Characterization of a phospholipase D from Streptomyces cinnamoneum SK43.003 suitable for phosphatidylserine synthesis.

A phospholipase D high producing strain with transphosphatidylation activity that is suitable for phosphatidylserine synthesis was screened by our laboratory and named as Streptomyces cinnamoneum SK43.003. The enzyme structural and biochemical properties were investigated using the molecular biology method. A 1521-bp fragment of the phospholipase D gene from Streptomyces cinnamoneum SK43.003 was amplified by PCR and encoded for 506 amino acids. The primary structure contained two conserved HKD and GG/S motifs. The pld gene was cloned and expressed in Escherichia coli. The purified enzyme exhibited the highest activity at a pH value of 6.0 andtemperature of 60°C. The enzyme was stable within a pH range of 4-7 for 24 h or at temperatures below 50°C. In addition, Triton X-100, Fe2+ , and Al3+ were beneficial to the enzyme activity, whereas Zn2+ and Cu2+ dramatically inhibited its activity. In a two-phase system, the enzyme could convert phosphatidylcholine to phosphatidylserine with a 92% transformation rate.

Characterization and enhanced extracellular overexpression of a new salt-activated alginate lyase.

BACKGROUND: Alginate lyases (EC 4.4.2.3/4.4.2.11) have been applied to produce alginate oligosaccharides, which have physiological advantages such as prebiotic and antidiabetic effects, and are of benefit in the food and pharmaceutical industries. Extracellular production of recombinant proteins in Escherichia coli presents advantages including simplified downstream processing and high productivity; however, the presence of certain signal peptides does not always ensure successful secretion, which make the extracellular production of alginate lyase in E. coli rarely reported but of great significance. RESULTS: A PL7 family alginate lyase, Aly01, with its native signal peptide from Vibrio natriegens SK42.001, was identified, characterized, and extracellularly expressed in E. coli. The enzyme specifically released trisaccharide from alginate and was strictly NaCl activated. Green fluorescent protein (GFP) was fused with the Aly01 signal peptide and successfully secreted in E. coli to expand the feasibility of using this signal peptide to produce other heterologous proteins extracellularly. Through a synergistic strategy of utilizing Terrific Broth (TB) medium supplemented with 120 mmol L-1 glycine and 10 mmol L-1 calcium, the lag phase of protein secretion was reduced to 3 h from 12 h; meanwhile calcium remedied glycine-related cell growth impairment, leading to further enhancement of overall enzyme productivity, reaching a maximum of 4.55 U mL-1 . CONCLUSION: A new salt-activated alginate lyase, Aly01, was identified and characterized. E. coli employed its signal peptide and extracellularly expressed both Aly01 and a GFP, which indicated the signal peptide of Aly01 could be a powerful tool for extracellular production of other heterologous proteins in E. coli. © 2021 Society of Chemical Industry.

Principal Component Analysis Method with Space and Time Windows for Damage Detection.

Long-term structural health monitoring (SHM) has become an important tool to ensure the safety of infrastructures. However, determining methods to extract valuable information from large amounts of data from SHM systems for effective identification of damage still remains a major challenge. This paper provides a novel effective method for structural damage detection by introduction of space and time windows in the traditional principal component analysis (PCA) technique. Numerical results with a planar beam model demonstrate that, due to the presence of space and time windows, the proposed double-window PCA method (DWPCA) has a higher sensitivity for damage identification than the previous method moving PCA (MPCA), which combines only time windows with PCA. Further studies indicate that the developed approach, as compared to the MPCA method, has a higher resolution in localizing damage by space windows and also in quantitative evaluation of damage severity. Finally, a finite-element model of a practical bridge is used to prove that the proposed DWPCA method has greater sensitivity for damage detection than traditional methods and potential for applications in practical engineering.

Microstructure Design of Lightweight, Flexible, and High Electromagnetic Shielding Porous Multiwalled Carbon Nanotube/Polymer Composites.

Multiwalled carbon nanotube/polymer composites with aligned and isotropic micropores are constructed by a facile ice-templated freeze-drying method in a wide density range, with controllable types and contents of the nanoscale building blocks, in order to tune the shielding performance together with the considerable mechanical and electrical properties. Under the mutual promotion of the frame and porous structure, the lightweight high-performance shielding is achieved: a 2.3 mm thick sample can reach 46.7 and 21.7 dB in the microwave X-band while the density is merely 32.3 and 9.0 mg cm-3 , respectively. The lowest density corresponds to a value of shielding effectiveness divided by both the density and thickness up to 104 dB cm2 g-1 , far beyond the conductive polymer composites with other fillers ever reported. The shielding mechanism of the flexible porous materials is further demonstrated by an in situ compression experiment.

Quantitative assessment of brain injury and concussion induced by an unintentional soccer ball impact.

BACKGROUND: Accidental impact on a player's head by a powerful soccer ball may lead to brain injuries and concussions during games. It is crucial to assess these injuries promptly and accurately on the field. However, it is challenging for referees, coaches, and even players themselves to accurately recognize potential injuries and concussions following such impacts. Therefore, it is necessary to establish a list of minimum ball velocity thresholds that can result in concussions at different impact locations on the head. Additionally, it is important to identify the affected brain regions responsible for impairments in brain function and potential clinical symptoms. METHODS: By using a full human finite element model, dynamic responses and brain injuries caused by unintentional soccer ball impacts on six distinct head locations (forehead, tempus, crown, occiput, face, and jaw) at varying ball velocities (10, 15, 20, 25, 30, 35, 40, and 60 m/s) were simulated and investigated. Intracranial pressure, Von-Mises stress, and first principal strain were analyzed, the ball velocity thresholds resulting in concussions at different impact locations were evaluated, and the damage evolution patterns in the brain tissue were analyzed. RESULTS: The impact on the occiput is most susceptible to induce brain injuries compared to all other impact locations. For a conservative assessment, the risk of concussion is present once the soccer ball reaches 17.2 m/s in a frontal impact, 16.6 m/s in a parietal impact, 14.0 m/s in an occipital impact, 17.8 m/s in a temporal impact, 18.5 m/s in a facial impact or 19.2 m/s in a mandibular impact. The brain exhibits the most significant dynamic responses during the initial 10-20 ms, and the damaged regions are primarily concentrated in the medial temporal lobe and the corpus callosum, potentially causing impairments in brain functions. CONCLUSIONS: This work offers a framework for quantitatively assessing brain injuries and concussions induced by an unintentional soccer ball impact. Determining the ball velocity thresholds at various impact locations provides a benchmark for evaluating the risks of concussion. The examination of brain tissue damage evolution introduces a novel approach to linking biomechanical responses with possible clinical symptoms.

Influence of centroid acceleration acquisition and filtering class on head injury criterion evaluation.

BACKGROUND: Although the Head Injury Criteria (HIC) has been widely applied to assess head impact injuries, it faces two outstanding problems: 1) HIC is affected strongly by the cut-off frequency when processing acceleration signals. And these cut-off frequencies are experiential and lack unified guidelines; 2) If the head was impacted on a different part, should the corresponding HIC threshold be the same? If these problems are not resolved, it could potentially lead to a critical misinterpretation of the safety assessment. METHODS: Finite element method was used to reconstruct head impacts. The head model includes tissues like skull, brainstem, cerebrospinal fluid, etc. The head model was impacted in the frontal, occipital, parietal or lateral direction with different impact velocities. Acceleration signals of the head model were extracted directly from the skull and the head centroid node. To obtain a robust HIC, the filtering class of acceleration signals were analyzed carefully. Then, the relation between rigid body HIC and the centroid node HIC were studied systematically. RESULTS: When the filtering class of rigid body acceleration and centroid node acceleration reached the cut-off frequency, the corresponding derivative of HIC tended to change smoothly. Using these cut-off frequencies, robust HICs were obtained. The rigid body HIC far exceeded that of centroid node HIC, such as 8, 9, 14 and 31 times exceeded in the frontal, occipital, parietal and lateral impact conditions, respectively. Moreover, approximate linear relations were found between the rigid body HIC and the centroid node HIC in different impact directions, respectively. From these relations, the injury thresholds of rigid body HIC of various directions were given quantitatively. CONCLUSIONS: The rational filtering class like CFC 800 and CFC 700 were given for rigid body HIC and centroid node HIC, respectively. The rigid body HIC had a significant discrepancy from the centroid node HIC. Linear relations between the rigid body HIC and centroid node HIC were found, and their slopes changed with impact directions. From these relations, we can adjust the injury thresholds reasonably if the head receives different impacts. These findings can effectively enhance the applicability of HIC.

Discovery of LWY713 as a potent and selective FLT3 PROTAC degrader with in vivo activity against acute myeloid leukemia.

Fms-like tyrosine kinase 3 (FLT3) has been validated as a therapeutic target for acute myeloid leukemia (AML). While a number of FLT3 kinase inhibitors have been approved for AML treatment, the clinical data revealed that they cannot achieve complete and sustained suppression of FLT3 signaling at the tolerated dose. Here we report a series of new, potent and selective FLT3 proteolysis targeting chimera degraders. The optimal compound LWY713 potently induced the degradation of FLT3 with a DC50 value of 0.64 nM and a Dmax value of 94.8% in AML MV4-11 cells with FLT3-internal tandem duplication (ITD) mutation. Mechanistic studies demonstrated that LWY713 selectively induced FLT3 degradation in a cereblon- and proteasome-dependent manner. LWY713 potently inhibited FLT3 signaling, suppressed cell proliferation, and induced cell G0/G1-phase arrest and apoptosis in MV4-11 cells. Importantly, LWY713 displayed potent in vivo antitumor activity in MV4-11 xenograft models.

CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality.

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a unique molecular subtype of metastatic castration-resistant prostate cancer (mCRPC). It remains unclear, however, whether CDK12 loss per se is sufficient to drive prostate cancer development-either alone, or in the context of other genetic alterations-and whether CDK12-mutant tumors exhibit sensitivity to specific pharmacotherapies. Here, we demonstrate that tissue-specific Cdk12 ablation is sufficient to induce preneoplastic lesions and robust T cell infiltration in the mouse prostate. Allograft-based CRISPR screening demonstrated that Cdk12 loss is positively associated with Trp53 inactivation but negatively associated with Pten inactivation-akin to what is observed in human mCRPC. Consistent with this, ablation of Cdk12 in prostate organoids with concurrent Trp53 loss promotes their proliferation and ability to form tumors in mice, while Cdk12 knockout in the Pten-null prostate cancer mouse model abrogates tumor growth. Bigenic Cdk12 and Trp53 loss allografts represent a new syngeneic model for the study of androgen receptor (AR)-positive, luminal prostate cancer. Notably, Cdk12/Trp53 loss prostate tumors are sensitive to immune checkpoint blockade. Cdk12-null organoids (either with or without Trp53 co-ablation) and patient-derived xenografts from tumors with CDK12 inactivation are highly sensitive to inhibition or degradation of its paralog kinase, CDK13. Together, these data identify CDK12 as a bona fide tumor suppressor gene with impact on tumor progression and lends support to paralog-based synthetic lethality as a promising strategy for treating CDK12-mutant mCRPC.

Improving thermostability of a PL 5 family alginate lyase with combination of rational design strategies.

Alginate lyases with strict substrate specificity possess potential in directed production of alginate oligosaccharides with specific composition. However, their poor thermostability hampered their applications in industry. In this study, an efficient comprehensive strategy including sequence-based analysis, structure-based analysis, and computer-aid ΔΔGfold value calculation was proposed. It was successfully performed on alginate lyase (PMD) with strict poly-ß-D-mannuronic acid substrate specificity. Four single-point variants A74V, G75V, A240V, and D250G with increased Tm of 3.94 °C, 5.21 °C, 2.56 °C, and 4.80 °C, respectively, were selected out. After ordered combined mutations, a four-point mutant (M4) was finally generated which displayed remarkable increase on thermostability. The Tm of M4 increased from 42.25 °C to 51.59 °C and its half-life at 50 °C was about 58.9-fold of PMD. Meanwhile, there was no obvious loss of enzyme activity (more than 90% retained). Molecular dynamics simulation analysis insisted that the improvement of thermostability might be attribute to the rigidified region A which might be caused by the newly formed hydrogen bonds and salt bridges introduced by mutations, the lower distance of original hydrogen bonds, and the more compact overall structures.

Hollow-Out Fe2O3-Loaded NiO Heterojunction Nanorods Enable Real-Time Exhaled Ethanol Monitoring under High Humidity.

The analysis of exhaled breath has opened up new exciting avenues in medical diagnostics, sleep monitoring, and drunk driving detection. Nevertheless, the detection accuracy is greatly affected due to high humidity in the exhaled breath. Here, we propose a regulation method to solve the problem of humidity adaptability in the ethanol-monitoring process by building a heterojunction and hollow-out nanostructure. Therefore, large specific surface area hollow-out Fe2O3-loaded NiO heterojunction nanorods assembled by porous ultrathin nanosheets were prepared by a well-tailored interface reaction. The excellent response (51.2 toward 10 ppm ethanol at 80% relative humidity) and selectivity to ethanol under high relative humidity with a lower operating temperature (150 °C) were obtained, and the detection limit was as low as 0.5 ppb with excellent long-term stability. The superior gas-sensing performance was attributed to the high surface activity of the heterojunction and hollow-out nanostructure. More importantly, GC-MS, diffuse reflectance Fourier transform infrared spectroscopy, and DFT were utilized to analyze the mechanisms of heterojunction sensitization, ethanol-sensing reaction, and high-humidity adaptability. Our integrated low-power MEMS Internet of Things (IoT) system based on Fe2O3@NiO successfully demonstrates the functional verification of ethanol detection in human exhalation, and the integrated voice alarm and IoT positioning functions are expected to solve the problem of real-time monitoring and rapid initial screening of drunk driving. Overall, this novel method plays a vital role in areas such as control of material morphology and composition, breath analysis, gas-sensing mechanism research, and artificial olfaction.

Bidirectional effects of oral anticoagulants on gut microbiota in patients with atrial fibrillation.

Background: The imbalance of gut microbiota (GM) is associated with a higher risk of thrombosis in patients with atrial fibrillation (AF). Oral anticoagulants (OACs) have been found to significantly reduce the risk of thromboembolism and increase the risk of bleeding. However, the OAC-induced alterations in gut microbiota in patients with AF remain elusive. Methods: In this study, the microbial composition in 42 AF patients who received long-term OAC treatment (AF-OAC group), 47 AF patients who did not (AF group), and 40 volunteers with the risk of AF (control group) were analyzed by 16S rRNA gene sequencing of fecal bacterial DNA. The metagenomic functional prediction of major bacterial taxa was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software package. Results: The gut microbiota differed between the AF-OAC and AF groups. The abundance of Bifidobacterium and Lactobacillus decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as Megamonas. In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus Ruminococcus but increased certain potential pathogenic taxa, such as genera Streptococcus, Escherichia-Shigella, and Klebsiella. The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that Bacteroidetes, Brucella, and Ochrobactrum were more abundant in the anticoagulated bleeding AF patients, Akkermansia and Faecalibacterium were more abundant in the non-anticoagulated-bleeding-AF patients. The neutrophil-to-lymphocyte ratio (NLR) was lower in the AF-OAC group compared with the AF group (P < 0.05). Ruminococcus was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score (P < 0.05), and the OACs-enriched species (Megamonas and Actinobacteria) was positively correlated with the prothrombin time (PT) (P < 0.05). Ruminococcus and Roseburia were negatively associated with bleeding events (P < 0.05). Conclusions: Our study suggested that OACs might benefit AF patients by reducing the inflammatory response and modulating the composition and abundance of gut microbiota. In particular, OACs increased the abundance of some gut microbiota involved in bleeding and gastrointestinal dysfunction indicating that the exogenous supplementation with Faecalibacterium and Akkermansia might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.

Single-Atom Cu Stabilized on Ultrathin WO2.72 Nanowire for Highly Selective and Ultrasensitive ppb-Level Toluene Detection.

Various catalysts are developed to improve the performance of metal oxide semiconductor gas sensors, but achieving high selectivity and response intensity in chemiresistive gas sensors (CGSs) remains a significant challenge. In this study, an in situ-annealing approach to synthesize Cu catalytic sites on ultrathin WO2.72 nanowires for detecting toluene at ultralow concentrations (Ra /Rg = 1.9 at 10 ppb) with high selectivity is developed. Experimental and molecular dynamic studies reveal that the Cu single atoms (SAs) act as active sites, promoting the oxidation of toluene and increasing the affinity of Cu single-atom catalysts (SACs)-containing sensing materials for toluene while weakening the association with carbon dioxide or water vapor. Density functional theory studies show that the selective binding of toluene to Cu SAs is due to the favorable binding sites provided by Cu SAs for toluene molecules over other gaseous species, which aids the adsorption of toluene on WO2.72 nanowires. This study demonstrates the successful atomic-level interface regulation engineering of WO2.72 nanowire-supported Cu SAs, providing a potential strategy for the development of highly active and durable CGSs.

In Operando Investigation of the Concentration Dependent NO2 Sensing Mechanism of Bi2S3 Nanorods at Low Temperatures and the Interference of O3.

The demand for gas sensors that can detect gases selectively at low temperatures has increased steadily over recent years. Most devices use semiconducting metal oxides as sensing materials which often require high operation temperatures and suffer from a lack of selectivity. Semiconducting metal sulfides were found to be a reasonable alternative for the application in sensing devices at low temperatures. Since metal sulfides are a relatively new class of materials applied in gas sensors, there is little work on sensing mechanisms and overall sensing characteristics of these materials. In this work, the authors investigated the sensing performance of Bi2S3 nanorods operated at 50 °C in the presence of several target gases and found a selective response to oxidizing gases. With the help of DC resistance measurements, diffuse reflectance infrared Fourier transform spectroscopy and work function measurements in a Kelvin Probe setup, the NO2 and O3 sensing mechanisms of Bi2S3 nanorods were revealed. While initially sulfur vacancies were the predominant reaction sites, the formation of nitrates became the key reaction in higher NO2 concentrations. Additionally, it was found that the reaction with O3 healed sulfur vacancies effectively inhibiting the reaction with NO2.

Characterization of a Novel Polysaccharide Lyase Family 5 Alginate Lyase with PolyM Substrate Specificity.

Alginate lyases (ALyases) have been widely applied in enzymatically degrading alginate for the preparation of alginate oligosaccharides (AOS), which possess a range of excellent physiological benefits including immunoregulatory, antivirus, and antidiabetic properties. Among the characterized ALyases, the number of ALyases with strict substrate specificity which possess potential in directed preparation of AOS is quite small. ALyases of polysaccharides lyase (PL) 5 family have been reported to perform poly-ß-D-mannuronic acid (Poly-M) substrate specificity. However, there have been fewer studies with a comprehensive characterization and comparison of PL 5 family ALyases. In this study, a putative PL 5 family ALyase PMD was cloned from Pseudomonas mendocina and expressed in Escherichia coli. The novel ALyase presented maximum activity at 30 °C and pH 7.0. PMD displayed pH stability properties under the range of pH 5 to pH 9, which retained more than 80% relative activity, even when incubated for 48 h. Product analysis indicated that PMD might be an endolytic ALyase with strict Poly M substrate specificity and yield disaccharide and trisaccharide as main products. In addition, residues K58, R66, Y248, and R344 were proposed to be the potential key residues for catalysis via site-directed mutation. Detailed characterization of PMD and comprehensive comparisons could supply some different information about properties of PL 5 ALyases which might be helpful for its application in the directed production of AOS.

Discovery of 3-Aminopyrazole Derivatives as New Potent and Orally Bioavailable AXL Inhibitors.

The receptor tyrosine kinase AXL is a promising target for anticancer drug discovery. Herein, we describe the discovery of 3-aminopyrazole derivatives as new potent and selective AXL kinase inhibitors. One of the representative compounds, 6li, potently inhibited AXL enzymatic activity with an IC50 value of 1.6 nM, and tightly bound with AXL protein with a Kd value of 0.26 nM, while was obviously less potent against most of the 403 wild-type kinases evaluated. Cell-based assays demonstrated that compound 6li potently inhibited AXL signaling, suppressed Ba/F3-TEL-AXL cell proliferation, reversed TGF-ß1-induced epithelial-mesenchymal transition, and dose-dependently impeded cancer cell migration and invasion. Compound 6li also showed reasonable pharmacokinetic properties in rats and exhibited significant in vivo antitumor efficacy in a xenograft model of highly metastatic murine breast cancer 4T1 cells. Taken together, this study provides a new potent and selective AXL inhibitor for further anticancer drug discovery.

Direct anterior approach versus posterolateral approach in total hip arthroplasty: a meta-analysis of results on early post-operative period.

BACKGROUND: This study was performed to compare the advantage and disadvantage of posterolateral approach (PLA) and direct anterior approach (DAA) in total hip arthroplasty (THA). METHODS: Relevant trials were identified via a search of the Cochrane Central Register of Controlled Trials and PubMed from inception to 1 June 2019. A meta-analysis was performed to compare postoperative perioperative and radiographic outcomes between DAA and PLA in THA with respect to the hospital stay, blood loss, incision length, operative time, complications, and femoral and cup component position. The Harris Hip Score (HHS) was also assessed before and after 6 months postoperatively. RESULTS: Nine eligible studies involving 22698 adult patients (DAA group, n = 2947; PLA group, n = 19751) were identified for analysis. Compared with the PLA group, the DAA group had shorter hospital stay and achieved better HHS within 6 months after operation (P < 0.05), but the HHS was no significant differences between the two groups over 6 months (P > 0.05). The DAA group had significantly longer operative time, more blood loss, and complications than the PLA group (P < 0.05). In addition, the femoral component positioned in neutral and cup component inclination angle was comparable between both groups (P > 0.05); however, cup component anteversion angle was significantly larger in the PLA group (P < 0.05). CONCLUSION: Patients in the DAA group had higher HHS within 6 months and shorter hospital stay. The DAA could offer rapid early functional recovery after THA compared with the PLA. However, the DAA group often required longer operative time and had more blood loss. Furthermore, there was a higher early complication rate. Therefore, we believe that the direct anterior approach was a more difficult technique. The surgeon should be a well-trained joint surgeon with extensive prior hip replacement experience before performing THA through a DAA, and DAA was not suitable for beginners performing THA. In addition, we did not observe the difference with regard to the femoral component position and cup component inclination angle except for the smaller cup component anteversion angle in DAA group.

Structure characterization and in vitro hypoglycemic effect of partially degraded alginate.

Alginate is a low-cost polysaccharide found abundantly in seaweeds which consists of mannuronate and guluronate, and it is considered a sustainable gum source for dietary fiber. To solve the high viscosity-related problems while retaining its physiological properties, four partially degraded alginate products (PDA1-4) with molecular weight of 1.05-0.40 × 105 g mol-1 and intrinsic viscosity of 170.9-38.9 mL g-1 were enzymatically prepared and characterized. 1H Nuclear magnetic resonance analysis showed the used alginate lyase had a preference to degrade guluronate-blocks. PDA1 and PDA2 presented random coil conformation, whereas PDA3 and PDA4 displayed compact spherical-coil conformation over random coil conformation in solution. In vitro assays suggested a glucose-adsorption capacity order of PDA1 < PDA2 < alginate < PDA3 < PDA4 and a glucose-diffusion retardation capacity order of PDA3 < PDA1 ≤ alginate < PDA2 < PDA4, indicating that partially degraded alginate reinforced the hypoglycemic effect, especially mannuronate-rich PDA4. Overall, the study may have important implications for development of PDA as dietary fiber with potential hypoglycemic activity.

Mechanical behaviors and probabilistic multiphase network model of polyvinyl alcohol hydrogel after being immersed in sodium hydroxide solution.

Because of the advantages of a uniform distribution of reinforcing particles and in situ preparation, in situ precipitation has become an important way to prepare magnetic and other smart hydrogels. An important step in this process is to immerse hydrogels in alkaline solution to implant magnetic particles. Previous studies generally have ignored the effect of this process on the network structure and mechanical properties of hydrogels. In this study, we immersed polyvinyl alcohol (PVA) hydrogel samples in sodium hydroxide solutions of different concentrations to study changes in mechanical properties, such as stress-strain relationship, self-recovery, and fracture failure. The results showed that after the immersion process, the hydrogel's tensile and compressive properties changed significantly, and the failure behavior changed from brittle fracture to ductile fracture. Through a microscopic mechanism, the alkaline solution caused a high degree of phase separation and crystallization within the polymer network, thereby changing the PVA hydrogel network from a single phase to a multiphase. Hence, we used a continuous multiphase network model with a certain probability distribution to describe this tensile behavior. This model well described the stress-strain relationship of the hydrogel from stretching to fracture and revealed that the macroscopic failure corresponded to the peak of fracture distribution. Studies have shown that attention should be paid to the influence of the in situ precipitation on the mechanical properties, and the probabilistic multiphase network model can be used to predict the mechanical behavior of hydrogels with multiple phase separation.

An Experimental Study on the Dynamic Mechanical Properties of Epoxy Polymer Concrete under Ultraviolet Aging.

Epoxy polymer concrete (EPC) is widely applied in engineering for its excellent mechanical properties. The impact loads and severe climatic conditions such as ultraviolet radiation, temperature change and rain erosion are in general for its engineering practice, potentially degrading the performance of EPC. In this paper, a procedure of accelerated aging for EPC, imitating the aging effect of ultraviolet radiation and hygrothermal conditions based on the meteorological statistics of Guangzhou city, was designed. After various periods of accelerated aging, the dynamic behaviors of EPC were studied by using a Split Hopkinson Pressure Bar (SHPB). The verification of the experimental data was performed. The two-stage dynamic compression stress-strain curves were obtained: (a) linear growth stage following by strain hardening stage at impact velocity 12.2 m/s and 18.8 m/s, (b) linear growth stage and then a horizontal stage when impact velocity is 25.0 m/s, (c) linear growth stage following by strain softening stage at impact velocity 29.2 m/s. The experimental results show that the specimens after longer accelerated aging tend to be more easily broken, especially at impact velocity 12.2 m/s and 18.8 m/s, while the strain rate is the main factor affecting the compression strength and stiffness. Ultimately the influence of strain rate and equivalent aging time on dynamic increase factor was revealed by a fitting surface.

Design, synthesis, and biological evaluation of diosgenin-indole derivatives as dual-functional agents for the treatment of Alzheimer's disease.

The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against H2O2 (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aß (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by H2O2 (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aß1-42 (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aß1-42 was -40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aß1-42. The predicted values of brain/blood partition coefficient (-0.733) and polar surface area (85.118 Å2) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by H2O2. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aß-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.