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A series of interactive experiments are conducted to analyze the drag reduction technology with a rotating disk apparatus that combines microgroove structure and drag‐reducing additives including polyethylene oxide (PEO), cetyltrimethyl ammonium chloride (CTAC), and sodium salicylate (NaSal). By varying the disk type, concentration of drag‐reducing additives, temperature, and Reynolds number (Re), the corresponding drag reduction rates are obtained effectively. The experimental results indicate that adding CTAC strengthens the heat degradation and shear resistance of PEO; while PEO can enhance the ability of CTAC to form micellar structures and balance energy distribution at low concentrations. Moreover, the synergistic effect of these two additives presents a better drag reduction performance with a maximum drag reduction rate of 24.1%; while the microgroove structure enhances the effect of active drag reduction. Therefore, the combination of active and passive drag reduction technology broadens the application of energy saving and consumption reduction in hydraulic rotating machinery. [ABSTRACT FROM AUTHOR]

In the practical application of hydraulic rotating machinery, it is essential to thoroughly explore drag reduction and rheological characteristics of drag-reducing additives to optimize machinery efficiency and reduce equipment consumption. This paper combines simulation and experimental approaches to investigate the drag-reduction performance and rheological properties of drag-reducing additives. Numerical simulations are initially conducted to investigate the shear-thinning properties of drag-reducing fluid and explore variations in drag-reduction rate. Turbulent phenomena characteristics are described by analyzing turbulent statistical quantities. Subsequently, the rheological behaviors of polyethylene oxide (PEO), cetyltrimethyl ammonium chloride (CTAC), and their mixed solutions under different conditions are scrutinized using a rotational rheometer. The findings indicate that the drag reduction effect amplifies as the rheological index n and characteristic time λ decrease. The numerical simulations show a maximum drag reduction rate of 20.18%. In rheological experiments, a three-stage viscosity variation is observed in single drag-reducing additives: shear thickening, shear thinning, and eventual stabilization. Composite drag-reducing additives significantly reduce the apparent viscosity at low shear rates, thereby strengthening the shear resistance of the system. [ABSTRACT FROM AUTHOR]

Yupingfeng granules (YPFG) is commonly used in the treatment of immunological diseases, inflammations, and pulmonary diseases. Several studies have found that chromones, flavones, and saponins were the major bioactive compounds of YPFG. However, few studies have reported accurate quantification methods of these compounds. This study aimed to establish a simple and rapid method by using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to determine 15 bioactive compounds in YPFG. The experimental parameters including extraction methods, extraction solvents, extraction time, solid–liquid ratio, and LC–MS/MS condition were optimized. The linearity, precision, repeatability, stability, and recovery of the established method were evaluated. The contents of 15 bioactive compounds in seven batches of YPFG samples were analyzed by the established method and the results were compared with the values determined by HPLC. The optimal extraction condition was to extract 0.1 g of YPFG by ultrasound with 50 mL 50% ethanol for 30 min. A Waters ACQUITY UPLCBEH C18 column using the 0.1% formic acid water solution and acetonitrile as mobile phase with a gradient elution was applied to the chromatographic separation. The linearity, precision, repeatability, stability, and recovery of the method were within acceptable ranges. Compared with HPLC analysis methods in Chinese Pharmacopoeia and literature, the established method was faster, simpler, more accurate, and more reliable. The method of simultaneous determination of 15 components in YPFG by LC–MS might provide a basis for the study of the bioactive compounds and the improvement of the quality standard of YPFG. [ABSTRACT FROM AUTHOR]

Natural products are treasure houses for modern drug discovery. Diphyllin is a natural arylnaphthalene lignan lactone isolated from the leaf of Astilboides tabularis. Studies have found that it possesses plenty of bioactivity characteristics. In this paper, we reviewed the structure, bioactivity, and mechanism of action of diphyllin and its derivatives. The references were obtained from PubMed, Web of Science, and Science Direct databases up to August 2023. Papers without a bio-evaluation were excluded. Diphyllin and its derivatives have demonstrated V-ATPase inhibition, anti-tumor, anti-virus, anti-biofilm, anti-inflammatory, and anti-oxidant activities. The most studied activities of diphyllin and its derivatives are V-ATPase inhibition, anti-tumor activities, and anti-virus activities. Furthermore, V-ATPase inhibition activity is the mechanism of many bioactivities, including anti-tumor, anti-virus, and anti-inflammatory activities. We also found that the galactosylated modification of diphyllin is a common phenomenon in plants, and therefore, galactosylated modification is applied by researchers in the laboratory to obtain more excellent diphyllin derivatives. This review will provide useful information for the development of diphyllin-based anti-tumor and anti-virus compounds. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic inflammatory disease, characterized by degradation of extracellular matrix, apoptosis of chondrocytes and inflammation in articular cartilage. Zinc finger E-box binding homebox 2 (ZEB2), a transcription repressor, has been demonstrated with anti-inflammatory role in some cells. The analysis from GEO data reveals that ZEB2 expression is upregulated in articular cartilage of OA patients and experimental OA rodents. This study aims to confirm the function of ZEB2 in OA process. The experimental OA was induced by anterior cruciate ligament transaction (ACLT) in rats, and the adenovirus loaded with ZEB2 coding sequence was intra-articularly injected into rats (1 × 10 PFU). The primary articular chondrocytes were stimulated by interleukin-1β (IL-1β) (10 ng/ml) to mimic the osteoarthritic injury, and transfected with the adenovirus carrying ZEB2 coding or silencing sequence. The apoptosis, content of extracellular matrix, inflammation, and the activity of NFκB signaling in chondrocytes and cartilage were determined. ZEB2 was highly expressed in osteoarthritic cartilage tissues and IL-1β-treated chondrocytes. The overexpression of ZEB2 restrained ACLT- or IL-1β administration-induced apoptosis, matrix degradation and inflammation in vivo or in vitro, evidenced by changed levels of cleaved caspase-3/PARP, collagen-II, aggrecan, matrix metalloproteinase 3/13, tumor necrosis factor-α and interleukin-6. Additionally, the phosphorylation of NFκB p65, IκBα and IKKα/β, and the nuclear translocation of p65 was blocked by ZEB2, implying inactivation of this signaling. ZEB2 mitigated osteoarthritic symptoms in rats and chondrocytes, and NFκB signaling might be involved. These findings may provide novel insights for clinical treatment of OA. [ABSTRACT FROM AUTHOR]

This study details microwave-absorbing materials made of natural rubber/nitrile butadiene rubber (NR/NBR) blends with multi-walled carbon nanotubes (MWCNTs) and molybdenum disulfide (MoS2). The mechanical blending method and the influences of fabrication on the morphology and microwave-absorbing performance of resulting compounds were logically investigated. It was found that interfacial differences between the fillers and matrix promote the formation of MWCNTs and MoS2 networks in NR/NBR blends, thus improving microwave-absorbing performance. Compared with direct compounding, masterbatch-based two-step blending is more conducive to forming interpenetrating networks of MWCNTs/MoS2, endowing the resulting composite with better microwave attenuation capacity. Composites with MWCNTs in NR and MoS2 in NBR demonstrate the best microwave-absorbing performance, with a minimum reflection loss of −44.54 dB and an effective absorption bandwidth of 3.60 GHz. Exploring the relationship between morphology and electromagnetic loss behavior denotes that such improvement results from the selective distribution of dual fillers, inducing networking and multi-component-derived interfacial polarization enhancement. [ABSTRACT FROM AUTHOR]

Simple Summary: Fall Armyworm Spodoptera frugiperda (Smith) is one of the most important agricultural pests, which seriously threatens agricultural production and food security in China. The Yangtze River Delta is an important passage for the northward migration of S. frugiperda in eastern China, connecting the year-round breeding area in South China and the major maize planting area in Northern China. Understanding the migration dynamics in this area is crucial for the forecasting and controlling of this pest throughout the country. Based on three years' data (2019–2021) in the Yangtze Delta, the migration timing, migration pathway, the source area of immigrants and the potential landing area of emigrants were identified. It revealed that S. frugiperda mainly migrated into the Yangtze River Delta in May and June, and their progenies further migrated northward to Northern China mostly in July and August. The results of this paper will be helpful to further understand the migratory rules of S. frugiperda, and to provide a theoretical basis for pest forecasting and pest control. The Yangtze River Delta, located in East China, is an important passage on the eastern pathway of the northward migration of fall armyworm Spodoptera frugiperda (Smith) in China, connecting China's year-round breeding area and the Huang-Huai-Hai summer maize area. Clarifying the migration dynamics of S. frugiperda in the Yangtze River Delta is of great significance for the scientific control and prevention of S. frugiperda in the Yangtze River Delta, even in the Huang-Huai-Hai region and Northeast China. This study is based on the pest investigation data of S. frugiperda in the Yangtze River Delta from 2019 to 2021, combining it with the migration trajectory simulation approach and the synoptic weather analysis. The result showed that S. frugiperda migrated to the Yangtze River Delta in March or April at the earliest, and mainly migrated to the south of the Yangtze River in May, which can be migrated from Guangdong, Guangxi, Fujian, Jiangxi, Hunan and other places. In May and June, S. frugiperda migrated further into the Jiang–Huai region, and its source areas were mainly distributed in Jiangxi, Hunan, Zhejiang, Jiangsu, Anhui and Hubei provinces. In July, it mainly migrated to the north of Huai River, and the source areas of the insects were mainly distributed in Jiangsu, Anhui, Hunan, Hubei and Henan. From the south of the Yangtze River to the north of the Huai River, the source areas of S. frugiperda were constantly moving north. After breeding locally, S. frugiperda can not only migrate to other regions of the Yangtze River Delta, but also to its surrounding provinces of Jiangxi, Hunan, Hubei, Henan, Shandong and Hebei, and even cross the Shandong Peninsula into Northeast China such as Liaoning and Jilin provinces. Trajectory simulation showed that the emigrants of S. frugiperda from the Yangtze River Delta moved northward, westward and eastward as wind direction was quite diverse in June–August. This paper analyzes the migration dynamics of S. frugiperda in the Yangtze River Delta, which has important guiding significance for the monitoring, early warning and the development of scientific prevention and control strategies for whole country. [ABSTRACT FROM AUTHOR]

This study evaluated the effectiveness of electronic self-management support interventions in reducing all-cause mortality, cardiovascular mortality, readmission rates, and HF-related readmission in heart failure patients. Following the PRISMA-P guidelines and PRISMS taxonomy, we searched Pubmed, Cochrane Library, and Embase for RCTs and trials of electronic health technologies for heart failure interventions. Develop support programs in advance for education, monitoring, reminders, or a combination of these to screen and categorize studies. The Cochrane ROB2 tool was used to assess the risk of bias. The monitoring interventions may improve all-cause mortality (OR 0.77, 95% CI 0.63 to 0.93) and cardiovascular mortality (OR 0.75, 95% CI 0.61 to 0.93) compared to usual care. Reminder interventions were associated with significantly reducing readmission rates (OR 0.07, 95% CI 0.00 to 0.94). Mixed interventions were most effective in reducing HF-related readmission rates (OR 0.75, 95% CI 0.56 to 0.99). Electronic self-management interventions, particularly monitoring and reminders, can potentially improve outcomes of heart failure patients, including reducing all-cause mortality, cardiovascular mortality, and readmission rates. The eHealth model and the combination of self-management are significant for long-term intervention in patients with HF to improve their quality of life and prognosis. • The monitoring interventions may improve all-cause mortality compared to usual care. • Reminders interventions were associated with a significant reduction in readmission rates. • Mixed interventions were most effective in reducing HF-related readmission rates. • For cardiovascular mortality, monitoring interventions were found to be the most effective. [ABSTRACT FROM AUTHOR]

Current publicly available tools that allow rapid exploration of linkage disequilibrium (LD) between markers (e.g., HaploReg and LDlink) are based on whole-genome sequence (WGS) data from 2,504 individuals in the 1000 Genomes Project. Here, we present TOP-LD, an online tool to explore LD inferred with high-coverage (∼30×) WGS data from 15,578 individuals in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. TOP-LD provides a significant upgrade compared to current LD tools, as the TOPMed WGS data provide a more comprehensive representation of genetic variation than the 1000 Genomes data, particularly for rare variants and in the specific populations that we analyzed. For example, TOP-LD encompasses LD information for 150.3, 62.2, and 36.7 million variants for European, African, and East Asian ancestral samples, respectively, offering 2.6- to 9.1-fold increase in variant coverage compared to HaploReg 4.0 or LDlink. In addition, TOP-LD includes tens of thousands of structural variants (SVs). We demonstrate the value of TOP-LD in fine-mapping at the GGT1 locus associated with gamma glutamyltransferase in the African ancestry participants in UK Biobank. Beyond fine-mapping, TOP-LD can facilitate a wide range of applications that are based on summary statistics and estimates of LD. TOP-LD is freely available online. [ABSTRACT FROM AUTHOR]

The three-dimensional organization of chromatin plays a critical role in gene regulation. Recently developed technologies, such as HiChIP and proximity ligation-assisted ChIP-Seq (PLAC-seq) (hereafter referred to as HP for brevity), can measure chromosome spatial organization by interrogating chromatin interactions mediated by a protein of interest. While offering cost-efficiency over genome-wide unbiased high-throughput chromosome conformation capture (Hi-C) data, HP data remain sparse at kilobase (Kb) resolution with the current sequencing depth in the order of 108 reads per sample. Deep learning models, including HiCPlus, HiCNN, HiCNN2, DeepHiC and Variationally Encoded Hi-C Loss Enhancer (VEHiCLE), have been developed to enhance the sequencing depth of Hi-C data, but their performance on HP data has not been benchmarked. Here, we performed a comprehensive evaluation of HP data sequencing depth enhancement using models developed for Hi-C data. Specifically, we analyzed various HP data, including Smc1a HiChIP data of the human lymphoblastoid cell line GM12878, H3K4me3 PLAC-seq data of four human neural cell types as well as of mouse embryonic stem cells (mESC), and mESC CCCTC-binding factor (CTCF) PLAC-seq data. Our evaluations lead to the following three findings: (i) most models developed for Hi-C data achieve reasonable performance when applied to HP data (e.g. with Pearson correlation ranging 0.76–0.95 for pairs of loci within 300 Kb), and the enhanced datasets lead to improved statistical power for detecting long-range chromatin interactions, (ii) models trained on HP data outperform those trained on Hi-C data and (iii) most models are transferable across cell types. Our results provide a general guideline for HP data enhancement using existing methods designed for Hi-C data. [ABSTRACT FROM AUTHOR]

First-principles density-functional theory calculations were performed to reveal the effect of surface polarization and structural deformation on the formation and stabilization of the polaron in two-dimensional Ruddlesden–Popper perovskites. Our results revealed that the orientational distribution of organic cations induces surface polarization. The surface dipole moment can be well featured by the c axis distances between N and the nearest I atoms. Structural deformation and surface dipole moments result in separate real-space distributions of hole and electron polarons. Our results also reveal that the structural deformation of the [PbI6] sublattices and surface polarization are closely related to the reorientation of organic cations and can be effectively modulated by it. This reorientation significantly impacts the stabilization of polarons. Our understandings provide insight into the nature of polarons in two-dimensional Ruddlesden–Popper perovskites and general guidance for the proper selection of organic cations in two-dimensional perovskites for suitable applications in photovoltaic and optoelectronic devices. [ABSTRACT FROM AUTHOR]

• Survival outcomes and acquired T790M mutation frequency of EGFR 19del subtypes with EGFR-TKI therapy are provided. • Patients with a deletion starting from E746del show better OS than those with other 19del subtypes. • Patients with the most common E746_A750del subtype have a higher frequency of acquired T790M mutation. • NGS is the recommended detection method. Exon 19 deletion (19del) is a sensitive mutation of epidermal growth factor receptor (EGFR) observed in non-small cell lung cancer (NSCLC), and consists of a large number of variants. It remains unclear whether 19del subtype impacts clinical outcomes following EGFR tyrosine kinase inhibitor (TKI) therapy. We systematically searched web databases and identified eligible studies comparing the clinical outcomes of various EGFR 19del subtypes with EGFR-TKIs. The hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS), as well as the risk ratio (RR) for objective response rate and the frequency of acquired T790M mutation were used as study endpoints. A total of eleven retrospective studies and one prospective study involving 1,630 NSCLC patients with EGFR 19del were included in this meta -analysis. Most of studies were from Asia, and the 19del subtypes in these studies were grouped differently. Patients harboring deletions starting from E746 had significantly longer OS than those with deletions starting from L747 (HR, 0.79; 95% CI: 0.65 to 0.96, P = 0.019), and relatively but not significantly longer PFS (HR, 0.86; 95% CI: 0.69 to 1.06, P = 0.160). Patients with E746_A750del, the most common 19del subtype, had a significantly higher frequency of acquired T790M mutation when treated with first- or second-generation EGFR-TKIs compared to those with other 19del subtypes (RR, 0.76; 95% CI: 0.64–0.89, P = 0.001). There were no differences in PFS between the E746_A750del group and the uncommon group, or between the 15-nucleotide deletion group and other patients. This is the first meta -analysis to present survival outcomes and acquired T790M mutation frequency in the context of EGFR 19del subtype with EGFR-TKI therapy. Patients with a deletion starting from E746 show better OS than those with other subtypes, and patients with E746_A750del subtype have a higher frequency of acquired T790M mutation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A consistent damage evolution rule is developed for the uniform expression of damage evolution of UHPC-CA at varying loading conditions. • A damage constitutive model is established for UHPC-CA with the driving and alleviating effects induced by the inclusions of coarse aggregate and steel fiber taken into consideration. • A user-defined UMAT subroutine is compiled for the numerical implementation of the proposed model. A suitable constitutive model for describing the mechanical behaviors of ultra-high performance concrete (UHPC) under various loading histories plays a vital role in analyzing its structural performance. In this work, a consistent elastoplastic damage model is developed for UHPC containing coarse aggregate (UHPC-CA) subjected to static and fatigue loads, in which the driving and alleviating effects induced by the inclusions of coarse aggregate and steel fiber are considered. For damage evolution, based on the acting mechanism of the non-uniformity of stress wave propagation determined by the loading rate on the mechanical responses of UHPC-CA, the loading rate is skillfully integrated into the damage evolution rule to achieve the consistent description of mechanical behaviors of UHPC-CA under static and fatigue loading conditions. Regarding plasticity growth, an empirical plastic deformation model is adopted to improve the computational efficiency of structural nonlinear analysis. To verify the applicability of the proposed model, a user-defined UMAT subroutine is further developed for the subsequent numerical implementation. The comprehensive comparisons between the numerical predictions and independent experimental results at both the material level and structural level solidly demonstrate the capacity of the consistent model to capture the main features concerning the mechanical performance of UHPC-CA subjected to different loading paths. [ABSTRACT FROM AUTHOR]

• A sodium alginate derived 3D SiCw@C composite aerogels were designed and fabricated. • SiCw@C aerogels have a hierarchically oriented micro-channel architecture. • The electromagnetic parameters of SiCw@C composite aerogels could be tuned by inducing different crosslinking cations. • SiCw@C-Fe exhibited good wave absorption performance at a thickness of 2 mm, RL min is −49.2 dB, and EAB is 3.6 GHz. Biomass-derived carbon aerogels are expected to be ideal candidates for electromagnetic wave (EMW) absorption due to their extensive sources, cheap cost, low density and abundant porosity. Herein, using the natural polymer sodium alginate (SA) as the carbon-based precursor and SiC nano-whiskers (SiC w) as the reinforcing material, a series of three-dimensional (3D) SiC w @C composite aerogels doped with different metal ions (Fe, Ni, Al) were designed and studied for lightweight and effective EMW absorption. The emergence of metal ions and three-dimensional conductive carbon networks enriches the loss mechanism of the composites. The results show that the SiC w @C-Al exhibits a considerable minimum reflection loss (RL min) value at 1.5 mm thickness (-28.7 dB) and a broad effective absorption bandwidth (EAB, RL < -10 dB) of 4.1 GHz. Meanwhile, SiC w @C-Fe has good wave absorption performance at a thickness of 2 mm, RL min is −49.2 dB, and EAB is 3.6 GHz. By adjusting the matching thickness of the Al3+ and Fe3+ crosslinked composite aerogel from 1.5 mm to 3.5 mm, the integrated EAB can cover the Ku-band, X-band and even C-band. The SA derived 3D SiC w @C composite aerogels open a new path for the design of lightweight and effective EMW absorption materials used in multi-frequency. [ABSTRACT FROM AUTHOR]

Sanguinarine is a quaternary ammonium benzophenanthine alkaloid found in traditional herbs such as Chelidonium , Corydalis , Sanguinarum , and Borovula. It has been proven to possess broad-spectrum biological activities, such as antitumor, anti-inflammatory, antiosteoporosis, neuroprotective, and antipathogenic microorganism activities. In this paper, recent progress on the biological activity and mechanism of action of sanguinarine and its derivatives over the past ten years is reviewed. The results showed that the biological activities of hematarginine and its derivatives are related mainly to the JAK/STAT, PI3K/Akt/mTOR, NF-κB, TGF-β, MAPK and Wnt/β-catenin signaling pathways. The limitations of using sanguinarine in clinical application are also discussed, and the research prospects of this subject are outlined. In general, sanguinarine, a natural medicine, has many pharmacological effects, but its toxicity and safety in clinical application still need to be further studied. This review provides useful information for the development of sanguinarine-based bioactive agents. [Display omitted] • Multiple pharmacological activities of sanguinarine and its derivatives were concluded. • Mechanism of action of sanguinarine and its derivatives were detailly reviewed. • Outlooks about sanguinarine-related research were presented and discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new lifetime profile platform was developed for rapid, high-throughput screening of drug libraries. • Repurposing of sodium stibogluconate as an inhibitor of the important DNA repair enzyme UDG. • Provides a proof-of-concept for using the time-resolved screening approach to discover repurposing opportunities. Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties. [ABSTRACT FROM AUTHOR]

Uncertainty in the failure mechanism and damage evolution of recycled aggregate concrete (RAC) due to complex components largely restricts the practical application of RAC in load-bearing members. In this study, a feasible concurrent macro-meso numerical approach is proposed to investigate the seismic performance of prefabricated recycled concrete shear wall (PRCSW), with an emphasis on revealing the failure mechanisms at both the material and structural scales. Specifically, RAC is regarded as a multiphase heterogeneous material that is represented by an elaborative mesoscale random aggregate model consisting of six phases. The collective mechanical responses of RAC are reasonably captured under various replacement rates of recycled aggregate (R ra = 0, 30%, 50%, 70%, and 100%) and volume fractions of old mortar (V om = 12%, 16%, 20%, and 24%). In addition to this, a practical concurrent macro-mesoscale model of PRCSW is established, in which the mesoscale model of RAC is exclusively exploited in the critical vulnerable regions (e.g., concealed beam, column, and bottom of wall limb), while the macroscale model is utilized for the remaining regions, striking a balance between computational efficiency and accuracy. To facilitate the numerical implementation, a highly effective approach using Linear Multi-Point Constraint (LMPC) is adopted to establish connections between models operating at varying scales, thus allowing for the simulation in parallel. Upon such a bottom-up numerical analysis, the results show that due to the significantly weakened properties of old mortar and the inclusion of associated interfacial transition zones (ITZs), the damage development and mechanical performance of RAC are quite different from that of ordinary concrete, manifesting as the amplified accumulation of damage around aggregates and severe fractures of recycled aggregates. Although the addition of RAC (R ra increases from 0 to 100%) is found to slightly weaken the horizontal seismic bearing capacity of PRCSW (decreased by 8.57%), its structural deformation capacity, however, is obviously compensated (increased by 34.42%), resulting in a marginal variation of energy dissipation capacity. The findings facilitate the utilization of substantial RAC in load-bearing members with higher confidence. • The failure mode and damage mechanism of RAC were revealed using a mesoscale model. • The seismic performance of PRCSW was studied upon a concurrent macro-mesoscale numerical approach. • A novel method upon LMPC was adopted for the concurrent macro-mesoscale numerical simulation. [ABSTRACT FROM AUTHOR]

Repaired unilateral cleft lip and palate (UCLP) is often accompanied by the deformity and asymmetry of the nasal region. Three‐dimensional analysis was performed to investigate the relationship between nasal soft‐ and hard‐tissue asymmetries, as well as the changes in nasal asymmetry with age, among children with repaired UCLP (age: 6–12 years). Forty‐seven patients were included in this study. Their computed tomography records were retrieved for analysis of the 3D asymmetry of 10 landmarks of the nasal soft and hard tissues. We observed that asymmetry was more severe in nasal hard tissues than in soft tissues, particularly in the sagittal dimension. Compared with patients aged 6–9 years old, patients aged 10 to 12 years old had significantly increased vertical asymmetry at the base of the alar groove (Gbase, p = 0.027) and the lateral point of the piriform aperture (LPA), (p < 0.001). The correlation between the LPA and the alar region was weak to moderate (r = 0.290 to 0.488). In conclusion, we found no evidence of growth and development in nasal hard‐tissue asymmetry among 6‐ to 12‐year‐old children with repaired UCLP, except for the vertical dimension. Nasal soft tissue exhibited a more preferable symmetry than hard tissue, and this could be attributed to the compensatory growth of nasal soft tissue, particularly in the vertical and sagittal dimensions. The weak to moderate correlations between nasal soft‐tissue asymmetry and hard‐tissue asymmetry were observed in the three dimensions. Surgeons should consider these factors when repositioning the nasal alar and controlling the size of the nostrils. [ABSTRACT FROM AUTHOR]

Purpose: Corticosteroid (CS) therapy for infectious and rheumatological diseases showed to decrease serum magnesium (Mg++) level and induce muscle atrophy in patients. The present study investigated the effects of Mg++ supplementation on preventing CS-induced muscle atrophy in an animal model, which provided experimental data for potential clinical translation. Methods: Twelve 24-week-old male Sprague–Dawley rats were treated with lipopolysaccharide (LPS) and CS methylprednisolone (MPS) to induce muscle atrophy, with half of the rats also given daily 50 mg/kg Mg++ oral supplementation. Additional six rats without LPS + CS treatments were used as normal controls. After treatment for 6 weeks, serum was collected for Mg++ quantification, animal dual-energy X-ray absorptiometry (DXA) was performed for tissue composition, and the extensor digitorum longus (EDL) was collected for muscle functional test and histology including muscle fiber size, intramuscular fat infiltration and fiber typing. In vitro myotube atrophy model was used to study the in vitro effect associated with in vivo muscle atrophy. Results: LPS + CS treatments induced hypomagnesemia while the serum Mg++ level was in normal range after Mg++ supplementation. DXA showed 53.0% lower fat percent and 29.7% higher lean mass in LPS + CS + Mg group when compared to LPS + CS group. Muscle functional test showed 22.2% higher specific twitch force and 40.3% higher specific tetanic force in LPS + CS + Mg group when compared to LPS + CS group. Histological analysis showed 4.1% higher proportion of muscle fibers area to total area and 63.6% lower intramuscular fat infiltration in EDL sections in LPS + CS + Mg group when compared to LPS + CS group. LPS + CS + Mg group had 33.0% higher area proportion and 29.4% higher cross-sectional area (CSA) of type IIb muscle fiber. Myoblast culture results showed that Mg++ supplementation group had larger myotube diameter. The mRNA expressions of the muscle atrophy marker genes MuRF1 and MAFbx were lower in Mg++ supplementation group both in vitro and in vivo. Conclusion: The current study demonstrated that Mg++ supplementation successfully alleviated CS-associated muscle atrophy in rats at both functional and morphology levels, indicating a translational potential for patients undergoing CS therapy. This study provided the evidence for the first time that Mg++ supplementation could prevent muscle atrophy—an adverse effect of CS therapy, currently also adopted for treating coronavirus disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

What is known and objective: The benefits of local infiltration analgesia (LIA) in knee arthroplasty (KA) have been well‐documented. However, it is unknown whether adding a corticosteroid to the composition of the LIA is beneficial. This study aimed to investigate the efficacy and safety of administering periarticular steroids intraoperatively in patients who underwent KA through a systematic review and meta‐analysis. Methods: A systematic search was conducted to identify relevant randomized controlled trials in the PubMed, Embase, Web of Science and Cochrane databases up to January 19th, 2021 to perform a meta‐analysis. Outcome variables included pain scores, total opioid consumption, knee range of motion (ROM) and postoperative complications. Results: Corticosteroid injections did not reduce pain scores at 6, 12, 24 or 72 h postoperatively, although a minimal degree of transient pain relief was achieved at 48 h postoperatively compared with those in the placebo group, nor was there a significant difference in total opioid consumption. However, patients receiving corticosteroids did exhibit a transient ROM increase on postoperative days 1, 2 and 3. Since the minimal clinically important difference (MCID) for ROM is unclear, it is unknown if the improvement in ROM is clinically significant. What is new and conclusion: Our specific end‐point analysis demonstrated that corticosteroid administration did not provide pain relief or reduce opioid consumption compared with placebo. However, corticosteroids might provide a statistically significant, though transient and minimal improvement in knee ROM after KA, although no firm conclusions about the benefits of administering corticosteroids in KA can be made based on the available evidence. [ABSTRACT FROM AUTHOR]

Background: Anthocyanins are the most important compounds for nutritional quality and economic values of blood orange. However, there are few reports on the pre-harvest treatment accelerating the accumulation of anthocyanins in postharvest blood orange fruit. Here, we performed a comparative transcriptome and metabolomics analysis to elucidate the underlying mechanism involved in seasonal drought (SD) treatment during the fruit expansion stage on anthocyanin accumulation in postharvest 'Tarocco' blood orange fruit. Results: Our results showed that SD treatment slowed down the fruit enlargement and increased the sugar accumulation during the fruit development and maturation period. Obviously, under SD treatment, the accumulation of anthocyanin in blood orange fruit during postharvest storage was significantly accelerated and markedly higher than that in CK. Meanwhile, the total flavonoids and phenols content and antioxidant activity in SD treatment fruits were also sensibly increased during postharvest storage. Based on metabolome analysis, we found that substrates required for anthocyanin biosynthesis, such as amino acids and their derivatives, and phenolic acids, had significantly accumulated and were higher in SD treated mature fruits compared with that of CK. Furthermore, according to the results of the transcriptome data and weighted gene coexpression correlation network analysis (WGCNA) analysis, phenylalanine ammonia-lyase (PAL3) was considered a key structural gene. The qRT-PCR analysis verified that the PAL3 was highly expressed in SD treated postharvest stored fruits, and was significantly positively correlated with the anthocyanin content. Moreover, we found that other structural genes in the anthocyanin biosynthesis pathway were also upregulated under SD treatment, as evidenced by transcriptome data and qRT-PCR analysis. Conclusions: The findings suggest that SD treatment promotes the accumulation of substrates necessary for anthocyanin biosynthesis during the fruit ripening process, and activates the expression of anthocyanin biosynthesis pathway genes during the postharvest storage period. This is especially true for PAL3, which co-contributed to the rapid accumulation of anthocyanin. The present study provides a theoretical basis for the postharvest quality control and water-saving utilization of blood orange fruit. [ABSTRACT FROM AUTHOR]

Background: Anthocyanins are the most important compounds for nutritional quality and economic values of blood orange. However, there are few reports on the pre-harvest treatment accelerating the accumulation of anthocyanins in postharvest blood orange fruit. Here, we performed a comparative transcriptome and metabolomics analysis to elucidate the underlying mechanism involved in seasonal drought (SD) treatment during the fruit expansion stage on anthocyanin accumulation in postharvest 'Tarocco' blood orange fruit. Results: Our results showed that SD treatment slowed down the fruit enlargement and increased the sugar accumulation during the fruit development and maturation period. Obviously, under SD treatment, the accumulation of anthocyanin in blood orange fruit during postharvest storage was significantly accelerated and markedly higher than that in CK. Meanwhile, the total flavonoids and phenols content and antioxidant activity in SD treatment fruits were also sensibly increased during postharvest storage. Based on metabolome analysis, we found that substrates required for anthocyanin biosynthesis, such as amino acids and their derivatives, and phenolic acids, had significantly accumulated and were higher in SD treated mature fruits compared with that of CK. Furthermore, according to the results of the transcriptome data and weighted gene coexpression correlation network analysis (WGCNA) analysis, phenylalanine ammonia-lyase (PAL3) was considered a key structural gene. The qRT-PCR analysis verified that the PAL3 was highly expressed in SD treated postharvest stored fruits, and was significantly positively correlated with the anthocyanin content. Moreover, we found that other structural genes in the anthocyanin biosynthesis pathway were also upregulated under SD treatment, as evidenced by transcriptome data and qRT-PCR analysis. Conclusions: The findings suggest that SD treatment promotes the accumulation of substrates necessary for anthocyanin biosynthesis during the fruit ripening process, and activates the expression of anthocyanin biosynthesis pathway genes during the postharvest storage period. This is especially true for PAL3, which co-contributed to the rapid accumulation of anthocyanin. The present study provides a theoretical basis for the postharvest quality control and water-saving utilization of blood orange fruit. [ABSTRACT FROM AUTHOR]

Doping manganese ions (Mn2+) in lead halide perovskites (LHPs) has been proven to be an efficient strategy to achieve excellent light-emitting performance. A self-trapped exciton on a MnX6 (X = Cl, Br, I) octahedron and associated energy transfer play critical roles in the broad-band emission of Mn-doped LHPs. In this work, we performed first-principles study on the effect of octahedral MnX6 deformation on the light emission in Mn-doped LHPs. It is revealed that the broad-band luminescence peak is associated with Mn 3d orbitals. Our results revealed that octahedral MnX6 deformation, which enhances the dispersion of the associated bands, plays an important role in the broad-band emission in Mn-doped LHPs. Furthermore, octahedral MnX6 deformation shows dependence on the halogen element and structural phase of LHPs. Our results proved that tuning octahedral MnX6 deformation is an efficient way to achieve the regulation of the luminescence performance of Mn-doped LHPs. Our predictive results may inspire further studies on the applications of doped Mn perovskites. [ABSTRACT FROM AUTHOR]

Background: In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy.Methods: All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events.Results: Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001).Conclusion: Although the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity. [ABSTRACT FROM AUTHOR]

This paper presents a study on the compressive behavior of a novel type of highly deformable hybrid FRP tubular columns. The columns consist of an FRP tube filled with large-size recycled concrete lumps (RCLs) as aggregates and flowable grout as the binding material, and are thus termed FRP-RCL-Grout (F-R-G) columns. The use of large-size RCLs (e.g., up to 63 mm RCLs for 200 mm circular columns) leads to a relatively high recycling ratio and facilitates the manufacturing process. The flowable grout can be easily poured/pumped into the FRP tube, leading to ease of construction, while the FRP tube acts as an effective lateral confining device. The experimental part of the study involved compression tests on F-R-G columns and similar columns for comparison, with the main test variables being the FRP tube thickness, the size of the RCLs, the compressive strength of the concrete for producing RCLs and the WP ratio of the grout. The test results showed that F-R-G columns possess excellent structural behavior including ample ductility, and clarified the effects of the key parameters. In addition, based on the test results, a simple yet accurate model is proposed to predict the strength of F-R-G columns. • A novel FRP tubular column form incorporating recycled concrete lumps and flowable grout is investigated. • The novel column is highly deformable with ample ductility. • The novel column form provides an effective method of using recycled concrete lumps for structural applications. • The use of flowable grout highly eases the construction of the column. [ABSTRACT FROM AUTHOR]

Summary Biclustering is a generalization of clustering used to identify simultaneous grouping patterns in observations (rows) and features (columns) of a data matrix. Recently, the biclustering task has been formulated as a convex optimization problem. While this convex recasting of the problem has attractive properties, existing algorithms do not scale well. To address this problem and make convex biclustering a practical tool for analyzing larger data, we propose an implementation of fast convex biclustering called COBRAC to reduce the computing time by iteratively compressing problem size along with the solution path. We apply COBRAC to several gene expression datasets to demonstrate its effectiveness and efficiency. Besides the standalone version for COBRAC, we also developed a related online web server for online calculation and visualization of the downloadable interactive results. Availability and implementation The source code and test data are available at https://github.com/haidyi/cvxbiclustr or https://zenodo.org/record/4620218. The web server is available at https://cvxbiclustr.ericchi.com. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Obstacle distance measurement is one of the key technologies for cable inspection robots on high-voltage transmission lines. This article develops a novel method based on binocular vision for extracting the feature points of images and reconstructing 3D scenes. The proposed method seamlessly incorporates camera calibration, dense stereo matching, and 3D reconstruction. We apply a novel calibration method to acquire intrinsic and extrinsic parameters and use an improved Semi-Global Matching (SGM) algorithm based on the least squares fitting interpolation to refine the basic disparity map. Based on the depth information of the optimized disparity map and the principle of binocular vision measurement, a model is established to estimate the distance of an obstacle from the cable inspection robot. Extensive experiments show that the proposed method achieves an estimation accuracy of less than 5% from 0.5 m to 5.0 m, offering extremely high distance estimation accuracy and robustness. The study improves the autonomy and intelligence of inspection robots used in the power industry. [ABSTRACT FROM AUTHOR]

To accurately and actively provide users with potentially interested information or services is the main task of a recommender system. Collaborative filtering is one of the most widely used recommendation algorithms, whereas it is suffering the issue of data sparsity that severely degrades recommendation quality. To address this issue, we propose a collaborative filtering recommendation algorithm based on bipartite graph partitioning co-clustering, called BPCF. Firstly, users and items are constructed into a bipartite graph for co-clustering, which is then mapped to the low-dimensional feature space. Then, the proposed algorithm computes the two types of improved similarities (cluster preference similarity and rating similarity) according to the clustering results and combines them. Based on the combined similarity, the user-based approach and item-based approach are adopted, respectively, to predict for an unknown target rating and these prediction results are fused. Experimental results show that the proposed method outperforms the state-of-the-art co-clustering collaborative filtering recommendation algorithms. [ABSTRACT FROM AUTHOR]

• The effects of steel-polypropylene hybrid fiber on the bond strength of deformed bar to concrete were investigated. • The mechanism of fiber reinforcement at multi-scale and multi-stages was discussed. • An analytical model for predicting the ultimate bond strength of HFRC specimen were proposed. This paper deals with the bond strength of deformed bar embedded in steel-polypropylene hybrid fiber reinforced concrete (HFRC) matrix. The benefits of hybrid fibers were evaluated through a series of monotonic/cyclic pull-out testing on 72 specimens. The influences of fiber characteristics, i.e. the volume fraction and aspect ratio, on the failure mode and the complete bond-slip responses were analyzed. Upon a simplified spring model, the effects of fiber reinforcement at different loading stages were further discussed. The results showed that for a well-confined HFRC specimen, the cyclic bond response at the pre-peak stage almost approached its monotonic response with slight reduction in the ultimate bond strength. Compared to the specimen made with plain concrete, the introduction of hybrid fibers could exert obvious positive influences on the bond strength, due to the synergetic effects in inhibiting the propagation of cracks at multi-scale and multi-stages. Finally, an analytical model was proposed to estimate the ultimate bond strength, in which the effects of fiber reinforcement, stirrup confinement and geometrical shape of deformed bar were taken into consideration. The model was subsequently well validated by various independent experimental results. [ABSTRACT FROM AUTHOR]

• A stochastic damage model based on an innovative spring system is proposed. • A random variable that specifies the failure displacement of micro spring elements is suggested. • The path-dependence and pressure-sensitivity of bond response are discussed. The bond behavior of reinforcing bars embedded in concrete has been widely evidenced to exhibit an obvious nonlinearity with a high degree of randomness. To cope with this phenomenon, a stochastic damage model based on an innovative spring system is proposed in this paper. To describe the stochastic feature of bond response, the model introduces a random variable that specifies the failure displacement of micro spring elements, and meanwhile, two evolution laws for the interfacial damage and sliding are also defined respectively. Moreover, the effects of loading history and lateral stress are incorporated into the model, which is capable of reproducing the path-dependence and pressure-sensitivity of bond behavior faithfully. Finally, the model is numerically implemented by exploiting an implicit backward Euler scheme and verified by a number of numerical trial tests and independent experimental results. The satisfactory validations may provide a beneficial reference to bring the stochastic nature of nonlinear interfacial debonding into future theoretical studies on the structural response of reinforced concrete structures. [ABSTRACT FROM AUTHOR]

Hard carbon stands out as one of the premier anodes for potassium‐ion batteries (PIBs), celebrated for its cost‐effectiveness, natural abundance, and high yield. Yet, its performance in PIBs remains subpar due to slow kinetics, a result of the large ionic radius of K‐ions. Herein, a unique lamellar N/O/S‐tri‐doped hard carbon (NOSHC) has been developed at an impressively low pyrolysis temperature of 500°C, showcasing a distinct "slope‐dominated" characteristic. NOSHC delivers superior rate performance with a dominant surface‐driven capacitive contribution (71.6% at a scan rate of 0.5 mV s−1), maintaining a robust reversible specific capacity of 125 mAh g−1 (half its peak) even at 5 A g−1. Its stability is equally commendable, as it sustains a substantial specific capacity of 265 mAh g−1 after 100 cycles at 0.1 A g−1 and retains 210 mAh g−1 post‐1000 cycles at 1 A g−1. Moreover, NOSHC undergoes continuous activation via potassiation/depotassiation during cycling. Rich heteroatom doping introduces a plethora of defects and vacancies, creating abundant active sites. The distinct lamellar structure, featuring minimal pores, optimizes K‐ions transport by shortening the diffusion length. This study unveils the potential of enhancing hard carbon anodes for PIBs by harnessing a low carbonization temperature approach. [ABSTRACT FROM AUTHOR]

Graphical abstract A facile colorimetric assay was developed for the accurate detection of H 2 O 2 and glucose with the CeO 2 /Y hybrid nanocomposite as a highly efficient peroxidase-mimicking nanozyme, which shows the synergistic effects of outstanding activity of highly dispersed CeO 2 nanoparticles and high surface area and pore volume of zeolite Y as support. Abstract Owing to the high costs and instability of natural enzymes, the development of enzyme mimics based on inorganic nanomaterials has attracted a wide concern in recent years. In this work, a stable nanocomposite composed of highly dispersed CeO 2 nanoparticles decorated on zeolite Y as support (CeO 2 /Y) was synthesized by a facile wet impregnation method, and the CeO 2 /Y nanocomposite was firstly proposed as an efficient peroxidase-mimicking nanozyme for accurate detection of H 2 O 2 and glucose. The best catalyst was the nanocomposite with CeO 2 to zeolite Y mass ratio of 0.20 (denoted as 20CeO 2 /Y), showing a better affinity and higher catalytic constant to the substrate of H 2 O 2 and 3,3′,5,5′-tetramethylbenzidine (TMB) than horseradish peroxidase (HRP) enzymes by the steady-state kinetic analysis. The enzyme-mimicking catalyst could be used over a wider range of pH and temperature for a long-time reuse in TMB oxidation. A facile colorimetric assay was set up for the accurate detection of H 2 O 2 and glucose, with the detection limits of 0.323 μM and 35.4 μM, respectively. The CeO 2 /Y-based peroxidase mimic was used to precisely detect the glucose concentration in real blood serum samples, exhibiting a great potential to be constructed as a reliable biosensor for glucose detection in some complex systems. The superior peroxidase-mimicking performance of CeO 2 /Y nanocomposite is attributed to the synergistic effects of outstanding activity of highly dispersed CeO 2 nanoparticles (5–10 nm) and adsorption properties of zeolite Y with large surface area (517 m2·g−1) and pore volume (0.329 cm3·g−1). [ABSTRACT FROM AUTHOR]

Highlights • Two novel evolution laws for damage variables and hardening plasticity are developed. • A function that can predict the reduction of bond strength reasonably is proposed. • Only a few identifiable parameters with sound physical meanings are required. Abstract An appropriate bond stress-slip model is of great significance in accurate prediction of the overall responses of a structure in terms of stiffness, bearing capacity, crack pattern distribution, as well as durability in whole lifecycle. In this paper, a damage-plasticity model within the thermodynamic framework is presented, aiming to simulate the bond behavior of steel reinforcement embedded in a well-confined fiber reinforced concrete. With the motivation to reproduce the bond responses faithfully, two novel evolution laws for internal damage variables and hardening plasticity are developed respectively. Meanwhile, a bond reduction function is also proposed, which is capable of reflecting the degradation law in two directions reasonably during the loading history. The model requires only a few identifiable parameters obtained from simple experiments, and each of the parameters has a clear physical meaning. Subsequently, the model is numerically implemented by means of a backward Euler algorithm, and the output is verified by various experimental results from literature. The comparisons with a satisfactory accuracy firmly testify the feasibility of the proposed approach, which pave the way for further theoretical studies on the structural response of FRC structures. [ABSTRACT FROM AUTHOR]

Abstract Targeting delivery system has been widely used in packaging drugs for medical therapies attributed to its high efficiency and efficacy. A Traditional Chinese Medicine (TCM) formula consisting of Herba Epimedii has previously been shown to effectively treat postmenopausal osteoporosis. We have subsequently found that icaritin, which was a flavonoid isolated from both Herba Epimedii and its serum metabolites after oral administration, inhibited the adipogenic capacity of bone mesenchymal stem cells (BMSCs) while promoted their osteogenesis. However, previous pharmacokinetic analyses have shown that icaritin had a short half-life in blood and only trace amounts of the molecule reach the bone tissue. To overcome this limitation, we developed a bone-targeting liposome containing an oligopeptide of eight aspartate residues (Asp8), which had previously been shown to specifically target the bone, encapsulating icaritin. In vivo, we found that the Asp8-icaritin-liposome enhanced bone formation in ovariectomized mice compared to an icaritin-liposome control lacking the Asp8 moiety. Through in vitro mechanistic studies we further found that icaritin inhibited adipogenesis through an Akt/GSK-3β/β-catenin signaling pathway. Taken together, our study shows that Asp8-liposome as a bone-targeting delivery system is effective to carry an osteogenic phytomolecule for facilitating and enhancing its therapeutic effects on the prevention of estrogen depletion-induced osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: To determine the role and rational application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant non-small-cell lung cancer (NSCLC). Method: Randomized controlled trials (RCTs) that compared the survival outcomes between adjuvant EGFR-TKIs and adjuvant chemotherapy or a placebo, or between different EGFR-TKI treatment durations for resected NSCLC, were eligible for inclusion. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effective measures using random-effect or fixed-effect models. Subgroup analysis was also performed. Results: Eleven RCTs involving 2102 EGFR-mutant NSCLC patients with or without EGFR-TKI adjuvant therapy were included. For all stage IB-IIIA NSCLC patients, EGFR-TKIs adjuvant therapy could not only significantly improve DFS (HR 0.43, 95% CI 0.30–0.63, P < 0.001) and 2- and 3-year DFS rates, but also improve OS (HR 0.72, 95% CI, 0.54–0.96, P = 0.024), compared with chemotherapy or the placebo. Further subgroup analyses indicated prolonged OS from first-generation EGFR-TKI adjuvant therapy in stage III patients, compared with chemotherapy or the placebo (HR for OS, 0.34; 95% CI, 0.18–0.63; P = 0.001). Of note, osimertinib adjuvant therapy led to the OS benefit expanding from stage III to stage II-III patients, with significantly improved DFS and a lower risk of brain recurrence, compared with the placebo. A 2-year treatment duration with EGFR-TKI adjuvant therapy showed a significantly lower recurrence risk than a ≤ 1-year duration. Conclusion: The DFS advantage from first-generation EGFR-TKI adjuvant therapy can translate into an OS benefit in stage III NSCLC patients. Osimertinib might be more suitable for adjuvant therapy than first-generation EGFR-TKIs, because of the lower recurrence rate and the potential OS benefit even in early-stage patients. The optimal treatment duration for EGFR-TKIs at different stages of disease needs to be validated. [ABSTRACT FROM AUTHOR]

FRP-confined concrete-encased cross-shaped steel columns (FCCSCs) are a new form of hybrid columns recently developed at the University of Wollongong. An FCCSC consists of a square FRP outer tube, a cross-shaped steel section and concrete filled in between. This sectional configuration ensures that the concrete is very effectively confined despite the square shape of the column. In addition, the cross-shaped steel section serves as the ductile longitudinal reinforcement for loads in the two lateral directions and its possible buckling is constrained by the FRP outer tube and the concrete, leading to a column that is highly ductile. In this paper, results from a series of stub column tests are presented to demonstrate the concept of the new column form. The experimental program involved the testing of FCCSC specimens as well as four types of similar column forms, namely, square FRP-confined plain concrete columns (SFCPCs), circular FRP-confined plain concrete columns (CFCPCs), concrete-encased cross-shaped steel columns and square plain concrete columns. The test results confirmed the excellent performance of FCCSCs. The test results also showed that compared with the concrete in SFCPCs and that in CFCPCs, the concrete in FCCSCs has a much larger ultimate axial strain and a larger compressive strength, when the same FRP tube is used. [ABSTRACT FROM AUTHOR]

Mn-doped halide perovskites as light-emitting materials have exhibited outstanding performance. However, the influence of Mn concentration on the luminescence performance is unclear. Herein we performed a theoretical study on the effect of Mn concentration on the luminescence behavior of Mn-doped perovskite CsPbCl 3. The results revealed an abnormal variation in the host photoluminescence peak, corresponding to bandgap transition of host CsPbCl 3 , with Mn concentration. The host bandgap shows a blue-shift first and a subsequent red-shift with increasing Mn concentration. Our theoretical analysis proved that the blue-shift in the host photoluminescence peak is attributed to the reduced antibonding between Pb s and Cl p orbitals atoms by Mn substituting Pb. The subsequent red-shift results from the shortened Pb–Cl bonds, pushing up the Pb s -Cl p antibonding states. Our work provides a further insight into the fundamental strategy of Mn doping for improving luminescence performance in perovskite-based light-emitting devices. [ABSTRACT FROM AUTHOR]

• Reliable 3D finite element models are developed for FRP-confined concrete-encased cross-shaped steel columns (FCCSCs). • An in-depth understanding on the complex confinement mechanism of FCCSCs is achieved. • The effects of key parameters on the mechanism and behaviour of FCCSCs are thoroughly examined. Fibre-reinforced polymer (FRP)-confined concrete-encased cross-shaped steel columns (FCCSCs) are an emerging type of hybrid columns. In an FCCSC, the concrete is subjected to combined confinement from the steel section and the FRP tube, leading to an enhanced load capacity and excellent ductility of the column. While several recent experimental studies have demonstrated the excellent structural performance of FCCSCs, the complex confinement mechanism behind their structural behaviour has not been clarified or thoroughly examined. This paper presents a comprehensive study aiming to investigate the confinement mechanism of FCCSCs. In this paper, the experimental observations of FCCSCs are first summarized, followed by three-dimensional FE modelling of the columns. The FE models, after being verified against the test results in various aspects, are used for a systematic parametric study. In this study, the complex interaction between the three components of FCCSCs (i.e., FRP tube, steel section and concrete) is illustrated explicitly and the effects of key parameters (i.e., flange width, flange thickness, web thickness and FRP tube thickness) are examined separately and thoroughly, leading to an in-depth understanding of the confinement mechanism of FCCSCs. In particular, through the examination on the distribution of steel flange-to-concrete normal pressure, it is shown quantitatively that the variations of the dimensions of the steel section in a practically wide range have only marginal effects on its confinement to the concrete, while the increase of FRP tube thickness tends to reduce the confinement effect from the steel section. [ABSTRACT FROM AUTHOR]

• A clinkerless ultra-high strength concrete (UHSC) was developed at room temperature. • The damage evolution and plasticity development of UHSC were investigated. • A unified temperature-dependent constitutive model was proposed. In this work, the uniaxial compressive behaviors of alkali-activated slag-based ultra-high strength concrete (AAS-UHSC) subjected to different temperatures were investigated, with an emphasis on the temperature-dependent stress-strain relation. To this end, 104 cylinder specimens with three steel fiber contents (0.5%, 1.0%, and 1.5%) and two water-to-binder (W/B) ratios (0.20 and 0.25) were tested upon the monotonic and cyclic compression performed at ambient temperature (20 ℃) and four elevated temperatures (200, 400, 600, and 800 ℃). The test results showed that the mechanical properties of AAS-UHSC in terms of elastic modulus, ultimate strength, energy dissipation, and post-peak softening can be effectively improved with the fiber inclusion, regardless of the W/B ratio. Moreover, AAS-UHSC exhibited a quite different plastic strain evolution law featured as two discontinuous stages due to the damage localization and possessed better energy dissipation capacity compared to OPC-based concretes. After being exposed to elevated temperatures, a consistent decline in compressive strength was observed as the temperature increased, with residual strength at 800 ℃ remaining around 10% of the ultimate compressive strength at 20 ℃. Based on the test results, a unified empirical temperature-dependent model was proposed to capture the main features of the constitutive compressive stress-strain relations of AAS-UHSC. The fairly good comparisons between test results and model predictions in different loading scenarios demonstrated a compromise between the accuracy and the generality of the model and contributed a beneficial addition to the understanding of nonlinear responses of AAS-UHSC. [ABSTRACT FROM AUTHOR]

EGFRvⅢ is an established target for immunotherapy of glioblastoma (GBM). Current study aims to explore the efficacy of EGFRvⅢ-targeted immunotoxin combined with temozolomide (TMZ) or T cell-engaged bispecific antibody for the treatment of GBM. We generated three rabbit monoclonal antibodies (R1, R2, and R6) that specifically bound to EGFRvⅢ, but not EGFR, with high affinity. Immunotoxins were made by fusing the scFv of these antibodies with engineered Pseudomonas exotoxin PE24. The in vitro cytotoxicity and specificity of the immunotoxins was rigorously validated by EGFRvⅢ and EGFR-expressed cell lines. The in vivo efficacy of immunotoxin monotherapy and in combination with TMZ or EGFRvⅢ-targeted bispecific antibody was evaluated in orthotopic and subcutaneous xenograft mouse models. EGFRvⅢ immunotoxins potently killed U87, U251 and GL261 cells that were forcefully expressing EGFRvⅢ, with IC 50 values bellow 1.2 ng/ml. In a subcutaneous model, multiple intratumoral injections of immunotoxin at a dose of 2 mg/kg resulted in complete tumor regression in 3/5 of mice. In a C57BL/6 orthotopic glioblastoma model transplanted with GL261 cells that expressed a mouse version of EGFRvⅢ, two injections of 10 micrograms of immunotoxin in the lateral ventricles significantly improved the survival, with 2/5 mice being completely cured. Furthermore, in a subcutaneous xenograft model transplanted with EGFRvⅢ-expressed U87 cells, a single intratumoral injection of immuntoxin followed by i.v. injections of TMZ or EGFRvⅢ-targeted bispecific antibody achieved complete regression in mice. Taken together, EGFRvⅢ immunotoxin combined with TMZ or T cell-engaged bispecific antibody offers promise for curative treatment of GBM. [Display omitted] • Three new monoclonal antibodies highly specific to EGFRvIII were generated. • Intratumoral injections of EGFRvIII immunotoxin eradicated tumors in mouse models. • Combination of EGFRvIII immunotoxin and TMZ had synergistic effect. • Combination of EGFRvIII immunotoxin with bispecific antibody had better efficacy. • Afore mentioned combinations warrant clinical trial for treatment of glioblastoma. [ABSTRACT FROM AUTHOR]

The performance of the bond between reinforcing bars and fiber reinforced concrete (FRC) plays an important role in determining the mechanical behavior of FRC structures when they are subjected to static or dynamic loadings. This paper presents an experimental study on the local bond performance of rebar embedded in steel-polypropylene hybrid fiber reinforced concrete (HFRC). A total of 102 specimens under monotonic and cyclic loading are investigated by means of pull-out tests. The main variables include fiber volume fraction and aspect ratio, concrete strength and stirrup confinement. The results show that the introduction of hybrid fibers had a synergetic effect on improving the bond performance in terms of peak bond strength and corresponding slip, resulting in a more ductile bond behavior. The improvement becomes more pronounced as the fibers content and concrete strength increase. With respect to the energy dissipation capacity, the hybrid fibers also exhibit a great influence. Specimens with higher fibers content always demonstrate a better energy dissipation capacity, while the opposite is true for increasing the aspect ratio of both fibers. Furthermore, two phenomenological models were proposed to predict the monotonic and cyclic bond behavior of well-confined HFRC specimens, in which the benefits of hybrid fibers were taken into account. The models, as well as involved equations, were verified by independent experimental results. [ABSTRACT FROM AUTHOR]

Early detection is proven to be the best chance for successful cancer treatment. MiRNAs, as ideal biomarkers, can identify cancer in the early stage. Therefore, development of highly sensitive and selective detection methods for miRNA is still anticipated. Here we report on a gold nanoparticles (AuNPs)-decorated graphene field-effect transistor (FET) biosensor for highly sensitive, selective and label-free detection of miRNA. The AuNPs-decorated graphene FET biosensor was fabricated by drop-casting the reduced graphene oxide (R-GO) suspension onto the sensor surface, and subsequently decorating AuNPs onto the surface of R-GO. After peptide nucleic acid (PNA) probe was immobilized on the AuNPs surface, miRNA detection was carried out via PNA–miRNA hybridization. It was found that the developed FET biosensor was able to achieve a detection limit as low as 10 fM. In addition, the biosensor enabled an accurate distinction of complementary miRNA from one-base mismatched miRNA and noncomplementary miRNA. What's more, this highly sensitive and selective assay was also applied to the detection of miRNA in serum samples, making it a potential method for diagnosis of gene-related diseases. [ABSTRACT FROM AUTHOR]

Graphene Hall elements (GHEs) with ultra-high sensitivity are fabricated based on chemical vapor deposition (CVD)-grown graphene, and then the sensitivity limit and the relative mechanism are explored. Through tuning the 2-D carrier concentration by applying back-gate voltage, GHE can reach its maximum current related sensitivity up to 2745 V/AT. A model considering both of electron and hole is developed to describe the sensitivity of GHEs well especially near the Dirac point. The maximum current sensitivity of GHEs is then proved to be inversely proportional to the residual carrier concentration in graphene on substrate, which is helpful to provide strategy for further optimizing GHEs. Compromise between performance and uniformity should be carried out as a GHE is used in practice. [ABSTRACT FROM AUTHOR]

A series of new tricyclic 1,5-benzothiazepine derivatives containing 2-(1,2,4-triazol-1-yl)quinoline were synthesized by the reaction of 1,5-benzothiazepine with benzohydroximinoyl chlorides via . The structures of the target compounds were confirmed by IR, 1H NMR, MS, elemental, and X-ray crystallographic analysis. [ABSTRACT FROM AUTHOR]

Loss of cervical range of motion (ROM) is a common complication after anterior cervical discectomy and fusion (ACDF). Recovery of cervical ROM is a goal for postoperative ACDF patients and is achieved through prescribed at-home neck exercises and physical therapy. Currently, cervical ROM is assessed periodically via physical examination by trained health care professionals. These methods, however, are incapable of continuous measurement of neck motion in a patient's naturalist environment. A skin-mounted, wireless, and wearable sensor that offers a noninvasive way to continuously monitor neck motion as well as heart rate, respiratory rate, energy expenditure, swallow count, and body orientation would hold significant clinical utility by tracking recovery, ensuring adherence to physical therapy, and providing warning of potentially deleterious excessive motion during the essential postoperative period. Develop and validate in healthy normal subjects a machine learning algorithm to classify 8 neck motions: right rotation, left rotation, right lateral bending, left lateral bending, flexion, extension, retraction, protraction Validate the algorithm in postoperative ACDF patients Evaluate clinician and patient usability of the sensor. On 11 healthy subjects (6 females, 5 males), the sensor was placed at the suprasternal notch, centered between the sternocleidomastoid tendons. Ten four-second samples of each of the 8 motions were collected from each subject (880 total neck motion samples). Each sample consisted of the output from the sensor's 3-axis accelerometer and gyroscope: x, y, and z linear accelerations and angular velocities. A convolutional neural network (CNN) model was developed using Python to perform 8-way classification using a step-wise classification scheme. A leave-one-out training/testing scheme was used in which a model was trained on 10 subjects and then tested on the remaining subject, which was iterated across all 11 subjects. Additionally, a random mixing training/testing scheme was used, which involved random mixing of all 880 samples, training on 80% of the mixed samples, and testing on the remaining 20%. Ongoing activities include direct measurement of neck motion in the ACDF population. Each motion produced a characteristic pattern of linear accelerations and angular velocities, which provided the features that were used for classification. The leave-one-out training/testing scheme yielded a mean accuracy of 84% (+/-12%), ranging from 57 to 94%. Ten trials of the random mixing training/testing scheme yielded a mean accuracy of 91% (+/- 1.0%). Flexion vs retraction and extension vs protraction were the most difficult signals to distinguish. Rotation, lateral bending, flexion, extension, retraction, and protraction produce unique motion patterns that can be measured with a wearable sensor containing a 3-axis accelerometer and gyroscope placed at the suprasternal notch. Rotation, lateral bending, flexion, and extension produced the most unique motion signatures. Linear accelerations and angular velocities, measured by accelerometer and gyroscope, respectively, can be strategically selected to perform a step-wise 8-way classification of these neck motions with relatively high accuracy. Validation of the algorithm in the surgical patient population, which is ongoing, could demonstrate the utility of wearable sensors in the ACDF patient population and significantly improve their quality of postoperative care. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Addition of fibers into cementitious composites has raised concern over decades, which enables considerable improvement in mechanical and dynamic properties of reinforced concrete (RC) members. In this paper, we present an experimental study on the seismic performance of steel–polypropylene hybrid fiber reinforced concrete (HFRC) columns, which is of vital significance to postearthquake serviceability of structures. A total of 24 specimens subjected to combined constant axial load and cyclic lateral force were investigated. The main variables involve fiber type, shear span ratio, axial compression ratio, and reinforcement ratio (longitudinal and transverse). The failure modes, ultimate bearing capacity and deformation capacity were analyzed. The experimental results showed that the presence of hybrid fibers in RC columns had positive influence on improving the seismic bearing capacity. The improvement ratio could reach to 15–20% when a relative high axial compression was applied. Moreover, in comparison to RC columns, HFRC columns exhibited a notable synergetic effect in terms of ductility and energy dissipation capacity, particularly for columns with a higher axial compression ratio. Subsequently, on the basis of principles of equilibrium and compatibility, analytical equations to estimate the seismic bending moment capacity and shearing force capacity were developed, which took into account the synergetic effect of hybrid fibers. The analytical solutions were then validated by the test results, and the correlations were observed in reasonable accuracy. [ABSTRACT FROM AUTHOR]

A series of novel 1,2,4-oxadiazoline derivatives containing 2-(1,2,4-triazol-1-yl)quinoline were synthesized by the reaction of imines with benzohydroximinoyl chlorides in the presence of Et3N via 1,3-diplolar . The structures of the target compounds were confirmed by IR, 1H NMR, MS, elemental, and X-ray crystallographic analysis. [ABSTRACT FROM AUTHOR]

A new coumarin, 4,6-dihydroxy-7-formyl-3-methylcoumarin (1), and an α-pyrone derivative, 6-[(7S,8R)-8-propyloxiran-1-yl]-4-methoxy-pyran-2-one (2), together with four known α-pyrone derivatives (3–6), were isolated from the broth extract of the plant endophytic fungusPestalotiopsis versicolor. Their structures were elucidated by extensive spectroscopic analysis and by comparison of the chemical shift values with those of related known compounds. [ABSTRACT FROM AUTHOR]

A series of new tricyclic 1,5-benzothiazepine derivatives were synthesized by the reaction of 1,5-benzothiazepine containing 2-phenoxy-quinoline with chloracetyl chloride and phenoxyacetyl chloride. The structures of the target compounds were confirmed by IR, 1H NMR MS, and elemental analysis. [ABSTRACT FROM AUTHOR]