Research on detecting structural damage at the earliest possible stage has been an interesting topic for decades. Among them, the vibration-based damage detection method as a global technique is ...especially pervasive. The present study reviewed the state-of-the-art on the framework of vibration-based damage identification in different levels including the prediction of the remaining useful life of structures and the decision making for proper actions. This framework consists of several major parts including the detection of damage occurrence using response-based methods, building reasonable structural models, selecting damage parameters and constructing objective functions with sensitivity analysis, adopting optimization techniques to solve the problem, predicting the remaining useful life of structures, and making decisions for the next actions. For each part, the commonly used methods were reviewed and the merits and drawbacks were summarized to give recommendations. This framework is aimed to guide the researchers and engineers to implement step by step the structure damage identification using vibration measurements. Finally, the future research work in this field is recommended.
Abstract
Retinal screening contributes to early detection of diabetic retinopathy and timely treatment. To facilitate the screening process, we develop a deep learning system, named DeepDR, that can ...detect early-to-late stages of diabetic retinopathy. DeepDR is trained for real-time image quality assessment, lesion detection and grading using 466,247 fundus images from 121,342 patients with diabetes. Evaluation is performed on a local dataset with 200,136 fundus images from 52,004 patients and three external datasets with a total of 209,322 images. The area under the receiver operating characteristic curves for detecting microaneurysms, cotton-wool spots, hard exudates and hemorrhages are 0.901, 0.941, 0.954 and 0.967, respectively. The grading of diabetic retinopathy as mild, moderate, severe and proliferative achieves area under the curves of 0.943, 0.955, 0.960 and 0.972, respectively. In external validations, the area under the curves for grading range from 0.916 to 0.970, which further supports the system is efficient for diabetic retinopathy grading.
Mesoporous silica SBA-15 supported iron and cobalt catalysts (Fe–Co/SBA-15) were prepared and used in the electrochemical (EC) enhanced heterogeneous activation of peroxydisulfate (PDS, S2O82−) ...process for the removal of Orange II. The effects of some important reaction parameters such as initial pH, current density, PDS concentration and dosage of Fe–Co/SBA-15 catalysts were investigated. The results showed that the decolorization efficiency was not significantly affected by the initial pH value, and it did increase with the higher PDS concentration, current density and Fe–Co/SBA-15 dosage. Both the sulfate radical (SO4·−) and the hydroxyl radical (OH) are considered as the primary reactive oxidants for the Orange II decolorization. The Fe–Co/SBA-15 catalyst maintained its high activity during repeated batch experiments. The intermediate products were identified by GC–MS analysis and a plausible degradation pathway is proposed accordingly. The removal efficiencies of chemical oxygen demand (COD) and total organic carbon (TOC) were 52.1% and 31.9%, respectively after 60 min of reaction time but reached 82.9% and 51.5%, respectively when the reaction time was extended to 24 h. Toxicity tests with activated sludge indicated that the toxicity of the solution increased during the first 30 min and then decreased as the oxidation proceeded.
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•Fe–Co/SBA-15 was fabricated and utilized in EC enhanced heterogeneous activation of PDS.•The effect of reaction parameters for the decolorization of Orange II was evaluated.•Possible reaction mechanism and the stability of Fe–Co/SBA-15 were investigated.•Main intermediates were determined and a plausible degradation pathway was proposed.•The toxicity of Orange II was eliminated after 24 h treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Spinal cord injury (SCI) is one of the most common devastating injuries, which causes permanent disabilities such as paralysis and loss of movement or sensation. The precise pathogenic mechanisms of ...the disease remain unclear, and, as of yet, there is no effective cure. Mesenchymal stem cells (MSCs) show promise as an effective therapy in the experimental models of SCI. MSCs secrete various factors that can modulate a hostile environment, which is called the paracrine effect. Among these paracrine molecules, exosome is considered to be the most valuable therapeutic factor. Thus, exosomes from MSCs (MSCs-exosomes) can be a potential candidate of therapeutic effects of stem cells. The present study was designed to investigate the effect of whether systemic administration of exosomes generated from MSCs can promote the function recovery on the rat model of SCI in vivo. In the present study, we observed that systemic administration of MSCs-exosomes significantly attenuated lesion size and improved functional recovery post-SCI. Additionally, MSCs-exosomes treatment attenuated cellular apoptosis and inflammation in the injured spinal cord. Expression levels of proapoptotic protein (Bcl-2-associated X protein) and proinflammatory cytokines (tumor necrosis factor alpha and interleukin IL-1β) were significantly decreased after MSCs-exosomes treatment, whereas expression levels of antiapoptotic (B-cell lymphoma 2) and anti-inflammatory (IL-10) proteins were upregulated. Further, administration of MSCs-exosomes significantly promoted angiogenesis. These results show, for the first time, that systemic administration of MSCs-exosomes attenuated cell apoptosis and inflammation, promoted angiogenesis, and promoted functional recovery post-SCI, suggesting that MSCs-exosomes hold promise as a novel therapeutic strategy for treating SCI.
N‐Heterocycles, such as pyrroles, pyrimidines, quinazolines, and quinoxalines, are important building blocks for organic chemistry and the fine‐chemical industry. For their synthesis, catalytic ...borrowing hydrogen and acceptorless dehydrogenative coupling reactions of alcohols as sustainable reagents have received significant attention in recent years. To overcome the problems of product separation and catalyst reusability, several metal‐based heterogeneous catalysts have been reported to achieve these transformations with good yields and selectivity. In this Minireview, we summarize recent developments using both noble and non‐noble metal‐based heterogeneous catalysts to synthesize N‐heterocycles from alcohols and N‐nucleophiles via acceptorless dehydrogenation or borrowing hydrogen methodologies. Furthermore, this Minireview introduces strategies for the preparation and functionalization of the corresponding heterogeneous catalysts, discusses the reaction mechanisms and the roles of metal electronic states, and the influence of support Lewis acid–base properties on these reactions.
This Minireview summarizes recent developments in which both noble and non‐noble metal‐based heterogeneous catalysts are used to synthesize N‐heterocycles from alcohols and N‐nucleophiles via acceptorless dehydrogenation or borrowing hydrogen methodologies. The strategies for the preparation and functionalization of heterogeneous catalysts, reaction mechanisms, and the roles of heterogeneous catalysts in these reactions are also discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to ...identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
Describe population pharmacokinetics of intravenous (IV) and subcutaneous (SC) tanezumab across Phase 2b/3 studies of osteoarthritis and chronic low back pain.
Methods
Data from 10 studies of IV ...or SC tanezumab (2.5–20 mg every 8 wk for up to 56 wk) were included in a multistep analysis. In Step 1, a 2‐compartment model with linear and nonlinear elimination (based on prior analysis of pre‐2015 IV osteoarthritis studies) was expanded to include other pre‐2015 studies. In Step 2, post‐2015 SC studies were combined into the model. Steps 3 and 4 evaluated impact of baseline nerve growth factor (NGF) and treatment‐emergent anti‐drug antibodies (TE ADA).
Results
SC bioavailability was estimated at 62–76%. The key disposition parameters CL, Vc, Vp and KM were estimated to be 0.133 L d−1, 2.6 L, 1.77 L and 31.2 μg L−1, respectively. Plasma tanezumab concentration was predicted to reach Cmax at 8.9–11.2 days following single and multiple SC administration in typical patients within the dose range of SC Phase 3 studies (2.5–10 mg every 8 wk). Exposure of a typical patient was similar between IV and SC for the second part of the dosing interval (wk 4–8). Covariates selected on the absorption parameters were weight, age, sex and injection site. Baseline NGF had minimal effect on maximum elimination capacity and TE ADA status was associated with slightly higher tanezumab clearance (6–7%).
Conclusion
Our model adequately described plasma tanezumab concentration vs. time following IV or SC administration. Weight was the most influential covariate with respect to absorption of tanezumab in comparison to patient population (osteoarthritis and chronic low back pain) or other demographics. There was no clinically relevant effect of baseline NGF or TE ADA on tanezumab PK.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The studies on synthesis of organosilicons via radical strategies since 2016 are reviewed, in which there are five main categories for the initiation of these radical silylations.
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...Organosilicon compounds play an important role in the fields of materials science, pharmacy, and organic synthesis. The development of effective approaches for the preparation of these compounds have also become a research focus in organic synthesis. In recent years, free radical synthesis of organosilicons has been vigorously developed, which generally has the advantages of milder synthesis conditions, higher yields and selectivity, and free of precious metal catalysts compared with traditional strategies. This article reviews research progresses in the synthesis of organosilicon compounds by free radical pathways since 2016. In most cases, the radical silylation is achieved based on the reaction of silyl radicals, which are triggered by four routes including peroxide, transition-metal-induced peroxide decomposition, alkali, photocatalysis. The alkyl radicals can also initiate the radical silylation for the generation of C(sp3)Si bonds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We aimed to comprehensively evaluate the immunologic landscape at baseline and upon chemotherapy in cervical cancer. The information should aid ongoing clinical investigations of checkpoint blockade ...immunotherapies in this disease setting.
A series of 109 cervical carcinoma patients was retrospectively assayed before and after neoadjuvant chemotherapy. Tumour-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, PD-L1) were assessed by immunohistochemistry. RNA sequencing analysis was performed on matched pre- and post-treatment fresh-frozen tissues.
At diagnosis, diverse immune cell types including CD20+ B cells, CD3+ T cells, CD56+ natural killer (NK) cells, and CD68+ macrophages were detected in different proportions of cervical carcinoma. Unsupervised hierarchical clustering evidently showed that CD4+ and CD8+ T cell abundance correlated with PD-L1 expression. Based on the immune infiltration patterns, the patients could be stratified into four groups with prognostic relevance, namely, 'immuno-active', 'immuno-medial', 'immuno-NK', and 'immuno-deficient'. Neoadjuvant chemotherapy was associated with increased CD4, CD8, CD20, and CD56 signals, most prominently in good responders. Transcriptomic data corroborated the improved anticancer immunity and identified immunosuppressive CD200 upregulation following chemotherapeutic intervention.
A subset of cervical cancer harbours active immune microenvironment, and chemotherapy treatment may further exert locoregional immunostimulation. Immune checkpoint inhibitors as combination or maintenance therapies warrant future exploration in clinic.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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