Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

Identification of FtfL as a novel target of berberine in intestinal bacteria.

BACKGROUND: Berberine (BBR) is a commonly used anti-intestinal inflammation drug, and its anti-cancer activity has been found recently. BBR can intervene and control malignant colorectal cancer (CRC) through intestinal microbes, but the direct molecular target and related mechanism are unclear. This study aimed to identify the target of BBR and dissect related mechanisms against the occurrence and development of CRC from the perspective of intestinal microorganisms. RESULTS: Here, we found that BBR inhibits the growth of several CRC-driving bacteria, especially Peptostreptococcus anaerobius. By using a biotin-conjugated BBR derivative, we identified the protein FtfL (formate tetrahydrofolate ligase), a key enzyme in C1 metabolism, is the molecular target of BBR in P. anaerobius. BBR exhibits strong binding affinity and potent inhibition on FtfL. Based on this, we determined the crystal structure of PaFtfL (P. anaerobius FtfL)-BBR complex and found that BBR can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active center. In addition, the enzymatic activities of FtfL homologous proteins in human tumor cells can also be inhibited by BBR. CONCLUSIONS: In summary, our study has identified FtfL as a direct target of BBR and uncovered molecular mechanisms involved in the anti-CRC of BBR. BBR interferes with intestinal pathogenic bacteria by targeting FtfLs, suggesting a new means for controlling the occurrence and development of CRC.

Effects on the Microstructure Evolution and Properties of Graphene/Copper Composite during Rolling Process.

Rolling treatments have been identified as a promising fabrication and deformation processing technique for graphene/metal composites with high performance. However, it is still a challenge to choose appropriate rolling parameters to achieve high strength, ductility and electrical conductivity of the composite simultaneously. In this study, graphene/Cu composites were prepared with an in situ growth method and rolling treatment. The effects of rolling deformation and temperature on the microstructural evolution of graphene and Cu grains, interface bonding between graphene and the matrix, mechanical and electrical properties were systemically investigated. The cold-rolled composite with 85% deformation displayed a maximum ultimate strength of 548 MPa, a high elongation of 8.8% and a good electrical conductivity of 86.2% IACS. This is attributed to oriented graphene arrangement and matrix grain refinement. Our research provides a comprehensive understanding for the rolling behavior of graphene/Cu composites, and can promote the development of graphene-based composites with high performance.

Three-Dimensional Macroporous rGO-Aerogel-Based Composite Phase-Change Materials with High Thermal Storage Capacity and Enhanced Thermal Conductivity.

Three-dimensional porous network encapsulation strategy is an effective means to obtain composite phase-change materials (PCMs) with high heat storage capacity and enhanced thermal conductivity. Herein, macroporous reduced graphene oxide (rGO) aerogels with adjustable pore size are prepared by the emulsion template method and hydrothermal reduction process. Further, the shape-stabilized rGO-aerogel-based composite PCMs are constructed after the combination of 3D porous rGO supports and paraffin wax (PW) through vacuum melting infiltration. By regulating the pore structure of the rGO aerogel network, the rGO-based composite PCMs achieve excellent energy storage properties with a phase-change enthalpy of 179.94 J/g for the loading amount of 95.61 wt% and an obvious enhancement in thermal conductivity of 0.412 W/m-1·K-1, which is 54.89% higher than pristine PW and enduring thermal cycling stability. The obtained macroporous rGO-aerogel-based composite PCMs with high thermal storage and heat transfer performance effectively broaden the application of PCMs in the field of thermal energy storage.

Programmable Acetylation Modification of Bacterial Proteins by a Cas12a-Guided Acetyltransferase.

Protein lysine acetylation (PLA) is a crucial post-translational modification in organisms that regulates a variety of metabolic and physiological activities. Many advances have been made in PLA-related research; however, the quick and accurate identification of causal relationships between specific protein acetylation events and phenotypic outcomes at the proteome level remains challenging due to the lack of efficient targeted modification techniques. In this study, based on the characteristics of transcription-translation coupling in bacteria, we designed and constructed an in situ targeted protein acetylation (TPA) system integrating the dCas12a protein, guiding element crRNA, and bacterial acetylase At2. Rapid identification of multiple independent protein acetylation and cell phenotypic analyses in Gram-negative Escherichia coli and Gram-positive Clostridium ljungdahlii demonstrated that TPA is a specific and efficient targeting tool for protein modification studies and engineering.

Role of TPEN in Amyloid-ß25-35-Induced Neuronal Damage Correlating with Recovery of Intracellular Zn2+ and Intracellular Ca2+ Overloading.

The overproduction of neurotoxic amyloid-ß (Aß) peptides in the brain is a hallmark of Alzheimer's disease (AD). To determine the role of intracellular zinc ion (iZn2+) dysregulation in mediating Aß-related neurotoxicity, this study aimed to investigate whether N, N, N', N'­tetrakis (2­pyridylmethyl) ethylenediamine (TPEN), a Zn2+­specific chelator, could attenuate Aß25-35­induced neurotoxicity and the underlying mechanism. We used the 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay to measure the viability of primary hippocampal neurons. We also determined intracellular Zn2+ and Ca2+ concentrations, mitochondrial and lysosomal functions, and intracellular reactive oxygen species (ROS) content in hippocampal neurons using live-cell confocal imaging. We detected L-type voltage-gated calcium channel currents (L-ICa) in hippocampal neurons using the whole­cell patch­clamp technique. Furthermore, we measured the mRNA expression levels of proteins related to the iZn2+ buffer system (ZnT-3, MT-3) and voltage-gated calcium channels (Cav1.2, Cav1.3) in hippocampal neurons using RT-PCR. The results showed that TPEN attenuated Aß25-35­induced neuronal death, relieved the Aß25-35­induced increase in intracellular Zn2+ and Ca2+ concentrations; reversed the Aß25-35­induced increase in ROS content, the Aß25-35­induced increase in the L-ICa peak amplitude at different membrane potentials, the Aß25-35­induced the dysfunction of the mitochondria and lysosomes, and the Aß25-35­induced decrease in ZnT-3 and MT-3 mRNA expressions; and increased the Cav1.2 mRNA expression in the hippocampal neurons. These results suggest that TPEN, the Zn2+-specific chelator, attenuated Aß25-35­induced neuronal damage, correlating with the recovery of intracellular Zn2+ and modulation of abnormal Ca2+-related signaling pathways.

Genistein Promotes Anti-Heat Stress and Antioxidant Effects via the Coordinated Regulation of IIS, HSP, MAPK, DR, and Mitochondrial Pathways in Caenorhabditis elegans.

To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected in Caenorhabditis elegans (C. elegans); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR in C. elegans. The results indicate that genistein substantially extended the lifespan of C. elegans under oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin in C. elegans under hydrogen peroxide (H2O2) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H2O2 and upregulated the expression of daf-16, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, and eat-2, whereas it downregulated the expression of age-1 and daf-2 in C. elegans; similarly, it upregulated the expression of daf-16, sod-3, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, jnk-1 skn-1, and eat-2, whereas it downregulated the expression of age-1, daf-2, gst-4, and hsp-12.6 in C. elegans at 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H2O2 conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H2O2 conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects in C. elegans via insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.

Losartan Potassium and Verapamil Hydrochloride Compound Transdermal Drug Delivery System: Formulation and Characterization.

In this study, we developed a sustained-release transdermal delivery system containing losartan potassium (LP) and verapamil hydrochloride (VPH). LP and VPH have low bioavailability and long half-life. Therefore, the development of an optimum administration mode is necessary to overcome these drawbacks and enhance the antihypertensive effect. A transdermal diffusion meter was used to determine the optimal formulation of LP-VPH transdermal drug delivery systems (TDDS). Based on in vitro results, a sustained-release patch was prepared. Physical characteristics, including quality, stickiness, and appearance, were evaluated in vitro, while pharmacokinetics and skin irritation were evaluated in vivo. The results showed that 8.3% polyvinyl alcohol, 74.7% polyvinylpyrrolidone K30, 12% oleic acid-azone, and 5% polyacrylic acid resin II provided an optimized TDDS product for effective administration of LP and VPH. Furthermore, in vitro and in vivo release tests showed that the system continuously released LP and VPH for 24 h. The pharmacokinetic results indicated that although the maximum concentration was lower, both the area under the curve from 0-time and the mean residence time of the prepared patch were significantly higher than those of the oral preparations. Furthermore, the prepared LP-VPH transdermal patch showed good stability and no skin irritation. The developed LP-VPH TDDS showed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it is an ideal formulation.

Excessive Zinc Ion Caused PC12 Cell Death Correlating with Inhibition of NOS and Increase of RAGE in Cells.

Zinc ion (Zn2+) is an important functional factor; however, excessive Zn2+ can be toxic. To understand the neurotoxicity of excessive Zn2+ and the underlying mechanism, PC12 cells were treated with excessive Zn2+ and Zn2+ plus N, N, N', N'-Tetrakisethylenediamine (TPEN), a zinc ion chelator agent. Trypan blue and 3-(4,5-dimethyl-2- thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays were used to test cell viability; the relative kits were used to detect the activity of NOS synthase and the content of the receptor for advanced glycation end product (RAGE) in cells. We observed that excessive zinc caused PC12 cell damage and that TPEN partially reversed cell damage caused by excessive zinc. In addition, excessive zinc decreased total nitric oxide synthase (TNOS) activity in cells, in which constitutive nitric oxide synthase (cNOS) activity was significantly reduced; however, inducible nitric oxide synthase (iNOS) activity was extremely promoted. Moreover, excessive zinc upregulated the expression of RAGE, and TPEN effectively reversed the increase in RAGE induced by excessive zinc ions. Therefore, we concluded that excessive zinc caused PC12 cell damage, correlating with the inhibition of NOS and increase of RAGE induced in cells.

Antiamyloid ß toxicity effect of genistein via activation of DAF-16 and HSP-16.2 signal pathways in Caenorhabditis elegans.

ß-Amyloid toxicity (Aß) is an important pathological factor of Alzheimer's disease (AD). Studies have shown that genistein can reduce the toxicity of Aß to a certain extent; however, the specific mechanism is still uncertain. In the study, we applied Caenorhabditis elegans strains expressing Aß peptides to evaluate the role of genistein inhibiting Aß toxicity and the undying mechanism. Genistein influencing the sterol metabolism pathway, the HSP-16.2 pathway, and lipofuscin in different strains of C. elegans were studied using reverse transcription-polymerase chain reaction, fluorescence labeling, RNA interference (RNAi), and so forth. Our results showed that genistein alleviated the paralysis of transgenic C. elegans strains. Furthermore, in AD C. elegans, genistein reduced the fluorescence of lipofuscin, downregulated the messenger RNA (mRNA) level of vit-3 and vit-6 which were related to the sterol metabolism pathway, significantly increased the mRNA level and protein level of HSP-16.2, increased the nuclear translocation of the DAF-16 transcription factor and increased the survival rate after heat stress, which was closely associated with HSP-16.2 levels. However, the paralysis-alleviating effect of genistein was greatly reduced because of RNAi-mediated inhibition of hsp-16.2, indicating that the anti-Aß toxicity effect of genistein was greatly dependent on HSP-16.2. The above results suggest that genistein inhibiting the toxicity of Aß in C. elegans, is involved in the modulation of the sterol metabolism pathway by promoting transcription factor DAF-16 translocation into the nucleus, increasing the expression level of HSP-16.2, and reducing the levels of lipofuscin through its antioxidant activity.

Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

OBJECTIVE: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. METHODS: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45ß, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. RESULTS: Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. CONCLUSION: Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

Protein acetylation-mediated cross regulation of acetic acid and ethanol synthesis in the gas-fermenting Clostridium ljungdahlii.

The autotrophic acetogen Clostridium ljungdahlii has emerged as a major candidate in the biological conversion of one-carbon gases (CO2/CO) to bulk chemicals and fuels. Nevertheless, the regulatory pathways and downstream metabolic changes responsible for product formation and distribution in this bacterium remain minimally explored. Protein lysine acetylation (PLA), a prevalent posttranslational modification, controls numerous crucial cellular functions. Herein, we revealed a novel cross-regulatory mechanism that uses both the PLA system and transcription factors to regulate the carbon flow distribution for product formation in C. ljungdahlii. The dominant acetylation/deacetylation system (At2/Dat1) in C. ljungdahlii was found to regulate the ratio of two major products, acetic acid and ethanol. Subsequent genetic and biochemical analyses revealed that the activities of Pta and AdhE1, two crucial enzymes responsible for acetic acid and ethanol synthesis, respectively, were greatly affected by their levels of PLA. We found that the acetylation statuses of Pta and AdhE1 underwent significant dynamic changes during the fermentation process, leading to differential synthesis of acetic acid and ethanol. Furthermore, the crucial redox-sensing protein Rex was shown to be regulated by PLA, which subsequently altered its transcriptional regulation on genes responsible for acetic acid and ethanol formation and distribution. Based on our understanding of this cross-regulatory module, we optimized the ethanol synthetic pathway by modifying the acetylation status (deacetylation-mimicked mutations of crucial lysine residues) of the related key enzyme, achieving significantly increased titer and yield of ethanol, an important chemical and fuel, by C. ljungdahlii in gas fermentation.

TPEN attenuates amyloid-ß25-35-induced neuronal damage with changes in the electrophysiological properties of voltage-gated sodium and potassium channels.

To understand the role of intracellular zinc ion (Zn2+) dysregulation in mediating age-related neurodegenerative changes, particularly neurotoxicity resulting from the generation of excessive neurotoxic amyloid-ß (Aß) peptides, this study aimed to investigate whether N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a Zn2+-specific chelator, could attenuate Aß25-35-induced neurotoxicity and the underlying electrophysiological mechanism. We used the 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay to measure the viability of hippocampal neurons and performed single-cell confocal imaging to detect the concentration of Zn2+ in these neurons. Furthermore, we used the whole-cell patch-clamp technique to detect the evoked repetitive action potential (APs), the voltage-gated sodium and potassium (K+) channels of primary hippocampal neurons. The analysis showed that TPEN attenuated Aß25-35-induced neuronal death, reversed the Aß25-35-induced increase in intracellular Zn2+ concentration and the frequency of APs, inhibited the increase in the maximum current density of voltage-activated sodium channel currents induced by Aß25-35, relieved the Aß25-35-induced decrease in the peak amplitude of transient outward K+ currents (IA) and outward-delayed rectifier K+ currents (IDR) at different membrane potentials, and suppressed the steady-state activation and inactivation curves of IA shifted toward the hyperpolarization direction caused by Aß25-35. These results suggest that Aß25-35-induced neuronal damage correlated with Zn2+ dysregulation mediated the electrophysiological changes in the voltage-gated sodium and K+ channels. Moreover, Zn2+-specific chelator-TPEN attenuated Aß25-35-induced neuronal damage by recovering the intracellular Zn2+ concentration.

Two-Dimensional Conjugated Benzo[1,2-b:4,5-b']diselenophene-Based Copolymer Donor Enables Large Open-Circuit Voltage and High Efficiency in Selenophene-based Organic Solar Cells.

A two-dimensional electron-rich fused-ring moiety (ClBDSe) based on benzo[1,2-b:4,5-b']diselenophene is synthesized. Three copolymers (PBDT-Se, PBDSe-T, and PBDSe-Se) are obtained by manipulating the connection types and number of selenophene units on the conjugated main chains with two 2D fused-ring units and two different π-bridges, respectively. In comparison with PBDT-Se and PBDSe-Se, PBDSe-T with benzo[1,2-b:4,5-b']diselenophene unit and thiophene π-bridge exhibits the deepest HOMO energy level and the strongest crystallinity in neat films. The PBDSe-T:Y6 blend film exhibits the best absorption complementarity, the most distinctive face-on orientation with proper phase separation, the highest carrier mobilities, and the lowest charge recombination among three blend films. Finally, the PBDSe-T:Y6-based device delivers an impressive power conversion efficiency (PCE) of 14.50 %, which is higher than those of PBDT-Se:Y6 and PBDSe-Se:Y6. Moreover, a decent open-circuit voltage (Voc ) of 0.89 V with a remarkably small energy loss of 0.44 eV is achieved for PBDSe-T:Y6. The efficiency of 14.50 % is the highest value for selenophene-containing copolymer-based binary organic solar cells (OSCs). This study provides evidence that introduction of 2D-benzo[1,2-b:4,5-b']diselenophene as a fused electron-rich unit with π-bridging into copolymeric donors is a valid strategy for providing high Voc and excellent PCE simultaneously in selenophene-based OSCs.

Study on Fabrication and Properties of Graphite/Al Composites by Hot Isostatic Pressing-Rolling Process.

Graphite/Al composites have attracted much attrition due to their excellent thermal properties. However, the improvement of thermal conductivity (TC) is limited by the difficulty in controlling the orientation of graphite and the poor wettability between graphite and aluminum. In this study, a novel process for fabricating the Graphite/Al composites is proposed, which involves fabricating graphite film and aluminum foil into laminate material. Then, taking a rolling method, the fractured and well oriented graphite film can help the composite achieve high TC while maintaining a certain strength. The result reveals that both single and total reduction have a significant influence on the diameter and orientation of the graphite, and by adjusting the process parameters, composites with high TC can be acquired at a relatively low reinforcement volume. This near-net-forming process can directly meet the thickness requirements for electronic packaging and avoids the exposure of graphite to the surface during secondary processing, which is promising to promote the application for high TC Graphite/Al composites in thermal management.

Development and evaluation of 1-deoxynojirimycin sustained-release delivery system: In vitro and in vivo characterization studies.

We aimed to establish a 1-Deoxynojirimycin (DNJ) sustained-release delivery system to improve the hypoglycemic effect of DNJ. We used a transdermal diffusion meter in an in vitro orthogonal experiment to determine the optimal composition of the DNJ sustained-release transdermal system. Based on the in vitro analysis results, a sustained-release patch was prepared, and its pharmacokinetics and other properties were determined in vivo. The results showed that 30% hydroxypropyl methylcellulose (K100M ), 14% carboxymethyl cellulose sodium and 26% oleic acid-azone compound as the matrix material, drug excipient, and penetration enhancer, respectively, produced an optimal DNJ sustained-release delivery system. In vitro release tests showed that the system slowly released DNJ within 12 hr, conforming to the Higuchi equation. In vivo experiments showed that the prepared patch had good hypoglycemic activity and continuously released DNJ within 10 hr. In vivo pharmacokinetic study results showed that compared to conventional patches, the prepared patch exhibited significantly different maximum concentration (Cmax ), time to achieve Cmax (Tmax ), and area under the curve from 0 to time t (AUC[0-t] ) as well as improved pharmacokinetics. In conclusion, the prepared DNJ patch has high stability, a sustained-release effect, and relatively good pharmacokinetics and is a safe dosage form that does not cause skin irritation.

Interfacial Structure of Carbide-Coated Graphite/Al Composites and Its Effect on Thermal Conductivity and Strength.

Graphite/Al composites had attracted significant attention for thermal management applications due to their excellent thermal properties. However, the improvement of thermal properties was restricted by the insufficient wettability between graphite and Al. In this study, silicon carbide and titanium carbide coatings have been uniformly coated on the graphite by the reactive sputtering method, and Graphite/Al laminate composites were fabricated by a hot isostatic pressing process to investigate the influence on thermal conductivity and mechanical properties. The results show that carbide coating can effectively improve the interfacial thermal conductance of SiC@Graphite/Al and TiC@Graphite/Al composites by 9.8 times and 3.4 times, respectively. After surface modification, the in-plane thermal conductivity (TC) of the composites with different volume fractions are all exceeding the 90% of the predictions. In comparison, SiC is more conducive to improving the thermal conductivity of composite materials, since the thermal conductivity of the 28.7 vol.% SiC@Graphite/Al reached the highest value of 499 W/m·K, while TiC is favorable for improving the mechanical properties. The finding is beneficial to the understanding of carbide coating engineering in the Graphite/Al composites.

Strengthening and Weakening Effects of Particles on Strength and Ductility of SiC Particle Reinforced Al-Cu-Mg Alloys Matrix Composites.

The strengthening and weakening effects of SiC particles on composite strength and ductility were studied. Al-Cu-Mg alloys matrices with three different mechanical properties were used. Their yield strength, ultimate strength, and elongation range from 90 to 379 MPa, 131 to 561 MPa, and 18% to 31%, respectively. SiC particles with sizes of 4, 8, 12, 15, 20, and 30 µm were used to reinforce these three matrices, separately, and the composites of eighteen combinations of the particle sizes and matrix strengths were manufactured. Yield strength, ultimate strength, elongation, and fracture morphology of these composites were characterized. Based on the analysis, the strengthening to weakening behavior on strength and ductility were comprehensively discussed. The critical particle size having the best ductility was obtained. The strengthening limit and match range of the particle and the matrix to achieve effective strengthening were defined as a function of the particle size and matrix strength. This work offers an important reference for optimization of mechanical properties of the particle-reinforced metal matrix composites.

Effect of the Particle Size and Matrix Strength on Strengthening and Damage Process of the Particle Reinforced Metal Matrix Composites.

Roles of the particle, strengthening, and weakening during deformation of the particle reinforced metal matrix composite, were studied using in situ technique. Composites with three different strengths Al-Cu-Mg alloy matrices reinforced by three sizes SiC particles were manufactured and subjected to in situ tensile testing. Based on in situ observation, damage process, fraction and size distribution of the cracked particles were collected to investigate the behavior of the particle during composite deformation. The presence of the particle strengthens the composite, while the particle cracking under high load weakens the composite. This strengthening to weakening transformation is controlled by the damage process of the particle and decided by the particle strength, size distribution, and the matrix flow behavior together. With a proper match of the particle and matrix, an effective strengthening can be obtained. Finally, the effective match range of the particle and the matrix was defined as a function of the particle size and the matrix strength.

Flexible and Expandable Robot for Tissue Therapies - Modeling and Design.

OBJECTIVE: Implantable technologies should be mechanically compliant with the tissue in order to maximize tissue quality and reduce inflammation during tissue reconstruction. We introduce the development of a flexible and expandable implantable robotic (FEIR) device for the regenerative elongation of tubular tissue by applying controlled and precise tension to the target tissue while minimizing the forces produced on the surrounding tissue. METHODS: We introduce a theoretical framework based on iterative beam theory static analysis for the design of an expandable robot with a flexible rack. The model takes into account the geometry and mechanics of the rack to determine a trade-off between its stiffness and capability to deliver the required tissue tension force. We empirically validate this theory on the benchtop and with biological tissue. RESULTS: We show that FEIR can apply the required therapeutical forces on the tissue while reducing the amount of force it applies to the surrounding tissues as well as reducing self-damage. CONCLUSION: The study demonstrates a method to develop robots that can change size and shape to fit their dynamic environment while maintaining the precision and delicacy necessary to manipulate tissue by traction. SIGNIFICANCE: The method is relevant to designers of implantable technologies. The robot is a precursor medical device for the treatment of Long-Gap Esophageal Atresia and Short Bowel Syndrome.