High-performance pyramid-SiNWs biosensor for NH3gas detection.

NH3is widely existed in the environment and is closely associated with various health issues. Additionally, detecting the small amounts of NH3exhaled by patients with liver and kidney diseases offers potential opportunities for painless early disease diagnosis. Therefore, there is an urgent need for a convenient, rapid, and highly sensitive real-time NH3monitoring method. This work presents a high-performance NH3sensor based on olfactory receptor-derived peptides (ORPs) on a pyramid silicon nanowires (SiNWs) structure substrate. First, we successfully fabricated the pyramid-SiNWs structure on a silicon substrate using a chemical etching method. Subsequently, by dehydrative condensation reaction between the amino groups on APTES and the carboxyl groups of ORPs, ORPs were successfully immobilized onto the pyramid-SiNWs structure. This methodology allows the ORPs sensor on the pyramid-SiNWs substrate to detect NH3as low as 1 ppb, which was the reported lowest limit of detection, with a higher response rate compared to ORPs sensors on flat SiNWs substrates. The sensors also exhibit good sensitivity and stability for NH3gas detection. The results show the feasibility and potential applications of ORPs-pyramid-SiNWs structure sensors, in the fields of food safety, disease monitoring, and environmental protection, etc.

Microstructure-united heterogeneous sodium alginate doped injectable hydrogel for stable hemostasis in dynamic mechanical environments.

Injectable hydrogels that can withstand compressive and tensile forces hold great promise for preventing rebleeding in dynamic mechanical environments after emergency hemostasis of wounds. However, current injectable hydrogels often lack sufficient compressive or tensile performance. Here, a microstructure-united heterogeneous injectable hydrogel (MH) was constructed. The heterogeneous structure endowed MH with a unique "microstructures consecutive transmission" feature, which allowed it to exhibit high compressive and tensile performance simultaneously. In this work, two types of sodium alginate doped hydrogels with different microstructures were physically smashed into microgels, respectively. By mixing the microgels, MH with one micro-pores featured microstructure and another nano-pores featured microstructure can be formed. The obtained MH can withstand both compressive and tensile forces and showed high mechanical performance (compressive modulus: 345.67 ± 10.12 kPa and tensile modulus: 245.19 ± 7.82 kPa). Furtherly, MH was proven to provide stable and sustained hemostasis in the dynamic mechanical environment. Overall, this work provided an effective strategy for constructing injectable hydrogel with high compressive and tensile performance for hemostasis in dynamic mechanical environments.

Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers. However, the vast dynamic range renders the profiling of proteomes extremely challenging. Here, we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY. Specifically, zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY (NaY-PPC), followed by conventional protein identification using liquid chromatography-tandem mass spectrometry. NaY was able to significantly enhance the detection of low-abundance plasma proteins, minimizing the "masking" effect caused by high-abundance proteins. The relative abundance of middle- and low-abundance proteins increased substantially from 2.54% to 54.41%, and the top 20 high-abundance proteins decreased from 83.63% to 25.77%. Notably, our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL, compared to only about 600 proteins identified from untreated plasma samples. A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states. In summary, this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Viscous, Hofmeister Effect-Enhanced Macromolecular Adhesives for Effective Bonding in Seawater.

Deployment of adhesives in natural seawater to in situ bonds is urgently needed in engineering fields. However, stable adhesion in natural seawater remains a challenge due to the turbulent environment and high ion concentration. Herein, we reported a viscous, macromolecular underwater adhesive enhanced by Hofmeister effect (EHUA) for practical application in dynamic seawater. EHUA was synthesized via a facile one-step copolymerization. After transferred into seawater, the solvent of EHUA was exchanged to seawater, and thereby hydrogen bonds inside the adhesive were activated and enhanced by Hofmeister effect. We demonstrated EHUA can adhere on the surface in turbulent seawater, and the adhesive strength could reach 1.691 MPa. In addition, the adhesives also exhibited long-term storage stability and convenient recyclability. These fascinating properties enable adhesives to seal leaky pipelines, repair damaged ships and construct buildings in turbulent seawater. This work may open an avenue for the design of adhesives for seawater environments.

Preparation of cellulose nanospheres via combining ZnCl2·3H2O pretreatment and p-toluenesulfonic hydrolysis as a two-step method.

Spherical nanocelluloses, also known as cellulose nanospheres (CNS), have controllable morphology and have shown advantages as green template material, emulsion stabilizer. Herein, CNS were prepared via a new two-step method, first pretreatment of microcrystalline cellulose (MCC) using ZnCl2·3H2O and then acid hydrolysis of regenerated cellulose (RC) via p-toluenesulfonic acid (p-TsOH). The shape, size, crystallinity of MCC were changed, and nubbly RC with smallest size (942 nm) was obtained after 2 h pretreatment by ZnCl2·3H2O. CNS with high 61.3% yield were produced after acid hydrolysis (67 wt% p-TsOH) of RC at 80 °C, 6 h. The analysis of Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) showed that CNS had an average diameter of 347 nm. CNS were present in precipitate after high-speed centrifugation, due to the high Zeta potential of -12 mV and large size. The structure of CNS was tested by Fourier Transfer Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Nuclear Magnetic Resonance (NMR), CNS had high crystallinity (cellulose II) of 61%. Thermal Gravimetric Analysis (TGA) indicated that CNS had high thermal stability (Tonset 303.3 °C, Tmax 332 °C). CNS showed poor re-dispersibility in water/ethanol/THF, 1 wt% CNS could be dissolved in ZnCl2·3H2O. 7.37% rod-like CNC were obtained after 6 h hydrolysis. FTIR proved that p-TsOH was recovered by re-crystallization. This study provided a novel, sustainable two-step method for the preparation of spherical CNS.

The Effect of Neoadjuvant Chemotherapy Combined With Brachytherapy Before Radical Hysterectomy on Stage IB2 and IIA Cervical Cancer: A Retrospective Analysis.

OBJECTIVE: This study aims to retrospectively evaluate and compare the clinical efficacy in patients with stage IB2 and IIA cervical cancer, who treated with neoadjuvant chemotherapy combined with brachytherapy or not before radical hysterectomy. METHODS: The data of patients who have diagnosed with stage IB2 and IIA cervical cancer between January 2010 and December 2013 were retrieved through the Hospital Information System (HIS) of Gansu Provincial Maternal and Child Health Hospital. Patients were divided into two groups: neoadjuvant chemotherapy combined with brachytherapy followed by radical hysterectomy group (NACT+BT Group) and direct radical hysterectomy group (RH Group). The rate of adjuvant radiotherapy, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. RESULTS: A total of 183 patients were included in this study with 82 in the NACT+BT group and 101 in the RH group. The median follow up duration was 44.9 months for the NACT+BT group and 38.1 months for the RH group. The 5-year PFS for NACT+BT Group was 93.8%, which was significantly higher compared to the RH group (77.2%, P= 0.0202). The rate of postoperative adjuvant pelvic radiotherapy was significantly lower in the NACT+BT group compared to the RH group (30.49% vs 79.21%; P <0.05). COX multivariate analysis showed that NACT+BT increased PFS by 29% compared with RH treatment, and Positive margin decreased PFS and OS by by 4.7 and 6.87 times, respectively. CONCLUSION: Neoadjuvant chemotherapy combined with brachytherapy followed by radical hysterectomy (NACT+BT) can extend PFS, reduce postoperative pathological risk, and postoperative adjuvant pelvic radiotherapy compared to the direct radical hysterectomy (RH).

PMPC Modified PAMAM Dendrimer Enhances Brain Tumor-Targeted Drug Delivery.

The excellent biocompatibility drug delivery system for effective treatment of glioma is still greatly challenged by the existence of blood-brain barrier, blood-brain tumor barrier, and the tissue toxicity caused by chemotherapy drugs. In this study, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is used for the first time for modifying third-generation poly(amidoamine) (PAMAM) to enhance their brain tumor-targeted drug delivery ability as well as simultaneously reducing the toxicity of PAMAM dendrimers and the tissue toxicity of the loaded doxorubicin (DOX). The cytotoxicity, the therapeutic ability in vitro, and the brain tumor-targeted ability of the PMPC modified PAMAM nanoparticles are further studied. Results indicate that PMPC, as a dual-functional modifier, can significantly reduce the cytotoxicity of PAMAM dendrimers, while efficiently target the brain tumor. In addition, the therapeutic effect of DOX-loaded PAMAM-PMPC in mice inoculated with U-87 is also studied in vivo. In comparison with DOX solution, DOX-loaded PAMAM-PMPC alleviates weight loss of tumor-inoculated mice and reduces the cardiotoxicity of DOX. The tumor growth inhibition, in vivo, is significantly increased up to (80.76 ± 1.66)%. In conclusion, this strategy of PMPC dual-functional targeted nanocarrier provides a new method for the delivery of chemotherapeutic drugs to treat glioma.

Boosting of the enhanced permeability and retention effect with nanocapsules improves the therapeutic effects of cetuximab.

Objective: The introduction of therapeutic antibodies (tAbs) into clinical practice has revolutionized tumor treatment strategies, but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs. Methods: We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention (EPR) effect. This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune system. The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo. Results: The accumulation of Nano(cetuximab) within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration, which was contrary to the biodistribution of native cetuximab. Nano(cetuximab) accumulated in tumor tissues via the EPR effect and released cetuximab. The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the EPR effect, which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab). Compared with single dose administration of native cetuximab, Nano(cetuximab) showed an effective tumor suppressive effect for 3 weeks. Conclusions: The nanocapsule-based delivery system efficiently delivered tAbs to tumor tissues and released them to boost the EPR effect, which facilitated further tumor accumulation of the tAbs. This novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs, and stimulated new ideas for antibody-based tumor therapy.

Systemic Delivery of Monoclonal Antibodies to the Central Nervous System for Brain Tumor Therapy.

As an essential component of immunotherapy, monoclonal antibodies (mAbs) have emerged as a class of powerful therapeutics for treatment of a broad range of diseases. For central nervous system (CNS) diseases, however, the efficacy remains limited due to their inability to enter the CNS. A platform technology is reported here that enables effective delivery of mAbs to the CNS for brain tumor therapy. This is achieved by encapsulating the mAbs within nanocapsules that contain choline and acetylcholine analogues; such analogues facilitate the penetration of the nanocapsules through the brain-blood barrier and the delivery of mAbs to tumor sites. This platform technology uncages the therapeutic power of mAbs for various CNS diseases that remain poorly treated.

Improved antifouling properties of photobioreactors by surface grafted sulfobetaine polymers.

To improve the antifouling (AF) properties of photobioreactors (PBR) for microalgal cultivation, using trihydroxymethyl aminomethane (tris) as the linking agent, a series of polyethylene (PE) films grafted with sulfobetaine (PE-SBMA) with grafting density ranging from 23.11 to 112 µg cm-2 were prepared through surface-initiated atom transfer radical polymerization (SI-ATRP). It was found that the contact angle of PE-SBMA films decreased with the increase in the grafting density. When the grafting density was 101.33 µg cm-2, it reached 67.27°. Compared with the PE film, the adsorption of protein on the PE-SBMA film decreased by 79.84% and the total weight of solid and absorbed microalgae decreased by 54.58 and 81.69%, respectively. Moreover, the transmittance of PE-SBMA film recovered to 86.03% of the initial value after cleaning, while that of the PE film recovered to only 47.27%. The results demonstrate that the AF properties of PE films were greatly improved on polySBMA-grafted surfaces.

Blood Exosomes Endowed with Magnetic and Targeting Properties for Cancer Therapy.

Exosomes are a class of naturally occurring nanoparticles that are secreted endogenously by mammalian cells. Clinical applications for exosomes remain a challenge because of their unsuitable donors, low scalability, and insufficient targeting ability. In this study, we developed a dual-functional exosome-based superparamagnetic nanoparticle cluster as a targeted drug delivery vehicle for cancer therapy. The resulting exosome-based drug delivery vehicle exhibits superparamagnetic behavior at room temperature, with a stronger response to an external magnetic field than individual superparamagnetic nanoparticles. These properties enable exosomes to be separated from the blood and to target diseased cells. In vivo studies using murine hepatoma 22 subcutaneous cancer cells showed that drug-loaded exosome-based vehicle delivery enhanced cancer targeting under an external magnetic field and suppressed tumor growth. Our developments overcome major barriers to the utility of exosomes for cancer application.

Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21 inhibitor and doxorubicin to treat glioma.

The combined treatment of chemotherapeutant and microRNA (miR) has been proven to be a viable strategy for enhancing chemosensitivity due to its synergistic effect for tumor therapy. However, the co-delivery of drugs and genes remains a major challenge as they lack efficient co-delivery carriers. In this study, three amphiphilic star-branched copolymers comprising polylactic acid (PLA) and polydimethylaminoethyl methacrylate (PDMAEMA) with AB3, (AB3)2,and (AB3)3 molecular architectures were synthesized respectively by a combination of ring-opening polymerization, atom transfer radical polymerization, and click chemistry via an "arm-first" approach. The star copolymers possessed a low critical micelle concentration (CMC) and formed nano-sized micelles with positive surface charges in water as well as exhibiting a much lower cytotoxicity than PEI 25 kDa. Nevertheless, their gene transfection efficiency and tumor inhibition ability showed a remarkable dependence on their molecular architecture. The (AB3)3 architecture micelle copolymer exhibited the highest transfection efficiency, about 2.5 times higher than PEI. In addition, after co-delivering DOX and miR-21 inhibitor (miR-21i) into LN229 glioma cells, the micelles could mediate escaping miR-21i from lysosome degradation and the release of DOX to the nucleus, which significantly decreased the miR-21 expression. Moreover, co-delivery of DOX and miR-21i surprisingly exhibited an anti-proliferative efficiency compared with DOX or the miR-21i treatment alone. These results demonstrated that amphiphilic star-branched copolymers are highly promising for their combinatorial delivery of genes and hydrophobic therapeutants.

Sequence-dependent synergistic inhibition of human glioma cell lines by combined temozolomide and miR-21 inhibitor gene therapy.

Down-regulation of microRNA-21 (miR-21) can induce cell apoptosis and reverse drug resistance in cancer treatments. In this study, we explored the most effective schedule of the miR-21 inhibitor (miR-21i) and Temozolomide (TMZ) combined treatment in human glioma cells. Three tumor cell lines, U251 phosphatase and tensin homologue (PTEN) mutant, LN229 (PTEN wild-type), and U87 (PTEN loss of function), were subjected to evaluate the antitumor effects of deigned treatments (a predose of miR-21i for 4/8 h and then a subsequent TMZ treatment, a predose of TMZ for 4/8 h and then a subsequent miR-21i treatment, or a concomitant treatment) in vitro. A synergistic antiproliferative and proapoptotic activity was only obtained in U251 and U87 cells when a predose was administered for 4 h before the treatment of the other therapeutic agent, while the best antitumor effect in LN229 cells was achieved by using the concomitant treatment. Our data indicate that the effect of sequence and timing of administration is dependent on the PTEN status of cell lines. The best suppression effect was achieved by a maximal inhibition of STAT3 and phosphorylated STAT3, in PTEN loss of function cells. Our results reveal that both the sequence and the timing of administration are crucial in glioma combination therapy.

Hollow poly(MPC-g-PEG-b-PLA) graft copolymer microcapsule as a potential drug carrier.

In this article, an amphiphilic graft copolymer composed of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) as the hydrophilic backbone, poly(L-lactic acid) (PLA) as the hydrophobic side-chains and polyethylene glycol (PEG) as the spacer was synthesized. Transmission electron microscopy revealed that the graft copolymer could self-assemble into hollow microcapsules when dialyzed in aqueous solution and particle sizes ranged from 200 to 300 nm, while the graft copolymer formed core-shell microspheres with the absence of PEG spacer. X-ray photoelectron microscope showed that MPC polymers were located at the surface of the microcapsules. The amounts of adsorbed bovine serum albumin and Fg on the microcapsules were significantly decreased than that on the conventional PLA particles (74% and 60%, respectively), well indicating the anti-adhesive property of the microcapsules. Paclitaxel was chosen as a prototype anticancer drug for the encapsulation and release studies, the results showed that the drug encapsulation efficiency was 89.3 ± 1.2% and the microcapsules exhibited controlled release behaviour.

Inhibition of C6 glioma in vivo by combination chemotherapy of implantation of polymer wafer and intracarotid perfusion of transferrin-decorated nanoparticles.

The objective of this study was to develop a combination chemotherapy of implantation of a 3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-loaded wafer and intracarotid perfusion of BCNU-loaded nanoparticles for glioma treatment in vivo. BCNU-loaded poly(D,L-lactic acid) (PLA) nanoparticles coated with transferrin (Tf) were prepared by a solvent evaporation/diffusion method using Tf as the emulsifier. X-ray photoelectron spectroscopy, Bratton-Marshall colorimetric assay and zeta-potential analysis confirmed the existence of Tf on the nanoparticles and their functional activities. BCNU-loaded PLA wafers were made of BCNU-loaded PLA microspheres. In vitro drug release behavior demonstrated that BCNU was released from the Tf-PLA nanoparticles and wafers in two distinct phases. The biodistribution of Tf-coated nanoparticles investigated by 99mTc-labeled single-photon emission computed tomography (SPECT) showed that the surface-containing Tf-PLA nanoparticles were concentrated in the brain. Inhibition of tumor growth in the C6 glioma-bearing animal model showed that combinational chemotherapy of BCNU-loaded wafer and BCNU-loaded PLA nanoparticles had a stronger inhibitory effect and prolonged the average survival time of rats (164%) compared with that of the control group. Furthermore, the tumors of this treatment group were not visible by examination at 4 weeks. The results of this study demonstrate for the first time that combination therapy of implantation of a BCNU-loaded wafer and intracarotid perfusion of BCNU-loaded nanoparticles may be a new strategy for glioma gene therapy.

Body mass index, recreational physical activity and female urinary incontinence in Gansu, China.

OBJECTIVE: To elucidate the influence of recreational physical activity, body mass index (BMI), and waist circumference on the risk of specific types of urinary incontinence. STUDY DESIGN: We conducted a population-based cross-sectional survey in Gansu, China among 2603 women aged 20 years or older. RESULTS: The study found that BMI was positively associated with urinary incontinence (P for trend=0.008) and the association was mainly observed for stress urinary incontinence (OR=1.4, 95% CI: 1.1, 1.9 for BMI=24.0-27.9 kg/m²; OR=2.3, 95% CI: 1.5, 3.6 for BMI ≥ 28.0 kg/m²; P for trend=0.0005). A positive association between stress incontinence (OR=1.7, 95% CI: 1.2, 2.5) and waist circumference was observed for women who had waist circumference between 70 cm and 75 cm compared to waist circumference less than 70 cm. Recreational physical activity was inversely associated with overall and mixed urinary incontinence (P for trend <0.0001 for both). A significant interaction between physical activity and waist circumference was found for overall (P=0.0007) and stress incontinence (P=0.001). CONCLUSIONS: The findings that physical activity inversely associated with urinary incontinence and its interaction with waist circumference warrant further investigation, particularly in prospective studies.

Development of transferrin functionalized poly(ethylene glycol)/poly(lactic acid) amphiphilic block copolymeric micelles as a potential delivery system targeting brain glioma.

The aim of present study is to conceive a biodegradable poly(ethylene glycol)-polylactide (PEG-PLA) copolymer nanoparticle which can be surface biofunctionalized with ligands via biotin-avidin interactions and used as a potential drug delivery carrier targeting to brain glioma in vivo. For this aim, a new method was employed to synthesize biotinylated PEG-PLA copolymers, i.e., esterification of PEG with biotinyl chloride followed by copolymerization of hetero-biotinylated PEG with lactide. PEG-PLA nanoparticles bearing biotin groups on surface were prepared by nanoprecipitation technique and the functional protein transferrin (Tf) were coupled to the nanoparticles by taking advantage of the strong biotin-avidin complex formation. The flow cytometer measurement demonstrated the targeting ability of the nanoparticles to tumor cells in vitro, and the fluorescence microscopy observation of brain sections from C6 glioma tumor-bearing rat model gave the intuitive proof that Tf functionalized PEG-PLA nanoparticles could penetrate into tumor in vivo.