Greatly Enhanced Accessibility and Reproducibility of Worm-like Micelles by In Situ Crosslinking Polymerization-Induced Self-Assembly.

Worm-like micelles have attracted great interest due to their anisotropic structures. However, the experimental conditions for obtaining worm-like micelles are very restricted, which usually causes seriously poor reproducibility. In this work, significantly enhanced accessibility of worm-like micelles is realized by in situ crosslinking polymerization-induced self-assembly (PISA). The reproducibility of worm-like micelles is greatly improved due to the significantly enlarged experimental windows of worm-like micelles in the morphology diagram. Moreover, the reliability of the methodology to enhance the accessibility of worm-like micelles has been demonstrated in various in situ crosslinking PISA systems. The greatly enhanced accessibility and reproducibility of worm-like micelles is undoubtedly cost-effective especially in scale-up production, which paves the way for further application of worm-like micelles with various compositions and functionalities.

Randomly Distributed Sulfur Atoms in the Main Chains of CO2 -Based Polycarbonates: Enhanced Optical Properties.

Polymeric materials possessing both high refractive indices and high Abbe numbers are much in demand for the development of advanced optical devices. However, the synthesis of such functional materials is a challenge because of the trade-off between these two properties. Herein, a synthetic strategy is presented for enhancing the optical properties of CO2 -based polycarbonates by modifying the polymer's topological structure. Terpolymers with thiocarbonate and carbonate units randomly distributed in the polymers' main chain were synthesized via the terpolymerization of cyclohexene oxide with a mixture of CO2 and COS in the presence of metal catalysts, most notably a dinuclear aluminum complex. DFT calculations were employed to explain why different structural sequence were obtained with distinct bimetallic catalysts. Varying the CO2 pressure made it possible to obtain terpolymers with tunable carbonate linkages in the polymer chain. More importantly, optical property studies revealed that terpolymers with comparable thiocarbonate and carbonate units exhibited a refractive index of 1.501 with an enhanced Abbe number as high as 48.6, much higher than the corresponding polycarbonates or polythiocarbonates. Additionally, all terpolymers containing varying thiocarbonate content displayed good thermal properties with Tg >109 °C and Td >260 °C, suggesting little loss in the thermal stability compared to the polycarbonate. Hence, modification of the topological structure of the polycarbonate is an efficient method of obtaining polymeric materials with enhanced optical properties without compromising thermal performance.

Polymerization-Induced Self-Assembly to Produce Prodrug Nanoparticles with Reduction-Responsive Camptothecin Release and pH-Responsive Charge-Reversible Property.

Polymerization-induced self-assembly has been demonstrated to be a powerful strategy for fabricating polymeric nanoparticles in the last two decades. However, the stringent requirements for the monomers greatly limit the chemical versatility of PISA-based functional nanoparticles and expanding the monomer family of PISA is still highly desirable. Herein, a camptothecin analogue (CPTM) is first used as the monomer in PISA. Prodrug nanoparticles with reduction-responsive camptothecin release behavior are fabricated at 10% solid concentration (100 mg g-1 ). Poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) are used as the macro RAFT agents to comediate the RAFT dispersion polymerization of CPTM in ethanol to produce the PHPMA/PDEAEMA-stabilized nanoparticles. The PDEAEMA chains become hydrophobic and are in the collapsed state at physiological pH values. In contrast, in the vicinity of an acidic tumor, the tertiary amine groups of PDEAEMA chains are rapidly protonated, leading to fast hydrophobic-hydrophilic transitions and charge reversal. Such fast charge-reversal results in enhanced cancer cell internalization of the prodrug nanoparticles, thus achieving superior anticancer efficacy.

Facile Synthesis of Well-Defined Branched Sulfur-Containing Copolymers: One-Pot Copolymerization of Carbonyl Sulfide and Epoxide.

Topological polymers possess many advantages over linear polymers. However, when it comes to the poly(monothiocarbonate)s, no topological polymers have been reported. Described herein is a facile and efficient approach for synthesizing well-defined branched poly(monothiocarbonate)s in a "grafting through" manner by copolymerizing carbonyl sulfide (COS) with epichlorohydrin (ECH), where the side-chain forms in situ. The lengths of the side-chains are tunable based on reaction temperatures. More importantly, enhancement in thermal properties of the branched copolymer was observed, as the Tg  value increased by 22 °C, compared to the linear analogues. When chiral ECH was utilized, semicrystalline branched poly(monothiocarbonate)s were accessible with a Tm  value of 112 °C, which is 40 °C higher than that of the corresponding linear poly(monothiocarbonate)s. The strategy presented herein for synthesizing branched polymers provides efficient and concise access to topological polymers.

Polymerization-Induced Self-Assembly of Functionalized Block Copolymer Nanoparticles and Their Application in Drug Delivery.

Drug delivery systems (DDS) based on functionalized polymeric nanoparticles have attracted considerable attention. Although great advances have been reported in the past decades, the fabrication efficiency and reproducibility of polymeric nanoparticles are barely satisfactory due to the intrinsic limitations of the traditional self-assembly method, which severely prevent further applications of the intelligent DDS. In the last decade, a new self-assembly method, which is usually called polymerization-induced self-assembly (PISA), has become a powerful strategy for the fabrication of the polymeric nanoparticles with bespoke morphology. The PISA strategy efficiently simplifies the fabrication of polymeric nanoparticles (combination of the polymerization and self-assembly in one pot) and allows the fabrication of polymeric nanoparticles at a relatively high concentration (up to 50 wt%), making it realistic for large-scale production of polymeric nanoparticles. In this review, the developments of PISA-based polymeric nanoparticles for drug delivery are discussed.

Efficient Fabrication of Photosensitive Polymeric Nano-objects via an Ingenious Formulation of RAFT Dispersion Polymerization and Their Application for Drug Delivery.

An ingenious formulation of RAFT dispersion polymerization based on photosensitive monomers of 2-nitrobenzyl methacrylate (NBMA) and 7-(2-methacryloyloxy-ethoxy)-4-methyl-coumarin (CMA) is reported herein. Various morphologies, such as spherical micelle, nanoworm, lamella, and vesicle, are fabricated at up to 20% solids content. Photoinduced cleavage of the NBMA moieties and dimerization of the coumarin moieties are simultaneously triggered upon UV (365 nm) irradiation. The former endows the cores of the nano-objects with abundant carboxyl groups, resulting in the transformation of the hydrophobic cores to hydrophilic ones. The latter induces the core-cross-linking of the nano-objects, which endows the nano-objects with enhanced structural stability and prevents the nanoparticle-to-unimer disassembly. The resultant nano-objects exhibit superior structural stability and excellent performances for drug delivery, including high drug loadings, pH-stimuli release, and high-efficient endosomal escape.

Identification and analysis of ZFPM2 as a target gene of miR-17-92 cluster in chicken.

The miR-17-92 cluster plays important roles in a variety of physiological and pathological processes in mammals. Previously, we showed that miR-17-92 cluster promotes chicken preadipocyte proliferation; however, the mechanism for its action is unknown. In order to explore the mechanism by which miR-17-92 cluster promotes chicken preadipocyte proliferation, CCK8 proliferation assay was performed to determine the effect of ZFPM2 knockdown on chicken preadipocyte proliferation. The results showed that ZFPM2 knockdown significantly promoted chicken preadipocyte proliferation (P<0.01). Consistent with the CCK8 results, the mRNA levels of cell proliferation marker genes, i.e., Cyclin D1, PCNA and Ki67, were markedly increased in the si-ZFPM2-transfected preadipocytes (P<0.01 or P<0.05). Bioinformatics analysis showed that there were two potential miRNA binding sites for the four individual members of miR-17-92 cluster in the ZFPM2 3'UTR, one for miR-17-5p and miR-20a and the other for miR-19a and miR-19b. To test whether ZFPM2 is a target for the miR-17-92 cluster, the ZFPM2 3'UTR reporter (psi-CHECK2-ZFPM2-3'UTR-WT) and its mutant reporter (psi-CHECK2-ZFPM2-3'UTR-MUT) were constructed. Reporter assays showed that overexpression of miR-17-92 cluster significantly inhibited the luciferase reporter activity of psi-CHECK2-ZFPM2-3'UTR-WT (P<0.01), as compared with control vector (empty pcDNA3.1). Transfection of miR-17-5p, miR-19a and miR-20a inhibitors increased the reporter activities of psi-CHECK2-ZFPM2-3'UTR-WT (P<0.01 or P<0.05). In contrast, transfection of miR-17-5p, miR-19a, and miR-20a inhibitors had no obvious effect on reporter activity of psi-CHECK2-ZFPM2-3'UTR-MUT. Further qRT-PCR analysis showed that miR-17-5p, miR-20a and miR-19a inhibitors significantly elevated the endogenous ZFPM2 mRNA expression (P<0.01 or P<0.05). Cotransfection of either miR-17-5p or miR-19a inhibitor and siZFPM2 showed that both inhibitors tended to reduce only slightly the promoting effect of siZFPM2 on chicken preadipocyte proliferation. Taken together, these data demonstrated that ZFPM2 is a target of miR-17-5p, miR-20a, miR-19a, and miR-19b, and that miR-17-92 cluster promotes chicken preadipocyte proliferation at least in part by targeting ZFPM2 and inhibiting its expression.

Fabrication of Reductive-Responsive Prodrug Nanoparticles with Superior Structural Stability by Polymerization-Induced Self-Assembly and Functional Nanoscopic Platform for Drug Delivery.

A highly efficient strategy, polymerization-induced self-assembly (PISA) for fabrication of the polymeric drug delivery systems in cancer chemotherapy is reported. Diblock prodrug copolymer, PEG-b-P(MEO2MA-co-CPTM) was used as the macro-RAFT agent to fabricate prodrug nanoparticles through PISA. The advantages of fabricating intelligent drug delivery system via this approach are as following: (1) Simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation in one-pot at relatively high concentration (100 mg/mL); (2) Almost complete monomer conversion allows direct application of the resultant prodrug nanoparticles without further purification; (3) Robust structures of the resultant prodrug nanoparticles, because the cross-linker was used as the comonomer, resulted in core-cross-linking simultaneously with the formation of the prodrug nanoparticles; (4) The drug content in the resultant prodrug nanoparticles can be accurately modulated just via adjusting the feed molar ratio of MEO2MA/CPTM in the synthesis of PEG-b-P(MEO2MA-co-CPTM). The prodrug nanoparticles with similar diameters but various drug contents were obtained using different prodrug macro-CTA. In consideration of the long-term biological toxicity, the prodrug nanoparticles with higher drug content exhibit more excellent anticancer efficiency due to that lower dosage of them are enough for effectively killing HeLa cells.

Functional analysis of the upstream regulatory region of chicken miR-17-92 cluster.

miR-17-92 cluster plays important roles in cell proliferation, differentiation, apoptosis, animal development and tumorigenesis. The transcriptional regulation of miR-17-92 cluster has been extensively studied in mammals, but not in birds. To date, avian miR-17-92 cluster genomic structure has not been fully determined. The promoter location and sequence of miR-17-92 cluster have not been determined, due to the existence of a genomic gap sequence upstream of miR-17-92 cluster in all the birds whose genomes have been sequenced. In this study, genome walking was used to close the genomic gap upstream of chicken miR-17-92 cluster. In addition, bioinformatics analysis, reporter gene assay and truncation mutagenesis were used to investigate functional role of the genomic gap sequence. Genome walking analysis showed that the gap region was 1704 bp long, and its GC content was 80.11%. Bioinformatics analysis showed that in the gap region, there was a 200 bp conserved sequence among the tested 10 species (Gallus gallus, Homo sapiens, Pan troglodytes, Bos taurus, Sus scrofa, Rattus norvegicus, Mus musculus, Possum, Danio rerio, Rana nigromaculata), which is core promoter region of mammalian miR-17-92 host gene (MIR17HG). Promoter luciferase reporter gene vector of the gap region was constructed and reporter assay was performed. The result showed that the promoter activity of pGL3-cMIR17HG (-4228/-2506) was 417 times than that of negative control (empty pGL3 basic vector), suggesting that chicken miR-17-92 cluster promoter exists in the gap region. To further gain insight into the promoter structure, two different truncations for the cloned gap sequence were generated by PCR. One had a truncation of 448 bp at the 5'-end and the other had a truncation of 894 bp at the 3'-end. Further reporter analysis showed that compared with the promoter activity of pGL3-cMIR17HG (-4228/-2506), the reporter activities of the 5'-end truncation and the 3'-end truncation were reduced by 19.82% and 60.14%, respectively. These data demonstrated that the important promoter region of chicken miR-17-92 cluster is located in the -3400/-2506 bp region. Our results lay the foundation for revealing the transcriptional regulatory mechanisms of chicken miR-17-92 cluster.

Formation of Hexagonally Packed Hollow Hoops and Morphology Transition in RAFT Ethanol Dispersion Polymerization.

Similar to the traditional self-assembly strategy, polymerization induced self-assembly and reorganization (PISR) can produce a myriad of polymeric morphologies through morphology transitions. Besides the chain length ratio (R) of the hydrophobic to the hydrophilic blocks, the chain mobility in the intermediate nano-objects, which is a requisite for morphology transition, is a determining factor in the formation of the final morphology. Although various morphologies have been fabricated, hexagonally packed hollow hoops (HHHs) with highly ordered internal structure have not, to the best of our knowledge, been prepared by PISR. In this article, the fabrication of HHHs through morphology transition from large compound vesicles to HHHs is reported. HHHs with highly regular internal structure may have significance in theoretical research and practical applications of nanomaterials.

[Modification by wheat germ agglutinin delays the ocular elimination of liposome].

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.

[Effects of platelets on the adhesion between leukocytes and liver sinusoidal endothelium cells as well as on the transendothelial migration of leukocytes undergoing hypoxia-reoxygenation].

OBJECTIVE: To investigate the effects of platelet on intercellular adhesion between leukocyte and liver sinusoidal endothelial cell(LSEC) and the transendothelial migration under the hypoxia-reoxygenation condition, as well as the role of relevant adhesion molecules. METHOD: LSEC was cultured for 24 hours under hypoxia condition and then reoxygenated for 2 hours (hypoxia-reoxygenation, HR). This hypoxia-reoxygenation model was used to simulate the clinical liver ischemia-reperfusion injury process (IRI). Platelets and leukocytes were labeled with fluorescence dye, and then the adhesion was detected by fluorescence microscope, fluorescence plate reader and laser scanning confocal microscope. Antibody blockage experiment was used to analyze the relevant adhesion molecules. RESULTS: The adhesion between platelets and LSEC was increased significantly after HR. The fluorescence intensity of adherent platelets increased from 142.10 ± 7.53 to 289.17 ± 20.00(P < 0.01). After H-R treatment and the addition of platelets, the number of adherent leukocytes increased markedly, and a significant statistical difference (360.71 ± 23.47 and 186.39 ± 17.96, P < 0.01) was found in comparing with the platelet deficient group. These adhesion processes could be blocked respectively by anti-GPIb, anti-GPIIb, anti-GPIIIa, anti-P-selectin, anti-CD31, anti-ICAM-1, anti-VCAM-1 and anti-ELAM-1. Confocal microscopy showed that platelets located between leukocytes and LSEC, and mediated their adhesion process. However, the adhesion of platelets to LSEC decreased the transendothelial migration of leukocytes (227.79 ± 16.51 and 167.27 ± 10.92, P < 0.05). CONCLUSION: During ischemia-reperfusion condition platelets adhere to the surface of LSEC, and then further mediate more adhesion processes between leukocytes and endothelial cells, as well as inhibit the transendothelial migration of leukocytes. The consequence is that large numbers of leukocytes were sequestrated within hepatic sinus, and deteriorate liver ischemia-reperfusion injury.

Differential activations of PKC/PKA related to microvasculopathy in diabetic GK rats.

Microvasculopathy is the most serious and predictable threat to the health of diabetic patients, which often results in end-stage renal disease, blindness, and limb amputations. Up to the present, the underlying mechanisms have remained elusive. Here, it was found that the differential activations of PKC/PKA were involved in diabetic microvasculopathy in diabetic GK rats. By real-time PCR, Western blot, immunohistochemistry, and enzyme activity assay, upregulation of PKC was prominent in kidney but was not significant in liver and brain. The expression and activity of PKA were lowered in kidney but comparable in brain and liver during diabetic nephropathy. Furthermore, the generation of reactive oxygen species, production of nitric oxide, and expression of inducible nitric oxide synthase induced by advanced glycation end products were inhibited by PKCß inhibitor LY-333531 or a PKA agonist in rat glomerular microvascular endothelial cells. Finally, albuminuria was significantly lowered by a PKA agonist and boosted by a PKA antagonist. It suggested that the differential activations of PKC/PKA related to microvasculopathy in diabetes and that activation of PKA may protect the diabetic microvasculature.

[Poly(arginine)8 enhanced intestinal absorption of insulin-loaded nanoparticles].

The purpose of this study is to investigate the feasibility of poly(arginine)8 (R8) modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a carrier for the oral delivery of insulin. Insulin-loaded PLGA nanoparticle (INS-NP) was prepared by a double emulsion-solvent evaporation method, and R8 was subsequently conjugated to the surface of the INS-NP via polyethylene glycol bridge (R8-INS-NP). The physical and chemical features of the nanoparticles were characterized, and insulin release was determined in vitro. The pharmacokinetics and pharmacodynamics were evaluated by in situ absorption study with the intestinal loop of rats. The blood glucose level was determined by glucose oxidize method and the serum insulin concentration was determined by radioimmunoassay (RIA). The mean diameter of INS-NP was (179.0 +/- 5.2) nm and the polydispersity index was 0.152 +/- 0.042, while the entrapment efficiency was (29.10 +/- 2.59) %. The in vitro release behavior of insulin showed an initial burst effect followed by a stage of slow release. After administrating 10 U x kg(-1) insulin to rats, R8-INS-NPs decreased the plasma glucose level much lower than INS-NPs, meanwhile, D-form R8 substantially enhanced intestinal absorption of insulin much more than L-form R8. Compared to subcutaneous injection, the relative bioavailabilities of insulin were 0.52%, 4.78%, 8.39%, and the pharmacological bioavailabilities were 2.07%, 3.90%, 8.24%, separately. The R8-modified nanoparticles promoted the intestinal absorption of insulin, which might be a potential approach for oral delivery of peptide, protein and even other hydrophilic macromolecules in the future.

[The function of bushen qiangdu recipe containing serum in OPG/RANKL pathway of ankylosing spondylitis patients].

OBJECTIVE: To study the mechanism of Bushen Qiangdu Recipe (BQR) for regulating osteoprotegerin receptor activator for nuclear factor kappa B ligand (OPG/RANKL) pathway in ankylosing spondylitis (AS). METHODS: Thirty active AS inpatients or outpatients were recruited from Department of CM Rheumatology, China-Japan Friendship Hospital from January to May 2009. All patients were treated with BQR for 3 successive months, one dose daily, once in the morning and once in the evening. Besides, 30 healthy volunteers were recruited. The serum of patients and volunteers were collected. The osteoblast cell lines hFOB1. 19 were divided into 3 groups: the pre-treatment group, the post-treatment group, and the healthy volunteer group (as the control group). All cell lines were cultured by corresponding culture medium containing each serum. The supernatant from osteoblast cell lines was collected. The protein content of OPG/RANKL was detected using ELISA, and the protein expression of OPG/RANKL was detected using RT-PCR. RESULTS: Compared with the control group, the OPG content, the mRNA and protein expressions of OPG, and the mRNA and protein expressions of OPG/RANKL all decreased, while the mRNA expression of RANKL increased in the pre-treatment group, showing statistical difference (P<0.05, P<0.01). Compared with the pre-treatment group, the OPG content, the mRNA and protein expressions of OPG significantly increased, and the mRNA and protein expressions of OPG/RANKL increased, while the mRNA expression of RANKL decreased in the post-treatment group, showing statistical difference (P<0.05, P<0.01). CONCLUSIONS: AS patients' serum could directly inhibit the expression of OPG in osteoblasts, promote the expression of RANKL, and down-regulate the OPG/RANKL ratio. BQR containing serum might promote the osteogenesis and inhibit the bone resorption possibly through directly up-regulating the OPG/RANKL ratio in osteoblast, thus inhibiting the differentiation and function of osteoclast.

[Relationship between Muscle Mass of Limbs and aGVHD in Patients with Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To explore the correlation of limb muscle mass and acute graft-versus-host disease. METHODS: Clinical data from 144 patients treated by allo-HSCT in Guangzhou First People's Hospital were collected and analyzed retrospectively. The age, sex, diagnosis, donor age, sex of the donors, preparative regimen, ATG dose, HLA match, graft source, and number of infused stem cells of the patients were collected as baseline information. Meanwhile, bioelectrical impedance principle (BIA) was used to measure the limb muscle mass, body weight, body mass index (BMI), waist-to-hip ratio, upper arm muscle circumference, triceps skinfold thickness, and body fat rate of the patients before and after transplantation, so as to compare the changes of limb muscle mass and investigate its correlation with aGVHD. RESULTS: It was found that 61.11% of allo-HSCT patients showed muscle mass loss, and the proportion of male and female was 35.42% and 25.69%, respectively. There were reduction in the body weight, BMI, upper arm muscle circumference and muscle mass of limbs after transplantation as compared with those before transplantation (P<0.05). By comparing with the cumulative incidence of aGVHD between the patients in low muscle mass group and normal muscle mass group, it was found that the cumulative incidence of Ⅱ-Ⅳdegree aGVHD in patients with low muscle mass (30.38%) was higher than those with normal muscle mass (8.93%), which showed statistical difference (P<0.05). Univariate analysis showed that muscle mass, the sex of the donors, and preparative regimen were the influencing factors of aGVHD (P<0.05). Binary logistic regression showed that low muscle mass was the independent risk factor affecting aGVHD (P<0.05). CONCLUSION: Patients treated by allo-HSCT shows a decline in muscle mass after transplantation, and the incidence of aGVHD is high in patients with low muscle mass. Therefore, the assessment of muscle quality in early stage in patients with HSCT can facilitate earlier detection of aGVHD.

Single nanosheet can sustainably generate oxygen and inhibit respiration simultaneously in cancer cells.

In a tumor, the abnormal cancer cell proliferation results in an insufficient O2 supply, and meanwhile cancer cells consume O2 very fast. The imbalance between a low oxygen supply and overwhelming oxygen consumption results in a low oxygen concentration in solid tumors. Therefore, in order to relieve hypoxia in tumors, it is necessary to not only sustainably generate O2, but also inhibit mitochondrial respiration simultaneously. Here, we found that a single Ti2C(OH)2 nanomaterial not only can sustainably generate O2 but also simultaneously highly inhibits mitochondrial respiration via binding phosphorylation proteins onto the surface in cancer cells. Ce6 was linked onto Ti2C(OH)2, forming Ti2C(OH)2-Ce6. Ti2C(OH)2-Ce6 could highly relieve hypoxia in tumors via the combination of sustainable O2 generation and respiration inhibition, produce enough 1O2 to kill cancer cells via PDT, and also effectively convert the absorbed light energy into thermal energy to kill cancer cell via PTT, thereby highly enhancing the cancer therapy.

Correction: Single nanosheet can sustainably generate oxygen and inhibit respiration simultaneously in cancer cells.

Correction for 'Single nanosheet can sustainably generate oxygen and inhibit respiration simultaneously in cancer cells' by Wei-Qiang Huang et al., Mater. Horiz., 2021, DOI: .

[Morphologic and functional characteristics of the immortalized human liver sinusoidal endothelial cell line].

OBJECTIVE: To investigate the morphologic and functional characteristics of the immortalized human liver sinusoidal endothelial cell line (LSEC line). METHODS: Immunofluorescence staining and fluorescence microscopy were used to detect the classic endothelial cell markers in LSEC line, and flow cytometry was used to analyze the purity of the human LSEC line. The morphology (including W-P bodies and surface fenestrations) and phagocytotic capacity of the human LSEC line were observed by transmission and scanning electron microscope. The proliferation curve of the human LSEC line was analyzed by MTT assay. The functional differences between the human LSEC line and human primary LSEC in expression of ELAM-1 and ICAM-1, activities of fibrinolysis (PAI-1, t-PA, u-PA), releasing of IL-6 and IL-8 were compared respectively by enzyme linked immunosorbent assay. Comparison of the susceptibility to hypoxia-reoxygenation induced apoptosis between the human LSEC line and human primary LSEC were investigated by TUNEL. RESULTS: The established human LSEC line maintained a high proliferative ability and has been passaged for more than 80 times in the absence of any growth factors. Immunofluorescence staining showed that the human LSEC line could express classic endothelial cell marks including von Willebrand Factor (vWF), and could take up acetylated low-density lipoproteins (Ac-LDL). The purity of the human LSEC line was confirmed over 95% by flow cytometric analysis. The W-P bodies and the phagocytosis of Dynabeads was demonstrated by transmission electron microscope. And fenestrations could be found cellular surface with scanning electron microscopy. When compared with human primary LSEC, the human LSEC line has an equivalent responsiveness to tumor necrosis factor in up-regulation of ELAM-1 and ICAM-1. The human LSEC line can also release PAI-1, t-PA, u-PA but can not release IL-6 and IL-8 to TNF-alpha. In contrast, human primary LSEC could release IL-6. The human LSEC line showed higher susceptibility to hypoxia-reoxygenation-induced apoptosis, and the percentage of apoptotic cells was as high as (38.4 +/- 6.7)%, while (28.6 +/- 4.5)% and (7.8 +/- 1.2)% respectively in primary LSEC and in human umbilical vein endothelial cells. CONCLUSIONS: The established human LSEC line maintains the special phenotypes and the major functional characteristics, and especially maintains the high susceptibility to hypoxia-reoxygenation-induced apoptosis. Therefore it is feasible to use this cell line for the study of liver ischemia-reperfusion injury.

Rhodanine-based Knoevenagel reaction and ring-opening polymerization for efficiently constructing multicyclic polymers.

Cyclic polymers have a number of unique physical properties compared with those of their linear counterparts. However, the methods for the synthesis of cyclic polymers are very limited, and some multicyclic polymers are still not accessible now. Here, we found that the five-membered cyclic structure and electron withdrawing groups make methylene in rhodanine highly active to aldehyde via highly efficient Knoevenagel reaction. Also, rhodanine can act as an initiator for anionic ring-opening polymerization of thiirane to produce cyclic polythioethers. Therefore, rhodanine can serve as both an initiator for ring-opening polymerization and a monomer in Knoevenagel polymerization. Via rhodanine-based Knoevenagel reaction, we can easily incorporate rhodanine moieties in the backbone, side chain, branched chain, etc, and correspondingly could produce cyclic structures in the backbone, side chain, branched chain, etc, via rhodanine-based anionic ring-opening polymerization. This rhodanine chemistry would provide easy access to a wide variety of complex multicyclic polymers.