DCPIB Attenuates Ischemia-Reperfusion Injury by Regulating Microglial M1/M2 Polarization and Oxidative Stress.

The inflammatory response plays an indispensable role in ischemia-reperfusion injury, the most significant of which is the inflammatory response caused by microglial polarization. Anti-inflammatory therapy is also an important remedial measure after failed vascular reconstruction. Maintaining the internal homeostasis of the brain is a crucial measure for suppressing the inflammatory response. The mechanism underlying the relationship between DCPIB, a selective blocker of volume-regulated anion channels (VRAC), and inflammation induced by cerebral ischemia-reperfusion injury is currently unclear. The purpose of this study was to investigate the relationship between DCPIB and microglial M1/M2 polarization-mediated inflammation after cerebral ischemia-reperfusion injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). DCPIB was administered by a lateral ventricular injection within 5 min after reperfusion. Behavioral assessments were conducted at 1, 3, and 7 days after tMCAO/R. Pathological injuries were evaluated using TTC assay, HE and Nissl staining, brain water content measurement, and immunofluorescence staining. The levels of inflammatory cytokines were analyzed using qPCR and ELISA. Additionally, the phenotypic variations of microglia were examined using immunofluorescence staining. In mouse tMCAO/R model, DCPIB administration markably reduced mortality, improved behavioral performance, and alleviated pathological injury. DCPIB treatment significantly inhibited the inflammatory response, promoted the conversion of M1 microglia to M2 microglia via the MAPK signaling pathway, and ultimately protected neurons from the microglia-mediated inflammatory response. In addition, DCPIB inhibited oxidative stress induced by cerebral ischemia-reperfusion injury. In conclusion, DCPIB attenuates cerebral ischemia-reperfusion injury by regulating microglial M1/M2 polarization and oxidative stress.

Multimorbidity Patterns and Associations with Gait, Balance and Lower Extremity Muscle Function in the Elderly: A Cross-Sectional Study in Northwest China.

Purpose: Fall is a common geriatric syndrome leading to various adverse outcomes in the elderly. Gait and balance disorders and decreased lower extremity muscle function are the major intrinsic risk factors of falls, and studies suggested that they were closely related to the underlying chronic conditions. This study aimed to explore the patterns of multimorbidity and determine the associations of these multimorbidity patterns with gait, balance and lower extremity muscle function. Patients and Methods: A cross-sectional survey of 4803 participants aged ≥60 years in Shaanxi Province, China was conducted and the self-reported chronic conditions were investigated. The 6-m walk test, timed-up-and-go test (TUG) and 5-sit-to-stand test (5-STS) were conducted to evaluate gait, balance, and lower extremity muscle function respectively. Latent class analysis was used to explore patterns of multimorbidity, and multivariate regression analysis was used to determine the associations of multimorbidity patterns with gait, balance, and lower extremity muscle function. Results: Five multimorbidity patterns were identified: Degenerative Disease Class, Cardio-metabolic Class, Stroke-Respiratory-Depression Class, Gastrointestinal Class, and Very sick Class, and they were differently associated with gait and balance disorders and decreased lower extremity muscle function. In particular, the multimorbidity patterns of Degenerative Disease Class and Stroke-Respiratory-Depression Class were closely associated with all the three risk factors of falls. Conclusion: There are significant differences in the impact of different multimorbidity patterns on the major intrinsic risk factors of falls in the elderly population, and appropriate multimorbidity patterns are closely related to the prediction of falls and can help to develop fall prevention strategies in the elderly.

Realizing Abundant Chirality Inversion of Supramolecular Nanohelices by Multiply Manipulating the Binding Sites in Molecular Blocks.

The induction of diverse chirality regulation in nature by multiple binding sites of biomolecules is ubiquitous and plays an essential role in determining the biofunction of biosystems. However, mimicking this biological phenomenon and understanding at a molecular level its mechanism with the multiple binding sites by establishing an artificial system still remains a challenge. Herein, abundant chirality inversion is achieved by precisely and multiply manipulating the co-assembled binding sites of phenylalanine derivatives (D/LPPF) with different naphthalene derivatives (NA, NC, NP, NF). The amide and hydroxy group of naphthalene derivatives prefer to bind with the carboxy group of LPPF, while carboxylic groups and fluoride atoms tend to bind with the amide moiety of LPPF. All these diverse interaction modes can precisely trigger helicity inversion of LPPF nanofibers. In addition, synergistically manipulating the carboxy and amide binding sites from a single LPPF molecule to simultaneously interact with different naphthalene derivatives leads to chirality regulation. Typically, varying the solvent may switch the interaction modes and the switched new interaction modes can be employed to further regulate the chirality of the LPPF nanofibers. This study may provide a novel approach to explore chirality diversity in artificial systems by regulating the intermolecular binding sites.

Target control based on edge dynamics in complex networks.

In the past decade, the study of the dynamics of complex networks has been a focus of research. In particular, the controllability of complex networks based on the nodal dynamics has received strong attention. As a result, significant theories have been formulated in network control. Target control theory is one of the most important results among these theories. This theory addresses how to select as few input nodes as possible to control the chosen target nodes in a nodal linear dynamic system. However, the research on how to control the target edges in switchboard dynamics, which is a dynamical process defined on the edges, has been lacking. This shortcoming has motivated us to give an effective control scheme for the target edges. Here, we propose the k-travel algorithm to approximately calculate the minimum number of driven edges and driver nodes for a directed tree-like network. For general cases, we put forward a greedy algorithm TEC to approximately calculate the minimum number of driven edges and driver nodes. Analytic calculations show that networks with large assortativity coefficient as well as small average shortest path are efficient in random target edge control, and networks with small clustering coefficient are efficient in local target edge control.

Damage Detection of Asphalt Concrete Using Piezo-Ultrasonic Wave Technology.

Asphalt concrete has been widely used in road engineering as a surface material. Meanwhile, ultrasonic testing technology has also been developed rapidly. Aiming to evaluate the feasibility of the ultrasonic wave method, the present work reports a laboratory investigation on damage detection of asphalt concrete using piezo-ultrasonic wave technology. The gradation of AC-13 was selected and prepared based on the Marshall's design. The ultrasonic wave velocities of samples were tested with different environmental conditions firstly. After that, the samples were destroyed into two types, one was drilled and the other was grooved. And the ultrasonic wave velocities of pretreated samples were tested again. Furthermore, the relationship between velocity and damaged process was evaluated based on three point bending test. The test results indicated that piezoelectric ultrasonic wave is a promising technology for damage detection of asphalt concrete with considerable benefits. The ultrasonic velocity decreases with the voidage increases. In a saturated water environment, the measured velocity of ultrasonic wave increased. In a dry environment (50 °C), the velocity the ultrasonic waves increased too. After two freeze-thaw cycles, the voidage increased and the ultrasonic velocity decreased gradually. After factitious damage, the wave must travel through or most likely around the damage, the ultrasonic velocity decreased. During the process of three point bending test, the ultrasonic velocity increased firstly and then decreased slowly until it entered into a steady phase. At last the velocity of ultrasonic wave decreased rapidly. In addition, the errors of the results under different test conditions need to be further studied.

Preparation and Characterization of RGDS/Nanodiamond as a Vector for VEGF-siRNA Delivery.

Small interfering RNA (siRNA) has great potential for treating or preventing diseases. Safe and efficient vectors are extremely needed for specific delivery of siRNA. Here VEGF-siRNA/RGDS/nanodiamond was prepared by conjugating Arg-Gly-Asp-Ser (RGDS) and VEGF-siRNA to nanodiamond delivery particles. VEGF-siRNA could be clinically used in anti-angiogenic gene therapy to inhibit tumor growth via the down-regulation of the expression of vascular endothelial growth factor (VEGF). The differential scanning calorimeter (DSC) analysis evidenced that RGDS and/or VEGF-siRNA were effectively linked to nanodiamond. The release assays indicated that in the presence of RGDS the release time of VEGF-siRNA was prolonged by 6 folds. This enabled VEGF-siRNA/RGDS/nanodiamond to release and transfer VEGF-siRNA in a long-acting manner, and thereby to significantly decrease the expression of VEGF mRNA and protein. Real-Time PCR analysis revealed that the expression of VEGF mRNA was decreased 87.56 ± 1.6% by VEGF-siRNA/RGDS/nanodiamond. Enzyme-Linked Immunosorbent Assay (ELISA) indicated that the expression of VEGF protein was down-regulated to 39.8 ± 1.8%. The down-regulation of VEGF protein expression was also observed in Western blotting experiments. In human umbilical vein endothelial cells (HUVEC) test, VEGF-siRNA/RGDS/nanodiamond decreased the formation of the tubes and exhibited no testable cytotoxicty. All the results consistently suggested that RGDS/nanodiamond is an ideal non-viral tumor-targeting vector for siRNA transfer, and VEGF-siRNA/RGDS/nanodiamond may be a promising regimen of gene therapy in carcinoma.

RGDS covalently surfaced nanodiamond as a tumor targeting carrier of VEGF-siRNA: synthesis, characterization and bioassay.

A nonviral tumor targeting vector for siRNA transfer is of importance. Here, a novel delivery system consisting of a covalent conjugate of NDCO-RGDS and VEGF-siRNA, NDCO-RGDS/VEGF-siRNA, was presented. In vitro, NDCO-RGDS/VEGF-siRNA released and transferred VEGF-siRNA in a long-acting manner. Compared to the control, NDCO-RGDS/VEGF-siRNA decreased the expression of VEGF mRNA and protein in HeLa cells by 88.41 ± 3.49% and 83.94 ± 2.00%, respectively. In vivo, NDCO-RGDS/VEGF-siRNA exhibited gene silencing and slowed tumor growth. FT-MS spectrum analysis revealed that NDCO-RGDS/VEGF-siRNA mainly distributed in tumor tissue of the treated S180 mice. Therefore NDCO-RGDS could be considered a promising nonviral tumor-targeting vector for siRNA transfer in tumor therapy.

Effect of subcellular localization of P21 on proliferation and apoptosis of HepG2 cells.

This study examined the effect of subcellular localization of P21 on the proliferation and apoptosis of HepG2 cells. The coding genes of the wild and the mutant P21 were amplified by mega primer PCR from the plasmid pCEP-WAF1 which contains human P21 cDNA in the nuclear localizational signal (NLS) sequence, and then inserted into the eukaryotic expression vector pDsRed1-C1. The recombinants were transfected into HepG2 cells. The transcription and expression of P21 were determined by RT-PCR and fluorescence microscopy. The cell proliferation was measured by MTT, and the cell cycle and apoptosis of HepG2 cells by flow cytometry. The results of restriction analysis, DNA sequencing and fluorescence microscopy confirmed the construction of the wild and the mutant P21 in the eukaryotic expression plasmid. The plasmid containing the mutant P21 was found to accelerate cell proliferation and the wild P21 plasmid to inhibit cell proliferation. Cell cycle analysis showed that the cell ratio of G(0)/G(1) in the wild type group was significantly increased as compared with that in the mutant type group, and cell apoptosis analysis revealed that the apoptosis rate in the wild type group was much higher than that in the mutant type group. It was concluded that the subcellular localization of P21 may contribute to the development of hepatic cancer.