Calmodulin Triggers Activity-Dependent rRNA Biogenesis via Interaction with DDX21.

Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and memory formation. However, the signaling cascades that couple neuronal activity to the translational events remain elusive. In this study, we identified the role of calmodulin (CaM), a conserved Ca2+-binding protein, in ribosomal RNA (rRNA) biogenesis in neurons. We found the CaM-regulated rRNA synthesis is Ca2+-dependent and necessary for nascent protein synthesis and axon growth in hippocampal neurons. Mechanistically, CaM interacts with nucleolar DEAD (Asp-Glu-Ala-Asp) box RNA helicase (DDX21) in a Ca2+-dependent manner to regulate nascent rRNA transcription within nucleoli. We further found CaM alters the conformation of DDX21 to liberate the DDX21-sequestered RPA194, the catalytic subunit of RNA polymerase I, to facilitate transcription of ribosomal DNA. Using high-throughput screening, we identified the small molecules batefenterol and indacaterol that attenuate the CaM-DDX21 interaction and suppress nascent rRNA synthesis and axon growth in hippocampal neurons. These results unveiled the previously unrecognized role of CaM as a messenger to link the activity-induced Ca2+ influx to the nucleolar events essential for protein synthesis. We thus identified the ability of CaM to transmit information to the nucleoli of neurons in response to stimulation.

Dietary γ-mangostin triggers immunogenic cell death and activates cGAS signaling in acute myeloid leukemia.

Immunogenic cell death (ICD), one of cell-death types through release of damage-associated molecular patterns from dying tumor cells, activates tumor-specific immune response and elicits anti-tumor immunity by traditional radiotherapy and chemotherapy. However, whether natural products could induce ICD in leukemia is not elucidated. Here, we report dietary γ-mangostin eradicates murine primary leukemic cells and prolongs the survival of leukemic mice. As well, it restrains primary leukemic cells and CD34+ leukemic progenitor cells from leukemia patients. Strikingly, γ-mangostin attenuates leukemic cells by inducing ICD as characterized by expression of HSP90B1, ANXA1 and IL1B. Additionally, γ-mangostin accelerates cytoplasmic chromatin fragments generation, promoting DNA damage response, and enhances cGAS activation, leading to up-regulation of chemokines. Meanwhile, it induces HDAC4 degradation and acetylated histone H3 accumulation, which promotes chemokines transcription. Ultimately, CD8+ T cell is activated and recruited by γ-mangostin-induced chemokines in the microenvironment. Our study identifies γ-mangostin triggers ICD and activates cGAS signaling through DNA damage response and epigenetic modification. Therefore, dietary γ-mangostin would act as a potential agent to provoke anti-tumor immunity in the prevention and treatment of leukemia.

A naturally occurring FXR agonist, alisol B 23-acetate, protects against renal ischemia-reperfusion injury.

The ligand-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating renal function. Activation of FXR by its specific agonists exerts renoprotective action in animals with acute kidney injury (AKI). In the present study, we aimed to identify naturally occurring agonists of FXR with potential as therapeutic agents in renal ischemia-reperfusion injury. In vitro and in vivo FXR activation was determined by a dual-luciferase assay, docking analysis, site-directed mutagenesis, and whole kidney transcriptome analysis. Wild-type (WT) and FXR knockout (FXR-/-) mice were used to determine the effect of potential FXR agonist on renal ischemia-reperfusion injury (IRI). We found that alisol B 23-acetate (ABA), a major active triterpenoid extracted from Alismatis rhizoma, a well-known traditional Chinese medicine, can activate renal FXR and induce FXR downstream gene expression in mouse kidney. ABA treatment significantly attenuated renal ischemia-reperfusion-induced AKI in WT mice but not in FXR-/- mice. Our results demonstrate that ABA can activate renal FXR to exert renoprotection against ischemia-reperfusion injury-induced AKI. Therefore, ABA may represent a potential therapeutic agent in the treatment of ischemic AKI.NEW & NOTEWORTHY In the present study, we found that alisol B 23-acetate (ABA), an identified natural farnesoid X receptor (FXR) agonist from the well-known traditional Chinese medicine Alismatis rhizoma, protects against ischemic acute kidney injury (AKI) in an FXR-dependent manner, as reflected by improved renal function, reduced renal tubular apoptosis, ameliorated oxidative stress, and suppressed inflammatory factor expression. Therefore, ABA may have great potential as a novel therapeutic agent in the treatment of AKI in the future.

Comparative efficacy and safety of PD-1/PD-L1 Inhibitors versus platinum-based chemotherapy for the first-line treatment of advanced non-small cell lung cancer: a meta analysis of randomized controlled trials.

OBJECTIVE: The main aim of this study was to systematically evaluate the efficacy and safety of inhibitors of programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials assessing the efficacy of PD-1/PD-L1 inhibitors relative to platinum-based chemotherapy for advanced NSCLC in PubMed, EMBASE, and Cochrane libraries from 2015 to 2020 were searched, along with review of studies at American Society of Clinical Oncology (ASCO) and European society for Medical Oncology (ESMO). Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) and odds ratios (OR) for adverse events (AE) were calculated using STATA and Revman software. RESULTS: PD-1/PD-L1 inhibitors alone or combined with chemotherapy significantly improved OS (HR = 0.82, 95% CI:0.74-0.91, P = 0.01 or HR = 0.74, 95% CI:0.67-0.82, P = 0.001). PD-1/PD-L1 inhibitors alone did not benefit PFS (HR = 0.99, 95% CI: 0.89-1.10, P = 0.892), while combination therapy led to prolonged PFS (HR = 0.61, 95% CI: 0.56-0.67, P < 0.001). Subgroup analysis showed that in NSCLC with PD-L1 ≥ 50%, treatment with PD-1/PD-L1 inhibitors alone significantly improved both PFS and OS. In patients subjected to the combined treatment regimen, we observed significant differences in PFS among groups stratified by PD-L1 expression (p < 0.001), immune drug type (p = 0.029), gender (p = 0.014) and liver metastasis (p = 0.035) and OS among groups stratified by immune drug type (p < 0.001), gender (P = 0.001) and smoking status (P = 0.041). Safety analysis showed that combination therapy increased chemotherapy-induced adverse events (AE), while PD-1/PD-L1 inhibitors alone were associated with a lower incidence of any grade of treatment-related AEs (TRAE). A higher incidence of Grade 3-5 TRAEs and hypothyroidism was observed with PD-1 inhibitors than PD-L1 inhibitors. CONCLUSIONS: First-line treatment of advanced NSCLC with immune monotherapy or immunochemotherapy confers a greater survival benefit than chemotherapy alone. Combination of chemotherapy with PD-1/PD-L1 inhibitors leads to an increase in adverse events, and PD-1 inhibitors offer enhanced survival benefits and fewer adverse events than PD-L1 inhibitors. Remarkably, female patients undergoing combination therapy had longer overall survival than male patients.

Source Tracking and Risk Assessment of Pharmaceutical and Personal Care Products in Surface Waters of Qingdao, China, with Emphasis on Influence of Animal Farming in Rural Areas.

The occurrence and potential sources of pharmaceuticals and personal care products (PPCPs) in surface waters from a large coastal city Qingdao, North China, were investigated. Forty-five compounds were analyzed by high-performance liquid chromatography-tandem mass spectrometry. The results showed that 28 compounds of PPCPs were detected. The most frequently detected compounds were atrazine, clarithromycin, nonylphenol, and bisphenol A with the detection rates > 90%. Paracetamol showed the highest concentration up to 4400 ng/L (mean 152.5 ng/L), followed by ampicillin (max. 2980 ng/L) with the highest mean concentration (229.3 ng/L), iopromide (max. 1744 ng/L, mean 74.5 ng/L), atrazine (max. 1612 ng/L, mean 96.1 ng/L), and bisphenol A (max. 1384 ng/L, mean 78.3 ng/L). The contamination levels and composition profiles of PPCPs along the rivers flowing through rural and urban areas and in seawater showed large spatial variability. Typical source markers and principle component analysis were used to track and differentiate the potential PPCP sources. The emphases of the study were the influence of animal farming in rural areas on PPCP composition profiles and the ecological risk. The results indicated that PPCPs in Qingdao surface water mainly came from three potential sources, i.e., treated wastewater (effluents from WWTPs), untreated wastewater, and nonpoint sources in agricultural areas.

Pharmaceutical and Personal Care Products in Surface Waters from the Inner City of Beijing, China: Influence of Hospitals and Reclaimed Water Irrigation.

Surface waters from five districts in the inner city of Beijing were collected for analysis of 43 target compounds of pharmaceuticals and personal care products (PPCPs) to understand the spatial distribution patterns of different groups of PPCPs in the central urban area of a metropolitan city characterized by many hospitals and public parks. The total concentrations of PPCPs showed large spatial variability, ranging from 71.1 to 2400 ng/L. The x-ray contrast medium iopromide was the compound with the highest concentrations. Pharmaceuticals showed similar spatial distributional patterns with large hospitals. Positive correlations between iopromide and pharmaceuticals were observed. In contrast, in general there is no correlation between iopromide and personal care products. The concentrations of PPCPs in the landscape waters were not high but were characterized by high proportions of acidic, nonsteroidal anti-inflammatory drugs with low or even negative removal efficiencies in the WWTP in Beijing, suggesting that the reclaimed water irrigation can be another source of PPCPs in surface waters in the inner city of Beijing.

The Extent of the Impact of a Fluorochemical Industrial Park in Eastern China on Adjacent Rural Areas.

High levels of perfluoroalkyl substances (PFASs) were observed in rural areas near a fluorochemical industrial park (FCIP) in the Yangtze River Delta region. The concentrations of total PFAS (∑PFASs) in soil, surface water, groundwater, and rainwater were in the range of 0.6-64.6 ng/g dry weight, 15.6-480.9, 4.8-614.6, and 13.4-542.2 ng/L, respectively. PFASs in rainwater and groundwater were higher than in surface water. The influence of the FCIP on rural soils extended to a distance of approximately 4 km based on the changes in PFAS compositions. The impact on surface water is mainly through direct river flow connected with contaminated sources, which may extend farther than 7 km in the case of unrestricted flow but much shorter distance for unconnected rivers. The penetration of PFASs in groundwater aquifers can extend as far as ca. 6 km, while direct water flow is the main transport route for PFASs. The influence radius of the FCIP can be as far as 60 km due to atmospheric precipitation.

Perfluoroalkyl Substances in Water from the Yangtze River and Its Tributaries at the Dividing Point Between the Middle and Lower Reaches.

The Yangtze River drainage basins are China's most important economic development zones and also the locations of several large-scale fluorine chemical industries. In order to reveal the contribution from the tributaries at the dividing point between the middle and lower reaches of the Yangtze River with respect to perfluorinated substances (PFASs), 17 PFAS compounds in surface water, groundwater, and tap water samples were analyzed in the tributary system of the Jiujiang section of the Yangtze River. The total concentrations of PFASs in the surface waters ranged from 7.8 to 586.2 ng/L. High proportion of short-chain compound PFBS in surface waters in Nanchang City, Poyang Lake, and the Yangtze River was observed which is likely of WWTPs' origin.

Current Contamination Status of Perfluoroalkyl Substances in Tapwater from 17 Cities in the Eastern China and Their Correlations with Surface Waters.

The contamination status of perfluoroalkyl substances (PFASs) were investigated in 64 tapwater samples collected from 17 cities and 45 surface water samples from adjacent areas in the eastern China. The total PFAS concentrations in tapwater ranged from 1.4 to 175 ng/L; relatively higher PFAS levels were observed in samples collected from the Yangtze River Delta region, which was similar to the geographical distribution pattern of PFAS levels observed in rivers and lakes. The highest total PFASs in tapwater was found in Changshu, where several fluorine-related industries are located, whereas the lowest was observed in Beijing. Significant positive correlations between PFAS compositions in tap water sample and their source waters were noted. Several industries such as paper, textile, and leather industries may contribute to the contamination of PFASs in tapwater.

Perfluorinated carboxylic and sulphonic acids in surface water media from the regions of Tibetan Plateau: Indirect evidence on photochemical degradation?

Perfluorinated surfactants and repellents are synthetic substances that have found numerous industrial and customer applications. Due to their persistence, at least two groups of these substances-perfluorinated carboxylic acids (PFCAs) and perfluorinated sulfonic acids (PFSAs)-are diffused widely in the environment. It is hypothesized that the Tibetan Plateau, is one of few unique places on the Earth, due to its topography, specifically the vast space and high elevation above sea level, geographic location, climate, high solar radiation, lack of industry, little urbanization and general lack of significant direct sources of pollution. There it is believed possible to gain an insight into atmospheric fate (possible photochemical degradation of higher molecular mass and formation of lower molecular mass PFCAs and PFSAs) of PFASs under un-disturbed environmental conditions. Ultratrace analytical method for PFCAs and PFSAs and use of transportation and field blanks, laboratory blanks and isotopically labelled surrogates for recovery control has allowed the determination of nine perfluorinated carboxylic acids and six perfluorinated sulfonic acids at ultra-trace levels in water based samples from the alpine dimension regions of the Tibetan Plateau, the eastern slope of Minya Konka peak at the eastern edge of the Tibetan Plateau, and also from the city of Chengdu from the lowland of the Sichuan Province in China. The specific compositional pattern of PFCAs and PFSAs and low levels of pollution with those compounds were observed in the central region of the Tibetan Plateau and in the region adjacent to the peaks of Minya Konka in the Eastern Tibetan Plateau. The fingerprint of the compositional pattern of PFCAs and PFSAs in water samples in the central region of the Tibetan Plateau and in the alpine region adjacent to the peaks of Minya Konka in the Eastern Tibetan Plateau may be explained by the result of photochemical degradation with dealkylation of longer chain compounds and formation of shorter chain compounds, which are more resistant to photochemical degradation.

MicroRNA-9 expression is a prognostic biomarker in patients with osteosarcoma.

BACKGROUND: The purpose of the present study was to examine the expression levels of microRNA-9 (miR-9) in osteosarcoma tissues and normal bone tissues, and investigate the relationships between miR-9 expression, clinicopathological features and the prognosis of patients with osteosarcoma. METHODS: The expression levels of miR-9 in osteosarcoma tissues and corresponding non-cancerous tissues were detected using a real-time quantitative assay. Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. RESULTS: Compared to non-cancerous bone tissues, the expression levels of miR-9 in osteosarcoma tissues were significantly elevated (P < 0.001). We found that the expression level of miR-9 was significantly associated with tumor size (P = 0.011), clinical stage (P = 0.009) and distant metastasis (P < 0.001). The Kaplan-Meier curve showed that patients with low miR-9 expression survived significantly longer than patients with high miR-9 expression (P = 0.0017). Multivariate analysis suggested that miR-9 expression level (P = 0.002) is an independent prognostic factors for overall survival. CONCLUSIONS: The findings of our study suggest that increased miR-9 expression has a strong correlation with the aggressive progression of osteosarcoma and its overexpression is a statistically significant risk factor affecting overall survival, suggesting that increased miR-9 expression could be a valuable marker of tumor progression and for prognosis of osteosarcoma.

Relightable Detailed Human Reconstruction from Sparse Flashlight Images.

We present a lightweight system for reconstructing human geometry and appearance from sparse flashlight images. Our system produces detailed geometry including garment wrinkles and surface reflectance, which are exportable for direct rendering and relighting in traditional graphics pipelines. By capturing multi-view flashlight images using a consumer camera equipped with an co-located LED (e.g., a cell phone), we obtain view-specific shading cues that aid in the determination of surface orientation and help disambiguate between shading and material. To enable the reconstruction of geometry and appearance from sparse-view flashlight images, we integrate a pre-trained model into a differentiable physics-based rendering framework. As the learned image features from synthetic data cannot accurately reflect the shading features on real images, which is crucial for the high-quality reconstruction of geometry details and appearance, we propose to jointly optimize the image feature extractor with two MLPs for SDF and BRDF prediction using the differentiable physics-based rendering. Compared with existing methods for relightable human reconstruction, our system is able to produce high-fidelity 3D human models with more accurate geometry and appearance under the same condition. Our code and data are available at http://github.com/Jarvisss/Relightable_human_recon.

Effects of intrinsic defects on methanthiol monolayers on Cu(111): a density functional theory study.

Density functional theory calculations were used to examine the effects of intrinsic surface defects of Cu(111) on the adsorption of methylthiol (CH3SH). The examination covers both the initial non-dissociative adsorption and the subsequent dissociation reaction pathways to form intermediate and final reaction products. By comparing the most probable adsorption structures likely formed after the adsorption of CH3SH on Cu(111) with and without the presence of adatoms (Cu(ad)) and vacancies, this computational work offers new insights about the geometry and thermodynamic stability of these structures. Particularly, it reveals a new type of surface complexes having two CH3S bonding to one Cu(ad) (referred therein as CH3S-Cu(ad)-CH3S). In addition, this work also yields new reaction dynamics results on transition states and activation barriers. The results reveal that the presence of Cu(ad) indeed significantly changes the kinetics of adsorption and dissociation of CH3SH on Cu(111). The most kinetically favorable reaction pathway turns out to be that involving the formation of a special surface complex formed by one Cu(ad) plus two CH3S fragments from the dissociation of CH3SH, with the two S atoms located at the bridge sites of Cu(111). Finally, this work also gives simulated scanning tunneling microscopic images for the most important adsorption species in the course of the transition from CH3SH∕Cu(111) to CH3S∕Cu(111), which may stimulate future experimental studies of self-assembled monolayers on practical metal substrates such as thiols on copper.

Comparison of isocentric C-arm 3-dimensional navigation and conventional fluoroscopy for C1 lateral mass and C2 pedicle screw placement for atlantoaxial instability.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of the study was to compare the precision of C1 lateral mass and C2 pedicle (C1LM-C2P) screw fixation for atlantoaxial instability using the isocentric C-arm 3-dimensional (Iso-C 3D) navigation versus conventional fluoroscopy. SUMMARY OF BACKGROUND DATA: The Iso-C 3D navigation has been widely used in spinal surgeries in recent years. The advantages of this navigation system compared with conventional fluoroscopy in C1LM-C2P screw fixation for atlantoaxial instability are not known. METHODS: Twenty-four patients diagnosed with atlantoaxial instability were treated with C1LM-C2P screw fixation in this study. The navigation group included 12 patients and the other 12 patients were in the conventional fluoroscopy group. The clinical and radiographic results were recorded and compared between the 2 groups. Patients were followed up with clinical examination and radiographs at a mean of 10.8 months. RESULTS: There were no significant differences between groups in the mean age, gender, and causes of atlantoaxial instability. Operative time was 130 ± 5.4 minutes in the navigation group versus 145 ± 6.5 minutes in the conventional fluoroscopy group. The mean blood loss in the navigation group was 304.2 ± 47.9 mL relative to 462.5 ± 55.4 mL in the conventional fluoroscopy group. The radiation time was significantly reduced using 3D navigation (47.5 ± 1.5 s vs. 64.0 ± 3.0 s). 95.8% (46/48) of 3D navigated screws and 83.3% (40/48) of fluoroscopy screws had no pedicle perforation. Each patient showed evidence of solid fusion after 6 months on cervical plain radiographies. CONCLUSION: On comparing the 2 imaging techniques, it was found that using Iso-C 3D navigation can significantly improve the accuracy of screw placement and decrease intraoperative fluoroscopic time and blood loss. This study demonstrates that Iso-C 3D navigation is a safe and effective means of guiding C1LM-C2P screw fixation for atlantoaxial instability.

Image-Based OA-Style Paper Pop-Up Design via Mixed-Integer Programming.

Origami architecture (OA) is a fascinating papercraft that involves only a piece of paper with cuts and folds. Interesting geometric structures 'pop up' when the paper is opened. However, manually designing such a physically valid 2D paper pop-up plan is challenging since fold lines must jointly satisfy hard spatial constraints. Existing works on automatic OA-style paper pop-up design all focused on how to generate a pop-up structure that approximates a given target 3D model. This article presents the first OA-style paper pop-up design framework that takes 2D images instead of 3D models as input. Our work is inspired by the fact that artists often use 2D profiles to guide the design process, thus benefited from the high availability of 2D image resources. Due to the lack of 3D geometry information, we perform novel theoretic analysis to ensure the foldability and stability of the resultant design. Based on a novel graph representation of the paper pop-up plan, we further propose a practical optimization algorithm via mixed-integer programming that jointly optimizes the topology and geometry of the 2D plan. We also allow the user to interactively explore the design space by specifying constraints on fold lines. Finally, we evaluate our framework on various images with interesting 2D shapes. Experiments and comparisons exhibit both the efficacy and efficiency of our framework.

Adaptive Optimization Algorithm for Resetting Techniques in Obstacle-Ridden Environments.

Redirected Walking (RDW) algorithms aim to impose several types of gains on users immersed in Virtual Reality and distort their walking paths in the real world, thus enabling them to explore a larger space. Since collision with physical boundaries is inevitable, a reset strategy needs to be provided to allow users to reset when they hit the boundary. However, most reset strategies are based on simple heuristics by choosing a seemingly suitable solution, which may not perform well in practice. In this article, we propose a novel optimization-based reset algorithm adaptive to different RDW algorithms. Inspired by the approach of finite element analysis, our algorithm splits the boundary of the physical world by a set of endpoints. Each endpoint is assigned a reset vector to represent the optimized reset direction when hitting the boundary. The reset vectors on the edge will be determined by the interpolation between two neighbouring endpoints. We conduct simulation-based experiments for three RDW algorithms with commonly used reset algorithms to compare with. The results demonstrate that the proposed algorithm significantly reduces the number of resets.

Minimally invasive open reduction of greater tuberosity fractures by a modified suture bridge procedure.

BACKGROUND: Most greater tuberosity fractures can be treated without surgery but some have a poor prognosis. The surgical procedures for avulsion fractures of the humeral greater tuberosity include screw fixation, suture anchor fixation, and plate fixation, all of which have treatment-associated complications. To decrease surgical complications, we used a modified suture bridge procedure under direct vision and a minimally invasive small incision to fix fractures of the greater tuberosity of the humerus. AIM: To investigate the clinical efficacy and outcomes of minimally invasive modified suture bridge open reduction of greater tuberosity evulsion fractures. METHODS: Sixteen patients diagnosed between January 2016 and January 2019 with an avulsion-type greater tuberosity fracture of the proximal humerus and treated by minimally invasive open reduction and modified suture bridges with anchors were studied retrospectively. All were followed up by clinical examination and radiographs at 3 and 6 wk, 3, 6 and 12 mo after surgery, and thereafter every 6 mo. Outcomes were assessed preoperatively and postoperatively by a visual analog scale (VAS), the University of California Los Angeles (UCLA) shoulder score, the American Shoulder and Elbow Surgeon score (ASES), and range of motion (ROM) for shoulders. RESULTS: Seven men and nine women, with an average age of 44.94 years, were evaluated. The time between injury and surgery was 1-2 d, with an average of 1.75 d. The mean operation time was 103.1 ± 7.23 min. All patients achieved bone union within 3 mo after surgery. VAS scores were significantly decreased (P = 0.002), and the mean degrees of forward elevation (P = 0.047), mean degrees of abduction (P = 0.035), ASES score (P = 0.092) were increased at 3 wk. The UCLA score was increased at 6 wk (P = 0.029) after surgery. The average degrees of external rotation and internal rotation both improved at 3 mo after surgery (P = 0.012 and P = 0.007, respectively). No procedure-related deaths or incision-related superficial or deep tissue infections occurred. CONCLUSION: Modified suture bridge was effective for the treatment of greater tuberosity evulsion fractures, was easier to perform, and had fewer implants than other procedures.

Pharmacological prevention of renal ischemia-reperfusion injury in a rat model.

INTRODUCTION: Renal ischemia-reperfusion injury (IRI) can lead to significant morbidity and mortality. It remains a leading cause of acute kidney injury and is therefore an important issue in trauma and renal transplant surgery. Various pharmaceutical agents have been used in an attempt to dampen the harmful effects of IRI but few have been shown to be useful clinically. Riluzole, Lidocaine and Lamotrigine have been demonstrated to show anti-ischaemic properties in other organs; however, their use has not been tested in the kidneys. We investigated Riluzole, Lidocaine and Lamotrigine for their preventive effects of renal IRI using a rat model. METHODS: Winstar rats (n = 48) were divided into four groups (n = 12 per group)-three treatment groups and one control group. Riluzole, Lidocaine and Lamotrigine were given prior to renal ischemia only (IO) or IRI. The degree of ischemia was measured by glutathione levels and a TUNEL assay was used to measure DNA fragmentation. RESULTS: Riluzole, Lidocaine and Lamotrigine pre-treatment each resulted in statistically higher glutathione levels compared to controls (P = 0.002; P = 0.007 and P = 0.005, respectively). Riluzole and Lidocaine were also effective at preventing depletion of glutathione following IO (P = 0.007 and P = 0.014 respectively), while Lamotrigine was ineffective in IO (P = 0.71). The degree of DNA fragmentation seen on the TUNEL assay was markedly reduced in all three-drug groups in both IO and IRI. DISCUSSION: Riluzole, Lidocaine and Lamotrigine all have anti-ischaemic effects in the rat kidney and can have potential therapeutic implications.

Fast 3D Indoor Scene Synthesis by Learning Spatial Relation Priors of Objects.

We present a framework for fast synthesizing indoor scenes, given a room geometry and a list of objects with learnt priors. Unlike existing data-driven solutions, which often learn priors by co-occurrence analysis and statistical model fitting, our method measures the strengths of spatial relations by tests for complete spatial randomness (CSR), and learns discrete priors based on samples with the ability to accurately represent exact layout patterns. With the learnt priors, our method achieves both acceleration and plausibility by partitioning the input objects into disjoint groups, followed by layout optimization using position-based dynamics (PBD) based on the Hausdorff metric. Experiments show that our framework is capable of measuring more reasonable relations among objects and simultaneously generating varied arrangements in seconds compared with the state-of-the-art works.

The Treatment of Subtrochanteric Fracture with Reversed Contralateral Distal Femoral Locking Compression Plate (DF-LCP) Using a Progressive and Intermittent Drilling Procedure in Three Osteopetrosis Patients.

OBJECTIVE: To describe the application of reversed contralateral distal femoral locking compression plate (DF-LCP) inserted through a progressive and intermittent drilling procedure in the treatment of osteopetrotic subtrochanteric fracture (OSF). METHODS: Three patients (one male and two females with an average age of 45.33 ± 11.09 years) with OSF hospitalized between September 2015 and September 2020, were included in this present study. Lateral approach was applied in all patients who accepted open reduction and internal fixation (ORIF) with a reversed contralateral DF-LCP inserted through a progressive and intermittent drilling procedure. The operation time and intraoperative blood loss were recorded to evaluate the efficiency of this surgical method. Physical examination and imaging examination of the fracture site were used to evaluate the fracture union status, the position and stability of the implant, and the alignment of the injured limb at 1, 3, 6, and 12 months after operation, then a subsequent visit was conducted at least once a year. Harris Hip Score (HHS) was used to evaluate the hip joint function at 6 and 12 months after operation. RESULTS: The average operation time was 140 ± 21.60 min (110, 160, and 150 min); The average intraoperative blood loss was about 333.33 ± 23.57 ml (300, 350, and 350 ml). The average follow-up time was 22.33 ± 7.41 months (29, 26, and 12 months). All patients achieved bone union with an average time of 6.67 ± 0.94 months (6, 8, and 6 months). At the time of 6 months after operation, case 1 and 3 were almost pain-free and could walk with full weight bearing while case 2 could walk only with partial weight bearing using a crutch. The HHS scores of cases 1, 2, and 3 were 84/100, 74/100, and 92/100, respectively. At the follow-up at 12 months after operation, the HHS score improved to 91/100, 81/100, and 96/100, respectively. The contralateral incomplete old subtrochanteric fracture was deteriorated in case 1 at 26 months after operation. After 3 months of limited weight bearing using a crutch, bone union was verified in radiograph imaging. Fresh contralateral subtrochanteric fracture occurred in case 2 at 26 months after operation, which was treated using a similar surgical approach, and its clinical outcome is under follow-up. Moreover, no perioperative complications including operation-related death, vascular/nerve injury, deep venous thrombosis, pulmonary embolism, and incision infection, and long-term complications involving malunion, nonunion, implant failure, ankylosis, heterotopic ossification, osteonecrosis, and osteomyelitis were identified. CONCLUSION: The application of reversed contralateral DF-LCP in OSF is practicable and reliable. Progressive and intermittent drilling is a safe and efficient method for implant insertion in this complicated situation.