Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective To investigate the therapeutic effects of copper-doped barium titanate(BaCuTiO4)piezoelectric materials combined with low-intensity pulsed ultrasound(LIPUS)to activate their piezoelectric-catalytic synergistic effect for treating implant-associated infections.Methods BaCuTiO4 coatings were synthesized on the surface of Ti-6Al-4V substrates using a hydrothermal method,and their surface morphology was characterized by scanning electron microscopy.The piezoelectric characteristics of the coatings were analyzed using a piezoresponse force microscope.An in vitro biofilm model of methicillin-resistant staphylococcus aureus(MRSA)was used,with barium titanate(BaTiO3)coatings serving as the control group.Under LIPUS intervention(1.0 W/cm2,1 MHz,10 min),the bacterial viability was assessed using colony counting to evaluate the antibacterial performance of the BaCuTiO4 coatings.Confocal microscopy was used to observe biofilm viability in different groups,assessing the biofilm removal capability of the coatings.Reactive oxygen species(ROS)generation in each group was detected using Rhodamine b as a probe to evaluate the catalytic efficiency of the coatings in generating ROS.Results Copper doping significantly reduced the piezoelectric coefficient of the coating(from 17.7 pm/V to 7.8 pm/V),bringing its piezoelectric performance closer to the requirements of natural bone tissues.Under LIPUS activation,the BaCuTiO4 coatings increased the generation efficiency of reactive oxygen species by 67.5％and effectively disrupted and removed biofilms formed by MRSA,achieving an antibacterial rate of 90.5％.Conclusions The BaCuTiO4 coatings achieve efficient antibacterial and biofilm-clearing functions through a piezoelectric-catalytic synergistic mechanism.Their piezoelectric properties are well-matched with natural bone tissues,promoting implant osseointegration.

Objective To investigate the therapeutic effects of copper-doped barium titanate(BaCuTiO4)piezoelectric materials combined with low-intensity pulsed ultrasound(LIPUS)to activate their piezoelectric-catalytic synergistic effect for treating implant-associated infections.Methods BaCuTiO4 coatings were synthesized on the surface of Ti-6Al-4V substrates using a hydrothermal method,and their surface morphology was characterized by scanning electron microscopy.The piezoelectric characteristics of the coatings were analyzed using a piezoresponse force microscope.An in vitro biofilm model of methicillin-resistant staphylococcus aureus(MRSA)was used,with barium titanate(BaTiO3)coatings serving as the control group.Under LIPUS intervention(1.0 W/cm2,1 MHz,10 min),the bacterial viability was assessed using colony counting to evaluate the antibacterial performance of the BaCuTiO4 coatings.Confocal microscopy was used to observe biofilm viability in different groups,assessing the biofilm removal capability of the coatings.Reactive oxygen species(ROS)generation in each group was detected using Rhodamine b as a probe to evaluate the catalytic efficiency of the coatings in generating ROS.Results Copper doping significantly reduced the piezoelectric coefficient of the coating(from 17.7 pm/V to 7.8 pm/V),bringing its piezoelectric performance closer to the requirements of natural bone tissues.Under LIPUS activation,the BaCuTiO4 coatings increased the generation efficiency of reactive oxygen species by 67.5％and effectively disrupted and removed biofilms formed by MRSA,achieving an antibacterial rate of 90.5％.Conclusions The BaCuTiO4 coatings achieve efficient antibacterial and biofilm-clearing functions through a piezoelectric-catalytic synergistic mechanism.Their piezoelectric properties are well-matched with natural bone tissues,promoting implant osseointegration.

Objective To investigate the biomechanical effects of lateral wedge insole(LWI)on internal tissues of the foot and ankle(including foot bones,joints,and ligaments).Methods A three-dimensional finite element model of the foot-insole-ground was developed and validated,and the plantar pressure distributions,contact pressures on joints,and peak stresses on metatarsals and major ligaments in barefoot model and insole intervention models at three key gait instants were explored.Results The 5° LWI model reduced the peak plantar pressure by 65.8％compared to the barefoot model.Insole interventions decreased the peak contact pressure at the cuneonavicular joint,but increased the peak contact pressure at the subtalar joint and peak stress at the 4th and 5th metatarsals.Conclusions This study quantitatively assesses the biomechanical effects of LWI on various parts of the foot and ankle,and suggests a design that can appropriately reduce the inclination angle of LWI at the 4th and 5th metatarsals.

Objective: To compare and investigate the physicochemical characteristics and antibacterial effect of ZnO nanofilms prepared by atomic layer deposition(ALD) at different deposition cycles. Methods: According to different ALD cycles, four groups were set up (control group, 300, 600 and 1 200 cycles group). Using DEZn and water as precursors, ZnO nanofilms were prepared by ALD on the surface of pure titanium specimens. Surface morphology of the films was observed by scanning electron microscope (SEM); the element composition and crystal type of the films were observed by energy dispersive spectrometer (EDS) and X-Ray Diffraction (XRD); the hydrophilicity and thickness of the films were detected by water contact angle detector and ellipsometer. The cytotoxicity of the films was evaluated by CCK-8 assay. The antibacterial effect against S. aureus in vitro of the films was evaluated by optical density method. Results: The surface morphology of the films was uniform and compact as shown through SEM. The grain size increased with the increase of the number of ALD cycles. EDS results showed that the films were mainly composed of Zn and O elements. XRD results confirmed that the composition of the films was ZnO. Results of water contact angle showed that the films were hydrophobic. The thickness of the films was nanoscale and there was a linear relationship between the thickness and ALD cycles. All experimental groups showed no cytotoxicity. The 1 200 cycles group showed the highest antibacterial rate of 65.9% and 52.3% at 24 and 48 hours respectively, which was the best among all experimental groups. Conclusion The ZnO nanofilms prepared by ALD at different cycles on pure titanium surface are uniform and compact. Thickness of the films increases with the increase of ALD cycles. The films have good biocompatibility and anti-S. aureus effect in vitro. The 1 200 cycles group has the best antibacterial effect.

Objective: To investigate the effects of fiber surface deposited with silicon dioxide films by atomic layer deposition on properties of dental fiber-reinforced composites. Methods : SiO2 films were deposited on the surface of quartz fiber by atomic layer deposition(ALD). Then the quartz fiber was used to manufacture fiber resin composites, which were divided into four groups: A(no soaking agent removal), B(soaking agent removed), C(soaking agent removed and silanization), and D(soaking agent removed, 600 ALD cycles performed and then silanization). Scanning electron microscopy, water contact angle test, hygroscopicity test, CCK8 test and three-point bending test were used to investigate the properties of fiber resin composites. Results: The surface morphology of the quartz fiber treated by ALD was smooth and had no obvious change compared with that before treatment. Moreover, the quartz fiber showed hydrophobicity after silanization. The results of three-point bending test revealed that the mechanical properties of fiber-resin composites modified by ALD were significantly improved(P<0.05). When viewed by scanning electron microscopy, a good interfacial bonding could be seen between quartz fibers and the resin matrix in Group D. In addition, it was found that Group D had low absorbability, low solubility and good biocompatibility. Conclusion It is shown that deposition of SiO2 films on the quartz fiber by ALD can significantly enhance the mechanical properties of fiber-reinforced composites.

Tenofovir dipivoxil fumarate (TDF) is a anti human immunodeficiency virus and hepatitis B virus drug, which is commonly used in clinic. The osteotoxicity of TDF has always been a key issue of clinical concern. The bone toxicity of TDF is related to hypophosphatemia secondary to renal tubular toxicity. At present, there are few systematic descriptions of bone metabolism changes caused by TDF. In this paper, the effects of TDF on bone metabolism are reviewed from 3 aspects: its effects on osteoblasts and osteoclasts, bone turnover, and bone structure and fracture.

Tenofovir dipivoxil fumarate (TDF) is a anti human immunodeficiency virus and hepatitis B virus drug, which is commonly used in clinic. The osteotoxicity of TDF has always been a key issue of clinical concern. The bone toxicity of TDF is related to hypophosphatemia secondary to renal tubular toxicity. At present, there are few systematic descriptions of bone metabolism changes caused by TDF. In this paper, the effects of TDF on bone metabolism are reviewed from 3 aspects: its effects on osteoblasts and osteoclasts, bone turnover, and bone structure and fracture.

The importance of structural variants(SVs)for human phenotypes and diseases is now recognized.Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed,few benchmarking procedures are available to confidently assess their performances in biological and clinical research.To facilitate the validation and application of these SV detection approaches,we established an Asian reference material by characterizing the genome of an Epstein-Barr virus(EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls.We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers,including 109x Pacific Biosciences(PacBio)continuous long reads(CLRs),22 x PacBio circular consensus sequencing(CCS)reads,104x Oxford Nanopore Technologies(ONT)long reads,and 114×Bionano optical mapping plat-form,and one de novo assembly-based SV caller using CCS reads.A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing,demonstrating the robustness of our SV calls.Combining trio-binning-based haplotype assemblies,we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions(CHCRs),which covered 1.46 gigabase pairs(Gb)and 6882 SVs supported by at least one diploid haplotype assembly.Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology,disease,and clinical research.