Effects of irradiation behavior on physicochemical properties of glassy radioactive contaminated soil containing various contents of actinides nuclear waste.

The evaluation of radiation resistance of the treated radioactive contaminated soil is crucial. The irradiation behavior of simulated radioactive soil waste irradiated with 1.5 MeV Xe20+ ions at fluences of 1 × 1012-1 × 1015 ions/cm2 was studied. Before the irradiation experiment, all the samples were sintered by microwave. The results showed that microwave sintering may be used to treat radioactive contaminated soil. In addition, the irradiation experiment results show that when the Nd2O3 content was low (<20 wt.%), the irradiation has little effect on the sample. When the Nd2O3 content was higher, the Vickers hardness of the sample (25 wt.%) decreased by 7 % at a fluence of 1 × 1015 ions/cm2, which may be due to the high Nd2O3 content that destroyed the overall stability of the glass waste form. The low normalized leaching rate of the irradiated sample (LRNd, ∼10-6 g·m-2·d-1) also proved that it had good aqueous durability. Moreover, the radiation resistance of the sample was illustrated by studying the influence mechanism of 1.5 MeV Xe20+ irradiation on radioactive contaminated soil. This work can help to study the environmental pollution problems of radioactive contaminated soil containing various contents of actinide nuclear waste.

Discontinuous low temperature stress and plant growth regulators during the germination period promote roots growth in alfalfa (Medicago sativa L.).

In high-cold regions, alfalfa is susceptible to cold damage during the seed germination. The effects of discontinuous low temperature stress and plant growth regulators (PGRs) on alfalfa were studied in response to the high day/night temperature differentials in the area. The experiments included seed germination, seedling cold tolerance and plant recovery. Variable temperatures (VT) of 0 °C/15 °C, 5 °C/20 °C and 10 °C/25 °C were set and seeds were soaked with alginate oligosaccharides (AOS), brassinolide (BR) and diethyl aminoethyl hexanoate (DA-6) during the germination period. Parameters such as seed germination and mean germination time (MGT), phenylalanine ammonia-lyase (PAL) activity and oligomeric proanthocyanidins (OPC) content of early seedlings, dry matter accumulation and root crown of the restored plants were analysed. The results showed that low variable-temperature (LVT) stress prolonged the MGT but had little inhibitory effect on germination percentage. Early seedlings adapted to LVT stress by regulating their own water and OPC content, PAL activity and other parameters. LVT induced early alfalfa seedlings to increase their underground biomass by shortening root length and increasing root diameter, and those that had accumulated more underground biomass had faster growth rates and higher total biomass when the ambient temperature rose. AOS also promoted an increase in root crown diameter and root dry weight. This research proved that LVT stress and AOS during the germination process can lead to better growth of alfalfa in high cold regions.

The evolution of anionic nanoclusters at the electrode interface in water-in-salt electrolytes.

Water-in-salt electrolytes (WiSEs) have attracted extensive attention as promising alternatives to organic electrolytes. The limited electrochemical stability windows (ESWs) of aqueous electrolytes are significantly widened by WiSEs. However, the actual ESWs are lower than predicted as the interphase with WiSEs is not as stable as the solid electrolyte interphase (SEI) in conventional lithium-ion batteries. Therefore, identifying the interface state in WiSEs is vital to understanding their electrochemical behavior. Here, the structure of the lithium bis(trifluoromethane sulfonyl)imide (LiTFSI) electrolyte near the interface of the carbon electrode (Ketjen black) was evaluated by experimental methods (neutron diffraction, Raman, and nuclear magnetic resonance spectroscopy) and molecular dynamics (MD) simulations. The results reveal that the introduction of carbon electrodes increases the size of the anionic nanoclusters and enhances the microphase separation at the interface. The MD simulations show that cation-π interactions are responsible for the evolution of anionic nanoclusters at the electrode interface. Moreover, lower charge transfer resistance is achieved at carbon-based electrodes due to the specific interface state. Our findings provide a strategy for introducing cation-π interactions between electrodes and electrolytes to improve the electrochemical performance.

SESNet: sequence-structure feature-integrated deep learning method for data-efficient protein engineering.

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet, a supervised deep-learning model to predict the fitness for protein mutants by leveraging both sequence and structure information, and exploiting attention mechanism. Our model integrates local evolutionary context from homologous sequences, the global evolutionary context encoding rich semantic from the universal protein sequence space and the structure information accounting for the microenvironment around each residue in a protein. We show that SESNet outperforms state-of-the-art models for predicting the sequence-function relationship on 26 deep mutational scanning datasets. More importantly, we propose a data augmentation strategy by leveraging the data from unsupervised models to pre-train our model. After that, our model can achieve strikingly high accuracy in prediction of the fitness of protein mutants, especially for the higher order variants (> 4 mutation sites), when finetuned by using only a small number of experimental mutation data (< 50). The strategy proposed is of great practical value as the required experimental effort, i.e., producing a few tens of experimental mutation data on a given protein, is generally affordable by an ordinary biochemical group and can be applied on almost any protein.

Dynamic assessment of coronary artery during different cardiac cycle in patients with coronary artery disease using coronary CT angiography.

INTRODUCTION: To evaluate the effect of the cardiac cycle for the coronary artery opening and coronary stenosis at the plaque to determine the phase of measuring maximum diameters required for coronary artery disease (CAD). METHODS: This retrospective study assessed data for 208 consecutive patients who underwent coronary computed tomography angiography (CTA). The cross-sectional area and diameters of the opening of the left main coronary artery (LM), left anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA), the stenosis rate of involved vessels were measured in 10 cardiac cycles. And all their dynamic changes were estimated by the linear mixed model. The relationship between stenosis rate and opening orifice were analyzed by monofactorial variance. RESULTS: The opening parameters and stenosis rate of the four main coronary arteries varied within the cardiac cycle (p < .05). The maximum opening area occurred at the 45%-55% phase; The range of stenosis rate varied approximately 11%-14% and the maximum stenosis rate was at the 65% phase. The degree of vascular stenosis for LM, LAD and LCX were not associated with their corresponding opening diameters, but were positively intercorrelation with each other. CONCLUSION: For patients with CAD, the maximum coronary artery stenosis rate were at 65% phase and the maximum value of coronary artery opening were at 45%-55% phase, which were chosen for the appropriate measurement and evaluation by CTA.

Effects of rehabilitation management on lifestyle and quality of life of patients with coronary heart disease after percutaneous coronary intervention based on behavior change theory.

BACKGROUND: The aim of this study was to assess the effects of rehabilitation management on the lifestyle and quality of life of patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI) based on the behavior change theory. METHODS: A total of 222 CHD patients admitted from January 2019 to April 2021 were randomly divided into research and control groups (N.=111). Control group was administered with routine postoperative nursing management, while research group received behavior changing nursing intervention. The quality-of-life scores, blood pressure and blood lipid levels before and after surgery, as well as length of hospitalization, treatment duration, symptom relief time, incidence rate of complications and nursing satisfaction were compared. RESULTS: After surgery, the length of hospitalization, treatment duration and symptom relief time were shorter, and the incidence rate of complications, levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower in research group than those in control group, while research group was better in physical function, social function, physiological functioning, physical pain, mental health, emotional functioning, vitality and overall health scores, satisfaction and high-density lipoprotein cholesterol (HDL-C) level than control group (P<0.05). CONCLUSIONS: The application of behavior change theory in the cardiac rehabilitation management of patients with CHD after PCI can improve the lifestyle and quality of life.

Icariin attenuates the calcification of vascular smooth muscle cells through ERα - p38MAPK pathway.

Objective: To investigate the relationship between icariin and the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and the signal pathway involved. Methods: We applied a universally accepted calcification model of VSMCs induced by ß glycerophosphate. Then the VSMCs calcification was observed by treatment with icariin and/or inhibitors of estrogen receptors (ERs) and p38-mitogen-activated protein kinase (MAPK) signaling. Results: Icariin inhibited osteoblastic differentiation and mineralization of VSMCs due to decreased ALP activity and Runx2 expression. Further study demonstrated that icariin exerted this suppression effect through activating p38-MAPK but not extracellular-regulated kinase, JNK or Akt. An inhibitor of p38-MAPK partially reversed the inhibitory effects of icariin on osteoblastic differentiation. Interestingly, treatment of VSMCs with an ER antagonist ICI182780 and a selective ERα receptor antagonist PPT attenuated icariin-mediated inhibition effect of VSMCs calcification, associated with suppression of p38-MAPK phosphorylation. Conclusions: Icariin inhibited the osteoblastic differentiation of VSMCs, and that the inhibitory effects were mediated by p38-MAPK pathways through ERα.

Proteome-wide 3D structure prediction provides insights into the ancestral metabolism of ancient archaea and bacteria.

Ancestral metabolism has remained controversial due to a lack of evidence beyond sequence-based reconstructions. Although prebiotic chemists have provided hints that metabolism might originate from non-enzymatic protometabolic pathways, gaps between ancestral reconstruction and prebiotic processes mean there is much that is still unknown. Here, we apply proteome-wide 3D structure predictions and comparisons to investigate ancestorial metabolism of ancient bacteria and archaea, to provide information beyond sequence as a bridge to the prebiotic processes. We compare representative bacterial and archaeal strains, which reveal surprisingly similar physiological and metabolic characteristics via microbiological and biophysical experiments. Pairwise comparison of protein structures identify the conserved metabolic modules in bacteria and archaea, despite interference from overly variable sequences. The conserved modules (for example, middle of glycolysis, partial TCA, proton/sulfur respiration, building block biosynthesis) constitute the basic functions that possibly existed in the archaeal-bacterial common ancestor, which are remarkably consistent with the experimentally confirmed protometabolic pathways. These structure-based findings provide a new perspective to reconstructing the ancestral metabolism and understanding its origin, which suggests high-throughput protein 3D structure prediction is a promising approach, deserving broader application in future ancestral exploration.

A random batch Ewald method for charged particles in the isothermal-isobaric ensemble.

We develop an accurate, highly efficient, and scalable random batch Ewald (RBE) method to conduct molecular dynamics simulations in the isothermal-isobaric ensemble (the NPT ensemble) for charged particles in a periodic box. After discretizing the Langevin equations of motion derived using suitable Lagrangians, the RBE method builds the mini-batch strategy into the Fourier space in the Ewald summation for the pressure and forces such that the computational cost is reduced to O(N) per time step. We implement the method in the Large-scale Atomic/Molecular Massively Parallel Simulator package and report accurate simulation results for both dynamical quantities and statistics for equilibrium for typical systems including all-atom bulk water and a semi-isotropic membrane system. Numerical simulations on massive supercomputing cluster are also performed to show promising central processing unit efficiency of the RBE.

Investigating Morphology and Breakage Evolution Characteristics of Railroad Ballasts over Distinct Supports Subjected to Impact Loading.

The ballast bed constantly degrades under the repeated applications of impact loading exerted by passing trains in terms of the particle size, shape, breakage, fouling, etc., thus significantly jeopardizing the in-service performance and operational safety of ballasted tracks. In this study, the morphology and breakage evolution characteristics of railroad ballasts of single- and multiple-size ranges were investigated from laboratory impact-load tests. Both a concrete block and sand layer were placed to mimic the distinct under-ballast supports. The degradation trends of the typical shape and breakage indices were comparatively quantified for different combinations of ballast particle sizes and shapes, under-ballast supports, impact energies, and number of impact-load applications (N). The results show that both shape and size affect ballast particle breakage, with shape being more influential. The breakage severity of flake-like particles is about 1.5-1.66 times and 1.25-1.5 times higher than those of regular and needle-like particles, respectively. Under impact loading, large and small single-size ballasts degrade mainly by breakage and abrasion, respectively. The modified fouling index (FI) of flake-like particles within 31.5-40 mm is about 3.6 times that of regular particles within 50-63 mm. The shape indices of the ballast particles within 31.5-40 mm exhibit the most profound changes. The severities of the ballast breakage and fines generation (or modified FI) increased by 50% and 74%, respectively, due to the increase in the under-ballast support stiffness by 100 times and the drop height of 80 cm, respectively. The convexity and ballast breakage index (BBI) are promising for quantifying particle-degradation trends, and their statistical correlation found herein is potentially useful for the transition of ballast-bed-maintenance management from the current plan-based scheduling to condition-based upgrading.

Dynamics of soil properties and bacterial community structure by mulched fertigation system in semi-arid area of Northeast China.

The agricultural irrigation and fertigation systems have a non-negligible impact on the soil microenvironment in arid and semi-arid areas. Therefore, studying the processes and changes of soil microenvironment under different plastic mulch drip irrigation systems can reveal the "soil-microbe" mechanism and provide a theoretical support for the optimal irrigation and nutrition management of maize in the semi-arid area of Northeast China. Three treatments were used for this study in the semi-arid area of northeast China, namely; mulched fertigation system (MF), drip irrigation system (DI), and farmers' practices system (FP). We used high-throughput sequencing to study the soil bacterial community structure targeting the 16S rRNA gene. The agricultural irrigation and fertigation systems significantly affected soil properties. MF significantly increased bacterial abundance and bacterial diversity and richness. Moreover, MF and DI markedly increased some relative abundance of beneficial bacterial. The bacterial network in MF was more conducive to the health and stability of the agroecosystem and the relationships among species in MF bacterial network were more complex. The agricultural irrigation and fertigation systems had indirect effects on community composition and bacterial diversity through soil organic carbon (SOC), ammonium nitrogen ( NH 4 + -N), nitrate nitrogen ( NO 3 - -N), pH, moisture, NH 4 + -N and NO 3 - -N had indirect effects on yield through bacterial community composition, bacterial diversity and bacterial abundance. These findings suggested that MF was the most effective treatment to improve soil bacterial abundance and diversity, and stabilize the functional quality of soil biological processes.

Universal dynamical onset in water at distinct material interfaces.

Interfacial water remains liquid and mobile much below 0 °C, imparting flexibility to the encapsulated materials to ensure their diverse functions at subzero temperatures. However, a united picture that can describe the dynamical differences of interfacial water on different materials and its role in imparting system-specific flexibility to distinct materials is lacking. By combining neutron spectroscopy and isotope labeling, we explored the dynamics of water and the underlying substrates independently below 0 °C across a broad range of materials. Surprisingly, while the function-related anharmonic dynamical onset in the materials exhibits diverse activation temperatures, the surface water presents a universal onset at a common temperature. Further analysis of the neutron experiment and simulation results revealed that the universal onset of water results from an intrinsic surface-independent relaxation: switching of hydrogen bonds between neighboring water molecules with a common energy barrier of ∼35 kJ mol-1.

Dual-layer spectral detector CT for contrast agent concentration, dose and injection rate reduction: Utility in imaging of the superior mesenteric artery.

PURPOSE: To investigate the feasibility of contrast agent and injection rate reduction for dual-layer spectral detector computed tomography (SDCT) imaging of the superior mesenteric artery (SMA) using virtual monochromatic image (VMI). METHODS: A total of 102 patients who underwent abdominal arterial phase-enhanced SDCT examination due to suspected abdominal diseases were prospectively selected and divided into control group, low concentration/dose groups (groups 370-0.7, 300-1.0, and 300-0.9) and low injection rate groups (groups 2-370 and 2-350). Compared with the control group, low concentration/dose groups and low injection rate groups lowered the concentration/dose or injection rate of the contrast agent to varying degrees. The raw data obtained in each group were reconstructed using hybrid-iterative reconstruction and projection spatial-spectral reconstruction algorithm. The image quality of the SMA in conventional images (CI) and in VMIs40-140 kiloelectron volt (keV) (interval: 10 keV) during the arterial phase was analyzed. Multiplanar reformation images and volume rendering images of the SMA were reconstructed. Image quality objective evaluation indexes included the CT values, contrast-to-noise ratio, signal-to-noise ratio, and diameter of the SMA. The diameter of the SMA was determined by the CT values profile curve and its full width at half maximum. Two doctors independently evaluated the subjective image quality of multiplanar reformation coronal images and volume rendering images according to a 5-point scale. Repeated analysis of variance and Friedman test were used to compare the differences in the objective evaluation indexes and subjective scores between VMIs and CI in the same group. The Dunnett's t-test or Dunnett's T3 test and Kruskal-Wallis H-test were used to compare the differences in the objective evaluation indexes and subjective scores between the experimental and control groups. RESULTS: VMIs of the SMA in each group had the best image quality at 60 keV, and VMI60 keV in each group were better than their respective CI to varying degrees. Although the objective (CT values, contrast-to-noise ratio, and signal-to-noise ratio) and subjective (subjective scores) indexes of CI in the low concentration/dose groups and low injection rate groups were lower than those of CI in the control group to varying degrees, these indexes of VMI60 keV in the low concentration/dose groups and group 2-370 were equal to or even better than the CI in the control group. CONCLUSIONS: VMI60 keV using SDCT could effectively reduce the contrast agent load while providing equivalent or better SMA image quality compared with CI obtained using a conventional contrast agent protocol. When the injection rate was lowered to 2.0 ml/s for a high-concentration contrast agent (370 mgI/ml), the SMA image quality at VMI60 keV was comparable with that of the CI in the control group.

Superscalability of the random batch Ewald method.

Coulomb interaction, following an inverse-square force-law, quantifies the amount of force between two stationary and electrically charged particles. The long-range nature of Coulomb interactions poses a major challenge to molecular dynamics simulations, which are major tools for problems at the nano-/micro-scale. Various algorithms are developed to calculate the pairwise Coulomb interactions to a linear scale, but poor scalability limits the size of simulated systems. Here, we use an efficient molecular dynamics algorithm with the random batch Ewald method on all-atom systems where the complete Fourier components in the Coulomb interaction are replaced by randomly selected mini-batches. By simulating the N-body systems up to 108 particles using 10 000 central processing unit cores, we show that this algorithm furnishes O(N) complexity, almost perfect scalability, and an order of magnitude faster computational speed when compared to the existing state-of-the-art algorithms. Further examinations of our algorithm on distinct systems, including pure water, a micro-phase separated electrolyte, and a protein solution, demonstrate that the spatiotemporal information on all time and length scales investigated and thermodynamic quantities derived from our algorithm are in perfect agreement with those obtained from the existing algorithms. Therefore, our algorithm provides a promising solution on scalability of computing the Coulomb interaction. It is particularly useful and cost-effective to simulate ultra-large systems, which is either impossible or very costly to conduct using existing algorithms, and thus will be beneficial to a broad range of problems at nano-/micro-scales.

Based on G-Series Mouse TH17 Array Study the Effect of Fluoride on C2C12 Cells Cytokines Expression.

C2C12 cells were cultured on medium containing fluoride (0, 1, and 2.5 mmol/L) for 48 h to investigate the effect of excessive fluoride on T helper 17 (Th17)-related cytokine expression profile in skeletal muscle cells, and the culture supernatant was collected and subjected for the detection of 18 cytokines via Th17 array. Results showed that compared with the control group, no differential expression proteins (DEPs) were found in the 1 mmol/L fluoride group; however, eight DEPs were upregulated in the 2.5 mmol/L fluoride group, including macrophage inflammatory protein-3α (MIP-3α), interleukin-21 (IL-21), IL-13, IL-17F, IL-28A, transforming growth factor type beta 1 (TGF-ß1), IL-23, and IL-17A. In addition, five DEPs (MIP-3α, IL-13, IL-21, TGF-ß1, and IL-17F) were upregulated in the 2.5 mmol/L fluoride group compared with the 1 mmol/L fluoride group. Gene ontology analysis revealed that the positive regulation of cytokine production, cytokine activity, receptor ligand activity, and cytokine receptor binding accounted for high percent of DEPs present. Kyoto Encyclopedia of Genes and Genomes analysis showed that these DEPs primarily involved 12 pathways enriched in the cytokine-cytokine receptor interaction and IL-17 signaling pathway after 2.5 mmol/L fluoride treatment. The results indicated that fluoride might induce cytotoxicity by disturbing Th17-related cytokine expression.

Anomalous sub-diffusion of water in biosystems: From hydrated protein powders to concentrated protein solution to living cells.

Water is essential to life and its translational motion in living systems mediates various biological processes, including transportation of function-required ingredients and facilitating the interaction between biomacromolecules. By combining neutron scattering and isotopic labeling, the present work characterizes translational motion of water on a biomolecular surface, in a range of systems: a hydrated protein powder, a concentrated protein solution, and in living Escherichia coli (E. coli) cells. Anomalous sub-diffusion of water is observed in all samples, which is alleviated upon increasing the water content. Complementary molecular dynamics simulations and coarse-grained numerical modeling demonstrated that the sub-diffusive behavior results from the heterogeneous distribution of microscopic translational mobility of interfacial water. Moreover, by comparing the experimental results measured on E. coli cells with those from a concentrated protein solution with the same amount of water, we show that water in the two samples has a similar average mobility, however the underlying distribution of motion is more heterogeneous in the living cell.

Decoupling between the translation and rotation of water in the proximity of a protein molecule.

The interaction between water and biomacromolecules is of fundamental interest in biophysics, biochemistry and physical chemistry. By combining neutron scattering and molecular dynamics simulations on a perdeuterated protein at a series of hydration levels, we demonstrated that the translational motion of water is slowed down more significantly than its rotation, when water molecules approach the protein molecule. Further analysis of the simulation trajectories reveals that the observed decoupling results from the fact that the translational motion of water is more correlated over space and more retarded by the charged/polar residues and spatial confinement on the protein surface, than the rotation. Moreover, around the stable protein residues (with smaller atomic fluctuations), water exhibits more decoupled dynamics, indicating a connection between the observed translation-rotation decoupling in hydration water and the local stability of the protein molecule.

Structural Analysis of an l-Cysteine Desulfurase from an Ssp DNA Phosphorothioation System.

DNA phosphorothioate (PT) modification, in which the nonbridging oxygen in the sugar-phosphate backbone is substituted by sulfur, is catalyzed by DndABCDE or SspABCD in a double-stranded or single-stranded manner, respectively. In Dnd and Ssp systems, mobilization of sulfur in PT formation starts with the activation of the sulfur atom of cysteine catalyzed by the DndA and SspA cysteine desulfurases, respectively. Despite playing the same biochemical role, SspA cannot be functionally replaced by DndA, indicating its unique physiological properties. In this study, we solved the crystal structure of Vibrio cyclitrophicus SspA in complex with its natural substrate, cysteine, and cofactor, pyridoxal phosphate (PLP), at a resolution of 1.80 Å. Our solved structure revealed the molecular mechanism that SspA employs to recognize its cysteine substrate and PLP cofactor, suggesting a common binding mode shared by cysteine desulfurases. In addition, although the distance between the catalytic Cys314 and the substrate cysteine is 8.9 Å, which is too far for direct interaction, our structural modeling and biochemical analysis revealed a conformational change in the active site region toward the cysteine substrate to move them close to each other to facilitate the nucleophilic attack. Finally, the pulldown analysis showed that SspA could form a complex with SspD, an ATP pyrophosphatase, suggesting that SspD might potentially accept the activated sulfur atom directly from SspA, providing further insights into the biochemical pathway of Ssp-mediated PT modification.IMPORTANCE Apart from its roles in Fe-S cluster assembly, tRNA thiolation, and sulfur-containing cofactor biosynthesis, cysteine desulfurase serves as a sulfur donor in the DNA PT modification, in which a sulfur atom substitutes a nonbridging oxygen in the DNA phosphodiester backbone. The initial sulfur mobilization from l-cysteine is catalyzed by the SspA cysteine desulfurase in the SspABCD-mediated DNA PT modification system. By determining the crystal structure of SspA, the study presents the molecular mechanism that SspA employs to recognize its cysteine substrate and PLP cofactor. To overcome the long distance (8.9 Å) between the catalytic Cys314 and the cysteine substrate, a conformational change occurs to bring Cys314 to the vicinity of the substrate, allowing for nucleophilic attack.

Differences between calcium rich and depleted alpha-lactalbumin investigated by molecular dynamics simulations and incoherent neutron scattering.

We present a study comparing atomic motional amplitudes in calcium rich and depleted alpha-lactalbumin. The investigations were performed by elastic incoherent neutron scattering (EINS) and molecular dynamics (MD) simulations. As the variations were expected to be very small, three different hydration levels and timescales (instrumental resolutions) were measured. In addition, we used two models to extract the mean square displacements (MSDs) from the EINS data, one taking into account the motional heterogeneity of the MSD. At a timescale of several nanoseconds, small differences in the amplitudes between the calcium enriched and depleted alpha-lactalbumin are visible, whereas at lower timescales no changes can be concluded within the statistics. The results are compared to MD simulations at 280 and 300 K by extracting the MSDs of the trajectories in two separate ways: first by direct calculation, and second by a virtual neutron experiment using the same models as for the experimental data. We show that the simulated data give qualitatively similar results as the experimental data but quantitatively there are differences. Furthermore, the distribution of the MSDs in the simulations suggests that the inclusion of heterogeneity is reasonable for alpha-lactalbumin, but a bi-or trimodal approach may be sufficient.

Circulating microRNA let­7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy.

Knee osteoarthritis (KOA) is a major cause of leg disability in the elderly population. Recently, the expression levels of circulating microRNA (miRNA) let­7e have been reported to be significantly reduced in KOA. The aims of the present study were to assess the feasibility of let­7e as a serum marker for detecting KOA and to explore the underlying mechanisms of its involvement. Based on previous studies and bioinformatics analysis, let­7e may regulate apoptosis and autophagy of articular chondrocytes. A total of 10 patients with KOA and 10 patients with trauma without KOA were recruited to examine the levels of let­7e in peripheral blood. Subsequently, KOA rat models were established, and the levels of let­7e in the cartilage and serum were examined, the expression of apoptotic proteins and autophagy­related proteins in the cartilage were investigated, and apoptotic and autophagic activities of primary cultured chondrocytes were also detected. In patients with KOA, let­7e levels in the peripheral serum were significantly decreased compared with the control group, and this result was confirmed in the peripheral serum and cartilage of KOA rats. In addition, the expression levels of proteins involved in the apoptotic pathway were increased in the cartilage of KOA rats, and apoptotic activity was increased. The expression of autophagy­related proteins beclin 1 and microtubule associated protein 1 light chain 3 ß (LC3B) II/LC3BI in the articular cartilage of KOA rats was lower compared with the controls, and autophagy was decreased. Si­Miao­San (SMS) treatment restored the expression of let­7e and reversed the changes in apoptosis and autophagy. Therefore, the present study provided additional evidence that circulating let­7e may be a potential serum biomarker for the diagnosis and treatment of KOA. Elevated apoptosis levels and decreased autophagy levels of cartilage tissue are involved in KOA, and treatment with SMS may reverse these effects.