectively. Gross morphology confirmed that the BMP­2­nHAP­COL scaffold microstructure conformed to the optimal characteristics of a bone tissue engineering scaffold. Furthermore, the BMP­2­nHAP­COL scaffold exhibited no biological toxicity and was demonstrated to promote BMSC adhesion, proliferation and differentiation. The BMP­2­nHAP­COL scaffold had good biocompatibility in vitro, and may therefore be modified further to construct an optimized scaffold for future bone tissue engineering.