Drought decreases cotton fiber strength by altering sucrose flow route.

The potential mechanisms by which drought restricts cotton fiber cell wall synthesis and fiber strength are still not fully understood. Herein, drought experiments were conducted using two cultivars of upland cotton (Gossypium hirsutum), Dexiamian 1 (drought-tolerant) and Yuzaomian 9110 (drought-sensitive). Results showed that drought notably reduced sucrose efflux from cottonseed coats to fibers by down-regulating the expression of GhSWEET10 and GhSWEET15 in outer cottonseed coats, leading to enhanced sucrose accumulation in cottonseed coats but decreased sucrose accumulation in fibers. Within cotton fibers, drought restricted the hydrolysis of sucrose to uridine-5'-diphosphoglucose by suppressing sucrose synthase activity, and drought favored the conversion of uridine-5'-diphosphoglucose to ß-1,3-glucan rather than cellulose by up-regulating GhCALS5. Hence, cellulose content was reduced, which was the main reason for the decreased fiber strength under drought. Moreover, drought promoted lignin synthesis by up-regulating the expression of Gh4CL4, GhPAL9, GhCCR5, GhCAD11, and GhCOMT6, which partly offset the negative influence of reduced cellulose content on fiber strength. Compared with Yuzaomian 9110, the drought-tolerance of Dexiamian 1 was evidenced by the following under drought conditions: (i) greater sucrose flow from seedcoat to fiber, (ii) less ß-1,3-glucan accumulation, and (iii) more lignin biosynthesis. Overall, this study provides new insights into the mechanism of reduced cotton fiber strength induced by drought.

Enhancing the production of recombinant adeno-associated virus in synthetic cell lines through systematic characterization.

Recombinant adeno-associated virus (rAAV) is among the most commonly used in vivo gene delivery vehicles and has seen a number of successes in clinical application. Current manufacturing processes of rAAV employ multiple plasmid transfection or rely on virus infection and face challenges in scale-up. A synthetic biology approach was taken to generate stable cell lines with integrated genetic modules, which produced rAAV upon induction albeit at a low productivity. To identify potential factors that restrained the productivity, we systematically characterized virus production kinetics through targeted quantitative proteomics and various physical assays of viral components. We demonstrated that reducing the excessive expression of gene of interest by its conditional expression greatly increased the productivity of these synthetic cell lines. Further enhancement was gained by optimizing induction profiles and alleviating proteasomal degradation of viral capsid protein by the addition of proteasome inhibitors. Altogether, these enhancements brought the productivity close to traditional multiple plasmid transfection. The rAAV produced had comparable full particle contents as those produced by conventional transient plasmid transfection. The present work exemplified the versatility of our synthetic biology-based viral vector production platform and its potential for plasmid- and virus-free rAAV manufacturing.

Etched stainless steel wire modified with conjugated microporous polymers-F6 for jacket-free stir bar sorptive extraction of benzoylureas in juice sample.

Benzoylurea (BU) insecticides have been widely used for pest control as third-generation insecticides. Considering that their residues in food may cause adverse effects on human health, the upper limits of BUs remaining in food have been set by the administration. Therefore, it is essential to develop a sensitive and efficient analytical method to determine the residues of BUs in food. Stir bar sorptive extraction (SBSE) is a novel sample preparation technique, and stainless steel wire (SSW) is an ideal substrate for an SBSE device. In this work, a novel SBSE device of SSW jacket-free stir bar with a dumbbell shape was designed and prepared. The conjugated microporous polymer CMP-F6, which possesses a porous structure, high hydrophobicity and rich fluorine-containing functional groups, was immobilized on the surface of SSW by the method of polyacrylonitrile glue adhesion. Compared with previous studies, which used SSW as a substrate, the method of etching partial SSW with hydrochloric acid, on the one hand, made the surface of SSW rough and easy to modify the extraction coating, and on the other hand, converted itself into a dumbbell-shaped structure, which is conducive to improving the extraction efficiency and stability of the SBSE device. The method of SBSE-HPLC-UV was established for determining five BUs. Owing to the hydrophobic interaction and F-F interaction between CMP-F6 and analytes, this method showed good extraction efficiency and had good linearity (R2 ≥ 0.9945) and high sensitivity (LODs in the range of 0.1-0.2 ng mL-1). It was used for the analysis of benzoylurea in an apple juice sample, and the recoveries were 74.3-117.9%.

Single-Ion Gel Polymer Electrolyte based on In-Situ UV Irradiation Cross-Linked Polyimide Complexed with PEO for Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) have become the research focus of energy storage products. Due to the combination of Li+ and the Lewis basic sites of polymer chains, anions move more than five times faster, which do not participate in the electrode reaction during the discharge cycles, leading to concentration polarization, voltage losses, and high internal resistance. To solve this phenomenon, in this work, a polymer network structure of single-ion polymer electrolyte-based polyimide (DPI-SIGPE) with plasticizer ethylene carbonate (EC)/dimethyl carbonate (DMC) is formed by in-situ cross-linking double bond polyimide, 4-styrene sulfonyl (benzenesulfonyl) imide, and cross-linking agent pentaerythritol tetra(2-thiol acetate) under UV irradiation. By incorporating the anion as a part of the polymer chain, DPI-SIGPE exhibits high lithium-ion conductivity of 2.7 × 10-4 S cm-1 at 30 °C and transference number of 0.87. Typical lithium stripping/plating cycling of 900 h demonstrates uniform lithium deposition impacted by DPI-SIGPE. Meanwhile, it has good dimensional thermal stability with no obvious shrinkage at 200 °C for 0.5 h and wide electrochemical window of 4.6 V. Thus, the polyimide-based cross-linked single-ion gel polymer electrolyte has the promising potential for application in LIBs.

Clinical investigation of gingival papilla recession after orthodontic treatment in adults.

OBJECTIVE: To investigate the incidence, severity, susceptibility sites of gingival papillary recession (GPR) in adults after orthodontic treatment and the clinical impact of tooth extraction on GPR. METHODS: A total of 82 adult patients were recruited and then divided into extraction and non-extraction groups according to whether the orthodontic teeth were extracted (teeth that needed to be extracted when performing orthodontic treatment). The gingival conditions of the two groups of patients before and after treatment were recorded using intraoral photos, and the incidence, severity and predilection sites of GPR after correction were investigated. RESULTS: The results indicated that GPR occurred in 29 patients after correction, with an incidence rate of 35.4%. A total of 1648 gingival papillae were recorded among the 82 patients after correction, of which 67 exhibited atrophy, with an incidence of 4.1%. All occurrences of GPR were classified as papilla presence index 2 (PPI 2) (mild). The condition is most likely to occur in the anterior tooth area, especially in the lower incisor area. The results indicated that the incidence of GPR was substantially higher in the extraction group than in the non-extraction group, with the difference statistically significant. CONCLUSION: Following orthodontic treatment, adult patients will have a certain proportion of mild GPR, which is more common in the anterior tooth area, especially the lower anterior tooth area.

A Stable PDLC Film with High Ageing Resistance from an Optimized System Containing Rigid Monomer.

With the switchability between transparent and light-scattering states, polymer-dispersed liquid crystals (PDLC) are widely used as smart windows, flexible display devices, projectors, and other devices. In outdoor applications, in addition to excellent electro-optical properties, there is also a high demand for film stability. In this work, a PDLC film with high mechanical strength and structural stability is prepared that can maintain stability at 80 °C for 2000 h. By choosing liquid crystals with a wide temperature range, adopting acrylate polymer monomers containing hydroxyl groups, and adjusting the polymer content, the PDLC film can work well from -20 °C to 80 °C. On this basis, the effects of the introduction of rigid monomers on the mechanical properties and electro-optical properties of PDLC films are investigated.

Light-Induced Topological Patterning toward 3D Shape-Reconfigurable Origami.

Shape-reconfigurable materials are crucial in many engineering applications. However, because of their isotropic deformability, they often require complex molding equipment for shaping. A polymeric origami structure that follows predetermined deformed and non-deformed patterns at specific temperatures without molding is demonstrated. It is constructed with a heterogeneous (dynamic and static) network topology via light-induced programming. The corresponding spatio-selective thermal plasticity creates varied deformability within a single polymer. The kinematics of site-specific deformation allows guided origami deployment in response to external forces. Moreover, the self-locking origami can fix its geometry in specific states without pressurization. These features enable the development of shape-reconfigurable structures that undergo on-demand geometry changes without requiring bulky or heavy equipment. The concept enriches polymer origamis, and could be applied with other polymers having similar chemistries. Overall, it is a versatile material for artificial muscles, origami robotics, and non-volatile mechanical memory devices.

Co-delivery of paclitaxel and doxorubicin using polypeptide-engineered nanogels for combination therapy of tumor.

Loading of chemotherapeutic agents into nanoparticles has been demonstrated to be an effective strategy for cancer therapy. However, simultaneous delivery of different functional drugs to tumor sites for chemotherapy still remains challenging. In this study, nanogels formed by an engineered coiled-coil polypeptide PC10A were designed and prepared as a carrier for co-delivery of paclitaxel (PTX) and doxorubicin (DOX) through ultrasonic treatment and electrostatic adsorption. The drug loading content and encapsulation efficiency of PTX and DOX in the PC10A/PTX/DOX nanogels were 5.98 wt%, 70 wt%, and 8.55 wt%, 83 wt%, respectively. Because the polypeptide PC10A was non-toxic and biodegradable, the PC10A/PTX/DOX nanogels exhibited good biocompatibility. Thein vitroandin vivoantitumor experiments showed that the PC10A/PTX/DOX nanogels possessed obviously synergistic therapy effect of tumors and lower side effects compared with free PTX/DOX. Therefore, the PC10A/PTX/DOX nanogels are promising to provide a new strategy for combination therapy of different functional drugs.

GDF15 induced by compressive force contributes to osteoclast differentiation in human periodontal ligament cells.

Orthodontic tooth movement (OTM) is initiated by mechanical force and featured as alveolar bone remodeling. Periodontal ligament cells (PDLCs) are one of the major cell components in periodontium and responsible for the signal transduction during OTM. Up to now, the mechanical stress-induced genetic alteration and mechanotransduction mechanisms in PDLCs still remain not fully understood. In this study, we identified a novel compressive force responsive gene, Growth differentiation factor 15 (GDF15), whose expression transcriptionally increased in human periodontal ligament cells (PDLCs) after exposure to the static compressive force in vitro. Functional analyses proved that GDF15 could promote osteoclast differentiation of the murine macrophage cell line RAW264.7 cells. Molecular investigation uncovered that GDF15 could promote the expression of several pro-inflammatory cytokines and RANKL/OPG ratio in PDLCs, while knockdown of GDF15 impaired their upregulation induced by compressive force. Additionally, administration of recombinant GDF15 protein stimulated the M1-like polarization of RAW264.7 cells and THP-1 induced macrophages. Mechanistically, siRNA-mediated suppression of GDF15 significantly disrupted the nuclear translocation of NF-κB and ERK phosphorylation in response to compressive force. Finally, Yes-associated protein (YAP) was demonstrated to be the upstream regulator of GDF15 in human PDLCs, implying a force-induced YAP-GDF15 regulation mechanism. Overall, these data suggested important roles of GDF15 in the functional modulation of both PDLCs and osteoclast progenitors in response to compressive force, providing novel insights into the molecular mechanism of mechanotransduction during OTM process.

Genomic analyses of heat stress transcription factors (HSFs) in simulated drought stress response and storage root deterioration after harvest in cassava.

Heat shock factors (HSFs) play crucial roles in various plant stress responses. However, the current knowledge about HSFs in cassava, an important crop, is still insufficient. In this research, we identified 32 cassava HSF genes (MeHSFs) and clustered them into three groups (A, B, C) based on phylogenetic analysis and structural characteristics. Conserved motif analyses showed that MeHSFs display domains characteristic to HSF transcription factors. Gene structure analyses suggested that 29 MeHSFs contained only two exons. All identified 32 cassava MeHSFs were distributed on 13 chromosomes. Their expression profiles revealed that the different MeHSFs were expressed differentially in different tissues, most high expression genes belonged to group A. The similar MeHSFs were up-regulated after treatment with both PEG and abscisic acid (ABA), which implied that these MeHSFs may participate in resistance to simulated drought stress associated with the ABA signaling pathway. In addition, several MeHSFs were induced during postharvest physiological deterioration (PPD) in cassava. Our results provided basic but important knowledge for future gene function analysis of MeHSFs toward efforts in improving tolerance to abiotic stress and PPD in cassava.

Cotton thread modified with ionic liquid copolymerized polymer for online in-tube solid-phase microextraction and HPLC analysis of nonsteroidal anti-inflammatory drugs.

Cotton fiber is a biodegradable material that possesses properties such as high specific area, adjustable shape, and hygroscopicity. In this work, organic polymer was directly in situ grown on the surface of cotton thread and packed into a poly(ether ether ketone) tube for online in-tube solid-phase microextraction. The novel strategy solves the problems like high backpressure and tedious optimization process of normal monolithic polymer-based in-tube solid-phase microextraction capillary. The quaternary ammonium typed ionic liquid of 1-allyl-methylimidazolium chloride, 4-vinylbiphenyl, and ethylene dimethacrylate were co-polymerized and in situ grown on the surface of cotton thread as extraction phase. The solid-phase microextraction tube showed excellent performance for the extraction of three nonsteroidal anti-inflammatory drugs including ketoprofen, naproxen, and flurbiprofen due to the strong ion exchange and hydrophobic interactions. After online coupling with a high-performance liquid chromatography system by six-port valve, the method was applied for the quantitative analysis of nonsteroidal anti-inflammatory drugs in human plasma samples showing good enrichment performance (enrichment factor between 263 and 279), high sensitivity, good linearity, and good reproducibility.

10-Year Results of Therapeutic Ratio by Intensity-Modulated Radiotherapy Versus Two-Dimensional Radiotherapy in Patients with Nasopharyngeal Carcinoma.

BACKGROUND: The purpose of this study was to verify 10-year results of survival and late toxicities and assess the ultimate therapeutic ratio of intensity-modulated radiotherapy (IMRT) versus two-dimensional radiotherapy (2DRT) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively reviewed the data from 1,276 patients with nonmetastatic NPC who received IMRT or 2DRT from January 2003 to December 2006. RESULTS: Of the 1,276 patients, 512 were treated with IMRT and 764 with 2DRT. Median follow-up was 115 months. At 10 years, the IMRT group demonstrated significantly better results than the 2DRT group in local failure-free survival (L-FFS; 90% vs. 84%; hazard ratio [HR], 0.57, 95% confidence interval [CI], 0.40-0.81; p = .001), failure-free survival (FFS; 69% vs. 58%; HR, 0.69, 95% CI, 0.57-0.83; p < .001), and overall survival (OS; 75% vs. 63%; HR, 0.62, 95% CI, 0.51-0.77; p < .001). Subgroup multivariate analyses showed that radiotherapeutic technique (IMRT vs. 2DRT) remained an independent prognostic factor for L-FFS in the T1 subgroup (HR, 0.30; 95% CI, 0.11-0.80; p = .02); for FFS in the stage II subgroup (HR, 0.42; 95% CI, 0.24-0.73; p = .002); and for OS in the stage I (HR, 0.20; 95% CI, 0.04-0.96; p = .04), stage II (HR, 0.39; 95% CI, 0.21-0.75; p = .004), and stage IVA-B (HR, 0.74, 95% CI, 0.56-0.98; p = .04) subgroups. The incidence of grade 3-4 temporal lobe necrosis, cranial neuropathy, eye damage, ear damage, neck soft tissue damage, trismus, and dry mouth was significantly lower in the IMRT group than in the 2DRT group. CONCLUSION: IMRT demonstrated an improved ultimate therapeutic ratio compared with 2DRT in patients with NPC after a 10-year follow-up, with significant improvement of L-FFS, FFS, and OS and decrease in most late toxicities. IMPLICATIONS FOR PRACTICE: The ultimate therapeutic ratio of intensity-modulated radiotherapy versus two-dimensional radiotherapy in patients with nasopharyngeal carcinoma is unclear. In this retrospective study of 1,276 patients with nonmetastatic nasopharyngeal carcinoma with a follow-up of 115 months, intensity-modulated radiotherapy demonstrated an improved ultimate therapeutic ratio compared with two-dimensional radiotherapy, with significant improvement of local failure-free survival, failure-free survival, and overall survival and decrease in most late toxicities and noncancer deaths. However, distant control remains insufficient with this treatment modality.

Evaluation of clinical outcomes of one-stage anterior and posterior surgical treatment for atlantoaxial tuberculosis complicated with neurological damage.

BACKGROUND: Surgical treatment is mainly used for atlantoaxial tuberculosis with neurological damage. However, the anatomic structure around the atlantoaxial joint is complex, and the position of vertebral body is deep, which increases the difficulty of the operation and it is challenging for the surgeon to develop surgical strategy. The purpose of this study was to evaluate the clinical outcomes of one-stage combined anterior and posterior surgical treatment approach for atlantoaxial tuberculosis with neurological impairment. METHODS: From January 2005 to January 2015, 12 patients suffering from atlantoaxial tuberculosis with neurological impairment were surgically treated by one-stage combined anterior and posterior approach. Preoperative CT scanning and MRI imaging showed unilateral or bilateral lateral mass destruction of the atlas, and varying destruction degrees of odontoid process, loss of atlantoaxial stability, and tuberculosis focus into the spinal canal resulting in the corresponding spinal cord compression in all patients. The preoperative neurological classifications were Class C for 4 cases, D for 8 cases according to the American Spinal Injury Association (ASIA) system. Quadruple sensitive anti-TB drug treatment was used in all 12 patients preoperative and postoperative. Patients' clinical symptoms and neurological function recovery were evaluated by comparing the Visual Analogue Scale (VAS) score, Neck Disability Index (NDI), Japanese Orthopedic Association (JOA) score and ASIA grading before operation and at the final follow-up. RESULTS: Mean surgical duration was 263.3 ± 43.6 min. Intraoperative blood loss was averagely 529.2 ± 169.8 ml. The average fusion period was 7.3 ± 1.5 months. No instrumentation loosening, migration or breakage was observed during the follow-up of 6.5 ± 2.9 years. The VAS, NDI and JOA scores were significantly changed to 1.00 ± 0.95, 9.50 ± 3.34 and 15.42 ± 1.44 at last follow-up (P < 0.05). The neurological function of all 12 patients was recovered to Class E according to the ASIA grading system. CONCLUSION: In the treatment of atlantoaxial tuberculosis with neurological impairment, one-stage combined anterior and posterior surgical approach have the ability to complete debridement and decompression, and reconstruction of the stability of the upper cervical spine.

Carbon Dots-Modified Nanoporous Membrane and Fe3O4@Au Magnet Nanocomposites-Based FRET Assay for Ultrasensitive Histamine Detection.

Histamine can be formed by enzymatic decarbonylation of histidine, which is an important indicator of seafood quality. A rapid and sensitive assay method is necessary for histamine monitoring. A fluorescence resonance energy transfer (FRET) assay system based on a carbon dot (CD)-modified nanoporous alumina membrane and Fe3O4@Au magnet nanocomposites has been developed for histamine detection in mackerel fish. CDs immobilized on nanoporous alumina membranes were used as donors, which provided a fluorescence sensing substrate for histamine detection. Fe3O4@Au magnet nanocomposites can not only act as acceptors, but also concentrate histamine from fish samples to increase detection sensitivity. Histamine was detected by the fluorescence signal changes of CDs capturing histamine by an immune reaction. The fluorescence signals of CDs were quenched by Fe3O4@Au magnet nanocomposites via the FRET mechanism. With an increase of histamine, the fluorescence intensity decreased. By recording fluorescence spectra and calculating intensity change, histamine concentration can be determined with a limit of detection (LOD) of 70 pM. This assay system can be successfully applied for histamine determination in mackerel fish to monitor the fish spoilage process in different storage conditions. It shows the potential applications of CDs-modified nanoporous alumina membranes and Fe3O4@Au magnet nanocomposites-based biosensors in the food safety area.

Polypropylene Glycol-Polyoxytetramethylene Glycol Multiblock Copolymers with High Molecular Weight: Synthesis, Characterization, and Silanization.

The high crystallization at room temperature and high cost of polyoxytetramethylene glycol (PTMG) have become obstacles to its application. To overcome these problems, a segment of PTMG can be incorporated into a block copolymer. In this work, polypropylene (PPO) glycol-polyoxytetramethylene (PPO-PTMG) multiblock copolymers were designed and synthesized through a chain extension between hydroxyl (OH)-terminated PPO and PTMG oligomers. The chain extenders, feed ratios of the catalyst/chain extender/OH groups, reaction temperature, and time were optimized several times to obtain a PPO-PTMG with low crystallization and high molecular weight. Multiblock copolymers with low crystallization and high average molecular weight (Mn = 1.0-1.4 × 104 Dalton) were harvested using m-phthaloyl chloride as the chain extender. The OH-terminated PPO-PTMG multiblock copolymer with high Mn and a functionality near two was further siliconized by 3-isocyanatopropyltrimethoxysilane to synthesize a novel silyl-terminated polyether. This polyether has an appropriate vulcanizing property and potential applications in sealants/adhesive fields.

A stretchable conductive Polypyrrole Polydimethylsiloxane device fabricated by simple soft lithography and oxygen plasma treatment.

This paper reports a simple method used to fabricate a stretchable conductive polypyrrole (PPy) rough pore-shape polydimethylsiloxane (p-PDMS) device. An abrasive paper is first used to imprint rough micro-structures on the SU-8 micromold. The p-PDMS microchannel is then fabricated using a standard soft-lithography process. An oxygen plasma treatment is then applied to form an irreversible sealing between the microchannel and a blank cover PDMS. The conductive layer is formed by injecting the PPy mixture into the microchannel which polymerizes in the rough pore-shape micro-structures; The PPy/p-PDMS hybrid device shows good electrical property and stretchability. The electrical properties of different geometrical designs of the PPy/p-PDMS microchannel under stretching were investigated, including straight, curved, and serpentine. Mouse embryonic fibroblasts (NIH/3 T3) were also cultured inside the PPy/p-PDMS device to demonstrate good biocompatibility and feasibility using the conductive and stretchable microchannel in cell culture microfluidics applications. Finally, cyclic stretching and bending tests were performed to evaluate the reliability of PPy/p-PDMS microchannel.

Redefining Molecular Amphipathicity in Reversing the "Coffee-Ring Effect": Implications for Single Base Mutation Detection.

The "coffee ring effect" is a natural phenomenon wherein sessile drops leave ring-shaped structures on the solid surfaces upon drying. It drives a nonuniform deposition of suspended compounds on the substrates, which adversely affects many processes, including surface-assisted biosensing and molecular self-assembly. In this study, we describe how the coffee ring effect can be eliminated by controlling the amphipathicity of the suspended compounds, for example, DNA modified with hydrophobic dye. Specifically, nuclease digestion of the hydrophilic DNA end converts the dye-labeled molecule into an amphipathic molecule (one with comparably weighted hydrophobic and hydrophilic ends) and reverses the coffee ring effect and results in a uniform disk-shaped feature deposition of the dye. The amphipathic product decreases the surface tension of the sessile drops and induces the Marangoni flow, which drives the uniform distribution of the amphipathic dye-labeled product in the drops. As a proof of concept, this strategy was used in a novel enzymatic amplification method for biosensing to eliminate the coffee ring effect on a nitrocellulose membrane and increase assay reliability and sensitivity. Importantly, the reported strategy for eliminating the coffee ring effect can be extended to other sessile drop systems for potentially improving assay reliability and sensitivity.

Differentiation of human dental pulp stem cells into neuronal by resveratrol.

Dental pulp stem cells (DPSCs) have been proposed as a promising source of stem cells in nerve regeneration due to their close embryonic origin and ease of harvest. Resveratrol (RSV) is a natural polyphenolic and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and neuroprotective activities. There is increasing evidence showing that RSV plays a pivotal role in neuron protection and neuronal differentiation. In this study, we isolated DPSCs from impacted third molars and investigated whether RSV induces neuronal differentiation of DPSCs. To avoid loss of DPSCs multipotency, all the experiments were conducted on cells at early passages. RT-PCR results showed that RSV-treated DPSCs (RSV-DPSCs) significantly increased the expression of the neuroprogenitor marker Nestin. When RSV-DPSCs were differentiated with neuronal induction media (RSV-dDPSCs), they showed a cell morphology similar to neurons. The expression of neuronal-specific marker genes Nestin, Musashi, and NF-M in RSV-dDPSCs was significantly increased. Immunocytochemical staining and Western blot analysis showed that the expression of neuronal marker proteins, Nestin, and NF-M, was significantly increased in RSV-dDPSCs. Therefore, we have shown that RSV treatment, along with the use of neuronal induction media, effectively promotes neuronal cell differentiation of DPSCs.

MSAll strategy for comprehensive quantitative analysis of PEGylated-doxorubicin, PEG and doxorubicin by LC-high resolution q-q-TOF mass spectrometry coupled with all window acquisition of all fragment ion spectra.

The covalent attachment of polyethylene glycol (PEG) to therapeutic compounds (known as PEGylation) is one of the most promising techniques to improve the biological efficacy of small molecular weight drugs. After administration, PEGylated prodrugs can be metabolized into pharmacologically active compounds so that PEGylated drug, free drug and released PEG are present simultaneously in the body. Understanding the pharmacokinetic behavior of these three compounds is needed to guide the development of pegylated theranostic agents. However, PEGs are polydisperse molecules with a wide range of molecular weights, so that the simultaneous quantitation of PEGs and PEGylated molecules in biological matrices is very challenging. This article reports the application of a data-independent acquisition method (MSAll) based on liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-q-q-TOF-MS) in the positive ion mode to the simultaneous determination of methoxyPEG2000-doxorubicin (mPEG2K-Dox) and its breakdown products in rat blood. Using the MSAll technique, precursor ions of all molecules are generated in q1, fragmented to product ions in q2 (collision cell), and subjected to TOF separation before precursor and product ions are recorded using low and high collision energies (CE) respectively in different experiments for a single sample injection. In this study, dissociation in q2 generated a series of high resolution PEG-related product ions at m/z 89.0611, 133.0869, 177.1102, 221.1366, 265.1622, 309.1878, and 353.2108 corresponding to fragments containing various numbers of ethylene oxide subunits, Dox-related product ions at m/z 321.0838 and 361.0785, and an mPEG2K-Dox specific product ion at m/z 365.0735. Detection of mPEGs and mPEG2K-Dox was based on high resolution extracted ions of mPEG and the specific compound. The method was successfully applied to a pharmacokinetic study of doxorubicin, mPEG2K (methylated polyethylene glycol 2K), and mPEG2K-doxorubicin in rats after a single intravenous injection of mPEG2K-doxorubicin. To the best of our knowledge, this is the first assay that simultaneously determines mPEG, Dox, and mPEG2K-Dox in a biological matrix. We believe the MSAll technique as applied in this study can be potentially extended to the determination of other PEGylated small molecules or polymeric compounds.

[Efficacy and Safety Evaluation of Liujin Runzao Concentrated Decoction in Treating Primary Sjögren's Syndrome].

Objective To evaluate the efficacy and safety of Liujin Runzao Concentrated Decoction (LRCD) for the treatment of primary Sjögren's syndrome (pSS). Methods Forty pSS patients with fluid depletion and distribution obstacles syndrome (FDDOS) were randomly assigned to the experimen- tal group and the control group according to 1:1 proportion. All patients received standard therapy: Radix Paeoniae alba total glycosides 600 mg, twice per day. Patients in the experimental group additionally took LRCD, 30 mL each time, twice per day. The therapeutic course for all was 4 weeks, and two courses for all. The improvement of dry mouth and dry eyes were comprehensively evaluated. Each outcome of composite index constitutions (integrals of dry eyes and dry mouth, salivary flow rate, Schirmer test) was respectively reported. Schirmer test and salivary flow rate were determined as well. Score of TCM syndrome, blood sedimentation,'immunoglobulin, and adverse drug reactions were observed. Results The effective rate of comprehensive effect for dry eyes and dry mouth improvement at the end of 8 weeks was 80% in the experimental group and 35% in the control group, with statistical difference (X² =8. 286, P <0. 05). As for the composition of comprehensive effect for dry eyes and dry mouth improvement: The score for dry eyes and dry mouth decreased in the two groups more after treatment than before treatment. The difference in pre-post treatment score for dry eyes and dry mouth at week 8 was higher in the experimental group than in the control group. The difference in pre-post treatment score at week 8 was 1. 71 (95% Cl: -0. 37 -3. 78) between the two groups (P <0. 05). The difference in pre-post treatment Schirmer test and salivary flow rate at week 8 was higher in the experimental group than in the control group, but with on statistical difference (P >0. 05). The difference in pre-post treatment Schirmer test and salivary flow rate at week 8 was 2. 74 mL/15 min (95% Cl: 0. 49 -4.98) and 0. 13 mm/5 min (95% Cl: 0. 92 -1. 23) between the two groups (P <0. 05). The score of TCM syndrome decreased more in the two groups, as compared with before treatment. The difference in pre-post treatment score of TCM syn- drome at week 8 was 1. 71 (95% CI: -1. 40 -4. 81) between the two groups (P >0. 05). One case of uri- nary tract infections occurred in the control group, while no obvious adverse event occurred in the exper- imental group. Conclusion Standard treatment combined LRCD showed better comprehensive effect for dry eyes and dry mouth in pSS patients with FDDOS, and was more safe.