Search

The production of reactive oxygen species (ROS) is susceptible to external excitation or insufficient supply of related participants (e.g., hydrogen peroxide (H2O2) and sensitizer), liming ROS-driven tumor treatment. Additionally, the lysosomal retention effect severely hinders the utilization of ROS-based nanosystems and severely restricted the therapeutic effect of tumors. Therefore, first reported herein an intelligent nanocatalyst, TCPP-Cu@MnOx ((MnII)1(MnIII)2.1(MnIV)2.6O9.35), and proposed a programmed ROS amplification strategy to treat tumors. Initially, the acidity-unlocked nanocatalyst was voluntarily triggered to generate abundant singlet oxygen (1O2) to mediate acid lysosomal ablation to assist nanocatalyst escape and partially induce lysosomal death, a stage known as lysosome-driven therapy. More unexpectedly, the high-yielding production of 1O2 in acid condition (pH 5.0) was showed compared to neutral media (pH 7.4), with a difference of about 204 times between the two. Subsequently, the escaping nanocatalyst further activated H2O2-mediated 1O2 and hydroxyl radical (•OH) generation and glutathione (GSH) consumption for further accentuation tumor therapy efficiency, which is based on the Fenton-like reaction and Russell reaction mechanisms. Therefore, in this system, a program-activatable TCPP-Cu@MnOx nanocatalyst, was proposed to efficiently destruct organelle-lysosome via 1O2 inducing, and stimulated H2O2 conversion into highly toxic 1O2 and •OH in cytoplasm, constituting an attractive method to overcome limitations of current ROS treatment.

Abstract Slide electrification is the spontaneous separation of electric charges at the rear of water drops sliding over solid surfaces. This study delves into how surfaces treated with a low-pressure plasma impact water slide electrification. Ar, O2, and N2 plasma treatment reduced the drop charge and contact angles on glass, quartz, and SU-8 coated with 1H,1H,2H,2H-perfluoroctyltrichlorosilane (PFOTS), and polystyrene. Conversely, 64% higher drop charge was achieved using electrode-facing treatment in plasma chamber. Based on the zeta potential, Kelvin potential, and XPS measurements, the plasma effects were attributed to alterations of the topmost layer's chemistry, such as oxidation and etching, and superficially charge deposition. The surface top layer charges were less negative after electrode-facing and more negative after bulk plasma treatment. As a result, the zeta potential was less negative after electrode-facing and more negative after bulk plasma treatment. Although the fluorinated layer was applied after plasma activation, we observed a discernible impact of plasma-glass treatment on drop charging. Plasma surface modification offers a means to adjust drop charges: electrode-facing treatment of the fluorinated layer leads to an enhanced drop charge, while plasma treatment on the substrate prior to fluorination diminishes drop charges, all without affecting contact angles or surface roughness.

Due to lithological and environmental differences, the weathering degree of stone heritage varies even within the same area. Various factors dominate the weathering process at different stages. Implementing preventive measures has reduced the impact of controllable factors such as human activities. However, salt weathering caused by atmospheric pollutants, water, and salt migration in rock formations has emerged as a major contributor to the deterioration of stone heritage. Understanding the re-weathering characteristics of stone cultural heritage at different weathering degrees is crucial for preventive protection. This study investigated the weathering status of Nanshiku Temple and designed an experimental scheme based on field monitoring data. By controlling the number of freeze-thaw cycles, stones with different weathering degrees were prepared, and sulfate weathering simulations were conducted. The results revealed severe damage to sandstone due to Na2SO4 crystallization. Higher initial weathering degrees resulted in more pronounced deterioration and faster weathering rates. Surface hardness analysis approximated the decay process using a logarithmic function within a certain range but could not fully capture the overall weathering of the stone. Uniaxial compressive strength showed a strong correlation with weathering indices like p-wave velocity. These findings provide a theoretical basis for preventive protection efforts in stone cultural heritage.

Aurantii fructus immaturus (AFI) and Magnoliae Officinalis Cortex (MOC) have been used to treat constipation in China for thousands of years. In this study, a mouse model of slow transit constipation (STC) was established by gavage of loperamide at a dose of 10 mg/kg bw/day for seven days. Seventy-two mice were randomly allocated to six groups (control, STC model, 3 g/kg AFI + MOC, 6 g/kg AFI + MOC, 12 g/kg AFI + MOC, and mosapride). A mixed aqueous extract of AFI and MOC was administered to the STC mice at the corresponding doses from the first day of modelling. Body weight, faecal water content, gastrointestinal transit time, and intestinal propulsion rate were evaluated. Serum levels of neurotransmitters and gastrointestinal hormones, colonic expression of aquaporins (AQP), and interstitial cells of Cajal (ICC) were assessed using ELISA, immunohistochemistry, and Western blot analysis. The abundance and diversity of the gut microbiota were analysed by 16S rRNA gene sequencing. The mixed aqueous extract significantly increased faecal water content and intestinal propulsion rate and shortened gastrointestinal transit time in STC mice. Furthermore, the administration of AFI and MOC significantly decreased serum vasoactive intestinal peptide (VIP), nitric oxide (NO), and somatostatin (SS) levels and increased serum motilin (MTL) levels in STC mice. The protein expression levels of AQP3 and AQP4 in the colon tissue of STC mice significantly decreased following AFI + MOC treatment, whereas those of AQP9 significantly increased. Moreover, the AFI + MOC treatment led to an increase in the number and functionality of ICCs. In addition, the relative abundances of Ruminococcus and Oscillospira increased in response to the administration of AFI + MOC in STC mice. In conclusion, the mixed aqueous extract of AFI and MOC promoted defaecation and increased intestinal mobility in STC mice. Its mechanisms of action involve modulatory effects on neurotransmitters, gastrointestinal hormones, AQPs, and ICCs. AFI + MOC treatment also improved the diversity and abundance of the gut microbiota in STC mice, particularly short-chain fatty acid-producing bacteria, which may play an important role in its beneficial effect on constipation.

Abstract Purpose Total-body PET imaging with ultra-high sensitivity makes high-temporal-resolution framing protocols possible for the first time, which allows to capture rapid tracer dynamic changes. However, whether protocols with higher number of temporal frames can justify the efficacy with substantially added computation burden for clinical application remains unclear. We have developed a kinetic modeling software package (uKinetics) with the advantage of practical, fast, and automatic workflow for dynamic total-body studies. The aim of this work is to verify the uKinetics with PMOD and to perform framing protocol optimization for the oncological Patlak parametric imaging. Methods Six different protocols with 100, 61, 48, 29, 19 and 12 temporal frames were applied to analyze 60-min dynamic 18F-FDG PET scans of 10 patients, respectively. Voxel-based Patlak analysis coupled with automatically extracted image-derived input function was applied to generate parametric images. Normal tissues and lesions were segmented manually or automatically to perform correlation analysis and Bland–Altman plots. Different protocols were compared with the protocol of 100 frames as reference. Results Minor differences were found between uKinetics and PMOD in the Patlak parametric imaging. Compared with the protocol with 100 frames, the relative difference of the input function and quantitative kinetic parameters remained low for protocols with at least 29 frames, but increased for the protocols with 19 and 12 frames. Significant difference of lesion K i values was found between the protocols with 100 frames and 12 frames. Conclusion uKinetics was proved providing equivalent oncological Patlak parametric imaging comparing to PMOD. Minor differences were found between protocols with 100 and 29 frames, which indicated that 29-frame protocol is sufficient and efficient for the oncological 18F-FDG Patlak applications, and the protocols with more frames are not needed. The protocol with 19 frames yielded acceptable results, while that with 12 frames is not recommended.

Abstract Background CD97 is the most widely expressed G protein-coupled receptor in the epidermal growth factor seven-span transmembrane family. It plays a vital role in cell adhesion, migration, and cell connection regulation. We explored the role of CD97 in hepatocellular carcinoma (HCC). Methods We evaluated CD97 mRNA expression in HCC using TNMplot and the Gene Expression Omnibus database. The clinical prognostic significance of CD97 in HCC patients was evaluated by gene expression profiling interactive analysis, the Kaplan–Meier plotter, and the UALCAN database. The Tumor Immune Estimation Resource (TIMER) and CIBERSORT databases were used to analyze the relationships among CD97, genes positively related with CD97, and tumor-infiltrating immune cells. Results CD97 was highly expressed in HCC tissues and was associated with an adverse prognosis. CD97 and genes positively related with CD97 were positively correlated with the abundance of tumor-infiltrating immune cells and strongly correlated with tumor-infiltrating macrophages (all r ≥ 0.513, P < 0.001). CD97 was positively correlated with M2 macrophage and tumor-associated macrophage markers (both r ≥ 0.464, P < 0.001). CD97 was found to be an immune-related gene in HCC and positively correlated with the TOX, PD-L1, PD-L2, CTLA4, and PD-1 immune checkpoint genes. CD97 copy number alterations affect the level of immune cell infiltration and mRNA expression. Conclusions CD97 can be used as a potential molecular marker of prognosis in HCC, which is associated with immune cell infiltration.

Abstract Objectives To validate a total-body PET-guided deep progressive learning reconstruction method (DPR) for low-dose 18F-FDG PET imaging. Methods List-mode data from the retrospective study (n = 26) were rebinned into short-duration scans and reconstructed with DPR. The standard uptake value (SUV) and tumor-to-liver ratio (TLR) in lesions and coefficient of variation (COV) in the liver in the DPR images were compared to the reference (OSEM images with full-duration data). In the prospective study, another 41 patients were injected with 1/3 of the activity based on the retrospective results. The DPR images (DPR_1/3(p)) were generated and compared with the reference (OSEM images with extended acquisition time). The SUV and COV were evaluated in three selected organs: liver, blood pool and muscle. Quantitative analyses were performed with lesion SUV and TLR, furthermore on small lesions (≤ 10 mm in diameter). Additionally, a 5-point Likert scale visual analysis was performed on the following perspectives: contrast, noise and diagnostic confidence. Results In the retrospective study, the DPR with one-third duration can maintain the image quality as the reference. In the prospective study, good agreement among the SUVs was observed in all selected organs. The quantitative results showed that there was no significant difference in COV between the DPR_1/3(p) group and the reference, while the visual analysis showed no significant differences in image contrast, noise and diagnostic confidence. The lesion SUVs and TLRs in the DPR_1/3(p) group were significantly enhanced compared with the reference, even for small lesions. Conclusions The proposed DPR method can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment while maintaining image quality.

Abstract Atomistic mechanisms of frictional energy dissipation have attracted significant attention. However, the dynamics of phonon excitation and dissipation remain elusive for many friction processes. Through systematic fast Fourier transform analyses of the frictional signals as a silicon tip sliding over a graphite surface at different angles and velocities, we experimentally demonstrate that friction mainly excites non-equilibrium phonons at the washboard frequency and its harmonics. Using molecular dynamics simulations, we further disclose the phononic origin of structural lubrication, i.e., the drastic reduction of friction force as the contact angle between two commensurate surfaces changes. In commensurate contacting states, friction excites a large amount of phonons at the washboard frequency and many orders of its harmonics that perfectly match each other in the sliding tip and substrate, while for incommensurate cases, only limited phonons are generated at mismatched washboard frequencies and few low order harmonics in the tip and substrate.

The orientated Mg-4.70Zn-0.38Y-0.14Zr alloy with high product of strength and elongation (PSE = 5346 MPa•%) was prepared using directional solidification technology. Electron Back Scatter Diffraction (EBSD) and High Resolution Transmission Electron Microscopy (HRTEM) were applied to explore the deformation mechanism and plasticity improvement of experimental alloys. Experiment results showed that the dominant deformation systems were non-basal slipping systems and compression twin pairs (CTPs). High critical resolved shear stress (CRSS) of non-basal slipping system increased the yield strength (180 MPa) and tensile strength (198 MPa). The CTP followed the geometrical relationship of TP1 (twinning plane of variant1)∥TP2 (twinning plane of variant2) and appeared in a wider misorientation range than tensile twin pair which was classified as twinning shear transmission and had high geometric coordination factor (m’). Calculation results showed that the stress concentration at the junction of CTP and grain boundaries was the same as inside the compression twin. 60% of x/ (0°≤x

Background and Aims: Mitochondria have a pivotal role in the quality of embryos and good development to a healthy embryo pregnancy. Also, mitochondrial dysfunction increases during the aging of the embryos. But there is still a debate about the main cause of mitochondrial dysfunction in the aged embryos. We investigate that effect of microtubule stabilizer (MTS) as Taxol, EpD and microtubule disturber (MTD) as VNB in the preimplantation embryo of the mouse. Method: We performed preimplantation embryo culture with MTS and MTD. Then we assess development ratio and mitochondria functional activity between control and MTS and MTD. We performed comparable analysis of mitochondrial motility between MTS treated and MTD treated embryos by confocal live imaging. Results: In the MTS treated embryos, well-developed embryos with microtubules formation were present in the ooplasm. However, in the MTD treated embryos group, less development and poor microtubule polymer formation was observed in the ooplasm. Microtubules was also demonstrated by depolymerization and the clustering form in the ooplasm of MTD treated embryos. The high dynamic movement of the cytoskeleton with a mitochondrion compared to the MTD treated embryos. Conclusion: Our data suggest that the new function of MTS as Taxol, EpD shows promoting competence of embryo development with enhanced activity of a mitochondrial function. Therefore, MTS is useful as a supplement in vitro culture media of embryos.

Abstract Background To investigate the influence of small voxel Bayesian penalized likelihood (SVB) reconstruction on small lesion detection compared to ordered subset expectation maximization (OSEM) reconstruction using a clinical trials network (CTN) chest phantom and the patients with 18F-FDG-avid small lung tumors, and determine the optimal penalty factor for the lesion depiction and quantification. Methods The CTN phantom was filled with 18F solution with a sphere-to-background ratio of 3.81:1. Twenty-four patients with 18F-FDG-avid lung lesions (diameter

Abstract Background The majority of mammalian genome is composed of non-coding regions, where numerous long non-coding RNAs (lncRNAs) are transcribed. Although lncRNAs have been identified to regulate fundamental biological processes, most of their functions remain unknown, especially in metabolic homeostasis. Analysis of our recent genome-wide screen reveals that Gm15441, a thioredoxin-interacting protein (Txnip) antisense lncRNA, is the most robustly induced lncRNA in the fasting mouse liver. Antisense lncRNAs are known to regulate their sense gene expression. Given that Txnip is a critical metabolic regulator of the liver, we aimed to investigate the role of Gm15441 in the regulation of Txnip and liver metabolism. Methods We examined the response of Gm15441 and Txnip under in vivo metabolic signals such as fasting and refeeding, and in vitro signals such as insulin and key metabolic transcription factors. We investigated the regulation of Txnip expression by Gm15441 and the underlying mechanism in mouse hepatocytes. Using adenovirus-mediated liver-specific overexpression, we determined whether Gm15441 regulates Txnip in the mouse liver and modulates key aspects of liver metabolism. Results We found that the expression levels of Gm15441 and Txnip showed a similar response pattern to metabolic signals in vivo and in vitro, but that their functions were predicted to be opposite. Furthermore, we found that Gm15441 robustly reduced Txnip protein expression in vitro through sequence-specific regulation and translational inhibition. Lastly, we confirmed the Txnip inhibition by Gm15441 in vivo (mice) and found that Gm15441 liver-specific overexpression lowered plasma triglyceride and blood glucose levels and elevated plasma ketone body levels. Conclusions Our data demonstrate that Gm15441 is a potent Txnip inhibitor and a critical metabolic regulator in the liver. This study reveals the therapeutic potential of Gm15441 in treating metabolic diseases.

Relationship extraction is a crucial step in the construction of a knowledge graph. In this research, the grid field entity relationship extraction was performed via a labeling approach that used span representation. The subject entity and object entity were used as training instances to bolster the linkage between them. The embedding layer of the RoBERTa pre-training model included word embedding, position embedding, and paragraph embedding information. In addition, semantic dependency was introduced to establish an effective linkage between different entities. To facilitate the effective linkage, an additional lexically labeled embedment was introduced to empower the model to acquire more profound semantic insights. After obtaining the embedding layer, the RoBERTa model was used for multi-task learning of entities and relations. The multi-task information was then fused using the parameter hard sharing mechanism. Finally, after the layer was fully connected, the predicted entity relations were obtained. The approach was tested on a grid field dataset created for this study. The obtained results demonstrated that the proposed model has high performance.

Abstract The aircraft weight and balance problem (WBP) defined in terms of selecting unit load devices (ULDs) from an available set and allocating them to specified positions in cargo holds. It is critical to aircraft safety as well as operational efficiency and profit. It is an NP‐hard problem combining characteristics of the knapsack problem and generalized assignment problems, as well as complex practical constraints. A mixed integer programming model is constructed to maximize the total payload and minimize the center of gravity (CG) deviation by considering the constraints of positions, weights, balance etc. In contrast to prior studies using a constant delta to limit CG deviation, a new set of CG envelope constraints is proposed based on the variation in actual CG under different statuses and precise describing CG. A linearizing strategy is further designed to simplify the nonlinear CG envelope constraints. The proposed model can be solved using commercial optimization software within a few seconds and maintain the CG within the designated CG envelope in all test instances; in contrast, the other (CG deviation‐based) method may result in flight hazards in some scenarios.

A series of γ-lactone derivatives (E)-4-arylidene-5-oxotetrahydrofuran derivatives were synthesized via a tandem Passerini 3CC/SN cyclization microwave-assisted one-pot method efficiently starting from Baylis Hillman acids, aryl glyoxals and isocyanides, and using ionic liquid as reaction medium. The products were characterized by hydrogen nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR). Single crystal X-ray analysis of the compound RPDFB clearly confirmed its assigned chemical structures. Meanwhile, the effects of four compounds (RPDFB, RPDFC, RPDFI, RPDFJ) on the growth inhibition activity of Gibberella zeae were detected, and found that the compound RPDFB has significant growth inhibition activity to Gibberella zeae.

We have synthesized Rhopaladins’ analog (2E,4E)-4-chlorobenzylidene-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) via a highly facile, inexpensive and green approach and verified the structural superiority of compound RPDPRH through molecular docking. Moreover, we further detected the anti-proliferation, apoptosis and HPV E6/E7 effects of RPDPRH on CaSki cells. Finally, we confirmed that compared with the previous compound (E)-N-(tert-butyl)-2-(4-chlorobenzoyl)-4-(4-fluorobenzylidene)-1-isopropyl-5-oxopyrrolidine-2-carboxamide (RPDPB), RPDPRH could better inhibit proliferation, induce apoptosis, and down-regulate HPV E6/E7 mRNA expression on Caski cells. And preliminary RT-PCR experiments have demonstrated that RPDPRH also could affect the expression of Bcl-2, Bax and Caspase-3 mRNA in Caski cells. In summary, RPDPRH has potential as an effective agent against cervical cancer and will play an important role in our subsequent research.

The current air cargo loading plan handles the Air Cargo Palletization Problem (ACPP) and the Aircraft Weight and Balance Problem (WBP) separately, which has an impact on the optimization of the payload and the aircraft’s center of gravity (CG). Thanks to improvements in computer processing power, the joint combinatorial optimization of ACPP and WBP is now feasible. Three integer linear programming models are proposed: a Bi-objective Optimization Model (BOM), a Combinatorial Optimization Model (COM), and an Improved Combinatorial Optimization Model (IOM). The objectives of the models are the maximum loading capacity and the lowest CG deviation from a specified target CG. The models also consider a wide range of restrictions in the actual packing and stowage procedures, such as volume, weight, loading position, aircraft balance, and other aspects of aircraft and unit load devices. Four scenarios with various conditional metrics for three models are solved for the B777F aircraft using Gurobi. The results of the computations demonstrate that the BOM has the fastest solution speed, but the CG deviation is the largest, and in several cases the CG deviation results are unacceptable. The COM has the longest solution time, which is difficult to tolerate in practice. Despite taking a little longer to solve computationally than the BOM, the IOM offers the best optimization solution.

The Wudaoliang–Changshagongma fault is one of the NW-trending faults located within the southern Bayan Har Block of the Tibetan Plateau in China. In this paper, we used high-resolution imagery and digital elevation model data to study the geomorphological and geological characteristics of the fault. Furthermore, the result also determined the fault trace and estimated the average horizontal slip rate of the fault since the late Quaternary to have been 2.6 ± 0.6 mm/a. This slip rate is approximately equivalent to that of the Awancang, Madoi–Garde, and Dari faults, which are also located within the block. Furthermore, the slip rates of these faults obtained by remote sensing and geological methods are consistent with GPS observations. It indicates that tectonic deformation within the block is continuous and diffuse. Using trenching study results and sedimentary radiocarbon dating, we identified four paleoearthquake events that occurred at 42,378–32,975, 33,935–20,663, 5052–4862, and after 673–628 cal BP, respectively. The recurrence intervals of large earthquakes on the faults within the block are much longer than those of the boundary faults, and the slip rates are also smaller, indicating that faults within the block play a regulatory role in the tectonic deformation of the Bayan Har Block.

Gynecological malignancy seriously threatens the physical and mental health of women. Shikonin is a naphthoquinone compound with a variety of biological activities. Studies have shown that shikonin can inhibit cell proliferation, promote cell apoptosis and induce cell necrosis. And in recent years, shikonin are also being increasingly used for the study of gynecological malignant diseases. Therefore, we reviewed the mechanism of action and structure optimization of shikonin in gynecological malignant tumors, in order to provide some reference for further research and development of related drug.

Glutamate-induced neuroexcitotoxicity could be related to the pathophysiology of some neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibiting N-Methyl-D-Aspartate (NMDA) receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicity via binding to its P2Y1 receptors. We found that excessive glutamate triggered cellular reactive oxygen species (ROS) overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicity via Erk1/2-mediated autophagy inhibition, implying the potential of ATP for the treatment of neurodegenerative disorders.

Abstract Background Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/β-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear. Methods RNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression. Results We demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/β-catenin pathway via ubiquitination of adenomatous polyposis coli (APC). Conclusion The current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.

Abstract Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction (MI). MicroRNA-146b (miR-146b) is an active regulator of immunomodulation, but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following MI remain largely unknown. Herein, miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia patients. Gain- and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac cells. Overexpression of miR-146b-5p activated fibroblast proliferation, migration, and fibroblast-to-myofibroblast transition, impaired endothelial cell function and stress survival, and disturbed macrophage paracrine signaling. Interestingly, the opposite effects were observed when miR-146b-5p expression was inhibited. Luciferase assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1 (IRAK1) and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1). Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death, and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine MI models. Local inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following MI.

In Brassica napus L. (rapeseed), complete genic male sterility (GMS) plays an important role in the utilization of heterosis. Although microRNAs (miRNAs) play essential regulatory roles during bud development, knowledge of how GMS is regulated by miRNAs in rapeseed is rather limited. In this study, we obtained a novel recessive GMS system, CN12AB. The sterile line CN12A has defects in tapetal differentiation and degradation. Illumina sequencing was employed to examine the expression of miRNAs in the buds of CN12A and the fertile line CN12B. We identified 85 known miRNAs and 120 novel miRNAs that were expressed during rapeseed anther development. When comparing the expression levels of miRNAs between CN12A and CN12B, 19 and 18 known miRNAs were found to be differentially expressed in 0.5–1.0 mm buds and in 2.5–3.0 mm buds, respectively. Among these, the expression levels of 14 miRNAs were higher and the levels of 23 miRNAs were lower in CN12A compared with CN12B. The predicted target genes of these differentially expressed miRNAs encode protein kinases, F-box domain-containing proteins, MADS-box family proteins, SBP-box gene family members, HD-ZIP proteins, floral homeotic protein APETALA 2 (AP2), and nuclear factor Y, subunit A. These targets have previously been reported to be involved in pollen development and male sterility, suggesting that miRNAs might act as regulators of GMS in rapeseed anthers. Furthermore, RT-qPCR data suggest that one of the differentially expressed miRNAs, bna-miR159, plays a role in tapetal differentiation by regulating the expression of transcription factor BnMYB101 and participates in tapetal degradation and influences callose degradation by manipulating the expression of BnA6. These findings contribute to our understanding of the roles of miRNAs during anther development and the occurrence of GMS in rapeseed.

Winter rapeseed (Brassica rapa L.) is an important oilseed crop in northwest China. Freezing stress severely limits its production and geographical distribution, and frequent extreme freezing events caused by climate change are increasing the chances of winter freeze-injury. However, the underlying mechanism of B. rapa response to freezing stress remains elusive. Here, B. rapa genome (v3.0) was used as a reference for the comparative transcriptomic analysis of Longyou 6 and Tianyou 2 (strong and weak cold tolerance, respectively) under different freezing stress. Before and after freezing stress, 5,982 and 11,630 unique differentially expressed genes (DEGs) between two cultivars were identified, respectively. After freezing stress, the GO terms in Tianyou 2 were mainly involved in “macromolecule biosynthetic process”, and those in Longyou 6 were involved in “response to stimulus” and “oxidoreductase activity”. Morphological and physiological results indicated that Longyou 6 retained a higher basal freezing resistance than Tinayou 2, and that cold acclimation could strengthen the basal freezing resistance. Freezing stress could activate the MAPK signal cascades, and the phosphorylation level of Longyou 6 showed a higher increase in response to freezing treatment than Tianyou 2. Based on our findings, it was speculated that the cell membrane of B. rapa perceives external signals under freezing stress, which are then transmitted to the nucleus through the cold-activated MAPK cascades and Ca2+-related protein kinase pathway, thus leading to activation of downstream target genes to enhance the freezing resistance of B. rapa.

The Internet is like a huge neural network that is thought to be built, linking all the information in the human brain, and the communication between people is a part of the communication in the whole society. Social products are the medium of communication between people, so the efficiency of social products directly affects the efficiency of people and even the whole society. This paper mainly focuses on social applications as the object to carry out research. This paper is dedicated to optimizing the user experience and social experience of mobile social products, optimizing the design strategies of each process of social products, and exploring the possibility and development direction of social products in the future. Firstly, it conducts in-depth research on the related theories of human social behavior based on the social relationship graph and summarizes the factors that affect the intimacy between nodes in the social relationship graph. Then, it discusses the role of these factors in designing social products and studies how to apply these factors to all aspects of product development. Then, this design method using intimacy factor is abstracted and summarized into a design model, which is convenient for product developers to understand and use. Finally, the practice shows that the mobile social design method based on the social relationship graph can effectively guide the design of mobile social products and provide users with an intimate and efficient social experience that can meet the social needs of users. The accuracy rate is effectively improved by 21%, which proves the value and prospect of the research, design, and development of this topic in the field of mobile social products.

Bamboo forest is a unique forest landscape that is mainly composed of herbal plants. It has a stronger capability to increase terrestrial carbon sinks than woody forests in the same environment, thus playing a special role in absorbing atmospheric CO2. Accurate and timely bamboo forest maps are necessary to better understand and quantify their contribution to the carbon and hydrological cycles. Previous studies have reported that the unique phenology pattern of bamboo forests, i.e., the on- and off-year cycle, can be detected with time-series high spatial resolution remote sensing (RS) images. Nevertheless, this information has not yet been applied in large-scale bamboo mapping. In this study, we innovatively incorporate newly designed phenology features reflecting the aforementioned on- and off-year cycles into a typical end-to-end classification workflow, including two features describing growing efficiency during the green-up season and two features describing the difference between annual peak greenness. Additionally, two horizonal morphology features and one tree height feature were employed, simultaneously. An experiment in southeast China was carried out to test the method’s performance, in which seven categories were focused. A total of 987 field samples were used for training and validation (70% and 30%, respectively). The results show that combining the time-series features based on spectral bands and vegetation indices and newly designed phenology and morphology patterns can differentiate bamboo forests from other vegetation categories. Based on these features, the classification results exhibit a reasonable spatial distribution and a satisfactory overall accuracy (0.89). The detected bamboo area proportion in 82 counties agrees with the statistics from China’s Third National Land Survey, which was produced based on high resolution images from commercial satellites and human interpretation (correlation coefficient = 0.69, and root mean squared error = 5.1%). This study demonstrates that the new scheme incorporating phenology features helps to map bamboo forests accurately while reducing the sample size requirement.

The influence of rock weathering caused by freezing–thawing on stone cultural relics cannot be ignored. For immovable stone cultural relics, different parts under different environmental conditions will be under different freeze–thaw actions and suffer different degrees of damage. In this paper, three typical freeze–thaw cycle tests of sandstone are designed, namely immersion test, capillary action test, and periodic saturation test. The macroscopic and microscopic morphologies of rock samples under different freeze–thaw cycles were analyzed. Weathering indicators such as porosity, water content, wave velocity, and surface hardness were tested, as well as uniaxial compressive strength. The variation law of weathering index and uniaxial compressive strength under different freezing–thawing cycles was obtained, and the quantitative relationship between each index parameter was further analyzed. The results show that under different freezing–thawing conditions, the apparent morphology of rock samples is different, and the trend of weathering indexes is similar, but the rate of change is different. The water content of rock has a great influence on the test results of wave velocity but has little influence on the surface hardness. The function relationship between weathering index and compressive strength under different freezing–thawing modes is similar, but the fitting parameters are different. Finally, the strength and wave velocity damage factors were used to quantitatively evaluate the degree of rock weathering. The results show that the immersion freeze–thaw damage is the highest, the periodic saturated freeze–thaw damage is the second highest, and the capillary freeze–thaw damage is the least highest. This is consistent with the field observation results. The conclusion of this paper can provide reference for the detection of stone cultural relics and provides a scientific basis for the anti-weathering protection of stone cultural relics.

Abstract Background Plant height is one of the most important agronomic traits in many crops due to its influence on lodging resistance and yield performance. Although progress has been made in the use of dwarfing genes in crop improvement, identification of new dwarf germplasm is still of significant interest for breeding varieties with increased yield. Results Here we describe a dominant, dwarf mutant G7 of Brassica napus with down-curved leaves derived from tissue culture. To explore the genetic variation responsible for the dwarf phenotype, the mutant was crossed to a conventional line to develop a segregating F2 population. Bulks were formed from plants with either dwarf or conventional plant height and subjected to high throughput sequencing analysis via mutation mapping (MutMap). The dwarf mutation was mapped to a 0.6 Mb interval of B. napus chromosome C05. Candidate gene analysis revealed that one SNP causing an amino acid change in the domain II of Bna.IAA7.C05 may contribute to the dwarf phenotype. This is consistent with the phenotype of a gain-of-function indole-3-acetic acid (iaa) mutant in Bna.IAA7.C05 reported recently. GO and KEGG analysis of RNA-seq data revealed the down-regulation of auxin related genes, including many other IAA and small up regulated response (SAUR) genes, in the dwarf mutant. Conclusion Our studies characterize a new allele of Bna.IAA7.C05 responsible for the dwarf mutant generated from tissue culture. This may provide a valuable genetic resource for breeding for lodging resistance and compact plant stature in B. napus.

Transcranial sonography (TCS) has gained increasing application for diagnosis of Parkinson's disease (PD) in clinical practice in recent years, because most PD patients, even in the early stage of PD, have abnormal hyperechogenicity of the substantia nigra (SN) in brainstem shown in TCS images. Therefore, the region of interest (ROI) for feature extraction should cover the SN region in a computer-aided diagnosis (CAD) system. The ROI size naturally affects the feature representation. However, there currently exist no unified standard for determining the size of ROI. In this work, we quantitatively compare the performance of TCS-based CAD with three sizes of ROIs, namely the entire midbrain (EM) region, the half of midbrain (HoM) region and the SN region. The experimental results on the original extracted features and the features by dimensionality reduction show that ROI covering the EM region achieves the overall best diagnosis performance. The results indicates that the neighboring regions around SN might also have abnormal symptoms, which cannot be clearly observed with naked eyes. It suggests that the large ROI includes more information for feature representation to improve the diagnosis performance of TCS-based CAD for PD.

ObjectiveThis study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC).MethodsCitron kinase (CIT) expression in ESCC tissues was analyzed based on the microarray dataset GSE20347, and CIT expression in ESCC cell lines was analyzed. Eca-109 cells were lentivirally transfected with shRNA-CIT (LV-shCIT) to knock down CIT, followed by investigation of cell proliferation and apoptosis. Nude mouse xenograft experiments were performed to evaluate the tumorigenicity of CIT-knockdown Eca-109 cells. Microarray analysis of Eca-109 cells transfected with LV-shCIT or LV-shNC and subsequent Ingenuity Pathway Analysis (IPA) were performed to identify CIT-related differentially expressed genes (DEGs) and signaling pathways. Furthermore, the expression of key DEGs was validated using the clinical samples of ESCC.ResultsCitron kinase (CIT) was highly expressed in ESCC tissues and cell lines. Knockdown of CIT suppressed Eca-109 cell proliferation and promoted apoptosis in vitro. Moreover, CIT knockdown significantly reduced tumorigenicity of Eca-109 cells in vivo. Microarray and IPA analysis showed that signaling by the Rho family GTPases pathway was significantly activated, and CIT intrinsically interacted with the protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), sequestosome 1 (SQSTM1), and interleukin 6 (IL6). Notably, the expression levels of PRKAA1 and SQSTM1 were upregulated in ESCC tissues, while the IL6 expression was downregulated.ConclusionOur findings confirm that CIT functions as an oncogene in ESCC. CIT may contribute to ESCC development by upregulating PRKAA1 and SQSTM1 as well as downregulating IL6. Citron kinase may serve as a promising therapeutic target for ESCC.

Thermosetting polymer materials with excellent mechanical properties are highly promising in cryogenic engineering applications. However, the research on the toughening mechanism of thermosetting materials at cryogenic temperatures is always difficult. Herein, one type of high strength hyperbranched epoxy composite was successfully fabricated, and the correlation between microstructure (free volume) and mechanical properties of the HPB/epoxy composites was studied. To disclose the correlations between mechanical properties and microstructures for these composites, positron annihilation lifetime (PAL) measurements were carried out. Thereafter, better impact and compression properties were observed for composites with smaller free volume holes. Meanwhile, the impact and tensile properties of the composites are positively correlated with the free volume holes fraction at 77 K. The correlation between microstructure and mechanical properties provide valuable information for regulating the cryogenic mechanical properties of thermosetting materials in the future.

This research revealed the crack generation of the highway embankment from the water losing shrinkage of the wet black cotton soil (BCS), which is a type of soil with high swell-shrink potential. The road seepage meter was used to test the permeability of filling materials, which was used to replace BCS. The moisture content and embankment deflection of BCS foundation were measured after the rainy season. Based on the coupled consolidation theory for unsaturated soil, the change in additional tension stress of the embankment induced by water loss shrinkage of BCS was simulated by Abaqus. The results indicated that the rainfall seeped into the foundation through highly permeable refill materials to result in BCS expansion and decrease the embankment strength. After the rainy season, the additional tensile stress caused by water loss shrinkage of BCS induces cracking of highway embankment, and the maximum cracking depth often appears at the shoulder of highway. The deep and wide cracks are easy to appear in the low embankment constructed on a thick BCS foundation under strong evaporation.

Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis. Effective biomarkers and specific therapeutic targets for HCC are therefore urgently needed. G protein-coupled estrogen receptor (GPER) plays a crucial role in numerous cancer types; however, its functions in HCC require further exploration. In the present study, we found a remarkable difference in GPER staining between tumor tissue (100/141, 70.9%) and matched non-tumor tissue (27/30, 90.0%). Compared with the GPER-negative patients, the GPER-positive patients with HCC were closely associated with female sex, negative hepatitis B surface antigen, small tumor size, low serum alpha fetoprotein level, and longer overall survival. Treatment with GPER-specific agonist G1 led to the sustained and transient activation of the EGFR/ERK and EGFR/AKT signaling pathways, respectively, in the HCC cell lines HCCLM3 and SMMC-7721, which express high levels of GPER. Interestingly, G1-induced EGFR/ERK signaling, rather than EGFR/AKT signaling mediated by GPER, was involved in decreasing cell viability by blocking cell cycle progression, thereby promoting apoptosis and inhibiting cell growth. Clinical analysis indicated that simultaneous high expression of GPER and phosphorylated-ERK (p-ERK) predicted improved prognosis for HCC. Finally, the activation of GPER/ERK signaling remarkably suppressed tumor growth in an HCC xenograft model, and this result was consistent with the in vitro data. Our findings suggest that specific activation of the GPER/ERK axis may serve as a novel tumor-suppressive mechanism and that this axis could be a therapeutic target for HCC.

Winter turnip rape (Brassica rapa L.) is an important overwintering oil crop that is widely planted in northwestern China. It considered to be a good genetic resource for cold-tolerant research because its roots can survive harsh winter conditions. Here, we performed comparative transcriptomics analysis of the roots of two winter turnip rape varieties, Longyou7 (L7, strong cold tolerance) and Tianyou2 (T2, low cold tolerance), under normal condition (CK) and cold stress (CT) condition. A total of 8,366 differentially expressed genes (DEGs) were detected between the two L7 root groups (L7CK_VS_L7CT), and 8,106 DEGs were detected for T2CK_VS_T2CT. Among the DEGs, two ω-3 fatty acid desaturase (FAD3), two delta-9 acyl-lipid desaturase 2 (ADS2), one diacylglycerol kinase (DGK), and one 3-ketoacyl-CoA synthase 2 (KCS2) were differentially expressed in the two varieties and identified to be related to fatty acid synthesis. Four glutamine synthetase cytosolic isozymes (GLN), serine acetyltransferase 1 (SAT1), and serine acetyltransferase 3 (SAT3) were down-regulated under cold stress, while S-adenosylmethionine decarboxylase proenzyme 1 (AMD1) had an up-regulation tendency in response to cold stress in the two samples. Moreover, the delta-1-pyrroline-5-carboxylate synthase (P5CS), δ-ornithine aminotransferase (δ-OAT), alanine-glyoxylate transaminase (AGXT), branched-chain-amino-acid transaminase (ilvE), alpha-aminoadipic semialdehyde synthase (AASS), Tyrosine aminotransferase (TAT) and arginine decarboxylase related to amino acid metabolism were identified in two cultivars variously expressed under cold stress. The above DEGs related to amino acid metabolism were suspected to the reason for amino acids content change. The RNA-seq data were validated by real-time quantitative RT-PCR of 19 randomly selected genes. The findings of our study provide the gene expression profile between two varieties of winter turnip rape, which lay the foundation for a deeper understanding of the highly complex regulatory mechanisms in plants during cold treatment.

When the mountain tunnel projects passing through the complex formation with coal, it happened along with disaster accidents such as gas outburst, gas combustion, and gas explosion. These disasters should seriously threaten the safety and life of the construction personnel and affect the normal operation of the tunnel construction. Ventilation is the most effective means to control gas, fire, dust, heat, and other disasters. To study the effects of different ventilation modes in highway gas tunnels, Fluent software was used to simulate forced ventilation, exhaust ventilation, and mixed ventilation in a high gas tunnel of a highway in Hunan. The distribution law of the airflow velocity and gas concentration of these three ventilation modes were obtained to determine the optimal ventilation system. It was shown that vortex zones of different ranges formed in the tunnel for all three ventilation modes, and the gas concentration was higher in the vortex zone than in other regions. Mixed ventilation of them is superior to the other two modes, showing the best ventilation effect with regard to airflow velocity and gas concentration.

The Yungang Grottoes, a World Heritage Site in Datong, consist of 252 caves that are noted for their collection of 5th- and 6th-century Buddhist grotto sculptures and reliefs. Various diseases have appeared in the grottoes under the general influence of natural and artificial factors. Bolt support is a commonly employed method for grotto reinforcement and has been widely applied in many projects. Small-diameter bolts have also been used in the reinforcement projects at the Yungang Grottoes, but the corresponding effect on the seismic performance of grottoes is still unclear. In this paper, a dynamic analysis via the numerical modelling of an ear grotto of the 19th grotto in Yungang is established, and the rock displacement, acceleration, and bolt axial force responses under a seismic wave are analyzed. The results show that the seismic dynamic responses of grottoes are greatly affected by the cliff structure. The displacement and acceleration responses of the cliff body vary greatly within the abrupt transition of the cliff structure. Based on this variation, the seismic capacity of small-diameter bolts in the vertical direction is greater than that in the horizontal direction. The axial force of a bolt is small at both ends of the bolt, large in the middle of the bolt, small on the top of a cliff, and large at the bottom of the cliff. Although the axial force is small, the upper rock mass of the grotto has a tendency to undergo relative movement compared with the outer rock mass. The results also indicate that based on the structural defects in the vertical direction of the cliff body caused by grotto excavation, the inclined angle of the bolt should be increased as far as possible or vertical support should be adopted to enhance the stability of the rock mass at the top of the grotto.

Background and objectiveWe aimed to predict the targets and signal pathways of Xiao-Chai-Hu-Tang (XCHT) in the treatment of colorectal cancer (CRC) based on network pharmacology, just as well as to further analyze its anti-CRC material basis and mechanism of action.MethodsWe adopted Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) databases to screen the active ingredients and potential targets of XCHT. CRC-related targets were retrieved by analyzing published microarray data (accession number GSE110224) from the Gene Expression Omnibus (GEO) database. The common targets were used to construct the "herb-active ingredient-target" network using the Cytoscape 3.8.0 software. Next, we constructed and analyzed protein-to-protein interaction (PPI) using BisoGenet and CytoNCA plug-in in Cytoscape. We then performed Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes using the R package of clusterProfiler. Furthermore, we used the AutoDock Tools software to conduct molecular docking studies on the active ingredients and key targets to verify the network pharmacological analysis results.ResultsWe identified a total of 71 active XCHT ingredients and 20 potential anti-CRC targets. The network analysis revealed quercetin, stigmasterol, kaempferol, baicalein, and acacetin as potential key compounds, and PTGS2, NR3C2, CA2, and MMP1 as potential key targets. The active ingredients of XCHT interacted with most CRC disease targets. We showed that XCHT's therapeutic effect was attributed to its synergistic action (multi-compound, multi-target, and multi-pathway). Our GO enrichment analysis showed 46 GO entries, including 20 biological processes, 6 cellular components, and 20 molecular functions. We identified 11 KEGG signaling pathways, including the IL-17, TNF, Toll-like receptor, and NF-kappa B signaling pathways. Our results showed that XCHT could play a role in CRC treatment by regulating different signaling pathways. The molecular docking experiment confirmed the correlation between five core compounds (quercetin, stigmasterol, kaempferol, baicalein, and acacetin) just as well as PTGS2, NR3C2, CA2, and MMP1.ConclusionIn this study, we described the potential active ingredients, possible targets, and key biological pathways responsible for the efficacy of XCHT in CRC treatment, providing a theoretical basis for further research.

Few studies have been conducted on the crack propagation law and failure characteristics of coal-rock combined body (CRCB) with prefabricated fissure. A sliding crack model was firstly presented to analyze the failure law of rock with a single fracture and the influence of the inclination angle of the fracture on the strength of the rock. The RFPA numerical models of the CRCB with different inclination angles of prefabricated fracture were then established to simulate the dynamic change process of crack propagation and shear stress of the CRCB with prefabricated fracture under uniaxial compression. The influence of the inclination angle of the fracture in the rock on the fracture expansion and failure characteristics of CRCB was further analyzed based on the acoustic emission data. The results showed that (1) when 2β=arctan1/μ, σcw takes the minimum value, and crack initiation is most likely to occur; (2) the strength of coal-rock assemblage shows different changing trends with the fracture inclination angle; (3) the secondary cracks of CRCB with prefabricated fracture of 0°, 15°, and 30° initiated and expanded near the tip of the main crack, and the secondary cracks of 45°, 60°, and 75° initiated and expanded from the tip of the main crack; (4) there are three failure modes of CRCB with prefabricated crack, the double-shear failure mode Λ, the tensile-shear composite failure mode along the fracture surface, and the tensile failure mode along the fracture surface; and (5) intact CRCB and CRCB with prefabricated crack when α=75° and α=90° have strong brittleness, and other CRCB with different prefabricated fracture inclination angles show a certain degree of postpeak plasticity. The results on the mechanical properties and damage characteristics of CRCB are of great significance for the safety and efficient mining of deep coal resources.

To address the large deformation of the surrounding rock of deep gob-side entry retaining under high stress, lithological characteristics of the surrounding rock and failure model of support body and their evolutionary processes are analyzed through field investigation and theoretical analysis. Failure mechanisms of surrounding rock and the technology to control it are studied systematically. The results show that the causes of the large deformation of the surrounding rock are weak thick mudstones with softening property and water absorption behavior, as well as its fragmentation, dilatancy, and long-term creep during strong disturbance and highly centralized stress states. The cross-section shape of the roadway after deformation and failure of the surrounding rock is obviously asymmetric in both the horizontal and vertical directions. Since the original system supporting the surrounding rock is unable to completely bear the load, each part of the supporting system is destroyed one after the other. The failure sequences of the surrounding rock are as follows: (1) roadway roof fracture in the filling area, (2) filling body fracture under eccentric load, (3) rapid subsidence of the roadway roof, and (4) external crack drum and rib spalling at the solid coal side. Due to this failure sequence, the entire surrounding rock becomes unstable. A partitioned coupling support and a quaternity control technology to support the surrounding rock are proposed, in which the roof of the filling area plays a key role. The technology can improve the overall stability of gob-side entry retaining, prevent support structure instability caused by local failure of the surrounding rock, and ensure the safety and smoothness of roadways.

Oxidative stress-induced neuronal damage has been implicated to play a dominant role in neurodegenerative disorders, such as Alzheimer’s disease (AD). Nicotine, a principal additive compound for tobacco users, is thought as a candidate to attenuate amyloid-β-mediated neurotoxicity and NMDA-induced excitotoxicity. Previous studies demonstrated that nicotine exerted this neuroprotective action on oxidative stress. However, the mechanisms underlying how nicotine contributes on oxidative injury in immortalized hippocampal HT-22 cells remain largely unknown. Therefore, in this study we investigated that the potential effects of nicotine on hydrogen peroxide (H2O2)-induced oxidative injury and underlying mechanisms in HT-22 cells. We found that pretreatment with nicotine at low concentrations markedly recovered the cell cycle that was arrested at the G2/M phase in the presence of H2O2 through reduced intracellular ROS generation. Moreover, nicotine attenuated H2O2-induced mitochondrial dysfunctions. Mechanistically, the application of nicotine significantly upregulated the levels of phosphorylated Erk1/2. The neuroprotective effects of nicotine, in turn, were abolished by PD0325901, a selective Erk1/2 inhibitor. Further obtained investigation showed that nicotine exerted its neuroprotective effects via specifically activating α7 nicotinic acetylcholine receptors (α7-nAChRs). A selective inhibitor of α7-nAChRs, methyllycaconitine citrate (MLA), not only completely prevented nicotine-mediated antioxidation but also abolished expression of p-Erk1/2. Taken together, our findings suggest that nicotine suppresses H2O2-induced HT-22 cell injury through activating the α7-nAChR/Erk1/2 signaling pathway, which indicates that nicotine may be a novel strategy for the treatment of neurodegenerative disorders.

Objective: Lung cancer is often associated with hypercoagulability. Thromboelastography provides integrated information on clot formation in whole blood. This study explored the possible relationship between thromboelastography and lung cancer. Methods: Lung cancer was staged according to the Tumor, Node, and Metastasis (TNM) classification system. Thromboelastography parameters in different stages of disease were compared. The value of thromboelastography for stage prediction was determined by area under the receiver operating characteristic curve analysis. Results: A total of 182 patients diagnosed with lung cancer were included. Thromboelastography parameters, including kinetics time, α-angle, and maximum amplitude, differed significantly between patients with metastatic and limited lung cancers ( P < 0.05). Kinetics time was significantly reduced and maximum amplitude was significantly increased in patients with stage I and II compared with stage III and IV tumors ( P < 0.05). TNM stage was significantly negatively correlated with kinetics time ( r = −0.186), and significantly positively correlated with α-angle ( r = 0.151) and maximum amplitude ( r = 0.251) (both P < 0.05). The area under the curve for kinetics time in patients with stage I cancer was 0.637 ( P < 0.05) and that for α-angle in stage ≥ II was 0.623 ( P < 0.05). The areas under the curves for maximum amplitude in stage ≥ III and stage IV cancer were 0.650 and 0.605, respectively (both P < 0.05). Thromboelastography parameters were more closely associated with TNM stage in patients with lung adenocarcinoma than in the whole lung cancer population. Conclusion: This study identified the diagnostic value of thromboelastography parameters for determining tumor stage in patients with lung cancer. Thromboelastography can be used as an independent predictive parameter for lung cancer severity.

In order to design a seismic timber beam, the effect of near-fault ground motion on timber beam has numerically been investigated, with reference to small displacement theory. The simulated near-fault ground motion is applied on the fixed base of a timber frame model. The beam is placed in single span of a timber frame. The beam has two different length sizes of 1.8 and 3.3 meters. The seismic load-displacement, seismic load-strain and strain-displacement have been calculated for all models and shown in graphs. The beam is designed with nonlinear analysis method and some mechanical properties for all models have been used, in numerical analysis. The numerical analysis results indicate that, the inertial interaction, energy dissipation and nonlinear deformation of beams in timber frames have directly related with frame span. In beams with a smaller length, higher seismic loading caused lower displacement. The displacement is reduced by reducing the length of the beam. The inertial interaction, energy dissipation and nonlinear deformation are changed respect to the length of the beam. The innovation of this paper is to develop cycling graphs by using ABAQUS, to improve design of timber frame and give an adequate explanation of seismic behavior of timber beam

Abstract This paper presents a general strong limit theorem for delayed sum of functions of random variables for a hidden time inhomogeneous Markov chain (HTIMC), and as corollaries, some strong laws of large numbers for HTIMC are established thereby.

Abstract Background The majority of stroke patients are inactive outside formal therapy sessions. Tailored activity feedback via a smartwatch has the potential to increase inpatient activity. The aim of the study was to identify the challenges and support needed by ward staff and researchers and to examine the feasibility of conducting a randomised controlled trial (RCT) using smartwatch activity monitors in research-naive rehabilitation wards. Objectives (Phase 1 and 2) were to report any challenges and support needed and determine the recruitment and retention rate, completion of outcome measures, smartwatch adherence rate, (Phase 2 only) readiness to randomise, adherence to protocol (intervention fidelity) and potential for effect. Methods First admission, stroke patients (onset

Abstract Background Patients with uremia have high cardiovascular disease morbidity and mortality despite having normal left ventricular ejection fraction (LVEF). Longitudinal strain (LS) can be associated with subtle changes in LV systolic function. The aim of this study was to use two-dimensional speckle-tracking echocardiography (2DSTE) to assess subclinical LV myocardial dysfunction and to explore strain-changing regularities in uremic patients with LVEF ≥ 55%. Methods The study population included 40 uremic patients and 40 healthy volunteers. 2DSTE was performed on all participants to assess peak LS in the basal, mid and apical LV (BLS, MLS and ALS) and the respective time to peak LS (T-BLS, T-MLS, T-ALS). Results BLS, MLS, and ALS were significantly decreased in the uremic group relative to healthy controls and LS increased going in a basal to apical direction in both groups. T-BLS, T-MLS and T-ALS was significantly increased in the uremic group compared with the control group. In uremic patients, T-BLS, but not T-MLS or T-ALS, was significantly delayed relative to the control group. Bivariate analysis of creatinine (Cr) or urea nitrogen and strain parameters revealed a correlation only between ALS and Cr. Conclusion 2DSTE can identify LV myocardial abnormalities in uremic patients with preserved LVEF at early stage, as well as some changing regularities of LS and T-LS in the left ventricle.

Abstract Background Practicing activities improves recovery after stroke, but many people in hospital do little activity. Feedback on activity using an accelerometer is a potential method to increase activity in hospital inpatients. This study’s goal is to investigate the effect of feedback, enabled by a Smart watch, on daily physical activity levels during inpatient stroke rehabilitation and the short-term effects on simple functional activities, primarily mobility. Methods/design A randomized controlled trial will be undertaken within the stroke rehabilitation wards of the Second Affiliated hospital of Anhui University of Traditional Chinese Medicine, Hefei, China. The study participants will be stroke survivors who meet inclusion criteria for the study, primarily: able to participate, no more than 4 months after stroke and walking independently before stroke. Participants will all receive standard local rehabilitation and will be randomly assigned either to receive regular feedback about activity levels, relative to a daily goal tailored by the smart watch over five time periods throughout a working day, or to no feedback, but still wearing the Smart watch. The intervention will last up to 3 weeks, ending sooner if discharged. The data to be collected in all participants include measures of daily activity (Smart watch measure); mobility (Rivermead Mobility Index and 10-metre walking time); independence in personal care (Barthel Activities of Daily Living (ADL) Index); overall activities (the World Health Organization (WHO) Disability Assessment Scale, 12-item version); and quality of life (the Euro-Qol 5L5D). Data will be collected by assessors blinded to allocation of the intervention at baseline, 3 weeks or at discharge (whichever is the sooner); and a reduced data set will be collected at 12 weeks by telephone interview. The primary outcome will be change in daily accelerometer activity scores. Secondary outcomes are compliance and adherence to wearing the watch, and changes in mobility, independence in personal care activities, and health-related quality of life. Discussion This project is being implemented in a large city hospital with limited resources and limited research experience. There has been a pilot feasibility study using the Smart watch, which highlighted some areas needing change and these are incorporated in this protocol. Trial registration ClinicalTrials.gov, NCT02587585. Registered on 30 September 2015. Chinese Clinical Trial Registry, ChiCTR-IOR-15007179. Registered on 8 August 2015.