Construction of a myoglobin scaffold-based biocatalyst for the biodegradation of sulfadiazine and sulfathiazole.

Sulfonamide antibiotics, a family of broad-spectrum antibiotic drugs, are increasingly used in aquaculture and are frequently detected in aquatic environments. This poses a potential threat to organisms and may cause the evolution of antimicrobial resistance. Therefore, it is important to develop an environmentally friendly and efficient biocatalyst to degrade sulfonamides (SAs) such as sulfadiazine (SD) and sulfathiazole (ST). Here, we realized the direct and efficient degradation of SD and ST using a hydrogen peroxide-dependent artificial catalytic system based on myoglobin (Mb). The arrangements of amino acids at positions 29, 43, 64, and 68 were found to influence catalytic activity. An L29H/H64D/V68I myoglobin mutant showed the best catalytic efficiency (i.e., kcat/Km = 720.42 M-1 s-1) against SD. Next, mutant H64D/V68I showed the best degradation rate against SD (i.e., 91.45 ± 0.16%). Moreover, L29H/H64D/V68I Mb was found to efficiently catalyze ST oxidation (kcat/Km = 670.08 M-1 s-1), while H64D/V68I had the best degradation rate against ST (i.e., 99.45 ± 0.23%). Our results demonstrate that SAs can be efficiently degraded by artificial peroxygenases constructed using a myoglobin scaffold. This therefore provides a simple and economical method for the biodegradation of SD and ST.

Gli1 marks a sentinel muscle stem cell population for muscle regeneration.

Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Although recent studies have started to characterize the heterogeneity of MuSCs, whether a subset of cells with distinct exists within MuSCs remains unanswered. Here, we find that a population of MuSCs, marked by Gli1 expression, is required for muscle regeneration. The Gli1+ MuSC population displays advantages in proliferation and differentiation both in vitro and in vivo. Depletion of this population leads to delayed muscle regeneration, while transplanted Gli1+ MuSCs support muscle regeneration more effectively than Gli1- MuSCs. Further analysis reveals that even in the uninjured muscle, Gli1+ MuSCs have elevated mTOR signaling activity, increased cell size and mitochondrial numbers compared to Gli1- MuSCs, indicating Gli1+ MuSCs are displaying the features of primed MuSCs. Moreover, Gli1+ MuSCs greatly contribute to the formation of GAlert cells after muscle injury. Collectively, our findings demonstrate that Gli1+ MuSCs represents a distinct MuSC population which is more active in the homeostatic muscle and enters the cell cycle shortly after injury. This population functions as the tissue-resident sentinel that rapidly responds to injury and initiates muscle regeneration.

From a Collapse-Prone, Insulating Ni-MOF-74 Analogue to Crystalline, Porous, and Electrically Conducting PEDOT@MOF Composites.

Electrically conductive porous metal-organic frameworks (MOFs) show great promise in helping advance electronics and clean energy technologies. However, large porosity usually hinders long-range charge transport, an essential criterion of electrical conductivity, underscoring the need for new strategies to combine these two opposing features and realize their diverse potentials. All previous strategies to boost the conductivity of porous MOFs by introducing redox-complementary guest molecules, conducting polymers, and metal nanoparticles have led to a significant loss of frameworks' porosity and surface areas, which could be otherwise exploited to capture additional guests in electrocatalysis and chemiresistive sensing applications. Herein, we demonstrate for the first time that the in situ oxidative polymerization of preloaded 3,4-ethylenedioxythiophene (EDOT) monomers into the polyethylenedioxythiophene (PEDOT) polymer inside the hexagonal cavities of an intrinsically insulating Ni2(NDISA) MOF-74 analogue (NDISA = naphthalenediimide N,N-disalicylate), which easily collapses and becomes amorphous upon drying, simultaneously enhanced the crystallinity, porosity, and electrical conductivity of the resulting PEDOT@Ni2(NDISA) composites. At lower PEDOT loading (∼22 wt %), not only did the Brunauer-Emmett-Teller surface area of the PEDOT@Ni2(NDISA) composite (926 m2/g) more than double from that of evacuated pristine Ni2(NDISA) (387 m2/g), but also its electrical conductivity (1.1 × 10-5 S/cm) soared 105 times from that of the pristine MOF, demonstrating unprecedented dual benefits of our strategy. At higher PEDOT loading (≥33 wt %), the electrical conductivity of Ni2(NDISA)⊃PEDOT composites further increased modestly (10-4 S/cm), but their porosity dropped precipitously as large amounts of PEDOT filled up the hexagonal MOF channels. Thus, our work presents a simple new strategy to simultaneously boost the structural stability, porosity, and electrical conductivity of intrinsically insulating and collapse-prone MOFs by introducing small amounts of conducting polymers that can not only reinforce the MOF scaffolds and prevent them from collapsing but also help create a much coveted non-native property by providing charge carriers and charge transport pathways.

Paroxetine Attenuates Chondrocyte Pyroptosis and Inhibits Osteoclast Formation by Inhibiting NF-κB Pathway Activation to Delay Osteoarthritis Progression.

Background: Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated inflammation and NLRP3-induced pyroptosis play essential roles in the development of OA. In this study, we examine whether paroxetine can inhibit pyroptosis and reduce osteoclast formation, thereby delaying the destruction of knee joints. Methods: We employed high-density cultures, along with quantitative polymerase chain reactions and Western blotting techniques, to investigate the effects of paroxetine on extracellular matrix synthesis and degradation. The expression levels of NF-κB and pyroptosis-related signaling pathway proteins were examined by Western blotting and immunofluorescence. Furthermore, the impact of paroxetine on RANKL-induced osteoclast formation was evaluated through TRAP staining and F-actin ring fluorescence detection. To investigate the role of paroxetine in vivo, we constructed a mouse model with destabilization of the medial meniscus (DMM) surgery. Safranin O-Fast Green staining, Hematoxylin-Eosin staining, and immunohistochemistry were conducted to observe the extent of knee joint cartilage deformation. In addition, TRAP staining was used to observe the formation of osteoclasts in the subchondral bone. Results: In the in vitro experiments with ATDC5, paroxetine treatment attenuated IL-1ß-induced activation of the pyroptosis-related pathway and suppressed extracellular matrix catabolism by inhibiting the NF-kB signaling pathway. In addition, paroxetine treatment decreased the expression of RANKL-induced osteoclast marker genes and reduced osteoclast formation. In animal experiments conducted in vivo, mice treated with paroxetine exhibited thicker knee cartilage with a smoother surface compared to the DMM group. Additionally, the formation of osteoclasts in the subchondral bone was reduced in the paroxetine-treated mice. Further analysis revealed that paroxetine treatment played a role in preserving the balance of the extracellular matrix and delaying knee joint degeneration. Conclusion: Paroxetine can inhibit pyroptosis and reduce osteoclast formation via inhibiting the NF-κB signaling pathway, suggesting that it may have therapeutic effects in patients with OA.

TT U-Net: Temporal Transformer U-Net for Motion Artifact Reduction Using PAD (Pseudo All-Phase Clinical-Dataset) in Cardiac CT.

Involuntary motion of the heart remains a challenge for cardiac computed tomography (CT) imaging. Although the electrocardiogram (ECG) gating strategy is widely adopted to perform CT scans at the quasi-quiescent cardiac phase, motion-induced artifacts are still unavoidable for patients with high heart rates or irregular rhythms. Dynamic cardiac CT, which provides functional information of the heart, suffers even more severe motion artifacts. In this paper, we develop a deep learning based framework for motion artifact reduction in dynamic cardiac CT. First, we build a PAD (Pseudo All-phase clinical-Dataset) based on a whole-heart motion model and single-phase cardiac CT images. This dataset provides dynamic CT images with realistic-looking motion artifacts that help to develop data-driven approaches. Second, we formulate the problem of motion artifact reduction as a video deblurring task according to its dynamic nature. A novel TT U-Net (Temporal Transformer U-Net) is proposed to excavate the spatiotemporal features for better motion artifact reduction. The self-attention mechanism along the temporal dimension effectively encodes motion information and thus aids image recovery. Experiments show that the TT U-Net trained on the proposed PAD performs well on clinical CT scans, which substantiates the effectiveness and fine generalization ability of our method. The source code, trained models, and dynamic demo will be available at https://github.com/ivy9092111111/TT-U-Net.

C-DTW for Human Action Recognition Based on Nanogenerator.

Sensor-based human action recognition (HAR) is considered to have broad practical prospects. It applies to wearable devices to collect plantar pressure or acceleration information at human joints during human actions, thereby identifying human motion patterns. Existing related works have mainly focused on improving recognition accuracy, and have rarely considered energy-efficient management of portable HAR systems. Considering the high sensitivity and energy harvesting ability of triboelectric nanogenerators (TENGs), in this research a TENG which achieved output performance of 9.98 mW/cm2 was fabricated using polydimethylsiloxane and carbon nanotube film for sensor-based HAR as a wearable sensor. Considering real-time identification, data are acquired using a sliding window approach. However, the classification accuracy is challenged by quasi-periodic characteristics of the intercepted sequence. To solve this problem, compensatory dynamic time warping (C-DTW) is proposed, which adjusts the DTW result based on the proportion of points separated by small distances under DTW alignment. Our simulation results show that the classification accuracy of C-DTW is higher than that of DTW and its improved versions (e.g., WDTW, DDTW and softDTW), with almost the same complexity. Moreover, C-DTW is much faster than shapeDTW under the same classification accuracy. Without loss of generality, the performance of the existing DTW versions can be enhanced using the compensatory mechanism of C-DTW.

SERS combined with the difference in bacterial extracellular electron transfer ability to distinguish Shewanella.

Shewanella plays an important role in geochemical cycle, biological corrosion, bioremediation and bioenergy. The development of methods for identifying Shewanella can provide technical support for its rapid screening, in-depth research into its extracellular respiratory mechanism and its application in ecological environment remediation. As a tool for microbial classification, identification and detection, Surface-enhanced Raman scattering (SERS) has high feasibility and application potential. In this work, bio-synthesized silver nanoparticles (AgNPs) were used as SERS substrates to effectively distinguish different types of Shewanella bacteria based on the difference in bacterial extracellular electron transfer (EET) ability. AgNPs were combined with the analyzed bacteria to prepare "Bacteria-AgNPs" SERS samples, which can strongly enhance the Raman signal of the target bacteria and reliably obtain spatial information of different molecular functional groups of each bacteria. Our developed approach can effectively distinguish between non-metal reducing and metal-reducing bacteria, and can further distinguish the three subspecies of Shewanella (Shewanella oneidensis MR-1, Shewanella decolorationis S12, and Shewanella putrefaciens SP200) at the genus and species level. The Raman signal enhancement is presumably caused by the excitation of local surface plasma (LSP) and the enhancement of surrounding electric field. Therefore, our developed method can achieve interspecific and intraspecies discrimination of bacteria. The proposed method can be extended to distinguish other metal-reducing bacteria, and the novel SERS active substrates can be developed for practical applications.

A Double-Layer Vehicle Speed Prediction Based on BPNN-LSTM for Off-Road Vehicles.

The accurate prediction of vehicle speed is crucial for the energy management of vehicles. The existing vehicle speed prediction (VSP) methods mainly focus on road vehicles and rarely on off-road vehicles. In this paper, a double-layer VSP method based on backpropagation neural network (BPNN) and long short-term memory (LSTM) for off-road vehicles is proposed. First of all, considering the motion characteristics of off-road vehicles, the VSP problem is established and the relationship between the variables in the problem is carefully analyzed. Then, the double-layer VSP framework is presented, which consists of speed prediction and information update layers. The speed prediction layer established by using LSTM is to predict vehicle speed in the horizon, and the information update layer built by BPNN is to update the prediction information. Finally, with the help of mining truck and loader operation scenarios, the proposed VSP method is compared with the analytical method, BPNN prediction method, and recurrent neural network (RNN) prediction method in terms of speed prediction accuracy. The results show that, under the premise of ensuring the real-time prediction performance, the average prediction error of the proposed BPNN-LSTM prediction method under two operation scenarios reduces by 48.14%, 35.82% and 30.09% compared with the other three methods, respectively. The proposed speed prediction method provides a new solution for predicting the speed of off-road vehicles, effectively improving the speed prediction accuracy.

Perioperative Clinical Features and Long-term Prognosis After Oblique Lateral Interbody Fusion (OLIF), OLIF With Anterolateral Screw Fixation, or OLIF With Percutaneous Pedicle Fixation: A Comprehensive Treatment Strategy for Patients With Lumbar Degenerative Disease.

OBJECTIVE: To compare the efficacy of oblique lateral interbody fusion (OLIF), OLIF combined with anterolateral screw fixation (OLIF-AF), and OLIF combined with percutaneous pedicle screw fixation (OLIF-PF) in the treatment of single-level or 2-level degenerative lumbar disease. METHODS: Between January 2017 and 2021, 71 patients were treated with OLIF and combined OLIF. The demographic data, clinical outcomes, radiographic outcomes, and complications were compared among the 3 groups. RESULTS: The operative time and intraoperative blood loss in the OLIF (p<0.05) and OLIF-AF (p<0.05) groups were lower than in the OLIF-PF group. Posterior disk height improvement in the OLIF-PF group was better than in the OLIF (p<0.05) and OLIF-AF (p<0.05) groups. In terms of foraminal height (FH), the OLIF-PF group was significantly better than the OLIF group (p<0.05), but there was no significant difference between the OLIF-PF and OLIF-AF groups (p>0.05) or between the OLIF and OLIF-AF groups (p>0.05). There were no significant differences in fusion rates, the incidence of complications, lumbar lordosis, anterior disc height, and cross-sectional area among the 3 groups (p>0.05). The OLIF-PF group had significantly lower rates of subsidence than the OLIF group (p<0.05). CONCLUSION: OLIF remains a viable option with similar patient-reported outcomes and fusion rates compared with surgeries that include lateral and posterior internal fixation while greatly reducing the financial burden, intraoperative time, and intraoperative blood loss. OLIF has a higher subsidence rate than lateral and posterior internal fixation, but most subsidence is mild and has no adverse effect on clinical and radiographic outcomes.

Chemodivergent Tandem Radical Cyclization of Alkene-Substituted Quinazolinones: Rapid Access to Mono- and Di-Alkylated Ring-Fused Quinazolinones.

Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.

PD184352 exerts anti-inflammatory and antioxidant effects by promoting activation of the Nrf2/HO-1 axis.

Osteoarthritis (OA) is a disabling joint disease characterized by cartilage degeneration. Reactive oxygen species (ROS)-induced oxidative stress is an important cause of early chondrocyte death. For this reason, we investigated PD184352, a small molecule inhibitor with potential anti-inflammatory and antioxidant activity. We evaluated the protective effect of PD184352 against destabilized medial meniscus (DMM)-induced OA in mice. The knee joints of the PD184352-treated group had higher Nrf2 expression and milder cartilage damage. Moreover, in in vitro experiments, PD184352 suppressed IL-1ß-induced NO, iNOS, PGE2 production, and attenuated pyroptosis. PD184352 treatment promoted antioxidant protein expression and reduced the accumulation of ROS by activating the Nrf2/HO-1 axis. Finally, the anti-inflammatory and antioxidant effects of PD184352 were shown to be partially dependent on Nrf2 activation. Our study reveals the potential role of PD184352 as an antioxidant and provides a new strategy for OA treatment.

Artificial optoelectronic spiking neuron based on a resonant tunnelling diode coupled to a vertical cavity surface emitting laser.

Excitable optoelectronic devices represent one of the key building blocks for implementation of artificial spiking neurons in neuromorphic (brain-inspired) photonic systems. This work introduces and experimentally investigates an opto-electro-optical (O/E/O) artificial neuron built with a resonant tunnelling diode (RTD) coupled to a photodetector as a receiver and a vertical cavity surface emitting laser as a transmitter. We demonstrate a well-defined excitability threshold, above which the neuron produces optical spiking responses with characteristic neural-like refractory period. We utilise its fan-in capability to perform in-device coincidence detection (logical AND) and exclusive logical OR (XOR) tasks. These results provide first experimental validation of deterministic triggering and tasks in an RTD-based spiking optoelectronic neuron with both input and output optical (I/O) terminals. Furthermore, we also investigate in simulation the prospects of the proposed system for nanophotonic implementation in a monolithic design combining a nanoscale RTD element and a nanolaser; therefore demonstrating the potential of integrated RTD-based excitable nodes for low footprint, high-speed optoelectronic spiking neurons in future neuromorphic photonic hardware.

How Do Repeated Viewings in Forest Landscapes Influence Young People's Visual Behaviors and Cognitive Evaluations?

BACKGROUND: With the spread of the COVID-19 epidemic, it has gradually become normal to periodically visit and enjoy forest landscape resources in the suburbs of cities. For designers and managers of forest landscapes, exploring change in the visual behaviors and cognitive evaluations of people who repeatedly view forest landscapes and the characteristics of this change will aid the design and sustainable utilization of forest landscape resources in the suburbs of cities. PURPOSE: From the perspective of users' preferences for forest landscape space, this study explored the changes in visual behavior characteristics and psychological preference characteristics for individuals who repeatedly view forest landscapes and their drivers under different preferences. METHODS: This study collected data from 52 graduate and undergraduate students. We used a difference test to compare the differences in the visual behavior coincidence degree and the changes in psychological evaluations; a descriptive statistical analysis to explore young peoples' likes and dislikes of landscape elements; and Spearman correlation analysis to explore the correlation between the psychological evaluations and visual behaviors. MAIN RESULTS: 1. At the second viewing, the participants' regression behavior tended to decrease for various spaces, and they were more inclined to view areas that they had not viewed before. In addition, at the second viewing, the degree of fixation behavior coincidence was generally low, and there were obvious differences across spaces; 2. The participants' feature evaluations and comprehensive evaluations for landscapes did not change significantly with their increased familiarity with the spaces; 3. There was a significant positive correlation between the participants' psychological evaluations of landscape stimuli and the degree of fixation coincidence when viewing the spaces, among which the rate of distant clarity and the degree of fixation behavior coincidence were significantly and positively correlated. Meanwhile, at the second viewing, the number of favorite elements in the lookout space, which belongs to high-preference spaces, noticeably increased.

Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways.

OBJECTIVES: Limonin has received significant attention due to its multiple biological effects, intervertebral disc degeneration (IDD) is also of interest due to the high prevalence of this disease. In this study, we determined the effects of limonin on IDD and the underlying mechanism of action to find novel ways to treat IDD. METHODS: An IL-1ß-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and necroptosis pathways and alterations in the extracellular matrix specific within the disc. KEY FINDINGS: Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model. CONCLUSIONS: Limonin could potentially delay IDD by inhibiting NP cell necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD.

Wetland Park Planning and Management Based on the Valuation of Ecosystem Services: A Case Study of the Tieling Lotus Lake National Wetland Park (LLNWP), China.

The valuation of wetland ecosystem services and the construction of environmental landscapes are generally recognized as contributing to the sustainable development of human wellbeing. The valuation of ecosystem services plays an important role in planning for the recovery of degraded wetlands and in urban wetland park management; however, the role of the valuation of ecosystem services is always ignored. To bring more intuitive awareness to the importance of the ecological functions of wetlands and to rationally plan wetland parks, the Lotus Lake National Wetland Park (LLNWP), an urban wetland park in Northeast China, was selected as the study area. We referred to the millennium ecosystem assessment (MA) method and calculated the valuation of this park using the market value, benefit transfer, shadow engineering, carbon tax, and travel cost. ArcGIS was used for remote sensing interpretation. The research results were as follows. LLNWP was classified under seven types of land-use. The functions of the ecosystem services included provisioning, regulating, supporting, and cultural services, and their total value in LLNWP was 11.68×108 CNY. Regarding the per-unit area value of the ecological service functions of different land types, it was found that forest swamp > herbaceous swamp > artificial wetland > permanent river > floodplain wetland. Combined with the characteristics of the functions of its ecosystem's services, LLNWP was divided into ecological and socio-cultural functions. Then, according to the main service functions of the different land types, we propose that the space in LLNWP can be reused, and proposal planning and management suggestions can be made with the aim of preserving the basic functions.

How Does the Experience of Forest Recreation Spaces in Different Seasons Affect the Physical and Mental Recovery of Users?

BACKGROUND: In recent years, increasing attention has been given to the recovery effect of the forest environment on physical and mental health. Therefore, providing users with a high-quality forest landscape space is a very important research topic for forest landscape designers and forest resource managers. MAIN PURPOSE: From the perspective of different seasons, this study explores the differences in landscape perceptions and physical and mental recovery of users when they experience different forest recreation spaces and the interactions between them. METHODS: First, this study used virtual reality video experience and questionnaires for participants. Then, the paired-samples t test, one-way ANOVA and the independent-samples t test were used for statistical analysis. Finally, we also used structural equation models to analyze the relationship between landscape perception and recovery. MAIN RESULTS: (1) The restoration effect and perception of forest recreation spaces on people are influenced by space types and seasonal factors. (2) People's restoration from forest environments is a gradual process from spatial cognition to emotional response. (3) The perception of the natural attributes and form of the recreation space plays a key role in the restorative effect of the environment to people, while the natural form is more important in spring than autumn. Based on the above conclusions, we suggest that the characteristic factors of the landscape environment and their different restoration effects for users in different dimensions should be considered when planning forest recreation space.

The role of climate, vegetation, and soil factors on carbon fluxes in Chinese drylands.

Drylands dominate the trend and variability of the land carbon (C) sink. A better understanding of the implications of climate-induced changes in the drylands for C sink-source dynamics is urgently needed. The effect of climate on ecosystem C fluxes (gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem productivity (NEP)) in drylands has been extensively explored, but the roles of other concurrently changing factors, such as vegetation conditions and nutrient availability, remain unclear. We used eddy-covariance C-flux measurements from 45 ecosystems with concurrent information on climate (mean annual temperature (MAT) and mean annual precipitation (MAP)), soil (soil moisture (SM) and soil total nitrogen content (soil N)), and vegetation (leaf area index (LAI) and leaf nitrogen content (LNC)) factors to assess their roles in C fluxes. The results showed that the drylands in China were weak C sinks. GPP and ER were positively correlated with MAP, while they were negatively correlated with MAT. NEP first decreased and then increased with increasing MAT and MAP, and 6.6 °C and 207 mm were the boundaries for the NEP response to MAT and MAP, respectively. SM, soil N, LAI, and MAP were the main factors affecting GPP and ER. However, SM and LNC had the most important influence on NEP. Compared with climate and vegetation factors, soil factors (SM and soil N) had a greater impact on C fluxes in the drylands. Climate factors mainly affected C fluxes by regulating vegetation and soil factors. To accurately estimate the global C balance and predict the response of ecosystems to environmental change, it is necessary to fully consider the discrepant effects of climate, vegetation, and soil factors on C fluxes, as well as the cascade relationships between different factors.

Anatomical and Biomechanical Stability of Single/Double Screw-Cancellous Bone Fixations of Regan-Morry Type III Ulnar Coronoid Fractures in Adults: CT Measurement and Finite Element Analysis.

OBJECTIVE: At present, it is still uncertain whether single screw has the same stability as double screws in the treatment of ulnar coronal process basal fracture (Regan-Morry type III). So, we aimed to compare the pull-out force and anti-rotation torque of anterior single/double screw-cancellous bone fixation (aSSBF, aDSBF) in this fracture, and further study the influencing factors on anatomical and biomechanical stability of smart screw internal fixations. METHODS: A total of 63 adult volunteers with no history of elbow injury underwent elbow CT scanning with associated three-dimensional reconstruction that enabled the measurements of bone density and fixed length of the proximal ulna and coronoid. The models of coronal process basal fracture, aSSBF and aDSBF, were developed and validated. Using the finite element model test, the sensitivity analysis of pull-out force and rotational torque was carried out. RESULTS: The pull-out force of aSSBF model was positively correlated with the density of the cancellous bone and linearly related to the fixed depth of the screw. The load pattern of pull-out force of aDSBF model was similar to that of aSSBF model. The ultimate torque of aDSBF model was higher than that of aSSBF model, but the load pattern of ultimate torque of both models was similar to each other when the fracture reset was satisfactory, and the screw nut attaches closely to coronoid process. Moreover, with enhancement of initial pre-tightening force, the increase of ultimate torque of both models was small. CONCLUSIONS: In addition to three pull-out stability factors of smart screw fixations, fracture surface fitting degree and nut fitting degree are the other two important anatomical and biomechanical stability factors of smart screw fixations both for rotational stability. When all pull-out stability and rotational stability factors meet reasonable conditions simultaneously, single or double screw fixation methods are stable for the treatments of ulnar coronoid basal fractures.

Centrosomal protein 120 promotes centrosome amplification and gastric cancer progression via USP54-mediated deubiquitination of PLK4.

Centrosomal protein 120 (CEP120) is a 120 kDa centrosome protein that plays an important role in centrosome replication. Overexpression of CEP120 can lead to centrosome duplicate abnormality, which is closely associated with tumorigenesis and development. However, there are no reports on the relationship between CEP120 and tumors. In our study, overexpression of CEP120 promoted centrosome amplification in gastric cancer (GC), and the role of CEP120 in promoting GC progression was demonstrated in vitro and in vivo. We demonstrated that CEP120 promotes centrosome amplification and GC progression by promoting the expression and centrosome aggregation of the deubiquitinating enzyme USP54, maintaining the stability of PLK4 and reducing its ubiquitination degradation. In conclusion, the CEP120-USP54-PLK4 axis may play an important role in promoting centrosome amplification and GC progression, thus providing a potential therapeutic target for GC.

Exosome-Delivered circSTAU2 Inhibits the Progression of Gastric Cancer by Targeting the miR-589/CAPZA1 Axis.

Background: Circular RNAs (circRNAs) are endogenous noncoding RNAs that play vital roles in many biological processes, particularly in human cancer. Recent studies indicate that circRNAs play an important role in tumor progression through exosomes. However, the specific functions of gastric cancer-derived exosomes and the role of circSTAU2 in gastric cancer (GC) remain largely unknown. Methods: Differentially expressed circRNAs in GC were identified by circRNA microarrays analysis and quantitative real-time polymerase chain reaction (qRT-PCR). The role of circSTAU2 in GC was verified by circSTAU2 knockdown and overexpression with functional assays both in vitro and in vivo. Fluorescence in situ hybridization (FISH), immunofluorescence, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, qRT-PCR and Western blot were adopted to evaluate the expression and regulatory mechanism of MBNL1, circSTAU2, miR-589 and CAPZA1. Furthermore, the role of exosomes was demonstrated by transmission electron microscopy and nano-sight particle tracking analysis. Results: CircSTAU2, mainly localized in the cytoplasm, was significantly downregulated in GC. CircSTAU2 overexpression inhibited GC cell proliferation, invasion and migration both in vitro and in vivo, while circSTAU2 knockdown had the inverse effect. CircSTAU2 could be wrapped in exosomes and delivered to recipient cells, and functioned as a sponge for miR-589 to relieve its inhibitory effect on CAPZA1, thus inhibiting GC progression. Furthermore, MBNL1 acted as the upstream RNA-binding protein of circSTAU2 and significantly influenced the circularization and expression of circSTAU2. Conclusion: Exosome-delivered circSTAU2 may act as a tumor suppressor that restrains GC progression via miR-589/CAPZA1 axis, which demonstrates a potential therapeutic target for GC.