RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone ...marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of
in BMSCs with
-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition,
:
-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.
Objectives
To compare the efficacy and safety of localization of small pulmonary nodules with microcoil and hookwire prior to surgical resection.
Methods
A total of 112 patients who underwent ...preoperative computed tomography (CT)-guided localization of small pulmonary nodules were enrolled in this single-center retrospective non-randomized cohort study between June 2016 and June 2017. Seventy-nine patients who underwent percutaneous localization with microcoils formed the microcoil group; the remaining 33 patients underwent percutaneous localization with hookwires (hookwire group). The primary outcomes were the success and complication rates of the procedure. Student’s
t
test was used for continuous variables, whereas chi-square analysis and logistic regression were used for dichotomous variables.
Results
Video-assisted thoracoscopic surgery (VATS) was successfully performed in all cases, without conversion to thoracotomy. The localization success rate was 94.9% (75/79) in the microcoil group and 93.9% (31/33) in the hookwire group (
p
= 0.836). Hookwire group (
p
= 0.000) and nodule location of the lower lobe (
p
= 0.012) were associated with an increased incidence of pneumothorax. Hookwire group (
p
= 0.027) and decreased nodule diameter (
p
= 0.024) were associated with an increased incidence of moderate to severe chest pain, as well as an increased incidence of overall complications.
Conclusions
Although the deployment of the microcoil was more complex and required more time than hookwire placement, microcoil localization was associated with fewer complications.
Key Points
•
CT-guided percutaneous localization using a microcoil and that using a hookwire are equally effective for localizing small pulmonary nodules prior to resection with video-assisted thoracoscopic surgery
.
•
Lung nodule localization using a microcoil was associated with fewer complications than localization using a hookwire
.
Accurate visual detection under poor illuminance is arguably an important and challenging practice for robot monitoring. The purpose of this study is to build detectors for inspection robot under ...nonuniform and poor lighting conditions. To this end, we propose an unsupervised lighting reflectance estimation framework for dark image detection unsupervised lighting reflectance estimation network (ULRE-Net). Based on lightness-color consistency, the "true color" of objects merely depends on the reflectance regardless of the variations of illuminance. The proposed ULRE-Net extracts robust features for detection by estimating a simple and differentiable expression of reflectance, and the method formulates reflectance estimation in an unsupervised learning manner without relying on image pairs. Thorough experiments are conducted to validate the veracity and generality of the proposed method over existing ones.
Objective
Hepatitis B virus X protein (HBx) is a pivotal factor for HBV-induced hepatitis. Herein, we sought to investigate HBx-mediated NLR pyrin domain containing 3 (NLRP3) inflammasome activation ...and pyroptosis under oxidative stress.
Methods
The effect of HBx on the NLRP3 inflammasome was analyzed by enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence in hepatic HL7702 cells. Pyroptosis was evaluated by western blotting, lactate dehydrogenase release, propidium iodide staining, and transmission electron microscopy. NLRP3 expression in the inflammasome from liver tissues was assessed by immunohistochemistry.
Results
In hydrogen peroxide (H
2
O
2
)-stimulated HL7702 cells, HBx triggered the release of pro-inflammatory mediators apoptosis-associated speck-like protein containing a CARD (ASC), interleukin (IL)-1β, IL-18, and high-mobility group box 1 (HMGB1); activated NLRP3; and initiated pro-inflammatory cell death (pyroptosis). HBx localized to the mitochondria, where it induced mitochondrial damage and production of mitochondrial reactive oxygen species (mitoROS). Treatment of HL7702 cells with a mitoROS scavenger attenuated HBx-induced NLRP3 activation and pyroptosis. Expression levels of NLRP3, ASC, and IL-1β in liver tissues from patients were positively correlated with HBV DNA concentration.
Conclusions
The NLRP3 inflammasome was activated by elevated mitoROS levels and mediated HBx-induced liver inflammation and hepatocellular pyroptosis under H
2
O
2
-stress conditions.
Background
Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, ...three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial.
Methods
In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern.
Results
Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank
P
= 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank
P
= 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%,
P
= 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months,
P
= 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all
P
> 0.05).
Conclusions
For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG.
Registration number
NCT02327481 (
http://clinicaltrials.gov
).
Graphical abstract
Gastric carcinoma (GC) is one of the highest cancer-mortality diseases with a high incidence rate in Asia. For surgically unfit but medically fit patients, palliative chemotherapy is the main ...treatment. The chemotherapy regimen of docetaxel, cisplatin and 5-fluorouracil (DCF) has been used to treat the advanced stage or metastatic GC. It is necessary to compare effectiveness and toxicities of DCF regimen with non-taxane-containing palliative chemotherapy for GC.
PubMed, EmBase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched to select relative randomized controlled trials (RCTs) comparing DCF to non-taxane-containing chemotherapy for patients with palliatively resected, unresectable, recurrent or metastatic GC. Primary outcome measures were 1-year and 2-year overall survival (OS) rates. Secondary outcome measures were median survival time (MST), median time to progression (TTP), response rate and toxicities.
Twelve RCTs were eligible and 1089 patients were analyzed totally (549 in DCF and 540 in control). DCF regimen increased partial response rate (38.8% vs 27.9%, p = 0.0003) and reduced progressive disease rate (18.9% vs 33.3%, p = 0.0005) compared to control regimen. Significant improvement of 2-year OS rate was found in DCF regimen (RR = 2.03, p = 0.006), but not of 1-year OS rate (RR = 1.22, p = 0.08). MST was significantly prolonged by DCF regimen (p = 0.039), but not median TTP (p = 0.054). Both 1-year OS rate and median TTP had a trend of prolongation by DCF regimen. Chemotherapy-related mortality was comparable (RR = 1.23, p = 0.49) in both regimens. In grade I-IV toxicities, DCF regimen showed a major raise of febrile neutropenia (RR = 2.33, p<0.0001) and minor raises of leucopenia (RR = 1.25, p<0.00001), neutropenia (RR = 1.19, p<0.00001), and diarrhea (RR = 1.59, p<0.00001), while in other toxicities there were no significant differences.
DCF regimen has better response than non-taxane containing regimen and could potentially improve the survival outcomes. The chemotherapy-related toxicity of DCF regimen is acceptable to some extent.
Human Immunodeficiency Virus 1 (HIV-1) co-receptor usage, called tropism, is associated with disease progression towards AIDS. Furthermore, the recently developed and developing drugs against ...co-receptors CCR5 or CXCR4 open a new thought for HIV-1 therapy. Thus, knowledge about tropism is critical for illness diagnosis and regimen prescription. To improve tropism prediction accuracy, we developed two novel methods, the extreme gradient boosting based XGBpred and the hidden Markov model based HMMpred. Both XGBpred and HMMpred achieved higher specificities (72.56% and 72.09%) than the state-of-the-art methods Geno2pheno (61.6%) and G2p_str (68.60%) in a 10-fold cross validation test at the same sensitivity of 93.73%. Moreover, XGBpred had more outstanding performances (with AUCs 0.9483, 0.9464) than HMMpred (0.8829, 0.8774) on the Hivcopred and Newdb (created in this work) datasets containing larger proportions of hard-to-predict dual tropic samples in the X4-using tropic samples. Therefore, we recommend the use of our novel method XGBpred to predict tropism. The two methods and datasets are available via http://spg.med.tsinghua.edu.cn:23334/XGBpred/. In addition, our models identified that positions 5, 11, 13, 18, 22, 24, and 25 were correlated with HIV-1 tropism.
Abstract
Progress in photonic crystals (PhCs) enables the advanced manipulation of light propagation, leading to strong light–matter interactions and unconventional applications. To explore the ...physical nature and realize the precise and efficient control of position‐dependent light–matter interactions, the direct deep‐subwavelength characterization of PhC states is pivotal. Here, the super‐resolved visualization of bulk states in the
z
‐direction asymmetric dielectric PhC is realized by characterizing the radiative local density of optical states, including the etched hole area. An accelerating voltage scanning approach is proposed to selectively probe bulk states and substrates, elucidating the electron–matter interactions affected by the electron‐beam energy. The bulk state energy is demonstrated to be confined inside structure holes as shown by the cathodoluminescence intensity mappings of PhCs with different geometrical parameters, enabling the design of a silicon‐based high‐quality cavity in the visible range. This work provides a deep investigation of the depth‐dependent interaction between the electron beam and dielectric PhCs, promoting the characterization of PhC delocalized modes. The deep‐subwavelength detail of bulk state benefits the future nanoscale manipulation of light–matter interactions and the optimization of quantum emission devices.
Rotating machinery is typical complex electromechanical equipment under nonstationary working conditions and hazardous environments, which is thus vulnerable to an unexpected fault. The currently ...wide-applied deep learning-based fault diagnosis methods for rotating machines require a huge amount of training data and can only extract features from independent samples. In this study, a semi-supervised self-correcting graph neural network (SSGNN) is proposed for fault diagnosis, which effectively extracts features from vibrational signals and generates a graph-structured representation of fault knowledge. First, a preprocessing layer is introduced to mine the propinquity of vibration samples and construct a graph, where circle loss is applied to enhance convergence. Second, the state transform algorithm is improved by proposing a graph convolutional layer for efficiently implementing state propagation. Finally, an alternate learning method is proposed based on the expectation maximization (EM) algorithm, in which the feature extraction network and graph structure are optimized alternately to reduce the training complexity. The proposed method is validated through experiments conducted on a publicly available dataset and a dynamic condition dataset obtained from a drivetrain dynamic simulator. The results show that the proposed method has higher accuracy and faster convergence speed compared to the state-of-the-art methods.
Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that ...administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using secondgeneration sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid β peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.
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