Hepatic Carcinoma Selective Nucleic Acid Nanovector Assembled by Endogenous Molecules Based on Modular Strategy.

We rationally formulated a nucleic acid nanovector platform utilizing endogenous molecules in the following steps: nucleic acids are initially packed by a multifunctional peptide and a cationic liposome to form positively charged ternary complexes through electrostatic interaction; then the ternary complexes were coated with hyaluronic acid (HA) to form negatively charged quaternary nanocomplexes (Q-complexes). Among the components of Q-complexes, the multifunctional peptide was composed of a poly-16-arginine (R16) and a hepatic tumor-targeted cell penetrating peptide (KRPTMRFRYTWNPMK); the cationic lipid component included DOTAP and fusogenic lipid DOPE; the HA component shielded the cationic ternary complexes and actively targeted the CD44 overexpressed on the surface of tumor cells. Q-complexes have showed a relatively high stability in the medium, and HA component partially separated from the nanocomplexes after the Q-complexes bound to the cancer cells. The Q-complexes showed significantly enhanced nucleic acid delivery activity than the corresponding quaternary complexes containing R16 and nonvisible cytotoxicity in SCMM-7721 cells. In vivo, a selected Q-complex HLP1R specifically targeted and entered tumor cells without affecting normal tissues. Furthermore, HLP1R wrapped survivin siRNA efficiently and silenced the targeting gene in the liver orthotropic transplantation tumor models and showed nontoxic in vivo. This study reveals that Q-complexes are reasonable and feasible gene therapeutic carriers.

Comparison of modification of a bacterial uricase with N-hydroxysuccinimide esters of succinate and carbonate of monomethoxyl poly(ethylene glycol).

Uricase after modification with monomethoxy poly(ethylene glycol) (mPEG) is currently the sole agent to treat refractory gout. For formulating Bacillus fastidious uricase, succinimidyl carbonate of mPEG-5000 (SC-mPEG5k) and succinimidyl succinate of mPEG-5000 (SS-mPEG5k) were compared. SC-mPEG5k possessed higher purity, comparable reaction rate constant with glycine but lower hydrolysis rate, and stronger effectiveness to modify amino groups. The uricase possessed two types of amino groups bearing a 25-fold difference in reactivity with SC-mPEG5k or SS-mPEG5k at pH 9.2. Oxonate and xanthine concentration-dependently protected the bacterial uricase from inactivation during PEGylation. With SC-mPEG5k at a molar ratio of 200 to uricase subunits and oxonate of 50 µM, the PEGylated uricase (1) retained about 73% of the original activity, (2) displayed about 10% reactivity to rabbit anti-sera recognizing the native uricase, (3) elicited IgG in rats accounting for about 5% of that by the native uricase, (4) exhibited circulation half-life time of about 25 H in cock plasma in vivo, and (5) concurrently maintained uric acid at lowered levels for over 20 H. Hence, PEGylation with SC-mPEG under the protection of a competitive inhibitor was a practical approach to formulation of the bacterial uricase; protection of enzymes by competitive inhibitors during PEGylation may have universal significance.

Diagnosis of Parkinson's Disease via the Metabolic Fingerprint in Saliva by Deep Learning.

Parkinson's disease (PD) is the second cause of the neurodegenerative disorder, affecting over 6 million people worldwide. The World Health Organization estimated that population aging will cause global PD prevalence to double in the coming 30 years. Optimal management of PD shall start at diagnosis and requires both a timely and accurate method. Conventional PD diagnosis needs observations and clinical signs assessment, which are time-consuming and low-throughput. A lack of body fluid diagnostic biomarkers for PD has been a significant challenge, although substantial progress has been made in genetic and imaging marker development. Herein, a platform that noninvasively collects saliva metabolic fingerprinting (SMF) by nanoparticle-enhanced laser desorption-ionization mass spectrometry with high-reproducibility and high-throughput, using ultra-small sample volume (down to 10 nL), is developed. Further, excellent diagnostic performance is achieved with an area-under-the-curve of 0.8496 (95% CI: 0.7393-0.8625) by constructing deep learning model from 312 participants. In conclusion, an alternative solution is provided for the molecular diagnostics of PD with SMF and metabolic biomarker screening for therapeutic intervention.

Nanofibrillar Poly(vinyl alcohol) Ionic Organohydrogels for Smart Contact Lens and Human-Interactive Sensing.

Hydrogel bioelectronics as one of the next-generation wearable and implantable electronics ensures excellent biocompatibility and softness to link the human body and electronics. However, volatile, opaque, and fragile features of hydrogels due to the sparse and microscale three-dimensional network seriously limit their practical applications. Here, we report a type of smart and robust nanofibrillar poly(vinyl alcohol) (PVA) organohydrogels fabricated via one-step physical cross-linking. The nanofibrillar network cross-linked by numerous PVA nanocrystallites enables the formation of organohydrogels with high transparency (90%), drying resistance, high toughness (3.2 MJ/m3), and tensile strength (1.4 MPa). For strain sensor application, the PVA ionic organohydrogel after soaking in NaCl solution shows excellent linear sensitivity (GF = 1.56, R2 > 0.998) owing to the homogeneous nanofibrillar PVA network. We demonstrate the potential applications of the nanofibrillar PVA-based organohydrogel in smart contact lens and emotion recognition. Such a strategy paves an effective way to fabricate strong, tough, biocompatible, and ionically conductive organohydrogels, shedding light on multifunctional sensing applications in next-generation flexible bioelectronics.

[Application of near infrared spectroscopy in analysis of wood properties].

There is substantial interest in the improvement of wood properties through genetic selection or a change in silviculture prescription. Tree breeding purpose requires measurement of a large number of samples. However, traditional methods of assessing wood properties are both time consuming and destructive, limiting the numbers of samples that can be processed, so new method would be needed to find. Near infrared spectroscopy (NIR) is an advanced spectroscopic tool for nondestructive evaluation of wood and it can quickly, accurately estimate the properties of increment core, solid wood or wood meal. The present paper reviews the advances in the research on the wood chemistry properties and anatomical properties using NIR.

Flexible Anti-Biofouling MXene/Cellulose Fibrous Membrane for Sustainable Solar-Driven Water Purification.

Solar-driven interfacial water evaporation is regarded as an effective, renewable, and environment-friendly technology for clean water production. However, biofouling caused by the nonspecific interaction between the steam generator and biofoulants generally hinders the efficient application of wastewater treatment. Herein, this work reports a facile strategy to fabricate flexible anti-biofouling fibrous photothermal membrane consisting of a MXene-coated cellulose membrane for highly efficient solar-driven water steam evaporation toward water purification applications. The as-prepared MXene/cellulose photothermal membrane exhibits light absorption efficiency as high as ∼94% in a wide solar spectrum range and a water evaporation rate up to 1.44 kg m-2 h-1 under one solar illumination. Also, the MXene/cellulose membrane shows very high antibacterial efficiency (above 99.9%) owing to the MXene coating as a highly effective bacteriostatic agent. Such a flexible, anti-biofouling, and high-efficiency photothermal membrane sheds light on practical applications in long-term wastewater treatments.

[Diel variations of hydrochemistry and influencing factors in a surface stream in subtropical karst area, SW China].

In order to understand the diel variation and influencing factors of hydrochemistry in a surface creek fed by karst subterranean river in a subtropical area, where is located at Guancun Village, Daliang Township, Rong'an County of Guangxi Zhuang Autonomous Region, China, two monitoring sites were set simultaneously to launch Guancun subterranean river outlet (G1) and surface creek mouth (G2), respectively. Physical and hydrochemical parameters including pH, dissolved oxygen (DO), water temperature (T) and specific conductivity (Spc) were measured at 15-minute intervals and water samples for analyzing major ions such as Ca2+, HCO3- and NO3- as well as delta3C(DIC) were collected at 2-hour intervals. The results showed that: (1) G1 and G2 sites were both HCO3- Ca type water, however the two monitoring sites showed different diel variations of hydrogeochemical process; (2) The physical and hydrochemical parameters (T, DO, pH, Spc) and major ions (Ca2+, Mg2+, Na+, K+, HCO3-, SO4(2-), NO3-, Cl- in G1 site were basically stable, while the physical and hydrochemical parameters (T, DO, pH, Spc) and major ions (Ca2+, HCO3- and NO3-) in G2 site displayed regular diel variation during monitoring; (3) The dissolved inorganic carbon (DIC) and delta13C values in G2 monitoring site showed reverse characteristics in diurnal fluctuations, where DIC decreased in daylight and increased at night while the delta13C value increased in daylight and decreased at night, DIC also showed a negative correlation with the delta13C value (correlation coefficient is -0. 87, P < 0.01) in G2 site. These results indicated that photosynthesis and respiration of aquatic plants, water temperature and degassing jointly affected diurnal variation of hydrochemistry and controlled the cycling process of internal matter in this surface creek fed by karst subterranean river.

Facile one-step coating approach to magnetic submicron particles with poly(ethylene glycol) coats and abundant accessible carboxyl groups.

PURPOSE: Magnetic submicron particles (MSPs) are pivotal biomaterials for magnetic separations in bioanalyses, but their preparation remains a technical challenge. In this report, a facile one-step coating approach to MSPs suitable for magnetic separations was investigated. METHODS: Polyethylene glycol) (PEG) was derived into PEG-bis-(maleic monoester) and maleic monoester-PEG-succinic monoester as the monomers. Magnetofluids were prepared via chemical co-precipitation and dispersion with the monomers. MSPs were prepared via one-step coating of magnetofluids in a water-in-oil microemulsion system of aerosol-OT and heptane by radical co-polymerization of such monomers. RESULTS: The resulting MSPs contained abundant carboxyl groups, exhibited negligible nonspecific adsorption of common substances and excellent suspension stability, appeared as irregular particles by electronic microscopy, and had submicron sizes of broad distribution by laser scattering. Saturation magnetizations and average particle sizes were affected mainly by the quantities of monomers used for coating magnetofluids, and steric hindrance around carboxyl groups was alleviated by the use of longer monomers of one polymerizable bond for coating. After optimizations, MSPs bearing saturation magnetizations over 46 emu/g, average sizes of 0.32 µm, and titrated carboxyl groups of about 0.21 mmol/g were obtained. After the activation of carboxyl groups on MSPs into N-hydroxysuccinimide ester, biotin was immobilized on MSPs and the resulting biotin-functionalized MSPs isolated the conjugate of streptavidin and alkaline phosphatase at about 2.1 mg/g MSPs; streptavidin was immobilized at about 10 mg/g MSPs and retained 81% ± 18% (n = 5) of the specific activity of the free form. CONCLUSION: The facile approach effectively prepares MSPs for magnetic separations.

Site-specific PEGylation of therapeutic proteins via optimization of both accessible reactive amino acid residues and PEG derivatives.

Modification of accessible amino acid residues with poly(ethylene glycol) [PEG] is a widely used technique for formulating therapeutic proteins. In practice, site-specific PEGylation of all selected/engineered accessible nonessential reactive residues of therapeutic proteins with common activated PEG derivatives is a promising strategy to concomitantly improve pharmacokinetics, allow retention of activity, alleviate immunogenicity, and avoid modification isomers. Specifically, through molecular engineering of a therapeutic protein, accessible essential residues reactive to an activated PEG derivative are substituted with unreactive residues provided that protein activity is retained, and a limited number of accessible nonessential reactive residues with optimized distributions are selected/introduced. Subsequently, all accessible nonessential reactive residues are completely PEGylated with the activated PEG derivative in great excess. Branched PEG derivatives containing new PEG chains with negligible metabolic toxicity are more desirable for site-specific PEGylation. Accordingly, for the successful formulation of therapeutic proteins, optimization of the number and distributions of accessible nonessential reactive residues via molecular engineering can be integrated with the design of large-sized PEG derivatives to achieve site-specific PEGylation of all selected/engineered accessible reactive residues.

A new practical system for evaluating the pharmacological properties of uricase as a potential drug for hyperuricemia.

The use of uricase-deficient mammals to screen formulations of engineered uricases as potential drugs for hyperuricemia involves heavy costs and presents a technical bottleneck. Herein, a new practical system was investigated to evaluate the pharmacological significance of a bacterial uricase based on its ability to eliminate uric acid in plasma in vitro, its pharmacokinetics in vivo in healthy rats, and the modeled pharmacodynamics in vivo. This uricase, before and after modification with the monomethyl ether of poly(ethylene glycol)-5000, effectively eliminated uric acid in vitro in rabbit plasma, but its action was susceptible to xanthine inhibition. After intravenous injection of the modified uricase without purification, a bi-exponential model fit well to uricase activities in vivo in the plasma of healthy rats; the half-life of the modified uricase was estimated without interference from the unmodified uricase leftover in the sample and was nearly 100-fold longer than that of the unmodified uricase. Using a model of the elimination of uric acid in vivo taking into account of uricase pharmacokinetics and xanthine inhibition, modeled pharmacodynamics supported that the half-life of uricase and its susceptibility to xanthine are crucial for the pharmacological significance of uricase. Hence, this practical system is desirable for doing preliminary screening of formulations of engineered uricases as potential drugs for hyperuricemia.