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• The effective permeability (EP) affected by network percolation is investigated. • A bimodal distribution of EP for isotropic network is found and analyzed. • Effects of fracture density, fracture–matrix permeability contrast are studied. • Finite-size effect of EP is revealed and studied. • Different EP characteristics of percolating and non-percolating samples are studied. This study investigates the effective permeability of fractured porous media with fracture density near the percolation threshold. A new equivalent matrix-fracture network (EMFN) model was introduced, the code was used to efficiently deal with the huge number of modeling works for steady state flow in fractured porous media. The numerical model was verified by comparing with two previous seepage methods. We conducted a series of Monte Carlo simulations to explore the relationship between permeability discontinuity and three factors, namely fracture density, contrast between fracture and matrix permeability, and the scale of research domain. It was found that the effective permeability presents a bimodal distribution with specified fracture density in the transition regime. Each bimodal function can be subdivided into two well-fitting log-normal functions according to the percolation state to obtain analyzable average permeabilities. The results revealed significant differences between percolating and non-percolating configurations in the response to the change of each of the three factors mentioned above. More importantly, the finite-size effect plays an important role when fracture density is lower than or close to the percolation threshold; but this effect disappears gradually as the increase of fracture density. A stereoscopic approach is introduced to rationalize the scale effect. [ABSTRACT FROM AUTHOR]

to observe the clinical effect of acupuncture by mángzhēn huīcì (relaxing needling with sharp long needle) on iliotibial band friction syndrome (ITBS). this was a two-arm randomized controlled trial with blinding of participants, outcome assessment and statistician. acupuncture-Moxibustion, Tuina and Orthopedics Department and the Orthopedics Department of Shanghai the Sixth People's Hospital, June 2018 to January 2021. a total of 64 patients with iliotibial band friction syndrome (ITBS). with a 1:1 ratio the patients were randomly assigned to either the conventional acupuncture group (CA, n=32) or the Relaxing Needling with Sharp Long Needle group (RNSLN, n=32). The CA group was treated by applying acupuncture at Jūliáo (居髎GB 29), Fēngshì (风市GB 31), Liángqiū (梁丘ST 34), Yánglíngquán (阳陵泉GB 34), and Ashi points (阿是穴) of the affected side, and the RNSLN group was treated by applying relaxing needling with sharp long needle at Jūliáo (居髎GB 29), Liángqiū (梁丘ST 34), and Ashi points of the affected side. Both groups were treated once every other day, 10 times as one course of treatment. the treatment effect was evaluated after one course of treatment by comparing their KSS scores and VAS scores, as well as overall response rate. Sixty-four patients were included in the final data analysis. There was no difference in KSS and VAS scores between the two groups before treatment (P >0.05). After treatment, the KSS score of the two groups was higher than that before treatment, the VAS score of the two groups was lower than that before treatment (P <0.05). The KSS score of the RNSLN group was higher than that of the CA group, and the VAS score of the RNSLN group was lower than that of the CA group (P <0.05). The overall response rate of the RNSLN group was 93.75%, higher than 75% of the control group (P <0.05). Each group has 1 case of subcutaneous bleeding as adverse event. Relaxing Needling with Sharp Long Needle could be more beneficial for iliotibial band friction syndrome (ITBS) compared with conventional acupuncture, and more evidence is required for its effectiveness before introducing the approach widely to clinical practice. [ABSTRACT FROM AUTHOR]

The artificial manipulation of exogenous molecules in living cells is a promising means to regulate cellular behaviors. However, the spatiotemporal control of self-assembly within the complex intracellular environment remains grand challenge. Herein, we report a controlled sequential assembly of DNA nanoparticles in living cells, responding to acidic environment in lysosome, which enables lysosome interference and subsequently regulates a series of cellular behaviors. Two types of ultra-long DNA chains (DNA-chain-1 and 2) synthesized via rolling circle amplification were compressed by magnesium ion to two DNA nanoparticles (DNP-1 and 2), respectively. In the acidic environment of lysosomes, both DNP-1 and DNP-2 dissociated to DNA chains, and the DNA chains were subsequently assembled through base-pairing to form a hydrogel. This sequential assembly process consumed hydrogen ions within the lysosome, decreased lysosomal acidity, and thus altered the hydrolase activity and lysosomal membrane permeability. The interference of sequential assembly on lysosomes promoted cell movement in human breast adenocarcinoma MCF-7 cells, with 81.19% and 36.24% enhancement in cell migration and invasion capacity, respectively; the level of cellular autophagy was increased by 170.00%. Our study provides a new strategy for the sequential assembly of exogenous DNA materials in living cells. [Display omitted] • Artificial manipulation of the assembly in living cells is important for cell regulation. • DNA nanoparticles are sequentially assembled in response to lysosomal acidic environment. • The sequential assembly promotes cell movement and enhances autophagy levels. • The sequential assembly achieves lysosomal interference and cell behavior regulation. [ABSTRACT FROM AUTHOR]

The treatment of myocardial infarction (MI) is hindered by a vicious cycle of the accumulation of reactive oxygen species (ROS) and overexpression of apoptotic factors. Implementing a co-delivery drug system that regulates the expression of ROS and apoptotic factors remains a critical challenge. Herein, we report a DNA nanocomplex that achieves the synergistic repair of MI injury by ROS scavenging and the attenuation of apoptotic factors expression. The DNA nanocomplex integrates a multitude of peroxidase-like nano-enzymes and gene drugs by precise molecular recognition and cascade hybridization chain reaction of two hairpin DNA monomers. The nano-enzyme, G-quadruplex with hemin intercalation, functions as glutathione peroxidase to scavenge excess ROS for alleviating the microenvironmental deterioration; the gene drug, miRNA-21, is responsible for silencing the expression of apoptotic-related factor PDCD4, to regulate metabolic dysfunction. Meanwhile, the design of adenosine triphosphate (ATP) aptamer in DNA nanocomplex facilitates the controlled release of miRNA-21 in cells. By combining the functions of ROS scavenging and apoptosis factor inhibition, DNA nanocomplex effectively alleviates the myocardial cell damage under hypoxia, achieving enhanced in vivo therapeutic effect for MI. This work provides a new strategy of disrupting the vicious cycle of metabolic dysfunction and microenvironmental deterioration at the infarcted area for MI treatment. [Display omitted] • A DNA nanocomplex system was constructed and loaded with peroxidase-like nanoenzymes and gene drugs. • By designing DNA sequence as ATP aptamers, miRNA in nanocomplex was controlled to be released within the target cells. • This system broke the vicious cycle of reactive oxygen species (ROS) accumulation and apoptotic factors overexpression. [ABSTRACT FROM AUTHOR]