A nanofluidic spiking synapse.

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.

A distal regulatory strategy of enzymes: from local to global conformational dynamics.

Modulating the distribution of various states in protein ensembles through distal sites may be promising in the evolution of enzymes in desired directions. However, the prediction of distal mutation hotspots that stabilize the favoured states from a computational perspective remains challenging. Here, we presented a strategy based on molecular dynamics (MD) and Markov state models (MSM) to predict distal mutation sites. Extensive MD combined with MSM was applied to determine the principally distributed metastable states interconverting at a slow timescale. Then, molecular docking was used to classify these states into active states and inactive ones. Distal mutation hotspots were targeted based on comparing the conformational features between active and inactive states, where mutations destabilize the inactive states and show little influence on the active state. The proposed strategy was used to explore the highly dynamic MHETase, which shows a potential application in the biodegradation of poly(ethylene terephthalate) (PET). Seven principally populated interrelated metastable states were identified, and the atomistic picture of their conformational changes was unveiled. Several residues at distal positions were found to adopt more H-bond occupancies in inactive states than active states, making them potential mutation hotspots for stabilizing the favoured conformations. In addition, the detailed mechanism revealed the significance of calcium ions at a distance from the catalytic centre in reshaping the free energy landscape. This study deepens the understanding of the conformational dynamics of α/ß hydrolases containing a lid domain and advances the study of enzymatic plastic degradation.

Clinical Effect of Personalized Adjustable Mandibular Advancement Device on Obstructive Sleep Apnea.

Aims/Background: Mandibular advancement devices are effective in treating mild or moderate obstructive sleep apnea (OSA), but such devices that are commonly used in clinical settings require further improvement. In this study, we evaluated the clinical effects of personalized adjustable mandibular advancement devices on mild or moderate OSA. Methods: Forty patients with mild or moderate OSA were randomly divided into experimental (personalized adjustable device) and control (traditional device) groups. Side effects, including increased salivation, dry mouth, muscle aches, and temporomandibular joint discomfort, were assessed. Respiratory markers during sleep, including the apnea-hypopnea index, mean blood oxygen saturation, lowest blood oxygen saturation and maximum apnea time, were evaluated using polysomnography. The upper airway cross-sectional area and temporomandibular joint morphology and motion trajectory were evaluated using cone beam computed tomography. Results: Side effects were significantly lower in the experimental group than in the control group. Respiratory marker levels were significantly restored post-treatment. Soft palate- and tongue-pharyngeal cross-sectional areas were significantly increased in both groups, but temporomandibular joint morphology or motion trajectory remained unchanged. Conclusion: The personalized adjustable mandibular advancement devices may reduce side effects and are effective in treating patients with OSA. Clinical Trial Registration: The study was registered and approved by the Chinese Clinical Trial Registry (ChiCTR2400080306). https://www.chictr.org.cn/showproj.html?proj=206538.

Effect of High Positive Acceleration (+Gz) Environment on Dental Implant Osseointegration:A Preliminary Animal Study.

OBJECTIVE: To observe the effect of high positive acceleration (+Gz) environment on dental implant osseointegration in a rabbit model and to investigate its mechanism. METHODS: Forty-eight New Zealand white rabbits were randomly divided into 6 groups. The rabbit's mandibular incisors were extracted and 1 implant was placed in each socket immediately. After 1 week of rest, the rabbits were exposed to a high +Gz environment, 3 times a week. The rabbits were sacrificed at 3 weeks (2 weeks +Gz exposure), 5 weeks (4 weeks +Gz exposure), and 12 weeks (4 weeks +Gz exposure and 7 weeks normal environment) after surgery, respectively. Specimens were harvested for micro-CT scanning, histological analysis, and real-time polymerase chain reaction examination. RESULTS: Compared with those in the control group, the mRNA expression levels of bone morphogenetic protein-2 (BMP-2), osteopontin (OPN), and transforming growth factor-ß1 (TGF-ß1) were significantly lower (P < 0.05), while the mRNA expression level of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL/osteoprotegerin (OPG) ratio were significantly higher (P < 0.05) at 3 weeks; values of bone volume fraction, trabecular number, bone-implant contact (BIC), and TGF-ß1 and OPG mRNA expression levels were significantly lower (P < 0.05), and the value of trabecular separation, RANKL mRNA expression level and RANKL/OPG ratio were significantly higher (P < 0.05) at 5 weeks; and the value of BIC was still significantly lower (P < 0.05) at 12 weeks in the experimental group. CONCLUSION: Early exposure to the high +Gz environment after implant surgery might have an adverse effect on osseointegration, and its mechanism could be related to the inhibition of osteoblast activity and promotion of osteoclast activity.

Glucan HBP-A increase type II collagen expression of chondrocytes in vitro and tissue engineered cartilage in vivo.

OBJECTIVE: Although chondroprotective activities have been documented for polysaccharides, the potential target of different polysaccharide may differ. The study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo, especially on the expression of type II collagen. METHODS: Chondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type II collagen. Chondrocyte viability was assessed after being treated with HBP-A in different concentrations. Morphological status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope (SEM). The constructs were treated with HBP-A and then injected to nude mice subcutaneously. Six weeks after transplantation, the specimens were observed through transmission electron microscopy (TEM). The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTs-5), aggrecan and type II collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction (PCR). The expression of type II collagen and matrix metalloproteinases-3 (MMP-3) in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: MMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration. In morphological study, there were significant appearance of collagen in those constructs treated by HBP-A. Accordingly, in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs, the expression of type II collagen was increased significantly in HBP-A group when compared with control group (P<0.001). CONCLUSIONS: The study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3, ADAMTs-5, and increasing of type II collagen expression.

[Comparison and analysis of human dentin matrix protein 1 promoter activity in three different cells].

OBJECTIVE: To observe and compare the luciferase activities of different length segments of human dentin matrix protein 1 promoter in human dental pulp stem cells (HDPSC), osteoblasts (OC) and Hela cells. METHODS: The differentlength desired DNA segments were obtained from 2 195 bp Dmp1 promoter cloned by PCR method. The amplified promoter segments with different length were cloned into luciferase report gene vector pGL3-Basic, the correct orientation of those inserts was verified by cutting with two different restrict enzymes. The luciferase activity was observed after different pGL3-PDmp1 vectors were transfected transiently into those three different-type cells. RESULTS: 6 Dmp1 promoter segments with different-length were obtained successfully, and luciferase report gene vectors with different promoter segments were successfully constructed after identified by restriction enzymes cutting. They had different luciferase activities when they were transfected transiently into HDPSC, and the region of -505(-)-193 bp and -935(-)-505 bp could be regarded as the specific promoters of Dmp1 promoter for HDPSC and OC respectively, which could include the basic regulatory elements. CONCLUSION: The correct clone of the upstream of human Dmp1 promoter segments with different length had been obtained, and they had strong luciferase activities in HDPSC and OC, but very low in Hela cell. These results will make an important basis for studying mineralized tissue-specific transcriptional regulation mechanisms of Dmp1.