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The carbon nanotube (CNT) reinforced aluminum sheet with 2.0 mm thickness was hot rolled. The friction stirring process (FSP) was applied to make the reinforcements dispersion uniform. A finite element simulation was conducted to optimize the forming parameters of a V-shaped skin part. It should be formed in two passes, and the bottom corner radius is advisable to be greater than R = 30 mm in the first pass. The V-shaped skin part was successfully formed and the profile accuracy error was less than 0.2 mm. The part's mechanical properties show that the composite sheet still keeps a high strength after two thermal procedures.

This research explores how central-city shopping districts could be transformed to support a post-Covid lifestyle, where people re-embrace community, local streets and walking while relying more on online shopping. By reviewing metropolitan/city development plans since the 1980s and mapping changes of retail provisions, urban environment and pedestrian movements in Melbourne’s Hoddle Grid in the twenty-first century, this paper shows that planning policies focusing on people-centred experiences in the central-city shopping district helped to improve retail resilience. This paper thus adds insights to understanding the relentless retail landscape changes and has implications for central-city retail planning in the post-Covid era.

Aluminum matrix composites have been widely used in aerospace and automotive fields due to their excellent physical properties. Cryogenic treatment was successfully adopted to improve the performance of aluminum alloy components, while its effect and mechanism on the aluminum matrix composite remained unclear. In this work, the effects of cryogenic treatment on the microstructure evolution and mechanical properties of 15%SiCp/2009 aluminum matrix composites were systematically investigated by means of Thermoelectric Power (TEP), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The results showed that TEP measurement can be an effective method for evaluating the precipitation characteristics of 15%SiCp/2009 aluminum matrix composites during aging. The addition of cryogenic treatment after solution and before aging treatment promoted the precipitation from the beginning stage of aging. Furthermore, the aging time for the maximum precipitation of the θ″ phase was about 4 h advanced, as the conduction of cryogenic treatment accelerates the aging kinetics. This was attributed to the great difference in the linear expansion coefficient between the aluminum alloy matrix and SiC-reinforced particles, which could induce high internal stress in their boundaries for precipitation. Moreover, the lattice contraction of the aluminum alloy matrix during cryogenic treatment led to the increase in dislocation density and micro defects near the boundaries, thus providing more nucleation sites for precipitation during the aging treatment. After undergoing artificial aging treatment for 20 h, the increase in dispersive, distributed precipitates after cryogenic treatment improved the hardness and yield strength by 4% and 16 MPa, respectively.

Fe-N-C represents the most promising non-precious metal catalysts (NPMCs) for the oxygen reduction reaction (ORR) in fuel cells, but often suffers from poor stability in acid due to the dissolution of metal sites and the poor oxidation resistance of carbon substrates. In this work, silicon-doped iron-nitrogen-carbon (Si/Fe-N-C) catalysts were developed by in situ silicon doping and metal-polymer coordination. It was found that Si doping could not only promote the density of Fe-N

Based on the time-independent rate equations and nonlinear Schrödinger equation, we simulate a 200 MHz all-polarization-maintaining (PM) mode-locked Yb-doped fiber laser. The cavity round trip evolution toward stable mode locking is present. Additionally, the gain coefficients along the gain fiber as well as the pulses, chirp, and spectra at different locations in the cavity are examined. The effects of chirped fiber Bragg grating parameters on the pulse shape and spectrum profile are also investigated. According to the calculations, we experimentally realize a 200 MHz femtosecond fiber laser with 115 mW output power. The timing jitter and integrated relative intensity noise are measured as 158 fs (1 kHz to 10 MHz) and 0.0513% (1 Hz to 300 kHz), respectively. Eventually, an amplified average power of 610 mW and 79 fs compressed pulses with a peak power of approximately 28 kW are obtained. The exhibited all-PM femtosecond fiber laser system can be adopted as the foundation for an optical frequency comb.

Adipose tissue macrophage (ATM) has been shown to play a key role in the pathogenesis of obesity-associated adipose tissue inflammation and metabolic diseases. However, the upstream factors that integrate the environmental signals to control ATM activation and adipose inflammation in obesity remain elusive. Here, we identify BAF60a, a subunit of the SWI/SNF chromatin remodeling complexes, as the central checkpoint regulator of obesity-induced ATM activation, adipose tissue inflammation and systemic metabolic impairment. BAF60a expression was robustly downregulated in the adipose tissue stromal vascular fractions (SVFs) in type 2 diabetic mice. Myeloid-specific BAF60a ablation (BaMKO) promotes ATM pro-inflammatory activation, exacerbating diet-induced obesity, insulin resistance and metabolic dysfunction. Conversely, myeloid-specific overexpression of BAF60a in mice attenuates macrophage pro-inflammatory activation. Mechanistically, transcriptome and chromatin landscape analyses demonstrate that BAF60a inactivation triggers the expression of pro-inflammatory gene program through chromatin remodeling. Moreover, motif analysis of ATAC-Seq and CUT&Tag-Seq data identifies the transcription factor Atf3 that physically interacts with BAF60a to suppress the pro-inflammatory gene expression, thereby controlling ATM activation and metabolic inflammation in obesity. Consistently, myeloid-specific Atf3 deficiency also promotes the pro-inflammatory activation of macrophage. Together, this work uncovers BAF60a/Atf3 axis as the key regulator in obesity-associated ATM activation, adipose tissue inflammation and metabolic diseases.

Pancreatic β cell plasticity is the primary determinant of disease progression and remission of type 2 diabetes (T2D). However, the dynamic nature of β cell adaptation remains elusive. Here, we establish a mouse model exhibiting the compensation-to-decompensation adaptation of β cell function in response to increasing duration of high-fat diet (HFD) feeding. Comprehensive islet functional and transcriptome analyses reveal a dynamic orchestration of transcriptional networks featuring temporal alteration of chromatin remodeling. Interestingly, prediabetic dietary intervention completely rescues β cell dysfunction, accompanied by a remarkable reversal of HFD-induced reprogramming of islet chromatin accessibility and transcriptome. Mechanistically, ATAC-based motif analysis identifies CTCF as the top candidate driving dietary intervention–induced preservation of β cell function. CTCF expression is markedly decreased in β cells from obese and diabetic mice and humans. Both dietary intervention and AAV-mediated restoration of CTCF expression ameliorate β cell dysfunction ex vivo and in vivo, through transducing the lipid toxicity and inflammatory signals to transcriptional reprogramming of genes critical for β cell glucose metabolism and stress response.

Background Nonalcoholic fatty liver disease (NAFLD), whose pathogenesis remains unelucidated, has become an increasingly prevalent disease globally requiring novel treatment strategies. This study aims to explore the role of leukocyte cell-derived chemotaxin 2 (LECT2), one of the known hepatokines, in the development of NAFLD. Methods The serum LECT2 level was evaluated in patients with NAFLD and male C57BL/6 mice fed a high-fat diet (HFD) for 8 weeks. Tail intravenous injection of adeno-associated virus that contained Lect2 short hairpin RNA or Lect2 overexpression plasmid was administered to mice to inhibit or increase hepatic Lect2 expression. Hepatic steatosis was evaluated by histological staining with haematoxylin and eosin and Oil Red O, and also by quantitative hepatic triglyceride measurements. RNA-seq was performed to discover the specific targets of LECT2 on NAFLD. Results Serum and hepatic LECT2 levels were elevated in NAFLD patients and HFD-fed mice. Inhibition of hepatic Lect2 expression alleviated HFD-induced hepatic steatosis and inflammation, whereas hepatic overexpression of Lect2 aggravated HFD-induced hepatic steatosis and inflammation. RNA-seq and bioinformatical analysis suggested that the signal transducers and activators of transcription-1 (STAT-1) pathway might play an indispensable role in the interaction between LECT2 and NAFLD. A STAT-1 inhibitor could reverse the accumulation of hepatic lipids caused by Lect2 overexpression. Conclusion LECT2 expression is significantly elevated in NAFLD. LECT2 induces the occurrence and development of NAFLD through the STAT-1 pathway. LECT2 may be a potential therapeutic target for NAFLD.

This paper explores how morphological conditions have mediated the evolution of live music venues in Melbourne. Three inner-city creative milieus have been selected in which the frequency of live music gigs shows different patterns of change: emergence, resilience and decline. The urban DMA—density, mix, access—of the study areas was mapped, as the synergies between these attributes have been linked to the emerging ‘atmosphere’ of creative places. The findings indicate that low residential density pockets within higher density neighbourhoods, mix of public–private interfaces including blank walls, fine grain, functional mix and permeability are key enablers of music clusters.

Excessive light exposure is a principal environmental factor, which can cause damage to photoreceptors and retinal pigment epithelium (RPE) cells and may accelerate the progression of age-related macular degeneration (AMD). In this study, oxidative stress, endoplasmic reticulum (ER) stress and autophagy caused by light exposure were evaluated in vitro and in vivo. Light exposure caused severe photo-oxidative stress and ER stress in photoreceptors (661W cells) and RPE cells (ARPE-19 cells). Suppressing either oxidative stress or ER stress was protective against light damage in 661W and ARPE-19 cells and N-acetyl-L-cysteine treatment markedly inhibited the activation of ER stress caused by light exposure. Moreover, suppressing autophagy with 3-methyladenine significantly attenuated light-induced cell death. Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells. Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury.

The large volume and weak environmental adaptability of fiber optical frequency combs (OFCs) have become the main obstacles for their applications in various fields. To address these issues, in this study, we present a compact, low-cost f-to-2f interferometer and fiber actuator with a large tuning range and a high control bandwidth for a 200-MHz OFC that is based on a 1.5-μm all-polarization-maintaining fiber mode-locked laser. By employing customized fiber-coupled gradient index lenses, our f-to-2f interferometer is encapsulated in a miniature tube with a diameter of only 4 mm and a length of 40 mm, which substantially reduces the optical section size of the frequency comb as compared to conventional devices. The carrier envelope offset beat with a signal-to-noise ratio of 40 dB is detected in a resolution bandwidth of 360 kHz. In addition, a laboratory-made piezoelectric transducer-driven mechanical actuator for repetition rate regulation exhibited a large tuning range of 106 kHz (corresponding to an effective temperature drift of 53 °C) and a high control bandwidth of approximately 1 kHz. This resulted in a robust repetition rate locking with an Allan deviation of 330 μHz at a gate time of 1 s and a residual integrated timing jitter of 418 fs [3 Hz to 1 MHz] when referenced to a hydrogen maser. Along with reducing the size and improving the environmental adaptability of the OFC, our design can also decrease the power consumption of the system significantly. Our findings provide a new direction to the development of OFCs for various applications.

This paper focused on FE simulations of the residual stress distributions and evolutions during a newly established manufacturing process (i.e. Solution heat treatment, Cold rolling and Constrained ageing) for the 1:1 industrial-sized aircraft T-section component, which is a problematic component that is currently experiencing the residual stress-induced distortion issue. The integrated FE simulation included three sub-models (i) quenching, (ii) 1.5% cold rolling and (iii) T74 constrained ageing, using two sets of validated constitutive equations. The evolutions and distributions of the residual stress after quenching, cold rolling and constrained ageing were predicted. The simulation results showed that using the given process parameters, the distribution of the residual stresses from quenching was completely reversed and reduced. The final residual stresses in the transverse (σx) and thickness direction (σy) were reduced to ~ 0 MPa. The final residual stress in the rolling direction (σz) followed a “parabolic” distribution, with tensile stresses at the surface while uniform compression stresses ( ~ 140 MPa) at the core. This distribution is expected to benefit the subsequent machining distortion control. The predicted residual stress distributions after each processing stage further verified the effectiveness of the manufacturing process in producing low and controllable residual stresses and provide direct simulation results for industrial-sized components, which are valuable for future industrial application.

ObjectsThe incidence of hepatocellular carcinoma (HCC) shows an obvious male dominance in rodents and humans. We aimed to identify the key autosomal liver-specific sex-related genes and investigate their roles in hepatocarcinogenesis.DesignTwo HCC cohorts (n=551) with available transcriptome and metabolome data were used. Class comparisons of omics data and ingenuity pathway analysis were performed to explore sex-related molecules and their associated functions. Functional assays were employed to investigate roles of the key candidates, including cellular assays, molecular assays and multiple orthotopic HCC mouse models.ResultsA global comparison of multiple omics data revealed 861 sex-related molecules in non-tumour liver tissues between female and male HCC patients, which denoted a significant suppression of cancer-related diseases and functions in female liver than male. A member of cytochrome P450 family, CYP39A1, was one of the top liver-specific candidates with significantly higher levels in female vs male liver. In HCC tumours, CYP39A1 expression was dramatically reduced in over 90% HCC patients. Exogenous CYP39A1 significantly blocked tumour formation in both female and male mice and partially reduced the sex disparity of hepatocarcinogenesis. The HCC suppressor role of CYP39A1 did not rely on its known P450 enzyme activity but its C-terminal region, by which CYP39A1 impeded the transcriptional activation activity of c-Myc, leading to a significant inhibition of hepatocarcinogenesis.ConclusionsThe liver-specific CYP39A1 with female-preferential expression was a strong suppressor of HCC development. Strategies to up-regulate CYP39A1 might be promising methods for HCC treatment in both women and men in future.

The effect of deep cryogenic treatment (DCT) on the artificial ageing kinetics of a SiC particles reinforced aluminum alloy composite (SiCp-Al) is experimentally studied in this paper. The evolutions of both macro-properties (i.e., yield strength and ultimate tensile strength) and microstructures (precipitates) have been investigated by a set of hardness tests, tensile tests, and microstructural observations (scanning electron microscope, SEM and transmission electron microscope, TEM) for a SiCp-Al composite material with conventional heat treatment (solution heat treatment + quenching + artificial ageing, CHT) or DCT (solution heat treatment + quenching + deep cryogenic + artificial ageing). The results show that SiCp could significantly accelerate the ageing kinetics of the composites. Meanwhile, compared with CHT conditions, DCT can further improve the yield strength (YS) and ultimate tensile strength (UTS) of the composite materials after artificial ageing. The microstructures show that DCT induces the generation of more thinner θ′ precipitates homogeneously distributed in the grains during artificial ageing compared with corresponding CHT conditions. A quantified analysis has been performed based on the microstructural data, and the calculated results further support the indication that the strengthening effect in DCT compared with CHT is mainly contributed by corresponding precipitation behavior.

Large tensile residual stresses generated during cold working processes could negatively affect the integrity and geometric accuracy of workpieces. The stress relief annealing is one of the fundamental issues in controlling the deformation of the cold-worked part. A novel residual stress relaxation model was proposed to predict the change of residual stress during the annealing process by considering the dislocation evolution mechanism and the plasticity theory. Copper workpieces were rolled with different rolling ratios and annealed under different heating temperatures and heating times. Hole-drilling experiments were conducted to measure the residual stresses for calibrating the proposed model. The calibrated model was then used to predict the change of residual stresses during annealing heat treatment. The results showed that the initial work hardening of workpieces had a great effect on the residual stress relaxation. Higher initial dislocation density hindered the residual stress relaxation during the annealing process. The results provided guidance on optimizing the annealing conditions for residual stress reduction.

In this paper, we study the distribution of consecutive patterns in the set of 123-avoiding permutations and the set of 132-avoiding permutations, that is, in S n ( 123 ) and S n ( 132 ) . We first study the distribution of consecutive pattern γ-matches in S n ( 123 ) and S n ( 132 ) for each length 3 consecutive pattern γ. Then we extend our methods to study the joint distributions of multiple consecutive patterns. Some more general cases are discussed in this paper as well.

Residual stresses (RS) are often induced through quenching of aluminum alloys and present a potential risk of developing crack or distortion in subsequent manufacturing processes. Study of methods to minimise the RS in quenched components is of practical importance. In this paper, cold rolling (CR) has been carried out to remove the RS in quenched AA7050 blocks. The CR effect on relaxing RS in quenched AA7050 blocks has been evaluated via the neutron diffraction (ND), X-ray diffraction (XRD) and contour techniques. The results reveal that although CR transforms near-surface residual stresses from large compression to large tension along the rolling direction, it results in remarkable RS relief in the core part of the material. An integrated finite element model for RS evolution through the CR process was put forward and has been validated by the experimental results.

Retinal degeneration is a major cause of severe vision loss and irreversible blindness and is characterized by progressive damage to retinal photoreceptor cells. Resveratrol (RSV) serves as an activator of the histone deacetylase, Sirt1, and has been shown to exert anti-oxidative properties. In this study, we mimicked retinal degeneration by subjecting photoreceptors (661 W cells) to glucose deprivation (GD) or light exposure. Under these conditions, we investigated the mechanisms underlying GD- or light exposure-induced cell death and the protective effect of RSV. We found that GD and light exposure resulted in mitochondrial dysfunction, oxidative stress, and cell death. Treatment of injured cells with RSV decreased the production of reactive oxygen species (ROS), improved the ratio of reduced/oxidized glutathione (GSH/GSSG), mitochondrial membrane potential and morphology, and reduced apoptosis. We used the caspase inhibitor, z-VAD-fmk, and a lentiviral-mediated shRNA knockdown of PARP-1 to reveal that GD and light exposure-induced cell death have different underlying mechanisms; GD triggered a caspase-dependent cell death pathway, whereas light exposure triggered a PARP-dependent cell death pathway. The level of caspase-9 and caspase-3, upregulated following GD, were reduced by treatment with RSV. Similarly, the level of PARP-1 and AIF, upregulated following light exposure, were decreased by treatment with RSV. Additionally, treatment with RSV elevated the protein expression and enzymatic activity of Sirt1 and a Sirt1 inhibitor reduced the protective effect of RSV against insult-induced cellular injuries, indicating that RSV's protective effect may involve Sirt1 activation. Finally, we investigated the neuroprotection of RSV in vivo. Administration of RSV to mice under extreme light exposure led to a suppression of the light-induced thinning of the outer nuclear layer (ONL) detected by hematoxylin and eosin (H&E) staining and restored retinal function evaluated by electroretinography (ERG). Taken together, our findings provide evidence that treatment with RSV has neuroprotective effects on both GD and light exposure-induced cell death pathways in photoreceptor cells.

Background: Increased permeability of the renal capillary is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall, and autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the adhesion junction. Methods: We obserned the effect of Ulinastatin in the septic rat model by using contrast-enhanced ultrasonography (CEUS) to evaluate perfusion of the renal cortex and medulla. Male adult Sprague-Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50 000 U/kg) was injected into the tail vein 1 hour after the operation. At 24 hours postoperatively, CEUS was performed to evaluate the renal microcirculation blood flow and microcirculation perfusion. Histological staining was used to evaluate kidney injury scores. Western blotting was used to assess the expression of VE-cadherin and LC3II, peripheral serum cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α levels), renal function (creatinine, urea nitrogen, and S-thrombomodulin level), and the urine neutrophil gelatinase-associated lipocalin level. Results: Compared with sham group, ulinastatin reduced the inflammatory response, maintained the expression of VE-cadherin, inhibited autophagy, and meliorated cortical and medullary perfusion.Conclusions: Ulinastatin effectively protects the adhesion junction and helps to ameliorate the perfusion of kidney capillaries during sepsis by inhibiting autophagy and the expression of inflammatory factors.

Hedyotis diffusa (HD) plus Scutellaria barbata (SB) have been widely used in antitumor clinical prescribes as one of herb pairs in China. We investigated the effect of aqueous extract from Hedyotis diffusa plus Scutellaria barbata at the equal weight ratio (HDSB11) in inhibiting the growth of murine non-small-cell lung cancer cell (NSCLC) line LLC in vivo and in vitro in this study. Compared with other aqueous extracts, HDSB11 showed the lowest IC50 in inhibiting cell proliferation at 0.43 mg/ml. Besides, HDSB11 effectively suppressed colony formation and induced cell apoptosis. The further assessment of HDSB11 on the murine Lewis-lung-carcinoma-bearing mouse model showed it significantly inhibited tumors’ bioluminescence at the dose of 30 g crude drug/kg. Mechanistically, HDSB11 attenuated the expressions of NLRP3, procaspase-1, caspase-1, PRAP, Bcl-2, and cyclin D1 and downregulated the phosphorylation levels of NF-κB, ERK, JNK, and p38 MAPK. In conclusion, HDSB11 could alleviate cell proliferation and colony formation and induce apoptosis in vitro and tumor growth in vivo, partly via NF-κB and MAPK signaling pathways to suppress NLRP3 expression.

Background The goal of our study is to investigate whether the methylation levels of AHCY and CBS promoters are related to the risk of cerebral infarction by detecting the methylation level of AHCY and CBS genes. Methods We extracted peripheral venous blood from 152 patients with cerebral infarction and 152 gender- and age-matched healthy controls, and determined methylation levels of AHCY and CBS promoters using quantitative methylation-specific polymerase chain reaction. We used the percentage of methylation reference (PMR) to indicate gene methylation level. Results We compared the promoter methylation levels of two genes (AHCY and CBS) in peripheral blood DNA between the cerebral infarction case group and the control group. Our study showed no significant difference in AHCY promoter methylation between case and control. Subgroup analysis by gender showed that the methylation level of AHCY in males in the case group was lower than that in the control group, but the difference was not statistically significant in females. In a subgroup analysis by age, there was no significant difference in the AHCY methylation level between the case and control in the young group (≤44 years old). However, the level of AHCY gene methylation in the middle-aged group (45–59 years old) was significantly higher and the aged group (≥60 years old) was significantly lower than that in the control groups. However, CBS promoter methylation levels were significantly lower in the case group than in the control group (median PMR: 70.20% vs 104.10%, P = 3.71E-10). In addition, the CBS methylation levels of males and females in the case group were significantly lower than those in the control group (male: 64.33% vs 105%, P = 2.667E-08; female: 78.05% vs 102.8%, P = 0.003). We also found that the CBS levels in the young (23–44), middle-aged (45–59), and older (60–90) groups were significantly lower than those in the control group (young group: 69.97% vs 114.71%; P = 0.015; middle-aged group: 56.04% vs 91.71%; P = 6.744E-06; older group: 81.6% vs 119.35%; P = 2.644E-04). Our ROC curve analysis of CBS hypomethylation showed an area under the curve of 0.713, a sensitivity of 67.4%, and a specificity of 74.0%. Conclusion Our study suggests that hypomethylation of the CBS promoter may be closely related to the risk of cerebral infarction and may be used as a non-invasive diagnostic biomarker for cerebral infarction.

Cationic lytic peptides (CLPs) have shown promise in treating bacterial infection and cancer via selective disruption of bacterial or cancer cell membranes. In this work, we used a CLP, C6, as a nanocarrier for a hydrophobic anticancer agent, ellipticine (EPT). The size of the resulting C6–EPT complex was ∼190 nm. The in vitro studies using A549 lung cancer cells showed an enhanced anticancer activity of the C6–EPT complex compared to that of C6 or the EPT control. This enhancement was found to correlate with the membrane disruption induced by C6, which facilitated the entry of EPT into cells. More importantly, the C6–EPT complex showed a higher selectivity than that of C6 towards cancer cells upon comparison of their cytotoxicities against A549 cells and NIH-3T3 fibroblast cells. The enhanced therapeutic activity was also found in in vivo studies using an A549 tumor-bearing BALB/c nude mice model. This study provides a new CLP strategy for the development of multifunctional drug delivery systems.

At the forefront of medicine, gene therapy provides an effective way to treat a range of diseases by regulating defective genes at the root of the disease. Short interfering RNAs (siRNAs) hold great promise as therapeutic agents in this domain; however, intracellular delivery remains a major obstacle to clinical applications of therapeutic siRNAs. Here we report a peptide designed to mediate siRNA delivery. This peptide, C6M1, is rationally designed to promote the endosomal escape ability of an existing peptide sequence. Formed C6M1–siRNA nanoscale complexes are able to deliver siRNA into cells and induce specific gene knockdown with low toxicity. The increased membrane disruption ability under acidic conditions of the peptide with tryptophan residue substitution may contribute to the enhanced gene silence efficacy. Intratumoral injection of the complexes results in a marked reduction of tumor growth through downregulation of antiapoptotic Bcl-2 protein in mice. In addition, the C6M1–siRNA complex was proven safe at transfection concentration by cytotoxicity assay. These results demonstrate that the C6M1–siRNA complex is a potent system for efficient gene delivery in vitro and in vivo.

Additional file 2: Supplementary Figure Legends. Figure S1. SIRT1 mRNA levels decreased in light-damaged 661 W cells compared to control cells. Quantitative real-time PCR analysis of SIRT1 mRNA expression. β-ACTIN was used as an endogenous control. SIRT1 expression levels were normalized to the mean expression levels of β-ACTIN. Lt: 1500 lx light exposure for 72 h. All experiments were repeated in triplicate and the results are shown as the means ± SEM (***: P

We provide an all fiber spectrally flat supercontinuum (SC) source generated by pumping a 20 m graded-index multimode fiber (MMF). The fiber pigtails of the all-fiber pump pulse laser and the MMF fused with a special method. After measuring the spectrum and the power, the output power extending from the visible to the mid-infrared is 2 W. To the best of our knowledge, this is the first watt-class and spectrally flat all fiber structured SC source based on graded-index MMF. Finally, we studied the evolution of the SC with increasing output power, which permitted us to more clearly recognize the nonlinear phenomena in the generation of the SC.

This article describes a novel cold working method for relaxing residual stresses in extra-long quenched T-section panels. Distortion led by quench-induced residual stresses in components is usuall...

Batch experiments were conducted to investigate the adsorption characteristics and mechanism of monothioarsenate (MTA) (99%) on sand, soil sediment, and goethite under different pH and solid-liquid ratio conditions. Results showed the following. ① When MTA ranged from 0.14 to 23.59, 0.19 to 41.27, and 0.27 to 32.02 mg·L

A novel set of unified constitutive equations has been developed and validated to describe stress relaxation ageing (SRA) behaviour of 7xxx series aluminium alloys. The model, based on dynamic ageing and power-law creep relations, can predict the stress relaxation, age hardening response and their interactions at different temperatures, through considering the microstructure evolutions (precipitate radius, volume fraction and dislocation density) during SRA. In addition, the model newly incorporates the effects of prior plastic strain. This model was verified through T74 multi-step SRA experiments for different pre-strain conditions. Excellent agreement was achieved between the predicted and experimental results for stress relaxation and yield strength variation. The evolution of micro-internal variables (e.g. normalised precipitate radius) within the model were calibrated by observing transmission electron microscopy (TEM) images both performed in this work and available in literature. The advanced constitutive model developed predicts the mechanical properties and residual stresses in components after ageing. Therefore, the model provides a valuable tool to optimise manufacturing processes leading to many benefits including reduced scrap rates and financial losses.

The slow kinetics of oxygen reduction reaction (ORR) occurring at the cathode of a proton exchange membrane fuel cell require the presence of an electrocatalyst to reduce overpotential. MPt alloy nanocrystals (NCs) have been investigated over the last decade as efficient catalysts for ORR and recent studies have shown that structurally-ordered MPt NCs, i.e., intermetallic NCs (iNCs), are more active and exhibit enhanced stability compared with the corresponding randomly alloyed analogues. This mini-review highlights the recent progress in iNC catalyst development for ORR with emphasis on correlating the synthesis-structure-activity relationship. Perspectives and possible research directions to enhance MPt iNC catalytic performance are also proposed.

A novel insight into the whole two-step stress relaxation ageing process during T74 multi–step ageing treatment (120 °C for 6 h and subsequently 177 °C for 7 h), which is typically experienced by extra-large aircraft components that contain high residual stresses, has been established. Stress relaxation ageing (SRA) tests, tensile tests and transmission electron microscopy (TEM) were performed on AA7050 samples to determine the relationship between internal microstructure and macroscopic behaviour during the stress relaxation and precipitate evolution process. Samples were subjected to SRA at different initial stresses (220–360 MPa) after being pre-strained to different extents (i.e. 0%, 1%, 3%). Room temperature tensile tests were then performed on interrupted SRA test specimens to examine the corresponding strengthening phenomenon. TEM was performed on a selection of peak–aged and T74 over–aged samples to study the precipitate distribution. At 120 °C typical stress relaxation behaviour was observed and the data followed a logarithmic curve. Subsequently at 177 °C, dislocation–creep dominated stress relaxation behaviour, with no apparent threshold stress, was observed. The absence of a threshold stress at 177 °C may be attributed to the continuous over-ageing phenomenon. The effect of pre-deformation levels and initial stresses on SRA has also been investigated. Pre-stretching, which creates uniformly distributed dislocations, promotes stress relaxation and ageing. No significant influence of initial stress level on SRA was observed at 120 °C, but noticeable effects were seen at 177 °C. The calculated stress exponent n at 177 °C is found independent of the initial stresses. These findings provide clear scientific guidance for residual stress reduction during the multi-step ageing process of AA7050 and provide the basis for residual stress prediction models.

Induced pluripotent stem cells (also called iPSCs) are somatic cells reprogrammed by overexpressing four nuclear transcriptional factors containing Sox2, Klf4, c-myc and Oct4 is the one of research hotspots. Its pluripotency, self-renewal capacity and wide accessibility to donor tissues have made possible the means for modified regenerative medicine. They are considered a possible basis of healthy tissue to cure diseases, like ophthalmic diseases, degenerative diseases, age-related macular degeneration (AMD), are primarily because of the weakening capability of photoreceptor cells, retinal ganglion cells (RGCs), retinal pigmented epithelium (RPE) or other retinal cells. And these retinal cells are unable to regenerate and currently there are no effective treatments to restore sight. iPSCs allow for the in vitro development of numerous varieties of retinal cells, and may treat these diseases by retinal transplantation. Although other stem cells could differentiate into retinal cells, iPSCs derived retinal cells might have numerous benefits as compared to other stem cell sources including embryonic stem (ES) cells. Mainly they would be directly obtained from the patient, therefore eradicating every probable chance of adverse immune responses. Second, making iPSCs just needs somatic cells, thus circumventing the valid ethical issues which limited the clinic use of ES cells derived from human. Third, iPSCs are parallel to ES cells in differentiation ability, they can be expanded in vitro and induced to differentiate into retinal cells, providing a renewable source for therapeutic applications and scientific researches. In this current review, we have concise latest progresses.

Since its inception more than a decade ago, gene silencing mediated by double-stranded small interfering RNA (siRNA) has been widely investigated as a potential therapeutic approach for a variety of diseases. However, the use of siRNA is hampered by its rapid degradation and poor cellular uptake in vitro and in vivo. Recently, peptide-based carriers have been applied to siRNA delivery, as an alternative to the traditional delivery systems. Here, a histidine-containing amphipathic amino acid pairing peptide, C6M3, which can form complexes with siRNA, was used as a new siRNA delivery system. This peptide exhibited a high affinity for siRNA and ability to efficiently deliver siRNA into the cells. The interaction of C6M3 with siRNA was investigated to determine the loading capacity of C6M3 at different peptide/siRNA molar ratios. At C6M3/siRNA molar ratio of 10/1, siRNA molecules were entirely associated with C6M3 as indicated by a gel electrophoretic assay and further confirmed by zeta potential analysis. The particle size distribution of the C6M3-siRNA complexes was studied using dynamic light scattering, which showed an intensity-based size distribution peaked approximately at 100 nm in RNase-free water and 220 nm in the Opti-MEM medium. C6M3 adopted a helical secondary structure in RNase-free water and became more so after forming complexes with siRNA. The interaction of siRNA with C6M3 is an entropy-driven spontaneous process, as determined by isothermal titration calorimetry (ITC) study. The efficiency of cellular uptake of the siRNA complexes at different C6M3/siRNA molar ratios was evaluated, and the results showed that C6M3 promoted efficient cellular uptake of siRNA into cells. Furthermore, a significant level of GAPDH gene silencing efficiency (69%) was achieved in CHO-K1 cells, with minimal cytotoxicity.

This work focuses on validating a model, which is defined using load controlled creep ageing data, from strain-controlled stress relaxation ageing tests. A set of phenomenological constitutive equations were proposed. The material constants within the equations were determined from multi-step (120 °C× 6 h +177 °C ×7 h) creep-ageing test data. Temperature effects on the internal state variables (i.e. precipitate size, volume fraction and dislocation density) were also considered. This model was further used to predict the stress relaxation phenomena under the same ageing condition. Although similar stress reduction trends and features were observed, the stress reduction was significantly over-predicted. The over-prediction of the stress reduction magnitude suggests that improvements should be applied to the current modelling method for simulating spring-back after creep age forming.

Context: Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited. Objective: We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved. Materials and methods: C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2 mg/kg), low (100 mg/kg) and high (300 mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism. Results: FSH administration at 100 and 300 mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300 mg/kg) treatment. Upon FSH (100 and 300 mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01–47.70%). Conclusion: This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.

Display Omitted A new status box method is proposed to perform the stock trend prediction.A new feature construction approach for status box is presented.A new hybrid classifier that integrates AdaBoost algorithm, genetic algorithm and probabilistic support vector machine.The status box method can solve the unbalance problem of the stock turning points classification. Stock trend prediction is regarded as one of the most challenging tasks of financial time series prediction. Conventional statistical modeling techniques are not adequate for stock trend forecasting because of the non-stationarity and non-linearity of the stock market. With this regard, many machine learning approaches are used to improve the prediction results. These approaches mainly focus on two aspects: regression problem of the stock price and prediction problem of the turning points of stock price. In this paper, we concentrate on the evaluation of the current trend of stock price and the prediction of the change orientation of the stock price in future. Then, a new approach named status box method is proposed. Different from the prediction issue of the turning points, the status box method packages some stock points into three categories of boxes which indicate different stock status. And then, some machine learning techniques are used to classify these boxes so as to measure whether the states of each box coincides with the stock price trend and forecast the stock price trend based on the states of the box. These results would support us to make buying or selling strategies. Comparing with the turning points prediction that only considered the features of one day, each status box contains a certain amount of points which represent the stock price trend in a certain period of time. So, the status box reflects more information of stock market. To solve the classification problem of the status box, a special features construction approach is presented. Moreover, a new ensemble method integrated with the AdaBoost algorithm, probabilistic support vector machine (PSVM), and genetic algorithm (GA) is constructed to perform the status boxes classification. To verify the applicability and superiority of the proposed methods, 20 shares chosen from Shenzhen Stock Exchange (SZSE) and 16 shares from National Association of Securities Dealers Automated Quotations (NASDAQ) are applied to perform stock trend prediction. The results show that the status box method not only have the better classification accuracy but also effectively solve the unbalance problem of the stock turning points classification. In addition, the new ensemble classifier achieves preferable profitability in simulation of stock investment and remarkably improves the classification performance compared with the approach that only uses the PSVM or back-propagation artificial neural network (BPN).

To investigate the prognostic value of the serum calcium level corrected by serum albumin (cCA) and corrected serum lactate dehydrogenase (LDH) level for the risk stratification for newly diagnosed multiple myeloma (MM) patients.The clinical data and survival of 186 newly diagnosed MM patients admitted to our hospital from June 1, 2015 to November 1, 2017 were collected. The patients's survival time was obtained by telephone and follow-up visits to patients and their families. The value of the prognostic system consisting of cCA levels and LDH levels in the survival time of MM patients was retrospectively analyzed. Moreover, the post-corrected hypercalcemia and high LDH as 2 factors were used for risk stratification, then according to these 2 factors, the MM patients were divided into 3 groups: group 1 (no risk factor), group 2 (1 risk factor) and group 3 (2 risk factors), and the effect of risk factors on the prognosis of MM patients was analyzed.The median follow-up time was 16 months. The cumulative OS rate of the post-corrected hypercalcemia group was lower than that of the non-hypercalcemia group. The 1-year cumulative OS rate in the 2 groups was 79.0%±6.7% and 88.6%±3.0%, the 3-year cumulative OS rate was 53.0%±10.5% and 74.6%±6.6% (P=0.016), respectively. The cumulative OS rate of the high LDH group [LDH ＞upper limit of normal (ULN), ULN=250 U/L] was lower than that in the normal LDH group. The 1-year cumulative OS rate in the 2 groups was 71.6%±8.6% and 90.0%±2.8%, the 2-year cumulative OS rate was 44.9%±12.1% and 83.1%±4.0%, respectively, and the median OS time was 19 months (95%CI: 15.32-23.34) and not reached (P=0.001). The risk stratification analysis showed that the median OS time of the 3 group was not reached (n=103, 57%), not reached (n=70, 39%) and 17 months (n=7, 4%, 95%CI: 5.19-28.41, P＜0.001). Patients with two risk factors had a prognosis worse than patients with 0-1 risk factor.The prognostic combination of corrected serum calcium and LDH levels may provide a basis for risk stratification and prognosis in MM patients in clinical practice.校正血钙与血清乳酸脱氢酶对初诊多发性骨髓瘤患者的预后价值.探讨以经血清白蛋白校正后血清钙(校正血钙，cCA)水平和血清乳酸脱氢酶（LDH）水平，作为危险因素建立的风险分层对初诊多发性骨髓瘤（MM）患者的预后价值.收集本院2015年6月1日至2017年11月1日收治的186例初诊MM患者的临床资料。对患者及家属进行电话随访及门诊就诊情况获得患者生存时间。回顾性分析由cCA水平及LDH水平组成的预后系统对MM患者生存时间的价值。以校正后高血钙和高LDH作为2个危险因素设计风险分层，将患者分为3组：第1组（无危险因素），第2组（1个危险因素）和第3组（2个危险因素），比较风险因素对MM患者预后的作用.中位随访时间16个月。校正后高钙组累积生存率低于非高钙组，2组的1年累积OS率分别为79.0%±6.7%和88.6%±3.0%，3年累积OS率分别为53.0%±10.5%和74.6%±6.6%（P=0.016）。高LDH组[LDH＞正常上限（ULN），ULN=250 U/L]累积生存率低于LDH正常组，2组的1年累积OS率分别为71.6%±8.6%和90.0%±2.8%，2年累积OS率分别为44.9%±12.1%和83.1%±4.0%，中位OS时间分别为19个月（95%CI：15.32-23.34）和未达到（P=0.001）。危险分组比较显示，第1组、第2组和第3组中位OS时间分别为未达到（n=103, 57%）、未达到（n=70, 39%）和17个月（n=7，4%，95%CI：5.19-28.41）（P＜0.001）。有2种危险因素的患者预后比0-1个危险因素的患者差.校正血钙和LDH水平的预后组合可以为临床实践中MM患者的风险分层和预后提供依据.

Limb spasms are phenomena of hyperreflexia that occur after spinal cord injury. Currently, the clinical treatment is less than ideal. Our goal is to develop a combination therapy based on individualized medicine to reduce spasticity after spinal cord injury. In this study, rats received a severe contusive injury at the T9 segment of the spinal cord, followed by gene therapy with adenoassociated virus encoding human neurotrophic factor 3 (AAV-NT3) and a 2-week exercise program starting at 4 weeks after injury. We quantified the frequency of spasms during a swimming test at 4 and 6 weeks after injury and confirmed the results of the swimming test by measuring the H-reflex of the plantar muscle. We obtained weekly hind limb exercise scores to assess the effect of the interventions in hind limb motor function improvement. Then, we used immunofluorescence to observe the immunoreactivity of spinal motor neurons, synaptophysin, cholinergic interneurons, and GABAergic interneurons. We also measured the expression of KCC2 in the spinal cord by western blot. We found that AAV-NT3 gene therapy, exercise, and combination therapy all attenuated the frequency of spasms in the swimming test conducted at 6 weeks after spinal cord injury and increased rate-dependent depression of H-reflex. Combination therapy was significantly superior to AAV-NT3 alone in protecting motor neurons. Recovery of KCC2 expression was significantly greater in rats treated with combination therapy than in the exercise group. Combination therapy was also significantly superior to individual therapies in remodeling spinal cord neurons. Our study shows that the combination of AAV-NT3 gene therapy and exercise can alleviate muscle spasm after spinal cord injury by altering the excitability of spinal interneurons and motor neurons. However, combination therapy did not show a significant additive effect, which needs to be improved by adjusting the combined strategy.

A novel manufacturing process, enabling the production of high quality (i.e. with low and controllable residual stress (RS) distributions and good mechanical properties) T-section 7xxx panels, has been established. This process provides a solution to residual stress induced distortion problems, which greatly concerns a range of industries, especially the aircraft industry. This process consists of three sequential steps — water quenching (WQ), cold rolling (CR) and constrained ageing (CA). The effectiveness of this process was experimentally verified through applying this process to laboratory sized 7050 T-section panels. The RS was measured by neutron diffraction and X-ray techniques, in addition to deflections and hardness at each processing stage. An integrated Finite Element (FE) model, including all three steps, was developed to simulate this manufacturing process and predict both the RS and the final strength distributions. It has been concluded that this novel process can effectively reduce the residual stresses from ±300 MPa to within ±100 MPa and produce T-section panels with required mechanical properties (i.e. hardness: ~159 HV10). A cold rolling level of 1.5% was found most appropriate. The residual stress and yield strength distributions were accurately predicted by FE, providing a valuable prediction tool to process optimization for industrial applications. Keywords: Residual stress, Neutron and X-ray diffraction, Integrated FE model, New manufacturing process, 7050 T-section

Let \(\mathscr {L}_n\) denote the set of all paths from [0, 0] to [n, n] which consist of either unit north steps N or unit east steps E or, equivalently, the set of all words \(L \in \{E,N\}^*\) with n E’s and n N’s. Given \(L \in \mathscr {L}_n\) and a subset A of \([n] = \{1, \ldots , n\}\), we let \(ps_{L}(A)\) denote the word that results from L by removing the \(i^{th}\) occurrence of E and the \(i^{th}\) occurrence of N in L for all \(i \in [n]-A\), reading from left to right. Then, we say that a paired pattern \(P \in \mathscr {L}_k\) occurs in L if there is some \(A \subseteq [n]\) of size k such that \(ps_L(A) = P\). In this paper, we study the generating functions of paired pattern matching in \(\mathscr {L}_n\).

A finite element model has been developed to determine the effectiveness of a cold compression technique to reduce the large residual stresses generated from quenching solution heat treated T-section components of aluminium alloy AA7050. To compress long components, a multi-step process is required with some amount of overlap. A parametric study has been performed to determine the effect of the compression ratio, friction coefficient, length of overlap and length of the T-section component on the residual stress distribution post-quenching and after subsequent cold compression. Generally, a percentage reduction in the peak residual stress of over 90% was found. The optimal parameters for residual stress relief by cold compression have been suggested from the cases considered.