Passive sampling hypothesis did not shape microbial species-area relationships in open microcosm systems.

The passive sampling hypothesis is one of the most important hypotheses used to explain the mechanism of species-area relationships (SAR) formation. This hypothesis has not yet been experimentally validated due to the confusion between passive sampling (a larger area may support more colonists when fully sampled) and sampling effects (more sampling effort will result in increased species richness when sampling is partial). In this study, we created an open microcosm system with homogeneous habitat, consistent total resources, and biodiversity background using Chinese paocai soup, a fermented vegetable, as a substrate. We made efforts to entirely exclude the influence of sampling effects and to exclusively obtain microorganisms from dispersal using microcosm and high-throughput sequencing techniques. However, in this study, passive sampling based on dispersal failed to shape SAR, and community differences were predominantly caused by species replacement, with only minor contributions from richness differences. Ecological processes including extinction and competitive exclusion, as well as underlying factors like temporal scales and the small island effects, are very likely to have been involved in the studied system. To elucidate the mechanism of SAR development, future studies should design experiments to validate the involvement of dispersal independently.

Hot melt extrusion technology for improved dissolution, solubility and "spring-parachute" processes of amorphous self-micellizing solid dispersions containing BCS II drugs indomethacin and fenofibrate: Profiles and mechanisms.

Many strategies have been employed to improve oral drug delivery. One such approach involves the use of supersaturable delivery systems such as amorphous self-micellizing solid dispersions (SmSDs). SmSDs have attracted more attention recently, but little is known regarding the impact of production methods on profiles and internal mechanisms of final SmSDs in spite of its importance. In this study, amorphous SmSDs containing self-micellizing Soluplus® and BCS II drug (either indomethacin (IND) or fenofibrate (FEN)) were generated using various methods: solvent evaporation (SOL), freeze-drying (FD), microwave radiation-quench cooling (MQC), and hot melt extrusion (HME). Microscopic morphology, amorphous state, thermal behavior, dissolution/solubility, and "spring-parachute" data were used to assemble physicochemical profiles for SmSD systems prepared using each method. Analysis of intermolecular interactions, solubilization, and crystallization inhibition further uncovered internal mechanisms explaining observed physicochemical properties. Generally, SmSD/IND and SmSD/FEN systems generated using HME exhibited superior dissolution, solubility, and spring-parachute profiles. The superior advantages of HME-generated SmSD/IND systems were attributed to relatively stronger intermolecular interactions than observed in SmSD/IND systems fabricated using other methods. Moreover, self-micellizing Soluplus® carrier was able to solubilize IND or FEN and suppress drug crystallization from a supersaturated state, which seemed to be an important mechanism for the properties enhancement caused by SmSD/FENHME. This knowledge should be useful for guiding further development of self-micellizing solid dispersions and for gaining deeper understanding of how HME technology can improve supersaturable drug delivery based on SmSDs strategy.

The Influence of Cellulosic Polymer's Variables on Dissolution/Solubility of Amorphous Felodipine and Crystallization Inhibition from a Supersaturated State.

The collective impact of cellulosic polymers on the dissolution, solubility, and crystallization inhibition of amorphous active pharmaceutical ingredients (APIs) is still far from being adequately understood. The goal of this research was to explore the influence of cellulosic polymers and incubation conditions on enhancement of solubility and dissolution of amorphous felodipine, while inhibiting crystallization of the drug from a supersaturated state. Variables, including cellulosic polymer type, amount, ionic strength, and viscosity, were evaluated for effects on API dissolution/solubility and crystallization processes. Water-soluble cellulosic polymers, including HPMC E15, HPMC E5, HPMC K100-LV, L-HPC, and MC, were studied. All cellulosic polymers could extend API dissolution and solubility to various extents by delaying crystallization and prolonging supersaturation duration, with their effectiveness ranked from greatest to least as HPMC E15 > HPMC E5 > HPMC K100-LV > L-HPC > MC. Decreased polymer amount, lower ionic strength, or higher polymer viscosity tended to decrease dissolution/solubility and promote crystal growth to accelerate crystallization. HPMC E15 achieved greatest extended API dissolution and maintenance of supersaturation from a supersaturated state; this polymer thus had the greatest potential for maintaining sustainable API absorption within biologically relevant time frames.

Deepened cellular/subcellular interface penetration and enhanced antitumor efficacy of cyclic peptidic ligand-decorated accelerating active targeted nanomedicines.

INTRODUCTION: Acceleration and improvement of penetration across cell-membrane interfaces of active targeted nanotherapeutics into tumor cells would improve tumor-therapy efficacy by overcoming the issue of poor drug penetration. Cell-penetrating peptides, especially synthetic polyarginine, have shown promise in facilitating cargo delivery. However, it is unknown whether polyarginine can work to overcome the membrane interface in an inserted pattern for cyclic peptide ligand-mediated active targeting drug delivery. Here, we conducted a study to test the hypothesis that tandem-insert nona-arginine (tiR9) can act as an accelerating component for intracellular internalization, enhance cellular penetration, and promote antitumor efficacy of active targeted cyclic asparagine-glycine-arginine (cNGR)-decorated nanoliposomes. METHODS: Polyarginine was coupled with the polyethylene glycol (PEG) chain and the cNGR moiety, yielding a cNGR-tiR9-PEG2,000-distearoylphosphatidylethanolamine conjugate. RESULTS: The accelerating active targeted liposome (Lip) nanocarrier (cNGR-tiR9-Lip-doxorubicin [Dox]) constructed in this study held suitable physiochemical features, such as appropriate particle size of ~150 nm and sustained-release profiles. Subsequently, tiR9 was shown to enhance cellular drug delivery of Dox-loaded active targeted systems (cNGR-Lip-Dox) significantly. Layer-by-layer confocal microscopy indicated that the tandem-insert polyarginine accelerated active targeted system entry into deeper intracellular regions based on observations at marginal and center locations. tiR9 enhanced the penetration depth of cNGR-Lip-coumarin 6 through subcellular membrane barriers and caused its specific accumulation in mitochondria, endoplasmic reticulum, and Golgi apparatus. It was also obvious that cNGR-tiR9-Lip-Dox induced enhanced apoptosis and activated caspase 3/7. Moreover, compared with cNGR-Lip-Dox, cNGR-tiR9-Lip-Dox induced a significantly higher antiproliferative effect and markedly suppressed tumor growth in HT1080-bearing nude mice. CONCLUSION: This active tumor-targeting nanocarrier incorporating a tandem-insert polyarginine (tiR9) as an accelerating motif shows promise as an effective drug-delivery system to accelerate translocation of drugs across tumor-cell/subcellular membrane barriers to achieve improved specific tumor therapy.

On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology.

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or Soluplus®, is a relatively new copolymer and a promising carrier of amorphous solid dispersions. Knowledge on the inherent properties of Soluplus® (e.g. cloud points, critical micelle concentrations, and viscosity) in different conditions is relatively inadequate, and the application characteristics of Soluplus®-based solid dispersions made by microwave methods still need to be clarified. In the present investigation, the inherent properties of a Soluplus® carrier, including cloud points, critical micelle concentrations, and viscosity, were explored in different media and in altered conditions. Ibuprofen, a BCS class II non-steroidal anti-inflammatory drug, was selected to develop Soluplus®-based amorphous solid dispersions using the microwave-quench cooling (MQC) method. Scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Raman spectroscopy (RS), and Fourier transform infrared spectroscopy (FT-IR) were adopted to analyze amorphous properties and molecular interactions in ibuprofen/Soluplus® amorphous solid dispersions generated by MQC. Dissolution, dissolution extension, phase solubility, equilibrium solubility, and supersaturated crystallization inhibiting experiments were performed to elucidate the effects of Soluplus® on ibuprofen in solid dispersions. This research provides valuable information on the inherent properties of Soluplus® and presents a basic understanding of Soluplus® as a carrier of amorphous solid dispersions.

Effect of External Electric Field on Substrate Transport of a Secondary Active Transporter.

Substrate transport across a membrane accomplished by a secondary active transporter (SAT) is essential to the normal physiological function of living cells. In the present research, a series of all-atom molecular dynamics (MD) simulations under different electric field (EF) strengths was performed to investigate the effect of an external EF on the substrate transport of an SAT. The results show that EF both affects the interaction between substrate and related protein's residues by changing their conformations and tunes the timeline of the transport event, which collectively reduces the height of energy barrier for substrate transport and results in the appearance of two intermediate conformations under the existence of an external EF. Our work spotlights the crucial influence of external EFs on the substrate transport of SATs and could provide a more penetrating understanding of the substrate transport mechanism of SATs.

[Radiation Environment Study of Near Space in China Area].

Aerospace activity in near space (20-50 km) has become a research hotspot for aviation big countries worldwide. Solar radiation study, as the prerequisite to carry out aerospace activity, is facing the barrier of lacking of observation in near space layer. Ozone is the most important factor that affects radiation value in this layer. Based on ECMWF reanalysis data, this input key parameter and its horizontal, vertical and temporal characteristics are analyzedwith results showing obvious regional features in temporal-spatial distribution and varieties. With meteorological data and surface parameters, near space over China is divided into 5 parts. Key factors' value is confirmed over each division. With SBDART radiation transfer model, solar radiation and ultraviolet radiation simulation in near space are conducted separately. Results show that it is influenced by latitude, total ozone and its vertical distribution, radiation varies under complex rules. The average year and monthly solar radiation strengthens changes with latitude reduction, while annual range changes reversely. Air absorbing is related to latitude and land-sea contrast and shows different values and seasonal variations. The ultraviolet radiation over South China Sea reaches its maximum value and minimum annual range, as well as minimum monthly range with value strengthening in summer and weakening in winter. In other areas radiation increases in summer while weakens in winter, monthly range shows double peaks with higher value in spring and autumn, lower in summer and winter. Air absorption in ultraviolet radiation is influenced by multiple factors, vertical varieties over areas besides South China Sea enhance in summer time. The vertical changes of monthly ranges affected by air absorption show consistence in higher and lower layer in June and July, while in other months ranges are bigger in higher layer.

Amino acids-incorporated nanoflowers with an intrinsic peroxidase-like activity.

Functional molecules synthesized by self-assembly between inorganic salts and amino acids have attracted much attention in recent years. A simple method is reported here for fabricating hybrid organic-inorganic nanoflowers using copper (II) ions as the inorganic component and natural amino acids as the organic component. The results indicate that the interactions between amino acid and copper ions cause the growth of the nanoflowers composed by C, N, Cu, P and O elements. The Cu ions and Cu(AA)n complexes containing Cu-O bond are present in the nanoflowers. The nanoflowers have flower-like porous structure dominated by the R groups of amino acids with high surface-to-volume ratios, which is beneficial for exerting its peroxidase-like activity depending on Fenton-like reaction mechanism with ABTS and Rhodamine B as the substrates. It is expected that the nanoflowers hold great promise as enzyme mimics for application in the field of biosensor, bioanalysis and biocatalysis.

[Rules and characteristics of crystallization inhibition of cellulose polymers against drugs in supersaturated states].

This study aims to explore the characteristics of crystallization inhibition by cellulose polymers at the supersaturated states of drugs. The study was performed by simulating supersaturated process and preparing supersaturated drug solid, and was carried out by measuring the content of drugs at different time points using dissolution apparatus. The types, amounts, ionic intensity and viscosity of cellulose polymers were examined to assess the crystallization inhibition effect on BCS II class drug indomethacin. HPMC E15 exhibited the strongest crystallization inhibition effect. The more added, more obvious crystallization suppression was observed against indomethacin. The decrease in viscosity and increase in ionic intensity led to an enhanced inhibition. The research provides a scientific guide for the crystallization inhibition of supersaturated drug by cellulose polymers.

RANKL, OPG and CTR mRNA expression in the temporomandibular joint in rheumatoid arthritis.

The calcitonin receptor (CTR) and receptor activator of nuclear factor κB ligand (RANKL) have been found to be involved in the differentiation of osteoclasts. The association between the RANKL:osteoprotegerin (OPG) expression ratio and the pathogenesis of bone-destructive rheumatoid arthritis (RA) has been described in several joints, but the available data for the temporomandibular joint (TMJ) are limited. The aim of the present study was to investigate the involvement of osteoclasts at sites of bone erosion by determining the CTR expression and the RANKL:OPG expression ratio in the TMJ in a collagen-induced arthritis (CIA) model. Forty-eight male Wistar rats were randomly divided into two groups: Control group, injected with saline solution for 6 weeks; and CIA group, injected with emulsion. The RANKL and OPG mRNA expression was significantly increased in immunized rats compared with that in non-immunized rats. The RANKL:OPG expression ratio on the trabecular bone surface was 9.0 and 6.4 in the CIA group at weeks 4 and 6, respectively, while the RANKL:OPG expression ratio in the controls was 1.0:2. CTR mRNA expression was significantly upregulated in immunized rats compared with that in non-immunized rats; the level of CTR mRNA in the CTR-positive osteoclasts on the trabecular bone surface was 10.9- and 7.8-fold higher in the CIA rats than that in the control rats at weeks 4 and 6, respectively. In conclusion, focal bone destruction in an experimental model of arthritis in the TMJ can be attributed to cells expressing CTR, a defining feature of osteoclasts. The expression of RANKL and OPG mRNA within the inflamed synovium provides an insight into the mechanism of osteoclast differentiation and function at the border of bone erosion in arthritis.

[Temperature effect on the hydrogen bonding behavior between DMSO and water in aqueous DMSO solutions studied by raman spectroscopy].

In the present paper, DMSO/H2O mixture with the ratio of volume 1:1 was measured in the cooling process by Raman spectroscopy, and the Raman assignments was made to the DMSO molecular and water molecular. The results showed that the behavior between intra-molecular hydrogen bonds and inter-molecular hydrogen bonds of DMSO and water leads to the change in the Raman spectra of the S==O stretching vibration of DMSO and the O--H stretching vibration of water. Further analysis showed that the hydrogen bond between DMSO and water was enhanced in the course of temperature decreasing process (27 to -30 degrees C), and the intramolecular hydrogen bonds between water and water replaced the intermolecular hydrogen bonds of DMSO and water in the course of temperature decreasing process (-30 to -60 degrees C). The research provides experimental basis for hydrogen bonding theory in aqueous solution.

[Influence of measurement errors of radiation in NIR bands on water atmospheric correction].

For standard algorithm of atmospheric correction of water, the ratio of two near-infrared (NIR) channels is selected to determine an aerosol model, and then aerosol radiation at every wavelength is accordingly estimated by extrapolation. The uncertainty of radiation measurement in NIR bands will play important part in the accuracy of water-leaving reflectance. In the present research, erroneous expressions were derived mathematically in order to see the error propagation from NIR bands. The errors distribution of water-leaving reflectance was thoroughly studied. The results show that the bigger the errors of measurement are made, the bigger the errors of water-leaving reflectance are retrieved, with sometimes the NIR band errors canceling out. Moreover, the higher the values of aerosol optical depth or the more the component of small particles in aerosol, the bigger the errors that appear during retrieval.

How does (E)-2-(acetamidomethylene)succinate bind to its hydrolase? From the binding process to the final result.

The binding of (E)-2-(acetamidomethylene)succinate (E-2AMS) to E-2AMS hydrolase is crucial for biological function of the enzyme and the last step reaction of vitamin B(6) biological degradation. In the present study, several molecular simulation methods, including molecular docking, conventional molecular dynamics (MD), steered MD (SMD), and free energy calculation methods, were properly integrated to investigate the detailed binding process of E-2AMS to its hydrolase and to assign the optimal enzyme-substrate complex conformation. It was demonstrated that the substrate binding conformation with trans-form amide bond is energetically preferred conformation, in which E-2AMS's pose not only ensures hydrogen bond formation of its amide oxygen atom with the vicinal oxyanion hole but also provides probability of the hydrophobic interaction between its methyl moiety and the related enzyme's hydrophobic cavity. Several key residues, Arg146, Arg167, Tyr168, Arg179, and Tyr259, orientate the E-2AMS's pose and stabilize its conformation in the active site via the hydrogen bond interaction with E-2AMS. Sequentially, the binding process of E-2AMS to E-2AMS hydrolase was studied by SMD simulation, which shows the surprising conformational reversal of E-2AMS. Several important intermediate structures and some significant residues were identified in the simulation. It is stressed that Arg146 and Arg167 are two pivotal residues responsible for the conformational reversal of E-2AMS in the binding or unbinding. Our research has shed light onto the full binding process of the substrate to E-2AMS hydrolase, which could provide more penetrating insight into the interaction of E-2AMS with the enzyme and would help in the further exploration on the catalysis mechanism.

[Improving accumulation-mode fraction based on spectral aerosol optical depth in Beijing].

In the present study, the authors put forward a parameterization method of correcting fine-mode Angstrom index with aerosol optical depth and volume distribution of aerosol derived from AERONET in Beijing over 2011. The parameterization method is coupled with aerosol optical depth spectral deconvolution algorithm to improve the accuracy of accumulation-mode fraction. The errors of estimated AMF are derived from underestimate of fine-mode Angstrom index errors. We calculate and simulate the extreme values of fine-mode Angstrom index, getting constraint conditions, and then establish the extreme values correction method. Results from sensitivity test suggest that extreme values of fine-mode Angstrom index are constrained in the reasonable range. Finemode Angstrom index and AMF are sensitive to normalized volume distribution of aerosol, ranging from 0.662 to 2.849 and from 0.08 to 0.84 due to different distribution. Mean deviation of accumulation-mode fraction is reduced from 0.072 to 0.044, and the difference is 38.89%, especially in winter and summer. Improving computational accuracy of accumulation-mode fraction can enhance that of anthropogenic aerosol optical thickness, and it has important significance of anthropogenic aerosol direct radiation force estimation and environmental quality assessment.

[Retrieval of dust fraction of atmospheric aerosols based on spectra characteristics of refractive indices obtained from remote sensing measurements].

Mineral dust is an important chemical component of aerosol, which has a significant impact on the climate and environmental changes. The spectral behavior of aerosol refractive indices at four wavelengths from 440 to 1 020 nm was analyzed based on one year observation obtained from Beijing AERONET site. The real parts of refractive index (n) in each band did not differ greatly, however the imaginary parts (k) showed a significant difference due to the absorption of mineral dust in aerosol. From 440 to 670 nm k decreased rapidly, while from 670 to 1 020 nm featured a lower, constant value. Accordingly, k(440 nm) could be considered separately with other three bands. Hence, we added mineral dust into the currently used three-component aerosol chemical model to form a new four-component model (i. e. BC, AS, dust and water) which is more suitable to represent the aerosol chemical composition. Then we presented a method to retrieve dust content in aerosols using this four-component model and refractive indices obtained from the sunphotometer measurements. Finally the dust content in aerosol was investigated under different weather conditions, i. e. clear, haze and dust in Beijing. The results showed that volume fractions of the dust component were 88%, 37% and 48% for clear, hazy and dusty day respectively, which was consistent with the coarse mode proportion in aerosols calculated from aerosol size distributions.

Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

[Stereoscopic remote sensing used in monitoring Enteromorpha Prolifra disaster in Chinese Yellow Sea].

In the summer 2008, Enteromorpha Prolifra broke out in Yellow Sea and East Sea on a large scale for the first time, and became a marine disaster. The authors constructed a stereoscopic monitoring system which monitored the disaster continuously, dynamically and in real time. The present paper introduced the construction of the stereoscopic monitoring system; through analyzing the spectral characteristics of Enteromorpha Prolifra and ocean water which were acquired in a field experiment, confirmed Enteromorpha Prolifra retrieval models based on multi-platform multi-sensor and multi-spectral remote sensing data, contrasted the different scale monitoring results, and analyzed the evolvement rules with time-series analysis. This system was applied to the Enteromorpha Prolifra emergency monitoring in the 29th Olympic sailing area. It was proved feasible and valuable for the Olympic safeguard.

[Simulation and analysis of polarization characteristics for real sea surface sunglint].

The sea surface sunglint is caused by specular reflectance. Water is a kind of dark target with a very low reflectance, so sunglint becomes a big noise in the aerial or aerospace remote sensing images; sunglint is strongly polarized, and can be a natural standard light source for polarized sensor in-flight calibration; sunglint also can be utilized to retrieve gaseous constituents and aerosol properties. For both de-noising and being standard light source, the radiative physic parameters should be calculated accurately. First, A 3-D sea surface model was constituted according to the Cox & Munk model; Second, the polarized radiative model of sunglint was deduced based on the 3-D sea surface model and polarized Fresnel reflectance law; Third, the sensitivities of solar-viewing relative azimuth, zenith, wind speed and wind direction were analyzed utilizing the polarized radiative model. The polarization characteristics analysis of sunglint provides a theoretical basis for the quantitative remote sensing retrievals which uses sunglint.

[Atmospheric correction method for HJ-1 CCD imagery over waters based on radiative transfer model].

Atmospheric correction is a bottleneck in quantitative application of Chinese satellites HJ-1 data to remote sensing of water color. According to the characteristics of CCD sensors, the present paper made use of air-water coupled radiative transfer model to work out the look-up table (LUT) of atmospheric corrected parameters, and thereafter developed pixel-by-pixel atmospheric correction method over waters accomplishing the water-leaving remote sensing reflectance with accessorial meteorological input. The paper validates the HJ-1 CCD retrievals with MODIS and in-situ results. It was found that the accuracy in blue and green bands is good. However, the accuracy in red or NIR bands is much worse than blue or green ones. It was also demonstrated that the aerosol model is a sensitive factor to the atmospheric correction accuracy.