Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid ...(HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1β to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1β increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.
Tuning to G(O) flat: Photoluminescence in graphene oxide (GO) suspensions can be tuned from red to blue emission (see scheme) by gradually changing the amounts of sp2‐ and sp3‐bonded carbon atoms ...through reduction of the surface oxide groups. Electron–hole recombination from two different types of excited states is proposed to explain the luminescence in GO at varying degrees of reduction.
Many countries actively promote the benefits of sports; in particular, water sports are popular among the younger generation. However, despite the mature development of equipment in diving, it ...requires relevant training to avoid decompression sickness. Sometimes when divers encounter emergencies and they may fail to alert the coach or other companions for rescues. Currently, some divers wear emergency equipment when conducting the exercise; yet, the cost is relatively high, and the operation is complicated that people tend to forget the process when facing emergencies. This article aims to develop a wearable device that has a safety alarm function based on the technique of machine learning. The features of the suggested device are as follows: (1) cost‐effective detectors for monitoring divers' conditions; (2) a combination of an Automatic Identification System (AIS) with a Global Positioning System (GPS) to send a safety alarm with the location of the diver; (3) utilize Bluetooth communication to detect if a diver left the safety range set by the coach; (4) the machine learning technique judges the health status of the diver; (5) the wearable device connects with swim goggles to deliver danger alarms, which enables divers to notice dangerous situations from the lights on the goggles. The approach suggested in this article primarily utilizes wearable devices to ensure divers' safety. The key feature of this device can prevent divers from sweeping away by currents or swimming into risky areas; meanwhile, the device can detect the risk of decompression sickness. The research executed an experiment to verify the design, and the results have proven the feasibility of the study. Additionally, with the cost‐effective detectors installed on the device, the presented equipment has the potential to make it universal and increase the safety of divers.
Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal ...degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye's accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic
mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.
The nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as ...wake) modulates membrane levels of GABA
receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour.
Background
Bones are the third most common site of metastasis, although bone metastasis (BM) incidence varies widely. This study investigated the incidence of BM in the most common cancers in Taiwan ...to present the recent treatment landscape in patients with organ‐specific cancers.
Methods
Data from the National Health Insurance Research Database of Taiwan were used to identify adult patients diagnosed with organ‐specific cancers between January 1, 2000 and December 31, 2015. Kaplan–Meier analysis was used to quantify cumulative BM incidence at follow‐up. BM incidences associated with different cancers were calculated comprehensively and stratified by sex, age group and follow‐up periods, and age‐ and sex‐adjusted hazard ratios (HRs) of BM were calculated using multivariate Cox regression analysis.
Results
Among 938 776 participants (mean follow‐up, 9.2 years), liver (19.6%), colorectal (17.1%) and lung (15.1%) cancers were most commonly associated with BM. The mean interval between a primary cancer diagnosis and BM was 2 years. BM incidence varied widely among cancers; lung cancer (3213 per 105 person‐years) was associated with the highest BM risk, followed by oesophageal, prostate and breast cancer. HRs of BM were significantly higher for lung cancer (HR = 8.1) than for other cancers.
Conclusion
The estimated BM incidence provided insight into oncological clinical practice trends in the Asia‐Pacific region. BM incidence may vary among populations. Understanding the principles of clinical evaluation in patients with cancer of unknown primary origin can facilitate appropriate treatment recommendations.
Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We ...previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use.
Although building information modelling (BIM) has revolutionized building design and construction management, it is still time-consuming for a BIM project team to coordinate with designers to resolve ...clashes during the pre-construction stages. During the construction stage, shop drawings frequently have to be revised because of cognitive differences between the designers and constructors. These two groups of people view the resolution of such clashes from their own perspectives because of differences in their inherent knowledge and experience. To effectively improve the project delivery time, one option is to reduce the number of model revisions during the construction stage. This could be done by providing a BIM model as a reference. In this model, design clashes can be resolved from the perspective of the constructor before discussions in design coordination meetings to find compromises. In this work, an artificial intelligence system for such design clash resolution was developed with machine learning and heuristic optimizing techniques. In the experiment, we present a real case of a student residence, in which the mechanical, electrical, and plumbing systems in the basement are used to validate the effectiveness of the proposed system. The experimental results show the feasibility and effectiveness of the proposed system.
•Resolving element clashes is a time-consuming task even in BIM projects.•Shop drawings still need to be revised because of construction issues.•A simulated annealing process is designed to simulate the clash resolving cycles.•A parallel learning procedure is employed to extract constructors’ knowledge.•A BIM add-in system is developed to tackle the issue based on SA and knowledge.
Abstract
This study examined the impact of assimilating 3D temperature and water vapor information in addition to radar observations in a multiscale weather system. A frontal system with extremely ...heavy rainfall over northern Taiwan was selected. Using the WRF–LETKF Radar Assimilation System, we performed three sets of observing system simulation experiments to assimilate radar observations with or without thermodynamic variables obtained using different methods. First, assimilating the radar data for 2 h showed better structure and short-term forecast than 1 h. Second, we assimilated radar data and thermodynamic variables from a perfect model simulation. The results of the analysis revealed that when a precipitation position error occurred in the background field, assimilating thermodynamic information with the radar data could correct the dynamic structure and shorten the spinup assimilation period, resulting in substantial improvements to the quantitative precipitation forecast. Third, we applied a thermodynamics retrieval algorithm for a feasibility study. With a warm and wet bias of the retrieved fields, assimilating the temperature data had significant impact on the midlevel of stratiform areas and the forecast of the heavy rainfall was consequently improved. Assimilating the water vapor information helped reconstruct the range and intensity of the cold pool, but the improvement of rainfall forecast was limited. The optimal results of analysis and short-term forecast were achieved when both retrieved temperature and water vapor fields were assimilated. In conclusion, assimilating thermodynamic variables in the precipitation system is feasible for shortening the spinup period of data assimilation and improving the analysis and short-term forecast.
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