Effect of Cross-Linking Density on Non-Linear Viscoelasticity of Vulcanized SBR: A MD Simulation and Experimental Study.

In recent years, there has been a growing interest in changes in dynamic mechanical properties of mixed rubber during dynamic shear, yet the influence of vulcanized characteristics on the dynamic shear behavior of vulcanized rubber, particularly the effect of cross-linking density, has received little attention. This study focuses on styrene-butadiene rubber (SBR) and aims to investigate the impact of different cross-linking densities (Dc) on dynamic shear behavior using molecular dynamics (MD) simulations. The results reveal a remarkable Payne effect, where the storage modulus experiences a significant drop when the strain amplitude (γ0) exceeds 0.1, which can be attributed to the fracture of the polymer bond and the decrease in the molecular chain's flexibility. The influence of various Dc values mainly resides at the level of molecular aggregation in the system, where higher Dc values impede molecular chain motion and lead to an increase in the storage modulus of SBR. The MD simulation results are verified through comparisons with existing literature.

[Helsmoortel-Van der Aa syndrome due to hotspot mutation of ADNP gene and a literature review].

OBJECTIVE: To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis. METHODS: Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed. RESULTS: The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c.2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents. CONCLUSION: Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.

[Gender difference in clinical manifestations of KBG syndrome due to variants of ANKRD11 gene].

OBJECTIVE: To explore gender difference in the clinical manifestations of two children with Keishi-Bukuryo-Gan syndrome (KBGS). METHODS: Clinical manifestations of the two children were reviewed. Genetic testing was carried out through next generation sequencing (NGS). Treatment was summarized, and the prognosis was followed up. RESULTS: Both children showed particular appearance including megatooth, abnormal hair distribution, hands' abnormality and language development delay. NGS revealed that both children have carried pathogenic variants of the ANKRD11 gene (c.1903_1907del and c.4911delT), which resulted in shifting of amino acid sequences starting from the Lysine and Proline at positions 635 and 1638, respectively. The female patient exhibited central precocious puberty. Her height has increased by 13 cm, and sex characteristics has retracted after treatment with leuprorelin for 23 months and recombinant human growth hormone for 1 month. CONCLUSION: Comparison of the two cases with different genders and summary of previously reported cases found that male KBGS patients have more obvious dysmorphisms such as triangular face, synophrys, ocular hypertelorism and vertebral body abnormality, with higher morbidity of epilepsy, mental retardation, autism, congenital heart disease, immune thrombocytopenia and other complications. KBGS is an autosomal dominant disease featuring more evident peculiar appearance and global development delay. Male patients often have multi-system involvement, and multidisciplinary cooperation is required for early recognition of particular features in order to improve the prognosis.

A Novel Variant in the Desmoplakin Gene in One Case of the Rare Carvajal Syndrome with Dilated Cardiomyopathy: A Case Report and Literature Review.

Carvajal syndrome is a rare hereditary cardiocutaneous syndrome caused by the variants of the desmoplakin (DSP) gene. In this study, we report a patient of Carvajal syndrome with a novel homozygous missense variant of DSP gene. We diagnosed a 7-year-old female patient with Carvajal syndrome characterized by dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia, who disclosed a novel homozygous missense variant c.4597C > T (p.Q1533X) in exon 6 of the DSP gene found for the first time. Both her parents were heterozygous for the identified nonsense variant c.4597C > T (p.Q1533X) in DSP gene but neither showed evidence of Carvajal syndrome, indicating that this novel variant causes the disease in an autosomal recessive manner. Genotypes of Carvajal syndrome are even broader than so far anticipated. When patients with dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia are found in clinical practice, Carvajal syndrome should be highly suspected, and family gene sequencing should be actively carried out.

Redox-responsive self-assembled podophyllotoxin twin drug nanoparticles for enhanced intracellular drug delivery.

Podophyllotoxin (PPT) is an active natural pharmaceutical component with potent anticancer activity. However, due to its poor water solubility and serious side effects, its medical applications are limited. In this work, we synthesized a series of PPT dimers, which can be self-assembled into stable nanoparticles of 124-152 nm in aqueous solution and can significantly increase the solubility of PPT in aqueous solution. In addition, PPT dimer nanoparticles exhibited high drug loading capacity (>80%) and could store at 4 °C in aqueous state with good stability for at least 30 d.In vitrorelease studies showed that nanoparticles with disulfide bonds (SS NPs) can quickly release (about 96.5% drug released within 24 h) the conjugated drug in PBS buffer (pH = 7.4) in the presence of DTT. Cell endocytosis experiments showed that SS NPs enhanced cell uptake (18.56 times higher than PPT for Molm-13, 10.29 times for A2780S and 9.81 times for A2780T) and maintained antitumor effect against human ovarian tumor cells (A2780S and resistant A2780T) and human breast cancer cells (MCF-7). In addition, the endocytosis mechanism of SS NPs was revealed that these nanoparticles were mainly up-taken by macropinocytosis-mediated endocytosis. We believe that these PPT dimer-based nanoparticles will become an alternative formula for PPT, moreover the assembly behavior of PPT dimer can be extended to other therapeutic drugs.

Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells.

Mitogen-activated protein kinase (MAPK) pathways are involved in stem cell differentiation. However, the odontoblastic differentiation-inducing effects by mineral trioxide aggregate (MTA) via MAPK pathways have not been clarified in human dental pulp stem cells (DPSCs). In this study we investigated the effects of MTA on cell viability and production of differentiation markers, and the involvement of MAPK signaling pathways in cultured human DPSCs. Cells were cultured with MTA, and the viability and differentiation productions of the cells were determined using the MTT assay and real-time PCR analysis, respectively. MAPK activation was measured by western blotting. MTA at concentrations of 20 and 10 mg/ml was toxic for human DPSCs. MTA significantly increased the expression of alkaline phosphatase (ALP), dentin sialophosphoprotein (DSPP), type I collagen (COLI), osteocalcin (OCN) and bone sialoprotein (BSP) mRNAs and induced the phosphorylation of p42 and p44 (p42/44), p38 and c-Jun N-terminal kinases 1 and 2 (JNK1/2) MAPK. Furthermore, the inhibitor of p42/44 MAPK attenuated the MTA-induced odontoblastic differentiation. These data indicated that MTA-induced odontoblastic differentiation of human DPSCs was via MAPK pathways, which may play a key role in the repair responses of dentin-pulp-like complexes.

Genetic and Phenotypic Spectrum of KBG Syndrome: A Report of 13 New Chinese Cases and a Review of the Literature.

KBG syndrome (KBGS) is a rare autosomal dominant inherited disease that involves multiple systems and is associated with variations in the ankyrin repeat domain 11 (ANKRD11) gene. We report the clinical and genetic data for 13 Chinese KBGS patients diagnosed by genetic testing and retrospectively analyse the genotypes and phenotypes of previously reported KBGS patients. The 13 patients in this study had heterozygous variations in the ANKRD11 gene, including seven frameshift variations, three nonsense variations, and three missense variations. They carried 11 variation sites, of which eight were previously unreported. The clinical phenotype analysis of these 13 patients and 240 previously reported patients showed that the occurrence rates of craniofacial anomalies, dental anomalies, global developmental delays, intellectual disability/learning difficulties, limb anomalies, and behavioural anomalies were >70%. The occurrence rates of short stature, delayed bone age, and spinal vertebral body anomalies were >50%. The frequency of global developmental delays and intellectual disability/learning difficulties in patients with truncated ANKRD11 gene variation was higher than that in patients with missense variation in the ANKRD11 gene (p < 0.05). Collectively, this study reported the genotypic and phenotypic characteristics of the largest sample of KBGS patients from China and discovered eight new ANKRD11 gene variations, which enriched the variation spectrum of the ANKRD11 gene. Variation in the ANKRD11 gene mainly caused craniofacial anomalies, growth and developmental anomalies, skeletal system anomalies, and nervous system anomalies. Truncated variation in the ANKRD11 gene is more likely to lead to global growth retardation and intellectual disability/learning difficulties than missense variation in ANKRD11.

The role of runt-related transcription factor 2 (Runx2) in the late stage of odontoblast differentiation and dentin formation.

Runx2, of the Runx family, is an essential transcription factor that controls bone and tooth development by regulating osteoblast and odontoblast differentiation. However, the function of Runx2 in late stage odontoblast differentiation is not clear. We studied the function of Runx2 in dentinogenesis by generating transgenic mice expressing Runx2 specifically in odontoblasts. We observed dentin formation in postnatal day 3 (P3), P7 and P28 mice and measured the expression levels of Runx2 and matrix proteins in dentin. The odontoblasts in transgenic mice (Tg) lost their tall columnar shape and polarization and dentinal tubules were absent. The dental pulp chamber was dramatically enlarged and the dentin in Tg mice was thinner. Osteoblast-like cells were seen instead of normal odontoblasts and were embedded in a bone-like matrix, indicating that dentin formation was replaced with bone. Predentin was disorganized possessing lacunae that contained odontoblasts. The mandibular molars of Tg mice showed noticeable defects by Micro-CT. Using quantitative real-time PCR, the expression of dentin matrix proteins, particularly dentin sialophosphoprotein (DSPP), was found to be upregulated in 3-day-old Tg mice and downregulated at 1 month of age. These findings indicate that Runx2 inhibited odontoblast terminal differentiation and induced transdifferentiation of odontoblasts to osteoblasts at the late cell differentiation stage. Therefore, Runx2 should be inhibited in odontoblasts to encourage normal cell maturation, differentiation and dentinogenesis.

Imitation of variable structural color in Paracheirodon innesi using colloidal crystal films.

Spacing variation of adjoining reflecting thin films in iridophore is responsible for the variable interference color in the paracheirodon innesi. On the basis of this phenomenon, colloidal crystal thin films with different structures are fabricated from monodisperse poly(styrene-methyl methacrylate-acrylic acid) (PSMA) colloids. The relationship between the colors and structures of the films is investigated and discussed according to the principle of light interference. A two-layer colloidal film having uniform color is researched and it displays diverse colors before and after swelling by styrene (St), which can be used to mimic the variable structural color of the paracheirodon innesi.

[The characterisitics of temperature/pH sensitive block copolymer micelles in vitro].

The dialysis method was employed to prepare blank and doxorubicin (DOX) loaded micelles formed by temperature- and pH- sensitive polyhistidine-co-polyDL-lactide-co-glycolide-co-polyethyleneglycol-co-polyDL-lactide-co-glycolide-co-polyhistidine (PHis-b-PLGA-b-PEG-b-PLGA-b-PHis). The critical micelle concentrations (CMC) of the copolymers were measured with Pyrene Fluorescent Probe Technique. The temperature- and pH- sensitive properties of the blank micelles solution were investigated by optical transmittance measurement. The morphology and diameter of DOX micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The entrapment rate and drug-loading rate were determined with dialysis method. The in vitro release study was further performed to examine the temperature- and pH-responsive drug release behavior from DOX-loaded micelles. The results indicated that the CMC, entrapment efficiency and drug-loaded amount of the micelles were 7.5 x 10(-3) g x L(-1), 85.2 +/- 3.1% and 10.4 +/- 4.5%, respectively. The DOX micelle was globular-shaped with a mean diameter of 91.1 +/- 15.8 nm. The transmittance of micelle solution consistently increased with the increasing temperature or decreasing pH. In comparison to the drug release profile at physiological conditions (37 degrees C, pH 7.4), the DOX-loaded micelles showed faster drug release rate at higher temperature (41 degrees C), lower pH (pH 7.0, pH 6.5, pH 5.0) or higher temperature and lower pH (41 degrees C, pH 5.0). This indicated that the micelles showed a temperature and pH-triggered drug release pattern. Base on the above results, it can be concluded that PHis-b-PLGA-b-PEG-b-PLGA-b-PHis block copolymer micelles which respond to temperature and pH stimuli are promising smart carriers for anti-tumor drugs with the advantages of temperature- and pH- triggered drug release.

[Preparation of adriamycin-loaded temperature/pH sensitive self-assembly block copolymer micelles].

The dialysis method was employed to load adriamycin into the micelles formed by temperature and pH sensitive polyhistidine-co-DL-lactide-co-glycolide-polyethylene glycol poly DL-lactide-co-glycolide-co-histidine (OLH-b-PLGA-b-PEG-b-PLGA-b-OLH). The critical micelle concentration (CMC) of the copolymer was measured with pyrene fluorescent probe method under different temperatures. The entrapment rate and drug-loading rate were determined with dialysis method. The diameter, morphology and surface potential of the copolymer micelles were investigated by corresponding instruments, respectively. The release behavior of adriamycin from copolymer micelles and the pH sensitivity were studied. The CMC of the copolymers ranged from 0.022 4 to 0.001 7 microg x mL(-1). The entrapment rate and drug-loading rate were 92.8% and 15.7%, respectively. The micelles have a mean diameter of (61.7 +/- 13.4) nm, and zeta potential was -9.88 mV. The in vitro adriamycin release rate increased with the pH dropping from 7.4 to 5.0. The results indicated that the CMC of the copolymers decreased as the raising of temperature, drug release behavior from the micelles possessed clearly pH sensitivity, and the copolymers may have a potential in targeted delivery system for anticancer drugs.

Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro.

BACKGROUND: Several studies have demonstrated that mesenchymal stem cells can ameliorate the inflammation of allergic rhinitis (AR) and correct the Th1/Th2 immune imbalance. METHODS: This study was performed to explore the immunomodulation properties of stem cells from human exfoliated deciduous teeth (SHEDs) in the treatment of AR in vivo and in vitro. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and then SHEDs or bone marrow mesenchymal stem cells (BMMSCs) were injected intravenously before challenge. We evaluated nasal symptoms, inflammatory infiltration of nasal mucosa, immunoglobulin secretion, cytokine production, and mRNA expression in the spleen. In addition, peripheral blood mononuclear cells (PBMCs) from AR patients were cultured with SHEDs or BMMSCs in the presence of phytohemagglutinin (PHA). PBMCs cultured alone with or without PHA served as controls. After 3 days of culture, we examined the effect of SHEDs on T lymphocyte proliferation, cytokine secretion, and the proportion of Foxp3+ Treg cells via flow cytometry. Finally, to determine the role of soluble factors (TGF-ß1, PGE2) in the immunomodulatory mechanism, a cytokine neutralization assay was performed. RESULTS: Nasal symptoms and inflammatory infiltration were significantly reduced after SHED administration. The OVA-specific IgE and IgG1 levels in serum were significantly decreased, and the increased IL-4, IL-5, IL-13, and IL-17A levels in the spleen after OVA challenge were markedly downregulated, while the level of IFN-γ was upregulated by SHED administration. The mRNA expression levels also changed correspondingly. SHEDs significantly inhibited the proliferation of T lymphocytes; increased the levels of IFN-γ, IL-10, PGE2, and TGF-ß1; decreased the levels of IL-4 and IL-17A; and induced the expansion of Treg cells in the coculture system. The neutralization of TGF-ß1 partly relieved the immunosuppression of SHEDs, but blocking PGE2 did not. In addition, SHEDs were superior to BMMSCs in inhibiting the Th2 immune response in vivo and inducing the expansion of Treg cells in vitro. CONCLUSION: These results suggest that SHEDs could correct the CD4+ T cell immune imbalance via Treg cells and may be potential therapeutic agents for the treatment of allergic diseases, such as AR, in the future.

Novel mutations in BMP1 induce a rare type of osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. OI patients of autosomal recessive inheritance are extremely rare, of which OI type XIII is attributable to mutation in BMP1 gene. CASE REPORT: Here, we detect the pathogenic mutations and analyze their relation to the phenotypes in a Chinese family with OI using next-generation sequencing (NGS) and Sanger sequencing. We also evaluate the efficacy of alendronate treatment in the patient with OI type XIII. The clinical phenotypes of the patient included recurrent fractures, muscle weakness, bone deformity, macrocephaly and elbow contractures, but no blue sclera or dentinogenesis imperfecta. High-resolution peripheral quantitative computed tomography revealed high bone mineral density and bone volume, but reduced trabecular numbers, increased porosity and comprised strength in this patient. Novel heterozygous mutations of c.1324G > T (p.Asp442Tyr) and c.148 + 1G > A in BMP1 gene were found in the proband, which would affect the CUB2 domain and the prodomain of mutant proteins. The parents were heterozygous carriers for the two mutations respectively, but with normal phenotype. CONCLUSIONS: We report for the first time that the novel pathogenic mutations in BMP1 can lead to the extremely rare OI type XIII, which exhibit unique characters of high bone mass, but with impaired bone microstructure and comprised bone strength. Alendronate is beneficial in increasing bone mineral density and decreasing bone resorption biomarkers, but concerns still remain whether it can reduce fracture incidence in this rare type of OI.

[Preparation of docetaxel-loaded pH-sensitive block copolymer micelles].

Basing on the synthesis of pH-sensitive amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-poly (D, L-lactide)(PEOz-PDLLA), this paper presents the preparation of docetaxel-loaded pH-sensitive block copolymer micelles using film dispersion method. The critical micelle concentration (CMC) was measured by pyrene fluorescent probe technique. The entrapment efficiency and drug-loaded amount were determined by HPLC. The morphology, diameter and surface potential of the micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential analyzer, respectively. The in vitro release behavior of DTX from polymeric micelles was investigated using dialysis method. The results indicated that the CMC, drug-loaded amount and entrapment efficiency of the micelles was 1.0 x 10(-3) g x L(-1), 15.0% and 91.1%, respectively. The micelles had a narrow size distribution, with a mean diameter of 28.7 nm. The micelle was globular-shaped and its zeta potential was (1.19 +/- 0.12) mV. In pH 7.4 PBS, docetaxel was released in a sustained manner from the micelles; while in PBS at pH 5.0, drug was released more rapidly, which suggested the pH-sensitive drug release behavior of the PEOz-PDLLA micelles. According to all the studies above, it can be concluded that the PEOz-PDLLA block copolymer micelles may be applied as promising drug delivery system for hydrophobic anti-tumor drugs.

[Preparation and study in vitro of long-circulating nanoliposomes of curcumin].

OBJECTIVE: To prepare the long-circulating nanoliposomes of curcumin. METHOD: The long-circulating nanoliposomes were prepared by ethanol infusion and the encapsulation efficiency was determindated by the mini-column centrifugation. The effect of some factors on the encapsulation efficiency, such as the buffer solutions, the weight ratio of curcumin to SPC, the weight ratio of SPC to Chol, the pH of buffer solution and the iron strength of water phase, was investigated respectively. Then the formulation was optimized by orthogonal design. RESULT: The encapsulation efficiency of the curcumin liposomes was (88.27 +/- 2.16)%, and the average diameter of the liposomes was (136 +/- 18) nm. There was no change on encapsulation efficency within 30 d. CONCLUSION: The preparation of curcumin liposomes was easy and practicable and the pharmaceutical characterization showed that the curcumin liposomes are stable.

[Preparation and in vitro tumor cells selectivity of sterically stabilized immunoliposomal peptides in bee venom].

Recently the use of peptides in bee venom (PBV) for cancer therapy has attracted considerable attention. In this study, the sterically stabilized liposomal PBV (PBV-SL) was prepared using soybean phosphatidylcholine, cholesterol, and cholesterol-PEG-COOH. The humanized antihepatoma disulfide-stabilized Fv (hdscFv25) was coupled to sterically stabilized liposomes using the N-hydroxysuccinimide ester method. The hdscFv25-immunoliposomes (SIL[hdscFv25]) were immunoreactive as determined by ELISA assay. SIL[hdscFv25] showed higher tumor cells selectivity. PBV-SIL[hdscFv25] can kill SMMC-7721 cells in vitro with higher efficiency than non-targeted liposomes. Whereas cytotoxicties were compared for Hela cells, no significant differences was observed between PBV-SIL[hdscFv25] and PBV-SL. Sterically stabilized immunoliposomal peptides in bee venom could be one drug targeting delivery system.

[Preparation and anti-oxidative activity of liposomal ferulic acid].

Ferulic acid (FA) was loaded into liposomes via calcium acetate gradient with (80.2 +/- 5.2)% entrapment efficiency. The average sizes of blank liposome and FA liposome were about 155 nm and 154 nm, respectively. The zeta potential of blank liposome and FA liposome were (13.14 +/- 1.67) mV and (4.12 +/- 0.05) mV, respectively. Unilamellar vesicles were present in freeze-fracture electron microscopy. In the pharmacodynamic studies, the protective effect of liposomal ferulic acid on tBHP-challenged U937 cells was measured with the morphology of cell injury, mitochondrial transmembrane potential alternation and cell viability assay used as index. The results of MTT assay, microscopy indicated that FA liposomes exhibited greater antioxidant activity than FA solution on U937 cell.

[Effects of tillage practices on photosynthetic performance diurnal variation during filling stage and grain yield of winter wheat]. / è€•ä½œæ–¹å¼å¯¹å†¬å°éº¦çŒæµ†æœŸå ‰åˆæ€§èƒ½æ—¥å˜åŒ–å’Œç±½ç²’äº§é‡çš„å½±å“.

Photosynthesis characteristics of winter wheat under different tillage practices during fil-ling stage are vital for dry matter accumulation, transfer, and yield development. A field experiment, including no-till with residue removal (NT), no-till with residue retention (NTS), rotary tillage with residue removal (RT), rotary tillage with residue retained (RTS), subsoiling with residue removal (DT), subsoiling with residue retained (DTS), plow tillage with residue removal (CT), and plow tillage with residue retained (CTS) was conducted at Wuqiao experimental station of China Agricultural University since October 2008. The diurnal variation of photosynthetic characteristics of flag leaf, photosynthetic response curve, and crop yield under different tillage practices were evaluated during winter wheat filing stage in this study. The results showed thatthe net photosynthetic rate and stomatal conductance of flag leaf both diurnally varied with the bimodal curve, and the net photosynthetic rates were higher under treatments with residue retained than those under with residue removal. Diurnal variation of intercellular carbon dioxide concentration was observed with a "V-shaped wide mouth" bimodal curve under all treatments. Daily transpiration rate exhibited "double peak curve", except for the "single peak curve" under DTS, RTS and RT. The stimulated net photosynthetic rate was increased by 20.0%, 21.7%, 19.7%, 21.5%, 0.8%, 12.1% and 4.2% under NT, DT, RT, CT, CTS, RTS, and CTS, compared with DTS, respectively. Photosynthetic response curves were fitted better under treatments with residue retained than under treatments with residue removal. As for crop grain yields, the highest one was observed under DTS, following by RTS and CTS, and the lowest under CT. Crop grain yield was increased by 10.8%, 1.3%, 2.1%, 5.4%, 11.9%, 12.4%, and 12.6% under DTS, compared with NTS, RTS, CTS, NT, DT, RT, and CT, respectively. Thus, residue retaining under different tillage practices (e.g. NTS and DTS) could mitigate the mid-day depression of photosynthesis, maintain a high photosynthetic rate of winter wheat, and improve the dry matter accumulation and crop production.

Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes.

This multi-center, randomized, double-blind, multiple dose-escalation study was conducted to assess the pharmacokinetics and pharmacodynamics of a newly developed polyethylene glycol (PEG)-conjugated glucagon-like peptide-1 (GLP-1) receptor agonist, PEX168 once weekly in Chinese patients with type 2 diabetes (T2DM). Fifty patients aged 20-65 years, either treatment-naive or having been treated with single oral antidiabetic agents were eligible. Antidiabetic agents were stopped for 14 days before the study was initiated. Patients were allocated randomly into groups with subcutaneous PEX168 or placebo once-weekly for 8 weeks followed by 6 weeks observation. From baseline to 8 weeks, HbA1c were decreased by up to 0.0, 0.2, 0.6, 0.9, and -0.4% in the 50, 100, 200, 300 µg PEX168 groups, and placebo group respectively. The mean elimination half-life of PEX168 was 131.8-139.8 hours. The mean tmax was 67.3 hours. Steady-state plasma PEX168 concentrations were attained after 4 weeks. PEX168 once-weekly were tolerable by the patients: adverse effects reported ranged from 'mild' to 'moderate'. The most frequent drug-related adverse effects were nausea, vomiting, and diarrhea of mild to moderate severity. Administration of the PEG-conjugated GLP-1 receptor agonist PEX168 resulted in dose-proportional pharmacokinetic and antidiabetic pharmacodynamic activity.

Preparation of cellulose based microspheres by combining spray coagulating with spray drying.

Porous microspheres of regenerated cellulose with size in range of 1-2 µm and composite microspheres of chitosan coated cellulose with size of 1-3 µm were obtained through a two-step spray-assisted approach. The spray coagulating process must combine with a spray drying step to guarantee the formation of stable microspheres of cellulose. This approach exhibits the following two main virtues. First, the preparation was performed using aqueous solution of cellulose as precursor in the absence of organic solvent and surfactant; Second, neither crosslinking agent nor separated crosslinking process was required for formation of stable microspheres. Moreover, the spray drying step also provided us with the chance to encapsulate guests into the resultant cellulose microspheres. The potential application of the cellulose microspheres acting as drug delivery vector has been studied in two PBS (phosphate-buffered saline) solution with pH values at 4.0 and 7.4 to mimic the environments of stomach and intestine, respectively.