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Abstract The permanent magnet eddy‐current coupler (PMEC) is a kind of non‐contact, stepless speed regulation device and has been widely used in transmissions. However, the current PMECs are coaxial and cannot achieve transmission and speed regulation in intersecting axes. An intersecting‐axis permanent magnet (PM) eddy current coupler (IPMEC), which consists of a disk‐type PM rotor and a barrel‐type conductive sheet (CS) rotor arranged with intersecting axes, is proposed. It generates eddy currents through the speed difference between the two rotors and uses the non‐contact electromagnetic force between the eddy currents and permanent magnets to transmit torque. During operation, the speed can be adjusted by altering the coupling area or air gap. A theoretical model of the IPMEC based on the equivalent magnetic circuit method is presented and verified by finite element simulation using ANSYS. Then, the effects of the pole number of the PMs, the radius of the CS rotor and the PM rotor on the performance were analysed, and the design method of the IPMEC was proposed. This study can be used to expand the application range of PMECs.

Understanding the recovery mechanism associated with the dislocation cell structure in 316L austenitic stainless steel produced by selective laser melting (SLM), as well as the role played by the accompanying segregation network, is crucial for tailoring the microstructures and mechanical properties of SLM-prepared components. In the present work, the evolution of the dislocation cells was investigated during isothermal annealing, and a recovery mechanism for the dislocation cell structure was proposed based on a combination of microstructural observations and recovery kinetics analysis. The results show that the high-density dislocations at the cell boundaries annihilate during prolonged annealing at 800 °C, resulting in the decomposition of the dislocation cells. The recovery kinetics analysis reveals that SLM-prepared 316L exhibits a lower recovery rate and requires significantly higher apparent activation energy during annealing compared to conventional 316L deformed by cold rolling. The segregation network plays an important role during the dislocation recovery process, which limits the dislocation reaction occurring within the cell boundaries at the early stage of recovery, impedes the dislocation motion after the decomposition of dislocation cells, and leads to a strong temperature dependence of recovery kinetics in SLM-prepared 316L.

Strengthening reinforced concrete (RC) columns utilizing advanced composites, including fiber-reinforced polymer (FRP), polyethylene terephthalate (PET) FRP, and engineered cementitious composite (ECC) has attracted extensive efforts for decades. Remarkable achievements have been made in understanding the performance of the retrofitted RC columns that failed in the strengthened area. However, localized strengthening may force failure to shift outside the retrofitted zone, and these cases are rarely reported in literature. This paper focuses on the seismic performance of shear-critical RC columns that failed outside the strengthened zone. The main test parameters considered are the axial compression force (ACF) ratio and the strengthening materials used (ECC, carbon FRP (CFRP)-ECC, or PET-ECC). The results indicate that the failure mode and failure zone depend on the strengthening conditions. Weak strengthening (ECC only) will not result in a shift of the failure zone but strong retrofitting combinations do (CFRP-ECC and PET-ECC). Although the shear failure shifted to the unstrengthened zone, strengthening can still significantly improve ductility, energy-dissipation capacity and stiffness. A larger ACF can change the failure modes from shear to flexural or from shear-flexural to shear-compression. Shear strength models with and without considering the ductility-based reduction effects are evaluated.

This study investigates particle governed thermal stability in lamellar-nanostructured Al–1.0%Si using in-situ transmission electron microscopy and post-mortem observations. Microstructural coarsening, dominated by Y-junction motion, is correlated with dispersed Si nanoparticles. Si particles within lamellae efficiently hinder dislocation movement during deformation, fostering a configuration with Si particles along incidental dislocation boundaries (IDBs). This particle–IDB configuration significantly impedes Y-junction motion, retarding lamellar coarsening. The enhanced pinning force from particle–IDB synergy, combined with direct pinning by Si particles, contributes to improved thermal stability in lamellar-nanostructured Al–1.0%Si.

Dislocation recovery lowering the driving force for recrystallization would be able to suppress the latter in Ni-based superalloy single crystals, but was believed unlikely due to their low stacking-fault energy. Defying this traditional wisdom, here we show that efficient recovery can be realized once the γ′-precipitates start to dissolve. Our microscopy evidence tracking the distribution/configuration of dislocations reveals that the shifting γ/γ′ interphase boundaries release the dislocations trapped there, facilitating their annihilation and rearrangement into low-energy network configurations. Our finding explains the success of a recent recovery protocol that kept superalloys as single crystals after supersolvus homogenization heat treatment.

Abstract Additive manufacturing (AM), known as 3D printing, enables rapid fabrication of geometrically complex copper (Cu) components for electrical conduction and heat management applications. However, pure Cu or Cu alloys produced by 3D printing often suffer from either low strength or low conductivity at room and elevated temperatures. Here, we demonstrate a design strategy for 3D printing of high strength, high conductivity Cu by uniformly dispersing a minor portion of lanthanum hexaboride (LaB6) nanoparticles in pure Cu through laser powder bed fusion (L-PBF). We show that trace additions of LaB6 to pure Cu results in an improved L-PBF processability, an enhanced strength, an improved thermal stability, all whilst maintaining a high conductivity. The presented strategy could expand the applicability of 3D printed Cu components to more demanding conditions where high strength, high conductivity and thermal stability are required.

Abstract Background Paclitaxel, a tubulin-binding agent, is a Food and Drug Administration-approved first-line drug for the treatment of non-small cell lung cancer (NSCLC), for both squamous and non-squamous cell lung carcinoma, with paclitaxel/carboplatin + bevacizumab a common chemotherapy regimen for stage IV non-squamous NSCLC; however, primary or acquired resistance to paclitaxel is gradually increasing, leading to treatment failure. Methods Our results show that Ras-related C3 botulinum toxin substrate 3 (RAC3) is overexpressed in cultured paclitaxel-resistant cells and that RAC3 expression levels are negatively correlated with sensitivity of lung adenocarcinoma cells to paclitaxel. Pulsatilla saponin D could inhibit RAC3 expression, and we hypothesize that it may block paclitaxel resistance. Further, we found that treatment with paclitaxel combined with Pulsatilla saponin D, can overcome lung adenocarcinoma cell resistance to paclitaxel alone in cell culture and mouse xenograft models.

Abstract Background The contribution of chronic kidney disease (CKD) to mortality in diabetic patients is unclear. This study aimed to explore the association between diabetics with CKD and mortality in middle-aged and elderly people of different ages. Methods Data were obtained from the China Health and Retirement Longitudinal Study, including 1,715 diabetic individuals, 13.1% of whom also had CKD. Diabetes and CKD were assessed by combining the physical measurements and self-reports. We fitted Cox proportional hazards regression models to examine the effect of diabetics with CKD on mortality in middle-aged and elderly people. The risk factors for death were further predicted based on age stratification. Results The mortality rate of diabetic patients with CKD (29.3%) was increased as compared to that of diabetic patients without CKD (12.4%). Diabetics with CKD were at a higher risk of all-cause mortality than those without CKD, with a hazard ratio of 1.921 (95% CI: 1.438, 2.566). Additionally, for participants 45 to 67 years of age, the hazard ratio was 2.530 (95% CI: 1.624, 3.943). Conclusions Our findings suggested that, for diabetics, CKD was a chronic stressor that led to death in middle-aged and elderly people, especially among participants aged 45 to 67 years.

Abstract Abnormal grain growth, a pervasive phenomenon witnessed during the annealing of nanocrystalline metals, precipitates a swift diminution of the distinctive properties inherent to such materials. Historically, conventional transmission electron microscopy has struggled to efficiently procure comprehensive five‐parameter crystallographic information from a substantial number of grain boundaries in nanocrystalline metals, thus inhibiting a deeper understanding of abnormal grain growth behavior within nanocrystalline materials. In this study, we utilize a high‐throughput characterization method—three‐dimensional orientation mapping in the TEM (3D‐OMiTEM) to characterize the crystallographic five‐parameter character of grain boundaries with an area of over 3.4 × 106 nm2 in an abnormally grown nanocrystalline nickel sample. When coupled with existing theoretical simulation results, it is discerned that the grain boundary population shows a relatively large scatter when it is correlated to the calculated grain boundary energy; the grain boundaries of abnormally grown grains exhibit lower grain boundary energy compared to those that have not undergone abnormal growth. Merging high‐throughput grain boundary information obtained from three‐dimensional orientation mapping data with grain boundary properties derived from high‐throughput theoretical calculations following the concept of materials genome engineering will undoubtedly facilitate further advancements in comprehending and discerning the interfacial behaviors of crystalline materials.

The remarkably high strength of nanocrystalline metals is of great interest to researchers and seems to open up many interesting design applications. However, a particularly vexing problem is the low ductility and microstructural instability of nanocrystalline metals that decreases their strength over time. In addition, there is a bottleneck of critical grain size in the fine-grain strengthening effect of nanocrystalline metals. How to stabilize the microstructure of nanocrystalline metals and how to obtain the ultimate strength of nanocrystalline metals and maintain some plasticity through grain refinement are hot topics in the frontier of materials science. Previous experimental works have well demonstrated that grain boundary (GB) segregation of solute atoms can effectively overcome the intrinsic disadvantages of nanocrystalline metals. However, the microscopic mechanisms are not well understood yet, which hinders the further optimization of the comprehensive mechanical properties of nanocrystalline metals through the concept of GB segregation engineering. With the rapid development of computational materials science in the past two decades, many studies have been carried out on the relationship between solute atoms and GB properties, and fruitful results have been achieved. In this paper, the latest advances in computational simulation of GB segregation of solute atoms in nanocrystalline metals are reviewed, including the effects of solute atoms on GB structure and energy, mechanical properties of the segregated GBs, and the microscopic deformation mechanism of the segregated GBs.

Among cancers, gastric cancer (GC) ranks third globally in morbidity and mortality, particularly in East Asia. Natriuretic peptide receptor A (NPRA), a receptor for guanylate cyclase, plays important roles in regulating water and sodium balance. Recent studies have suggested that NPRA is involved in tumorigenesis, but its role in GC development remains unclear. Herein, we showed that the expression level of NPRA was positively correlated with gastric tumor size and clinical stage. Patients with high NPRA expression had a lower five-year survival rate than those with low expression, and NPRA was identified as an independent predictor of GC prognosis. NPRA knockdown suppressed GC cell proliferation, migration and invasion. NPRA overexpression enhanced cell malignant behavior. Immunohistochemistry of collected tumor samples showed that tumors with high NPRA expression had higher peroxisome proliferator-activated receptor α (PPARα) levels. In vivo and in vitro studies showed that NPRA promotes fatty acid oxidation and tumor cell metastasis. Co-IP showed that NPRA binds to PPARα and prevents PPARα degradation. PPARα upregulation under NPRA protection activates arnitine palmitoyl transferase 1B (CPT1B) to promote fatty acid oxidation. In this study, new mechanisms by which NPRA promotes the development of GC and new regulatory mechanisms of PPARα were identified.

OBJECTIVES This population-based, prospective cohort study investigated the association between glaucoma and mortality in older adults. METHODS Participants aged 45 years or older at baseline (47.9% male) were enrolled in 2011 for the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was observed during 7 years of follow-up. The baseline data were collected in the 2011 CHARLS, and participants were followed up for 7 years (until 2018). The risk of all-cause mortality was investigated using Cox proportional-hazards regression with age as the time scale, adjusting for significant risk factors and comorbid conditions. RESULTS Among the 14,803 participants included, the risk of all-cause death was significantly higher among people with glaucoma than among those without glaucoma, after adjustment for other confounders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04 to 2.03). In a subgroup analysis based on the mean age of death, among those who were 75 years and older (n=1,231), the risk of all-cause death was significantly higher in patients with glaucoma than in those without glaucoma (HR, 1.89; 95% CI, 1.24 to 1.89). CONCLUSIONS Participants with glaucoma had a higher risk of all-cause mortality, especially those aged 75 years and above. Our findings revealed potential mechanisms underlying an association between glaucoma and all-cause mortality. They also highlighted the importance of glaucoma management to prevent premature death in middle-aged and older adults.

Additively manufactured Ti alloys exhibit spatially dependent microstructures and mechanical properties owing to the intrinsic thermal cycling. Here the authors develop new Ti alloys with uniform mechanical properties through a rational alloy design.

The heteroepitaxial growth of crystalline 2D materials is usually based on single-crystal substrates. Here, the authors demonstrate that single-crystal graphene and hexagonal boron nitride films can be successfully grown on wafer-scale copper foils with tailored twin boundaries.

The perennial woody plant Hydrangea arborescens ‘Annabelle’ is of great research value due to its unique mechanism of flower development that occurs in the current year, resulting in decorative flowers that can be enjoyed for a relatively long period of time. However, the mechanisms underlying the regulation of current-year flower development in H. arborescens ‘Annabelle’ are still not fully understood. In this study, we conducted an associated analysis to explore the core regulating network in H. arborescens ‘Annabelle’ by combining phenological observations, physiological assays, and transcriptome comparisons across seven flower developmental stages. Through this analysis, we constructed a gene co-expression network (GCN) based on the highest reciprocal rank (HRR), using 509 differentially expressed genes (DEGs) identified from seven flowering-related pathways, as well as the biosynthesis of eight flowering-related phytohormones and signal transduction in the transcriptomic analysis. According to the analysis of the GCN, we identified 14 key genes with the highest functional connectivity that played critical roles in specific development stages. We confirmed that 135 transcription factors (AP2/ERF, bHLH, CO-like, GRAS, MIKC, SBP, WRKY) were highly co-expressed with the 14 key genes, indicating their close associations with the development of current-year flowers. We further proposed a hypothetical model of a gene regulatory network for the development of the whole flower. This model suggested that the photoperiod, aging, and gibberellin pathways, along with the phytohormones abscisic acid (ABA), gibberellin (GA), brassinosteroid (BR), and jasmonic acid (JA), work synergistically to promote the floral transition. Additionally, auxin, GA, JA, ABA, and salicylic acid (SA) regulated the blooming process by involving the circadian clock. Cytokinin (CTK), ethylene (ETH), and SA were key regulators that affected flower senescence. Additionally, several floral integrators (HaLFY, HaSOC1-2, HaAP1, HaFULL, HaAGL24, HaFLC, etc.) were dominant contributors to the development of H. arborescens flowers. Overall, this research provides a comprehensive understanding of the dynamic mechanism underlying the entire process of current-year flower development, thereby offering valuable insights for further studies on the flower development of H. arborescens ‘Annabelle’.

An improved artificial bee colony algorithm (IABC) was proposed to solve the problems of the k-means clustering (KMC) algorithm, such as poor global search ability, sensitive selection of initial cluster center, randomness of initialization, precocity and slow convergence of the original artificial bee colony (ABC) algorithm. To improve the efficiency of iterative optimization process, a fitness function adapted to KMC algorithm and a position updating formula based on global guidance were constructed. By comparing the improved artificial bee colony algorithm with the original artificial bee colony algorithm and particle swarm optimization algorithm, it is confirmed that IABC algorithm converges speed block and overcomes the shortcoming of the original algorithm which is easy to fall into local optimal solution. IABC algorithm is combined with KMC to get better clustering effect, and the algorithm is used to select typical wind power output scenarios, which plays an important role in actual production.

OBJECTIVES This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p

The hydrodynamic thrust slider and journal bearings as well as hydrodynamic lubricated gears with the merit of energy conservation by the wall slippage are reviewed. The principle for designing these hydrodynamic contacts is to artificially set the wall slippage on the stationary surface in the hydrodynamic inlet zone. To design the wall slippage on the moving surface in the hydrodynamic outlet zone can also give additional benefits. The technical merits of these mechanical components are the improved load-carrying capacity and the lowed friction coefficient, i.e., the energy conservation due to the wall slippage. Owing to the designed wall slippage, the carried load of the hydrodynamic step bearing can be increased by 200%~400% while its friction coefficient can be reduced by 50%~85%, and the load-carrying capacity of the hydrodynamic journal bearing can be increased by nearly 100% while at the same time, its friction coefficient can be reduced by more than 60%. For hydrodynamic lubricated gear contacts, by covering ultrahydrophobic or oilphobic coatings on the slower moving surface, the friction coefficient can be approaching to vanishing and the contact load-carrying capacity can be increased very significantly for large slide-roll ratios under medium or heavy loads.

Conventional ultrafine grains can generate high-strength Mg alloys, but non-equilibrium grain boundaries deteriorates their corrosion resistance. Here, the authors present ultrafine grained Mg alloys with dense twins that display high strength and reduced corrosion rate by one order of magnitude.

BackgroundInflammatory Bowel Diseases (IBDs) have been emerging in recent years with the advance of global industrialization and diet pattern transformation. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), enriched in fish oils, have well-known human health promotion. Evidence on the association of fish oil supplementation with the risk of developing IBDs was scarce. This study aimed to examine the association between the use of fish oil supplements and the risk of developing inflammatory bowel diseases (IBDs) among the general population.MethodsWe conducted a prospective cohort study of 447,890 participants aged 40–69 years from the UK Biobank. A touch screen questionnaire was used to get the data about fish oil intake at baseline. Incident diagnoses of IBDs were ascertained by the International Classification of Diseases (ICD-9 and ICD-10) or self-report. Cox proportional hazards model was applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of developing IBDs and their subtypes.ResultsWe documented 1,646 incident cases of IBDs, including 533 incident cases of Crohn’s disease (CD) and 1,185 incident cases of ulcerative colitis (UC) during an average of 8 years of follow-up. After multivariate adjustment, the use of fish oil was associated with a 12% lower risk of IBDs (HR: 0.88, 95% CI: 0.78–0.99, p = 0.03) compared with non-consumers. For subtypes of IBDs, fish oil supplementation was inversely associated with a 15% lower risk of UC (HR: 0.85, 95% CI: 0.75–0.99, p = 0.02) but was not correlated with the risk of CD (p = 0.22). Besides, fish oil supplementation showed a significant inverse correlation with baseline CRP levels (β = –0.021, p < 0.001) and a positive association with baseline albumin levels (β = 0.135, p < 0.001) after adjustment for multiple variates.ConclusionHabitual intake of fish oil supplements was associated with a lower risk of IBDs and UC. Fish oil users tended to have lower baseline C-reactive protein levels and higher baseline albumin levels compared with non-users. It was concluded that fish oil supplement use may be recommended for the prevention and control of IBDs.

PurposeTo investigate the safety and efficacy of a reverse puncture device (RPD) and specimen eversion of the rectum for resection in total laparoscopic proctectomy.MethodsIn a prospective study from August 2019 to March 2021, 40 patients underwent a procedure with an RPD and specimen eversion of the rectum for total laparoscopic low rectal cancer resection, that is natural orifice specimen extraction surgery (NOSES), were included in the NOSES group. Forty patients in the control group underwent conventional laparoscopic radical resection for low rectal cancer and were included in the LAP group. Intraoperative- and postoperative-related indicators, recovery and inflammatory factors, quality of life (QOL) and mental health were compared.ResultsAll operations were successfully completed. Compared with the LAP group, the NOSES group showed better short-term outcomes, such as time to eating, postoperative pain, and especially postoperative incision-related complications. At the same time, postoperative inflammatory factor levels, psychological trauma, life-related anxiety and depression scores, and QOL were better in the NOSES group than in the LAP group.ConclusionsThe application of an RPD and specimen eversion of the rectum for total laparoscopic low rectal cancer resection is a technically feasible and safe approach with a short-term curative effect.

Most alloys become mechanically brittle at very low temperatures. Here, an austenitic Fe-30Mn-0.11C steel exhibits high toughness, strength and elongation at liquid nitrogen temperatures, reaching a Charpy impact toughness of 453 J.

An Mg-3Gd (wt.%) sample with gradient rolling strains (ε = 0–0.55) was prepared using a wedge-shaped plate after one-pass hot rolling, allowing a high-throughput characterization of microstructure and texture over a wide strain range within one hot-rolled plate. The microstructure and texture evolutions were characterized as a function of rolling strain for the as-hot-rolled sample and as a function of annealing temperature for the subsequently annealed samples. The deformed microstructure showed a gradual change with increasing rolling strain, i.e., from a deformation twins-dominant structure in the low strain range of 0–0.20, to a shear bands-dominant structure in the higher strain range of 0.20–0.55. The recrystallization behavior during annealing showed a clear correlation between the recrystallization nucleation site and the deformed microstructure. However, a weak recrystallization texture with non-basal texture components was formed over almost the entire strain range. This work demonstrates a high-throughput experimental strategy using a wedge-shaped sample to investigate the effect of various processing parameters, such as strain and annealing temperature, on the evolution of microstructure, texture, and mechanical properties, which could accelerate the optimization of processing parameters and microstructural design.

Recent studies have revealed that circRNAs can affect tumor DNA damage and repair, apoptosis, proliferation, and invasion and influence the transport of intratumor substances by acting as miRNA sponges and transcriptional regulators and binding to proteins in a variety of ways. However, research on the role of circRNAs in cancer radiotherapy and chemoresistance is still in its early stages. Chemotherapy is a common approach to oncology treatment, but the development of tumor resistance limits the overall clinical efficacy of chemotherapy for cancer patients. The current study suggests that circRNAs have a facilitative or inhibitory effect on the development of resistance to conventional chemotherapy in a variety of tumors, suggesting that circRNAs may serve as a new direction for the study of antitumor drug resistance. In this review, we will briefly discuss the biological features of circRNAs and summarize the recent progression of the involvement of circRNAs in the development and pathogenesis of cancer chemoresistance.

Abstract Background Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated. Methods RNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM). Results CircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model. Conclusions CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.

Nanostructured metals possess various excellent properties and offer the potential for a wide range of applications. Improvements in the properties and performance of nanostructured metal components motivate a complete characterization of the microstructures and crystallographic orientations of nanostructured metals with nanoscale spatial resolution. Two well developed orientation mapping techniques for such characterization are electron backscatter diffraction (EBSD) in the scanning electron microscope and precession electron diffraction (PED) using diffraction spots in the transmission electron microscope. However, these methods can only characterize the structure in two dimensions. It is still a great challenge to characterize grains in three dimensions, i.e. from the interior of the nanostructured metals. Recently, three-dimensional orientation mapping in the transmission electron microscope (3D-OMiTEM) was developed and further improvements of this technique are introduced in this paper. Utilization of these orientation mapping techniques for structural and orientational characterizations are demonstrated by examples of surface-deformed metals with gradient nanostructures, and a sputtered gold film of nano-islands containing nanograins. The merits and challenges of each of these techniques are discussed and suggestions for further developments are proposed.

BackgroundMany studies have reported the roles of the extracellular hypoxia microenvironment in the tumorigenesis and metastasis of multiple cancers. However, long noncoding RNAs (lncRNAs) that induce cancer oncogenicity and metastasis of pancreatic cancer (PC) under hypoxia conditions remain unclear.MethodsIn PC cells, the expression levels of lncRNAs in different conditions (normoxia or hypoxia) were compared through RNA sequencing (RNA-seq). The effects of the zinc finger E-box-binding homeobox 1 (ZEB1-AS1) antisense lncRNA on PC cells cultured in normoxia/hypoxia medium were measured through gain and loss-of-function experiments. Fluorescence in situ hybridization and luciferase reporter assays in addition to in vivo studies were utilized to explore the adaptive mechanisms of ZEB1-AS1 in the hypoxia-promoted proliferation, migration, and invasion ability of PC cells. Moreover, the level of ZEB1-AS1 and its associated targets or pathways were investigated in both PC and pancreatic normal tissues.ResultsRNA-seq revealed that ZEB1-AS1 was significantly upregulated in PC cells under hypoxia conditions. The ZEB1-AS1 expression level was closely associated with poor prognosis of PC patients. Knockdown of ZEB1-AS1 suppressed the proliferation, migration, and invasion of PC cells in vitro as well as PC xenograft tumor growth in vivo. In PC cells, RNAi-mediated reduction of ZEB1-AS1 inhibited zinc finger E-box-binding homeobox 1 (ZEB1), while ZEB1-AS1 overexpression rescued ZEB1 expression, indicating that ZEB1-AS1 promotes ZEB1 expression. Moreover, hypoxia-inducible factor-1α (HIF-1α)induced the expression of ZEB1-AS1 by binding to the ZEB1-AS1 promoter, which contains a putative hypoxia response element (HRE). Mechanistically, ZEB1-AS1 scaffolded the interaction among HIF-1α, ZEB1, and histone deacetylase 1 (HDAC1), leading to deacetylation-mediated stabilization of HIF-1α. We further revealed that ZEB1 induced the deacetylase capacity of HDAC1 to suppress the acetylation or degradation of HIF-1α, improving HIF-1α assembly. Thus, hypoxia-induced ZEB1-AS1 facilitated ZEB1 transcription and the stability of HIF-1α, which promoted the metastasis of PC cells. Clinically, dysregulated ZEB1 and HIF-1α expression was significantly correlated with histological grade, lymphatic metastasis, and distant metastasis in PC patients.ConclusionsOur results emphasized that the positive reciprocal loop of HIF-1α/ZEB1-AS1/ZEB1/HDAC1 contributes to hypoxia-promoted oncogenicity and PC metastasis, indicating that it might be a novel therapeutic target for PC.

Martensitic transformation can easily induce a maximum hardness value of 800–900 HV (Vickers hardness) for steels with carbon contents of 0.6 wt.% and above. However, the occurrence of martensitic transformation in pure iron requires exceptionally high cooling rates (105–106°C/s), and the maximum achievable hardness is only about 150 HV. Here we report an extreme hardness of 830 HV in pure iron obtained through high pressure induced martensitic transformation at a rather slow cooling rate of just 10°C/s. This unprecedented strength originates from the formation of twin-related martensitic laths with an average thickness of 3.8 nm.

Abstract Background Currently, WeChat is widely used in disease education for patients with Crohn’s disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. Methods In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. Results Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn’s and Colitis Foundation (CCCF) (73%), “IBD Academic Officer” (21%) and “IBD in love” (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients’ expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p

Abstract Background Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of noncoding RNAs whose functions are related to the pathogenesis of cancer, but, in CDDP resistance of GC remains unknown. Methods circAKT3 (hsa_circ_0000199, a circRNA originating from exons 8, 9, 10, and 11 of the AKT3 gene) was identified by RNA sequencing and verified by quantitative reverse transcription PCR. The role of circAKT3 in CDDP resistance in GC was assessed both in vitro and in vivo. Luciferase reporter assay, biotin-coupled RNA pull-down and fluorescence in situ hybridization (FISH) were conducted to evaluate the interaction between circAKT3 and miR-198. Functional experiments were measured by western blotting, a cytotoxicity assay, clonogenic assay and flow cytometry. Results The expression of circAKT3 was higher in CDDP-resistant GC tissues and cells than in CDDP-sensitive samples. The upregulation of circAKT3 in GC patients receiving CDDP therapy was significantly associated with aggressive characteristics and was an independent risk factor for disease-free survival (DFS). Our data indicated that circAKT3 promotes DNA damage repair and inhibits the apoptosis of GC cells in vivo and in vitro. Mechanistically, we verified that circAKT3 could promote PIK3R1 expression by sponging miR-198. Conclusions circAKT3 plays an important role in the resistance of GC to CDDP. Thus, our results highlight the potential of circAKT3 as a therapeutic target for GC patients receiving CDDP therapy.

Abstract Background CircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. ‘MiRNA sponge’ is the most reported role played by circRNAs in many tumours. The AKT/mTOR axis is a classic signalling pathway in cancers that sustains energy homeostasis through energy production activities, such as the Warburg effect, and blocks catabolic activities, such as autophagy. Additionally, the AKT/mTOR axis exerts a positive effect on EMT, which promotes tumour metastasis. Methods We detected higher circNRIP1 expression in gastric cancer by performing RNA-seq analysis. We verified the tumour promotor role of circNRIP1 in gastric cancer cells through a series of biological function assays. We then used a pull-down assay and dual-luciferase reporter assay to identify the downstream miR-149-5p of circNRIP1. Western blot analysis and immunofluorescence assays were performed to demonstrate that the circNRIP1-miR-149-5p-AKT1/mTOR axis is responsible for the altered metabolism in GC cells and promotes GC development. We then adopted a co-culture system to trace circNRIP1 transmission via exosomal communication and RIP experiments to determine that quaking regulates circNRIP1 expression. Finally, we confirmed the tumour suppressor role of microRNA-133a-3p in vivo in PDX mouse models. Results We discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. MiR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviours of circNRIP1. Moreover, it was proven that circNRIP1 can be transmitted by exosomal communication between GC cells, and exosomal circNRIP1 promoted tumour metastasis in vivo. We also demonstrated that quaking can promote circNRIP1 transcription. In the final step, the tumour promotor role of circNRIP1 was verified in PDX models. Conclusions We proved that circNRIP1 sponges miR-149-5p to affect the expression level of AKT1 and eventually acts as a tumour promotor in GC.

The multireceptor tyrosine kinase inhibitor sorafenib is a Food and Drug Administration-approved first-line drug for the treatment of advanced liver cancer that can reportedly extend overall survival in patients with advanced hepatocellular carcinoma (HCC). Primary and acquired resistance to sorafenib are gradually increasing however, leading to failure of HCC treatment with sorafenib. It is therefore crucial to study the potential mechanism of sorafenib resistance. The results of the current study indicate that neurite outgrowth inhibitor protein B receptor (NgBR) is overexpressed in cultured sorafenib-resistant cells, and that its expression is negatively correlated with the sensitivity of liver cancer cells to sorafenib. Artesunate can inhibit the expression of NgBR, and it may block sorafenib resistance. Herein we report that sorafenib treatment in combination with artesunate overcomes HCC resistance to sorafenib alone in a cell culture model.

Reinforced concrete (RC) beams that are shear-strengthened by externally bonded (EB) fiber reinforced polymer (FRP) often offer limited structural enhancement. This is due to the inherent weaknesses of EB-FRP strengthening, including the premature debonding of the FRP, its brittle rupture, and inadequate deformation capacity of the strengthening system. In this paper, two techniques of shear strengthening using U-wrapped carbon FRP (CFRP) and effective anchoring devices are proposed and tested with the aim of enhancing both the shear strength and the ductility of retrofitted RC beams. One of the techniques involves a hybrid-bonded (HB) CFRP system with adjustable normal pressure applied to the CFRP U-strips, and the other features the CFRP U-strips fastened by an H-type end anchor (EA). The main test variables of the former and latter shear-strengthening systems are the degree of pressure applied to the CFRP U-strips and the width of the deformation segment (or axial stiffness) of the H-type EA, respectively. The results indicate that both strengthening systems significantly enhanced the shear capacity and ductility of the strengthened RC beams. Compared with the control member, the increments in shear capacity were as high as 54.6 and 68.5% for beams retrofitted with the HB-FRP and the EA FRP systems, respectively, and their deflections at peak shear load increased by 43.9 and 84.1%, respectively. The shear failure modes were found to be related to the parameters used in both the HB-FRP and the EA FRP systems. The critical diagonal crack (CDC) inclination of all specimens was less than 45°, ranging from 38° to 44°. Both positive and negative shear interactions were observed between Vf and Vc plus Vs.

The dual function of a carbon fiber-reinforced polymer (CFRP) bar working as reinforcement and impressed current cathodic protection (ICCP) anode for reinforced concrete structures has been proposed and researched in this paper. The ICCP tests with different current densities and polarization durations were first conducted for the concrete with high chloride content. After the ICCP application, pull out tests were then performed to investigate the bond behaviors of CFRP bars. Experimental results have shown the effectiveness of the new-type ICCP system with the CFRP bar as the anode on corrosion protection. The ICCP system provided electrons to the steel bar continuously and brought the potential of the steel bar down to the immunity region. Under the anodic polarization with a large current density of 100 mA/m2, the CFRP bar-concrete interface presented acidification and the chemical adhesion on the interface was decreased significantly. However, for cases in the experiment, the ICCP application had an insignificant influence on the ultimate bond strength.

Gastric cancer (GC) is a major health problem worldwide because of its high morbidity and mortality. Considering the well-established roles of miRNA in the regulation of GC carcinogenesis and progression, we screened differentially expressed microRNAs (miRNAs) by using The Cancer Genome Atlas (TCGA) and the GEO databases. We found that miR-3174 was the most significantly differentially expressed miRNA in GC. Ectopic miR-3174 expression was also detected in clinical GC patient samples and cell lines and associated with poor patient prognosis. Apoptosis and autophagic cell death are two types of programmed cell death, whereas both are deficient in gastric cancer. Our functional analyses demonstrated that miR-3174 inhibited mitochondria-dependent apoptosis and autophagic cell death in GC. Moreover, high expression of miR-3174 also resulted in Cisplatin resistance in GC cells. Using bioinformatics analyses combined with in vitro and in vivo experiments, we determined that miR-3174 directly targets ARHGAP10. Notably, ARHGAP10 promoted mitochondria-dependent apoptosis by enhancing p53 expression, which was followed by Bax trans-activation and caspase cleavage. ARHGAP10 also facilitated autophagic cell death by suppressing mammalian target of rapamycin complex 1 (mTOC1) activity. Our results reveal a potential miRNA-based clinical therapeutic target that may also serve as a predictive marker for GC.

Background/Aims: There is little published data on the role of FOXP3 in gastric cancer. Methods: FOXP3 expression and localization in gastric cancer tissues and cells were examined by immunohistochemistry, RT-PCR, flow cytometry, western blot, and laser confocal microscopy. CCK8, plate clone, wound healing, and transwell insert assays were performed for gastric cancer cells. Potential molecules and signaling pathways were screened using high-throughput transcriptome sequencing. Results: FOXP3 expression in gastric cancer tissues was higher than that in para-carcinoma tissues. It was restricted to the cytoplasm of para-carcinoma tissues, but was observed in the cytoplasm or/and nuclei of gastric cancer tissues. FOXP3 expression was positively correlated with pathological grading, and was detected in gastric cancer and GES-1 cells, where it was expressed in the cytoplasm alone, or in both the cytoplasm and the nucleus. FOXP3 overexpression promoted cell proliferation, migration, and invasion, while FOXP3 knockdown suppressed these effects. Furthermore, RT-PCR and ELISA confirmed that FOXP3 upregulation resulted in increased TGF-β expression and secretion in gastric cancer cells. Conclusion: FOXP3 expression was associated with degree of gastric cancer differentiation. In addition, upregulated and ectopic tumoral FOXP3 can promote gastric cancer proliferation, migration, and invasion, partly through the TGF-β pathway.

This study was conducted to sequence, assemble, annotate, and characterize the complete chloroplast (cp) genome sequence of Ulmus lanceaefolia. The result showed that the cp genome was 158,652 bp in length with 35.63% GC content, including a large single-copy (LSC) region of 87,119 bp, a small single-copy (SSC) region of 18,697 bp and an inverted repeat sequence (IRa/IRb) region of 26,418 bp, which was a typical tetrad structure. We had identified a total of 132 genes, including 87 protein-coding genes, eight rRNA genes, and 37 tRNA genes. The phylogenetic trees were constructed based on the cp genome sequences of U. lanceaefolia and 12 plants in the NCBI database, and the phylogenetic positions of U. lanceaefolia in the Ulmaceae were identified.

We report on the efficient diode-pumped continuous-wave laser operation of a Nd:YAG crystal at several wavelengths by using a simple and compact two-mirror laser cavity and an undoped YAG thin plate acting as a Fabry-Pérot (F-P) etalon. We thus obtain a high-power single-wavelength laser operation at about 1073 nm with a maximum output power of 5.58 W and a laser slope efficiency of about 36.6%, with respect to absorbed pump power, which is believed to be the highest output power ever obtained with Nd:YAG at 1073 nm. We also achieve dual-wavelength laser operation at 1064 and 1078 nm, with a maximum output power of 1.57 W, and triwavelength laser operation at 1061, 1064, and 1078 nm, with a maximum output power of 2.16 W. This is the first demonstration, to the best of our knowledge, of a diode-pumped Nd:YAG laser at 1078 nm.

An Fe-23Cr-8.5Ni alloy was used as a model material to study the grain size effect on the mechanical behavior of metastable duplex metal. Alloy samples with different grain sizes ranging from 0.1 to 2 μm were prepared by cold-rolling and annealing. A structural refinement to about 0.1 μm results in a high yield strength but very limited ductility. A significant improvement of ductility occurred at the grain size of about 0.4 μm. A further increase in grain size results in a decreased strength and a slightly improved ductility. The alloy with a grain size of about 0.4 μm exhibits an excellent combination of strength and ductility, where the yield strength and tensile elongation are increased up to 738 MPa and 29% as compared to 320 MPa and 33% of a coarse-grained (about 2 μm) sample, respectively. The origin of the excellent mechanical properties was attributed to the unique deformation characteristics associated with the transformation induced plasticity and the development of back stress.

Exploring structural effects that influence both the mechanics and magnetism in nanocrystalline materials, particularly extremely-fine nanograined ones with grain sizes down to several nanometers, is of high interest for developing multifunctional materials combining superior mechanical and magnetic performances. We found in this work that electrodeposited extremely-fine nanograined Ni-P alloys exhibit a significant enhancement of magnetization, simultaneously along with an increase in hardness, after low-temperature annealing. The relaxation of non-equilibrium structures, precipitation of the second phase and the segregation of P atoms to grain boundaries (GBs) during annealing have then been sequentially evidenced. By systematically comparing the variations in macroscopic and microstructural investigation results among several Ni-P alloys with different P contents, we suggest that the second phase has little effect on magnetization enhancement, and essentially both the structural relaxation and GB segregation can play important roles in hardening by governing GB stability, and in the improvement of magnetization by enhancing Ni–Ni atom exchange interactions.

The realization of reducing concrete self-weight is mainly to replace ordinary aggregates with lightweight aggregates; such replacement usually comes with some intrinsic disadvantages in concrete, such as high brittleness and lower mechanical properties. However, these shortages can be effectively remedied by external confinement such as fiber reinforced polymer (FRP) jacketing. To accurately predict the stress-strain behavior of lightweight concrete with lateral confinement, it is necessary to properly understand the coupling effects that are caused by diverse aggregates types and confinement level. In this study, FRP-confined lightweight concrete cylinder with varying aggregate types were tested under axial compression. Strain gauges and linear variable displacement transducers were used for monitoring the lateral and axial deformation of specimens during the tests. By sensing the strain and deformation data for the specimens under the tri-axial loads, the results showed that the lateral to axial strain relation is highly related to the aggregate types and confinement level. In addition, when compared with FRP-confined normal weight aggregate concrete, the efficiency of FRP confinement for lightweight concrete is gradually reduced with the increase of external pressure. Replace ordinary fine aggregate by its lightweight counterparts can be significantly improved the deformation capacity of FRP-confined lightweight concrete, meanwhile does not lead to the reduction of compressive strength. Plus, this paper modified a well-established stress-strain model for an FRP-confined lightweight concrete column, involving the effect of aggregate types. More accurate expressions pertaining to the deformation capacity and the stress-strain relation were proposed with reasonable accuracy.