Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13.

Autophagy is an important intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles. We report a potent small molecule inhibitor of autophagy named "spautin-1" for specific and potent autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and frequently monoallelically lost in human cancers. Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Our study provides a molecular mechanism involving protein deubiquitination that connects two important tumor suppressors, p53 and Beclin1, and a potent small molecule inhibitor of autophagy as a possible lead compound for developing anticancer drugs.

Yin and yang regulation of stress granules by Caprin-1.

Stress granules (SGs) are cytoplasmic biomolecular condensates containing proteins and RNAs in response to stress. Ras-GTPase-activating protein binding protein 1 (G3BP1) is a core SG protein. Caprin-1 and ubiquitin specific peptidase 10 (USP10) interact with G3BP1, facilitating and suppressing SG formation, respectively. The crystal structures of the nuclear transport factor 2-like (NTF2L) domain of G3BP1 in complex with the G3BP1-interacting motif (GIM) of Caprin-1 and USP10 show that both GIMs bind to the same hydrophobic pocket of G3BP1. Moreover, both GIMs suppressed the liquid-liquid phase separation (LLPS) of G3BP1, suggesting that Caprin-1 likely facilitates SG formation via other mechanisms. Thus, we dissected various domains of Caprin-1 and investigated their role in LLPS in vitro and SG formation in cells. The C-terminal domain of Caprin-1 underwent spontaneous LLPS, whereas the N-terminal domain and GIM of Caprin-1 suppressed LLPS of G3BP1. The opposing effect of the N- and C-terminal domains of Caprin-1 on SG formation were demonstrated in cells with or without the endogenous Caprin-1. We propose that the N- and C-terminal domains of Caprin-1 regulate SG formation in a "yin and yang" fashion, mediating the dynamic and reversible assembly of SGs.

Identification of ROS and KEAP1-related genes and verified targets of α-hederin induce cell death for CRC.

In this study, we analyzed and verified differentially expressed genes (DEGs) in ROS and KEAP1 crosstalk in oncogenic signatures using GEO data sets (GSE4107 and GSE41328). Multiple pathway enrichment analyses were finished based on DEGs. The genetic signature for colorectal adenocarcinoma (COAD) was identified by using the Cox regression analysis. Kaplan-Meier survival and receiver operating characteristic curve analysis were used to explore the prognosis value of specific genes in COAD. The potential immune signatures and drug sensitivity prediction were also analyzed. Promising small-molecule agents were identified and predicted targets of α-hederin in SuperPred were validated by molecular docking. Also, expression levels of genes and Western blot analysis were conducted. In total, 48 genes were identified as DEGs, and the hub genes such as COL1A1, CXCL12, COL1A2, FN1, CAV1, TIMP3, and IGFBP7 were identified. The ROS and KEAP1-associated gene signatures comprised of hub key genes were developed for predicting the prognosis and evaluating the immune cell responses and immune infiltration in COAD. α-hederin, a potential anti-colorectal cancer (CRC) agent, was found to enhance the sensitivity of HCT116 cells, regulate CAV1 and COL1A1, and decrease KEAP1, Nrf2, and HO-1 expression significantly. KEAP1-related genes could be an essential mediator of ROS in CRC, and KEAP1-associated genes were effective in predicting prognosis and evaluating individualized CRC treatment. Therefore, α-hederin may be an effective chemosensitizer for CRC treatments in clinical settings.

Synthesis of Multifluoromethylated γ-Sultines by a Photoinduced Radical Addition-Polar Cyclization.

Despite the significance of sultines in synthesis, medicine, and materials science, the chemistry of sultines has remained unexplored due to their inaccessibility. Herein, we demonstrate the development of a photoredox-catalyzed multifluoromethyl radical addition/SO2 incorporation/polar cyclization cascade approach to multifluoromethylated γ-sultines. The reactions proceed by single electron transfer induced multifluoromethyl radical addition to an alkene followed by SO2 incorporation, and single-electron reduction for polar 5-exo-tet cyclization. Key to the success of the protocol is the use of easily oxidizable multifluoroalkanesulfinates as bifunctional reagents. The reactions proceed with excellent functional-group tolerance to deliver γ-sultines in moderate to excellent yields.

Triterpenoids of Rhus chinensis Supressed Colorectal Cancer Progress by Enhancing Antitumor Immunity and CD8 + T Cells Tumor Infiltration.

The absence of CD8+ T cells in the tumor center has become a major obstacle in the immunotherapy of colorectal cancer. Therefore, new therapeutic strategies are urgently needed to promote the accumulation of CD8+ T cells in the tumor center. Previous studies have shown that triterpenoid of Rhus chinensis (TER) is involved in the proliferation and apoptosis of colorectal cancer cells, and can regulate their immune activity, but its mechanism needs to be further elucidated. In this study, the antitumor effect and adaptive immune response of TER on tumor-bearing mice were evaluated and compared with 5-fluorouracil. The results showed that TER could significantly inhibit tumor growth and prolong the survival time of tumor-bearing mice. The In Vivo studies have shown that TER can not only enhance antitumor immunity and promote the accumulation of CD8 + T cells to tumor sites, but also inhibit tumor progression by regulating the expression of PD-1 and PD-L1 and significantly reducing the mortality of mice. Our study demonstrated for the first time that TER has oncolytic effect, and recruited adaptive immune cells to enhance the efficacy of anti-PD-1/PD-L1 in colorectal cancer, which provides a potential therapeutic target for combined immunotherapy of colorectal cancer.

The stiffness of transplanted kidneys changes with time after renal transplantation.

BACKGROUND: Kidney transplantation is one of the most effective ways to treat end-stage kidney disease. However, 5000 renal transplant recipients start or restart dialysis because of chronic allograft nephropathy (CAN) every year in the United States. Detecting changes in the stiffness of transplanted kidneys can help diagnose transplanted kidney disease. PURPOSE: To explore changes in the stiffness of transplanted kidneys after renal transplantation using shear wave elastography (SWE). MATERIAL AND METHODS: This study conducted consecutive follow-up observations on 10 patients after kidney transplantation. SWE examination was performed in the first week, second week, first month, second month, third month, fourth month, fifth month, and sixth month after surgery. This study also analyzed the graft stiffness of 86 patients with stable renal function recovery one month after surgery. RESULTS: The results show that there is a change in the stiffness of the transplanted kidney over time after renal transplantation. It decreases rapidly within one month after renal transplantation and tends to be stable after one month. The mean renal cortical and pyramidal stiffness of patients with stable renal function were 28.48 ± 4.27 kPa and 21.97 ± 3.90 kPa, respectively. CONCLUSION: Consecutive stiffness measurement of transplanted kidneys is an effective method for monitoring the function of transplanted kidneys. According to the change in transplanted kidney stiffness, we can designate a more scientific review plan to determine the functional status of the transplanted kidney.

Prediction of tumor size in patients with invasive ductal carcinoma using FT-IR spectroscopy combined with chemometrics: a preliminary study.

Precise detection of tumor size is essential for early diagnosis, treatment, and evaluation of the prognosis of breast cancer. However, there are some errors between the tumor size of breast cancer measured by conventional imaging methods and the pathological tumor size. Invasive ductal carcinoma (IDC) is a common pathological type of breast cancer. In this study, serum Fourier transform infrared spectroscopy (FT-IR) combined with chemometric methods was used to predict the maximum diameter and maximum vertical diameter of tumors in IDC patients. Three models were evaluated based on the pathological tumor size measured after surgery and included grid search support vector machine regression (GS-SVR), back propagation neural network optimized by genetic algorithm (GA-BP-ANN), and back propagation neural network optimized by particle swarm optimization (PSO-BP-ANN). The results show that three models can accurately predict tumor size. The GA-BP-ANN model provided the best fitting quality of the largest tumor diameter with the determination coefficients of 0.984 in test set. And the GS-SVR model provided the best fitting quality of the largest vertical tumor diameter with the determination coefficients of 0.982 in test set. The GS-SVR model had the highest prediction efficiency and the lowest time complexity of the models. The results indicate that serum FT-IR spectroscopy combined with chemometric methods can predict tumor size in IDC patients. In addition, compared with traditional imaging methods, we found that the experimental results of the three models are better than traditional imaging methods in terms of correlation and fitting degree. And the average fitting error of PSO-BP-ANN and GA-BP-ANN models was less than 0.3 mm. The minimally invasive detection method is expected to be developed into a new clinical diagnostic method for tumor size estimation to reduce the diagnostic trauma of patients and provide new diagnostic experience for patients. Graphical Abstract.

Bisphenol A(BPA), BPS and BPB-induced oxidative stress and apoptosis mediated by mitochondria in human neuroblastoma cell lines.

The analogues of biphenol A (BPA), including bisphenol S (BPS) and bisphenol B (BPB), are commonly used to replace the application of BPA in containers and wrappers of daily life. However, their safeties are questioned due to their similar chemical structure and possible physiological effects as BPA. To investigate the neurotoxic effects of BPA, BPS, and BPB as well as their underlying mechanism, IMR-32 cell line from male and SK-N-SH cell line from female were exposed respectively to BPA, BPS and BPB with concentrations of 1 nM, 10 nM, 100 nM, 1 µM, 10 µM, and 100 µM for 24 h. Additionally, 24 h exposure of BPA combining epigallocatechin gallate (EGCG) (4 µM and 8 µM for IMR-32 and SK-N-SH respectively) were conducted. Results demonstrated that BPs exposure could promote reactive oxygen species production and increase level of malondialdehyde (MDA) while decrease levels of superoxide dismutase (SOD). Intensive study revealed that after exposure to BPA mitochondrial membrane potential (MMP) dropped down and the protein expression levels of Bak-1, Bax, cytochrome c and Caspase-3 were up-regulated but Bcl-2 were down-regulated significantly. Moreover, apoptosis rate was raised and cell activity declined remarkably in the neuroblastoma cells. All the effects induced by BPA could be alleviated by the adding of EGCG, which similar alleviations could be inferred in IMR-32 and SK-N-SH cells induced by BPS and BPB. Furthermore, BPS showed lower neurotoxic effects compared to BPA and BPB. Interestingly, the neurotoxic effects of BPA on IMR-32 cells were significantly higher than those on SK-N-SH cells. In conclusion, the results suggested that BPA, BPS and BPB could induce oxidative stress and apoptosis via mitochondrial pathway in the neuroblastoma cells and male is more susceptible to BPs than female.

Binary Nanoparticle Superlattices for Plasmonically Modulating Upconversion Luminescence.

Engineering a facile and controllable approach to modulate the spectral properties of lanthanide-doped upconversion nanoparticles (UCNPs) is always an ongoing challenge. Herein, long-range ordered, distinct two-dimensional (2D) binary nanoparticle superlattices (BNSLs) composed of NaREF4 :Yb/Er (RE = Y and Gd) UCNPs and plasmonic metallic nanoparticles (Au NPs), including AB, AB3 , and AB13 lattices, are fabricated via a slow evaporation-driven self-assembly to achieve plasmonic modulation of upconversion luminescence (UCL). Optical measurements reveal that typical red-green UCL from UCNPs can be effectively modulated into reddish output in BNSLs, with a drastically shortened lifetime. Notably, for AB3 - and AB13 -type BNSLs with more proximal Au NPs around each UCNP, modified UCL with fine-structured spectral lineshape is observed. These differences could be interpreted by the interplay of collective plasmon resonance introduced by 2D periodic Au arrays and spectrally selective energy transfer between UCNPs and Au. Thus, fabricating UCNP-Au BNSLs with desired lattice parameters and NP configurations could be a promising way to tailor the UCL through controlled plasmonic modulation.

Correlation Between Endorectal Ultrasound and Magnetic Resonance Imaging for Predicting the Circumferential Resection Margin in Patients With Mid-Low Rectal Cancer Without Preoperative Chemoradiotherapy.

OBJECTIVES: To assess the correlation between endorectal ultrasound (ERUS) and magnetic resonance imaging (MRI) in predicting the circumferential resection margin (CRM) status of patients with mid-low rectal cancer without preoperative chemoradiotherapy. METHODS: Twenty patients with rectal cancer who did not receive preoperative chemoradiotherapy and underwent ERUS and MRI examinations before total mesorectal excision from May 2018 to April 2019 were included in this study. The patient and tumor characteristics, lymph nodes, tumor stages, ERUS and MRI predictors of the CRM status, and postoperative pathologic results were recorded. The closest distance between the deepest portion of lesion invasion and the mesorectal fascia was independently measured on MRI and ERUS images by 2 observers. The observers were blinded to the pathologic results. Measurements from ERUS and MRI were compared. RESULTS: The mean distance between the distal edge of the lesion and the anal verge was 5.7 cm (range, 3.1-8.1 cm). The ERUS and pathologic evaluations of CRM involvement were consistent in 90% of the cases. The MRI and pathologic evaluations of CRM involvement were concordant in 95% of the cases. The Cohen κ coefficient of ERUS and MRI was 0.608 (P = .007). The correlation coefficient of ERUS and MRI for assessing the closest distance from the edge of cancer invasion to the mesorectal fascia was 0.99 (P = .0005). CONCLUSIONS: Endorectal ultrasound and MRI assessments of the preoperative CRM status appear to be highly consistent. Endorectal ultrasound can be used as a complementary tool with MRI to predict the CRM status of patients with mid-low rectal cancer without preoperative chemoradiotherapy.

Monolithic Integration of Silicon Nanowire Networks as a Soft Wafer for Highly Stretchable and Transparent Electronics.

Assembling nanoscale building blocks into an orderly network with a programmable layout and channel designs represents a critical capability to enable a wide range of stretchable electronics. Here, we demonstrate the growth-in-place integration of silicon nanowire (SiNW) springs into highly stretchable, transparent, and quasicontinuous functional networks with a close to unity interconnection among the discrete electrode joints because of a unique double-lane/double-step guiding edge design. The SiNW networks can be reliably transferred to a soft elastomer substrate, conformally attached to highly curved surfaces, or deployed as self-supporting/movable membranes suspended over voids. A high stretchability of >40% is achieved for the SiNW network on an elastomer, which can be employed as a transparent and semiconducting thin-film material endowed with a high carrier mobility of >50 cm2/(V s), Ion/Ioff ratio >104, and a tunable transmission of >80% over a wide spectrum range. Reversibly stretchable and bendable sensors based on the SiNW network have been successfully demonstrated, where the local strain distribution within the spring network can be directly observed and analyzed by finite element simulations. This SiNW network has a unique potential to eventually establish a new generically purposed waferlike platform for constructing soft electronics with Si-based hard performances.

Idiomarina mangrovi sp. nov., isolated from rhizosphere soil of a mangrove Avicennia marina forest.

A Gram-staining negative, aerobic, motile and rod-shaped bacterium, designated ZQ330T, was isolated from rhizosphere soil of a mangrove (Avicennia marina) forest of Zhangzhou, Fujian Province, China. The growth range of NaCl concentration was 0.5-10.0 % (w/v), with an optimum at 2.5-3.0 % (w/v), the temperature range for growth was 10-40 °C, with an optimum at 28-30 °C, the pH range for growth was pH 6.0-9.5, with an optimum at pH 7.5. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ZQ330T exhibited less than 97.0 % sequence similarity to all type strains with validly published names and revealed that strain ZQ330T formed a distinct lineage in the genus Idiomarina. The average nucleotide identity, and in silico DNA-DNA hybridization values between strain ZQ330T and the reference strains were 64.8-69.9 % and 27.5-28.4 %, respectively. Chemotaxonomic analysis indicated that the main respiratory quinone was Q-8, the predominant cellular fatty acids were iso-C15 : 0, iso-C17 : 0, summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1ω9c), iso-C15 : 1F, C16 : 0, C18 : 0, summed feature 3 (C16 : 1ω8c and/or iso-C16 : 1 2-OH) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified glycolipid, an unidentified aminolipid, an unidentified phospholipid and two unidentified lipids. Based on the genotypic, phenotypic, chemotaxonomic and phylogenetic features, strain ZQ330T is considered to represent a novel species, for which the name Idiomarina mangrovi sp. nov. is proposed. The type strain is ZQ330T (=MCCC 1K03495T=KCTC 62455T).

Three-dimensional speckle-tracking echocardiography for evaluating myocardial motion in patients with cardiorenal syndrome.

Because of better awareness and understanding of its pathophysiology, the cardiorenal syndrome (CRS) is more often diagnosed and better managed. The echocardiographic evaluation of CRS now benefits from three-dimensional speckle tracking echocardiography (3D-STE), which allows multidimensional and real-time evaluation of regional myocardial and overall cardiac function, and helps assessing the degree of myocardial damage. This article describes the application of 3D-STE in evaluating the myocardial motion in patients with CRS.

CAD-CAM-fabricated interim fixed complete-arch implant-supported restorations based on the existing dentition.

An interim restoration is often used to assess the patient's functional and esthetic needs for implant-supported complete-arch fixed prostheses. A digital protocol for accurately transferring information from the existing dentition to the interim restoration is required. The purpose of this clinical report was to describe a digital workflow to fabricate an interim fixed restoration by using the vertical dimension of occlusion and occlusal relationship from the original dentition to provide an accurate, efficient, and predictable computer-aided design and computer-aided manufacturing (CAD-CAM) interim complete-arch implant-supported restoration.

FoxO1 expression in osteoblasts modulates bone formation through resistance to oxidative stress in mice.

Accumulation of reactive oxygen species (ROS) induced by oxidative stress (OS) affects cell survival, cell function and even results in cell death. As a major transcription factor of forkhead O (FoxOs) family, FoxO1 orchestrates multiple osteoblastic biological processes, thus regulating osteoblast physiology and bone metabolism. However, the outcome of osteoblast behaviors varies under different physiological and pathological conditions. Also, the underlying impact of FoxO1 on oxidative stress and further on bone metabolism still remains unclear. In this study, using osteoblast-specific FoxO1 knockout (FoxO1OB-/-) mice, we investigated the potential roles of FoxO1 on bone formation and osteoblast bioactivity under physiological condition. We show herein that FoxO1-knockout decreased bone volume and bone formation rate in FoxO1OB-/- mice, which might be related to the decreased osteoblasts number. We also found that FoxO1-knockout increased apoptosis-related caspase-3 activity of osteoblasts, and inhibited the expression of osteogenic phenotypic markers (i.e. Runx2, Osx, ALP and OPN), leading to reduced osteoblasts differentiation. The alterations of bone formation and osteoblasts bioactivity were further testified to be linked to the elevated intracellular oxidative stress levels in FoxO1-deficient osteoblasts. Besides, administration of the antioxidant N-acetyl-l-cysteine (NAC) normalized the increased ROS levels in FoxO1-deficient osteoblasts, restoring the decreased osteoblasts differentiation, suppressing apoptosis-related caspase-3 activity, and promoting the expression of osteogenic markers in FoxO1-deficient osteoblasts. These results together illustrated that as a major regulator in redox homeostasis and osteoblast physiology, FoxO1 provides a favorable intracellular environment for osteoblast functions by defensing against the adverse effects of oxidative stress.

Non-thermal plasma reduces periodontitis-induced alveolar bone loss in rats.

Periodontitis, a chronic infectious disease induced by microbial biofilm, is one of the most common diseases worldwide. Scaling and root planning (SRP) has always been recognized as the typical treatment. However, the therapeutic efficiency is often limited due to the intraoperative bleeding and the limitations of instruments. Non-thermal atmospheric plasma (NTP) appears to be a potential tool for periodontitis due to its promising biofilm degradation and decontamination effects. In this study, we investigated the role of NTP, as an adjuvant approach for the treatment of ligature-induced periodontitis in rats. Herein we showed that SRP or SRP-NTP application attenuated the periodontitis-induced alveolar bone loss, reflected by the increased BV/TV value and the decreased CEJ-AB distance, which might be related to the lower detection rate of periodontal pathogen in SRP and SRP-NTP groups. Besides, SRP-NTP rats showed less bone loss and lower CEJ-AB distance than that of SRP group at 30d post treatment, indicating a more comprehensive and long-lasting effect of SRP-NTP. A remarkable decrease of osteoclast number and lower expression of RANKL was also detected in SRP-NTP rats. In addition, expression of inflammatory-related cytokines such as TNF-α and IL-1ß decreased significantly in SRP-NTP group, while IL-10 level increased substantially. These results together illustrated that a combination of SRP and NTP treatment was an effective way to prevent periodontitis progress, which reduced alveolar bone loss and promoted periodontium restoration in ligature-induced periodontitis rats. In conclusion, non-thermal plasma treatment may be considered as a feasible and effective supplementary approach to control periodontitis.

An Estimate of Natural Gas Methane Emissions from California Homes.

We estimate postmeter methane (CH4) emissions from California's residential natural gas (NG) system using measurements and analysis from a sample of homes and appliances. Quiescent whole-house emissions (i.e., pipe leaks and pilot lights) were measured using a mass balance method in 75 California homes, while CH4 to CO2 emission ratios were measured for steady operation of individual combustion appliances and, separately, for transient operation of three tankless water heaters. Measured quiescent whole-house emissions are typically <1 g CH4/day, though they exhibit long-tailed gamma distributions containing values >10 g CH4/day. Most operating appliances yield undetectable CH4 to CO2 enhancements in steady operation (<0.01% of gas consumed), though storage water heaters and stovetops exhibit long-tailed gamma distributions containing high values (∼1-3% of gas consumed), and transients are observed for the tankless heaters. Extrapolating results to the state-level using Bayesian Markov chain Monte Carlo sampling combined with California housing statistics and gas use information suggests quiescent house leakage of 23.4 (13.7-45.6, at 95% confidence) Gg CH4, with pilot lights contributing ∼30%. Emissions from steady operation of appliances and their pilots are 13.3 (6.6-37.1) Gg CH4/yr, an order of magnitude larger than current inventory estimates, with transients likely increasing appliance emissions further. Together, emissions from residential NG are 35.7 (21.7-64.0) Gg CH4/yr, equivalent to ∼15% of California's NG CH4 emissions, suggesting leak repair, improvement of combustion appliances, and adoption of nonfossil energy heating sources can help California meet its 2050 climate goals.

A large-inner-diameter multi-walled carbon nanotube-based dual-drug delivery system with pH-sensitive release properties.

A novel dual-drug delivery system (DDDS) for cancer chemotherapy has been established by employing highly purified and mildly oxidized large-inner-diameter multi-walled carbon nanotubes (LID-MWCNTs) as the vector. The LID-MWCNTs were modified with the antitumor drugs, cisplatin (CDDP) and doxorubicin (DOX). CDDP was encapsulated inside the nanotube vectors by a wet-chemical approach while DOX was attached to the external surfaces through non-covalently interaction. The loading efficiencies of CDDP and DOX were as high as 84.56 and 192.67%, respectively. Notably, after CDDP was encapsulated inside the nanotubes, a three-level blocking strategy, which included polyethylene glycol, folic acid and DOX, was employed to block the CDDP exits at different levels. The pH-sensitive release profile of CDDP was demonstrated using a modified characterization method, as well as that of DOX. Finally, the anticancer activity of the DDDS on MCF-7 cells was tested and a synergistic effect was recorded. This work is part of our LID-MWCNTs based drug delivery system studies, and provides a basis for developing a novel comprehensive antitumor treatment that combines chemotherapy and photothermal therapy.

Effects of Low-Intensity Pulsed Ultrasound on Implant Osseointegration in Ovariectomized Rats.

OBJECTIVES: To investigate the effect of low-intensity pulsed ultrasound (US) on periimplant bone healing and osseointegration under osteoporotic conditions. METHODS: Seventy-two 12-week-old female Sprague Dawley rats received bilateral ovariectomies. Twelve weeks later, titanium implants were bilaterally placed in the proximal tibial metaphysis. The right tibia was exposed to low-intensity pulsed US (40 mW/cm2, spatial and temporal average) for 20 min/d starting the 2nd day after implantation, and the left tibia served as a control without stimulation. The rats were randomly assigned to 6 groups of 12 each according to the US duration (group 1: weeks 0­2, 280 minutes; group 2: weeks 0­4, 560 minutes; group 3: weeks 0­6, 840 minutes; group 4: weeks 0­8, 1120 minutes; group 5: weeks 0­10, 1400 minutes; group 6: weeks 0­12, 1680 minutes). At the end of the 2nd, 4th, 6th, 8th, 10th, and 12th weeks, the rats were euthanized, and bilateral tibias were harvested. Peri-implant bone volume and bone-implant contact were assessed by micro­computed tomography; the implantbone interface was assessed histologically; and implant fixation strength was determined by a removal torque test. RESULTS: Low-intensity pulsed US increased bone-implant contact at the 4th, 6th, 8th, 10th, and 12th weeks (P = .019, .017, <.001, <.001, and <.001, respectively) and periimplant bone volume at all times (P = <.001, .002, .012, .007, .005, and .010). Removal torque on the US side was improved at the 6th, 8th, 10th, and 12th weeks (P= .012, <.001, .006, and .009). Ultrasound evoked a favorable bone response in the histologic study. CONCLUSIONS: Low-intensity pulsed US might enhance new bone formation, especially at an early stage, and improve osseointegration in osteoporotic bone as an auxiliary method. However, further studies are needed to elucidate the mechanisms underlying its action.

Effects of Low-Intensity Pulsed Ultrasound on Implant Osseointegration in Ovariectomized Rats.

OBJECTIVES: To investigate the effect of low-intensity pulsed ultrasound (US) on peri-implant bone healing and osseointegration under osteoporotic conditions. METHODS: Seventy-two 12-week-old female Sprague Dawley rats received bilateral ovariectomies. Twelve weeks later, titanium implants were bilaterally placed in the proximal tibial metaphysis. The right tibia was exposed to low-intensity pulsed US (40 mW/cm2 , spatial and temporal average) for 20 min/d starting the 2nd day after implantation, and the left tibia served as a control without stimulation. The rats were randomly assigned to 6 groups of 12 each according to the US duration (group 1: weeks 0-2, 280 minutes; group 2: weeks 0-4, 560 minutes; group 3: weeks 0-6, 840 minutes; group 4: weeks 0-8, 1120 minutes; group 5: weeks 0-10, 1400 minutes; group 6: weeks 0-12, 1680 minutes). At the end of the 2nd, 4th, 6th, 8th, 10th, and 12th weeks, the rats were euthanized, and bilateral tibias were harvested. Peri-implant bone volume and bone-implant contact were assessed by micro-computed tomography; the implant-bone interface was assessed histologically; and implant fixation strength was determined by a removal torque test. RESULTS: Low-intensity pulsed US increased bone-implant contact at the 4th, 6th, 8th, 10th, and 12th weeks (P = .019, .017, <.001, <.001, and <.001, respectively) and peri-implant bone volume at all times (P = <.001, .002, .012, .007, .005, and .010). Removal torque on the US side was improved at the 6th, 8th, 10th, and 12th weeks (P= .012, <.001, .006, and .009). Ultrasound evoked a favorable bone response in the histologic study. CONCLUSIONS: Low-intensity pulsed US might enhance new bone formation, especially at an early stage, and improve osseointegration in osteoporotic bone as an auxiliary method. However, further studies are needed to elucidate the mechanisms underlying its action.