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An experimental work is presented that aims to improve our understanding of water–rock reaction, under both neutral and acidic conditions, and its effects on the mechanical deterioration of sandstone in Chongqing, southwest China, where a lot of heritage rock statues are carved in the same strata. SCB tests were conducted to evaluate the weakening of fracture toughness of Chongqing sandstone after water and acid erosions, and a high-speed camera was employed to capture its cracking behaviors under different hydrochemical conditions. Microstructural observation was also carried out to investigate the cracking path at a micro-scale, and the chemical analyses of sandstone soaking water in a duration of up to 120 days allows to reveal the evolving process of water–rock reaction. The results show that compared to acid solutions of pH = 3 and 5, the strength weakening effect of distilled water on Chongqing sandstone is more severe. Crack propagation rates captured by the high-speed camera vary between 20 and 60 mm/s in the SCB tests. There is no significant difference in the data for dry and water-saturated samples, and the same for the samples in the two acid fluids. Yet the crack growth rates of the latter two groups are apparently greater than those of the former two. The chemical reaction between water / acid solutions and Chongqing sandstone is mainly pertinent to the cementation and grain boundaries, which weakens grain contacts and promote crack propagation. This mechanism results in a low KIC, long crack length, i.e., more tortuosity along grain boundaries, and high crack propagation rate. [ABSTRACT FROM AUTHOR]

A particle-based discrete element model combined with digital image processing to take into account the grain geometry and size distribution is used to investigate the mechanical and microcracking behavior of Beishan granite (BG), a typical crystalline rock potential for nuclear waste disposal in China. First, the procedure to construct a digital image-based grain-based model is introduced. The unsupervised K-means clustering algorithm is used to determine mineral boundaries, and four micro-parameters are assigned according to the Weibull distribution to reflect micro-heterogeneity of rock. Then, the model is calibrated to the macro-properties of BG obtained from laboratory tests, and consistency between model simulation and laboratory test results of both microcracking processes and failure modes is found. It is shown that intragrain cracks are initiated successively in quartz, feldspar, and mica; and their numbers in quartz and feldspar are much more than that in mica. Crack cluster, forking cracks and cataclastic microcracking are typical in quartz, while the "voids" is found in mica. Grain property heterogeneity has a significant impact on micro-cracking behavior and macro-properties of the model, with greater heterogeneity resulting in a lower uniaxial compression strength and elastic modulus, and a more scattered distribution of microcrack inclination. The modeling procedures presented here provide an effective method for investigating mechanical and damage behavior of granites, with specific consideration of heterogeneity involving the distribution of mineral grains and their mechanical properties. [ABSTRACT FROM AUTHOR]

We have studied the photophysics of tetrafurylethene, an aggregation‐induced emission luminogen with exceptionally short intramolecular O−O distances of 2.80 Å and a significant red‐shifted morphochromism (27 nm) when going from the aggregate to the crystal. The short O−O distances, which are substantially smaller than the sum of the van der Waals radii (3.04 Å), are due to the fact that the oxygen atoms act as an electronic bridge connecting the furan rings on opposite ends of the central double bond, giving rise to a circular delocalization of the π‐electron density across the rings. In the excited state the O−O distance is further reduced to 2.70 Å; the increased O−O interaction causes a narrowing of the HOMO–LUMO gap, resulting in the red morphochromism of the emission. Our results show the structural origin of the red‐shifted emission lies in close O−O contacts, paving the way for understanding the clusteroluminescence of oxygen‐rich non‐conjugated systems that emit visible light. [ABSTRACT FROM AUTHOR]

We have studied the photophysics of tetrafurylethene, an aggregation‐induced emission luminogen with exceptionally short intramolecular O−O distances of 2.80 Å and a significant red‐shifted morphochromism (27 nm) when going from the aggregate to the crystal. The short O−O distances, which are substantially smaller than the sum of the van der Waals radii (3.04 Å), are due to the fact that the oxygen atoms act as an electronic bridge connecting the furan rings on opposite ends of the central double bond, giving rise to a circular delocalization of the π‐electron density across the rings. In the excited state the O−O distance is further reduced to 2.70 Å; the increased O−O interaction causes a narrowing of the HOMO–LUMO gap, resulting in the red morphochromism of the emission. Our results show the structural origin of the red‐shifted emission lies in close O−O contacts, paving the way for understanding the clusteroluminescence of oxygen‐rich non‐conjugated systems that emit visible light. [ABSTRACT FROM AUTHOR]

The aim of this study was to construct recombinant adenovirus vector carrying a short hairpin RNA (shRNA) that can exclusively target cyclooxygenase-2 (COX-2) gene expression and observe its inhibitory effect on hepatic fibrosis. We designed and synthesized three oligonucleotide sequences, and cloned those into a shuttle vector, pYr-1.1-hU6-EGFP, after annealing. The restriction-enzyme digestion and sequencing analyses confirmed that the constructed recombinant eukaryotic expression vector was correct. A recombination reaction using LR Clonase was performed for the pYr-1.1-hU6-EGFP COX-2shRNA and the adenovirus vector pAd/BL-DEST to form Ad-COX-2shRNA. The adenoviruses containing the recombinant plasmids were transfected into hepatic stellate cells (HSCs). The transfection efficiency of the three COX-2 shRNAs exceeded 70%. Reverse transcription PCR (RT-PCR) and western blot confirmed that the target gene expression was decreased at the level of mRNA and protein, and the interference effect of COX-2 shRNA-1 was better than that of the other two COX-2 shRNAs. COX-2 shRNA-1 recombinant adenovirus vectors (1 × 109 PFU/mL) were injected via the tail vein into rats fed a high-fat diet with a 40% carbon tetrachloride peanut oil lavage, which induced liver fibrosis. Rats were euthanized at the end of the 12th week, and their liver was removed. Liver expression of COX-2 mRNA and protein was detected by RT-PCR and immunohistochemistry, respectively. RT-PCR and immunohistochemistry showed that COX-2 shRNA-1 inhibited COX-2 expression in liver tissue. Hematoxylin/eosin and Masson staining showed that COX-2 shRNA-1 ameliorated the severity of liver fibrosis. The COX-2 shRNA eukaryotic expression vectors were constructed successfully and COX-2 shRNA-1 ameliorated liver fibrosis. [ABSTRACT FROM AUTHOR]

The effect of grain size heterogeneity on the mechanical and microcracking behavior of Lac du Bonnet (LdB) granite during heating, cooling, and uniaxial compression loading is investigated using a grain-based model. By defining a grain size heterogeneity index H, the heterogeneity induced by variation of grain size distribution can be explicitly incorporated into the grain-based model quantitatively. Five modelled LdB granite samples with different grain size heterogeneity indices ranging 0.19–1.22 are established. The results suggest that the grain size heterogeneity and treatment temperature have critical impacts on the mechanical properties of modelled LdB granite samples. With the increase of temperature and grain size heterogeneity index, the mechanical properties show a decreasing trend. Several empirical formulations are developed to predict the temperature-dependent mechanical properties of modelled LdB granite samples with different grain size heterogeneity indices. Generally, modelled LdB granite samples with greater grain size heterogeneity index has a lower temperature of brittle-ductile transition. In terms of microcracking behavior, both temperature and grain size heterogeneity affect it, including number, density, orientation, and distribution. As the temperature increases, the number and related density of thermal stress-induced cracks increase. Generally, the amount of thermal stress in modelled LdB granite samples during heating increases with the increases of grain size heterogeneity index. The controlling factor of the failure pattern of samples gradually changes from the presence of thermal stress-induced cracks to grain size heterogeneity as the model progresses from relatively homogeneous (H ranging 0.19–0.76) to heterogeneous (H ranging 0.93–1.22). Highlights: Explicitly incorporate grain size heterogeneity induced by grain size distribution into a grain-based model. Reveal the effect of grain size heterogeneity on mechanical properties and microcracking behavior of Lac du Bonnet granite at different temperatures. Propose empirical formulations to quantify the temperature-dependent mechanical properties of Lac du Bonnet granite with grain size heterogeneity index. [ABSTRACT FROM AUTHOR]

Understanding the microcracking mechanisms and associated acoustic characteristics involved in the creep of heterogeneous granite at the grain scale is of high importance in practical engineering. To perform this task, a series of creep numerical simulations were conducted on granite with a single pre-existing open flaw using a grain-based parallel-bonded stress corrosion model. We investigated the effect of flaw inclination angle on the creep behavior and discussed the significance of microstructure. The results suggest that the axial strain, secondary creep strain rate and time-to-failure all depend strongly and nonlinearly on the flaw inclination angle. Creep failure is mainly induced by the initiation, propagation and coalescence of microcracks, and the dominant types are inter-grain tension cracks and intra-grain tension cracks. The b value, source types and distribution of acoustic emission events are associated with the flaw inclination angle and driving-stress ratio. Tensile sources account for the majority of the total number of acoustic emission sources, while shear and implosive acoustic emission sources are larger in magnitude. The model with higher heterogeneity creeps at a faster rate under the same applied constant axial stress. The higher number of acoustic emission events at each creep stage of such model indicates that the relatively heterogeneous microstructure provides more paths for the growth of microcracks during creep loading. As the heterogeneity increases, the secondary creep strain rate rises and the b value decreases. The position of the final macroscale shear band of pre-cracked granite is more affected by pre-existing flaw compared to its microstructure. Highlights: An extended grain-based parallel-bonded stress corrosion (GB-PSC) model was proposed to simulate the creep and associated acoustic behavior of granite. Voronoi tessellations to provide a more realistic representation of the microstructure of granite. Effects of open flaw inclination angle on creep behavior of pre-cracked granite were systematically investigated and the significance of microstructure were discussed. The acoustic emission characteristics of mineral boundaries and interiors during creep loading were obtained using the moment tensor analysis. [ABSTRACT FROM AUTHOR]

The ministry of education has started "Excellent Open Course" after the project of "Teaching Quality and Teaching Reformation in Higher Education", and it already has a large amount of high quality courses. However, it is not enough. The popularization and sharing of these high quality resources desperately need quality platform. Only then, we can improve higher education's quality and serve learning society construction. For that, this article tries to make a comprehensive survey on relevant typical platforms internal and abroad, absorb the good aspects. By drawing lessons from CNKI which is good at resource retrieval, and Taobao which is good at user interface and combining the international demand and existing technology, the paper tries to consider deeply about the development trend of interactive, mobilizing and open sourcing; These are what we provide for optimizing the excellent open course platform; including firstly from platform module distribution, and then from platform service mechanism distribution. All these are in order to make excellent open courses get better support. [ABSTRACT FROM AUTHOR]

Aggregation-induced emission (AIE) has been harnessed in many systems through the principle of restriction of intramolecular rotations (RIR) based on mechanistic understanding from archetypal AIE molecules such as tetraphenylethene (TPE). However, as the family of AIE-active molecules grows, the RIR model cannot fully explain some AIE phenomena. Here, we report a broadening of the AIE mechanism through analysis of 10,10′,11,11′-tetrahydro-5,5′-bidibenzo[a,d][7]annulenylidene (THBDBA), and 5,5′-bidibenzo[a,d][7]annulenylidene (BDBA). Analyses of the computational QM/MM model reveal that the novel mechanism behind the AIE of THBDBA and BDBA is the restriction of intramolecular vibration (RIV). A more generalized mechanistic understanding of AIE results by combining RIR and RIV into the principle of restriction of intramolecular motions (RIM). [ABSTRACT FROM AUTHOR]

Background: The BCRP/ABCG2 transporter, which mediates drug resistance in many types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus encoding a shRNA targeting the ATP-binding domain of this protein was used to screen for highly efficient agents that could reverse drug resistance and improve cell sensitivity to drugs, thus laying the foundation for further studies and applications. Methodology/Principal Findings: To target the ATP-binding domain of BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target sequences starting from the 270th, 745th and 939th bps of the 6th exon, were constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi) that conferred significant knockdown effects were screened using a drug-sensitivity experiment and flow cytometry. The human choriocarcinoma cell line JAR, which highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the tumor tissue was determined using immunohistochemistry, fluorescent quantitative RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2-tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor tissue were determined using in situ hybridization. V-BCRPi increased the sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis-promoting effects of 5-FU in the tumor. Conclusions/Significance: The goal of the in vivo and in vitro studies was to screen for an RNA interference recombinant retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V-BCRPi) to inhibit its function. A new method to improve the chemo-sensitivity of breast cancer and other tumor cells was discovered, and this method could be used for gene therapy and functional studies of malignant tumors. [ABSTRACT FROM AUTHOR]

Dibenzothiophene- and dibenzofuran-functionalized ethanes were synthesized by the McMurry coupling reaction. The luminogens are faintly emissive when molecularly dissolved in good solvents, but emit intensively when aggregated as nanoparticles in poor solvents or fabricated as solid thin films, demonstrating the phenomenon of aggregation-induced emission (AIE). Their organic light-emitting diode (OLED) applications were explored, utilizing the AIE effect. Electroluminescence devices with the configuration of indium tin oxide (ITO)/ N,N′-di(1-naphthyl)- N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (NPB; 60 nm)/dye (20 nm)/1,3,5-tri(1-phenyl-1 H-benzo[ d]imidazol-2-yl)phenyl (TPBi; 10 nm)/tris(8-hydroxyquinoline)aluminum (Alq3; 30 nm)/LiF (1 nm)/Al (100 nm) were fabricated. The OLED device emits at 510 nm with a maximum luminescence and external quantum efficiency of 104 cd/m2 and 2.1 %, respectively. The OLED behavior of the E/ Z isomers was also studied. [ABSTRACT FROM AUTHOR]

Multi-layer slopes are widely found in clay residue receiving fields. A generalized horizontal slice method (GHSM) for assessing the stability of multi-layer slopes that considers the energy dissipation between adjacent horizontal slices is presented. In view of the upper-bound limit analysis theory, the energy equation is derived and the ultimate failure mode is generated by comparing the sliding surface passing through the slope toe (mode A) with that below (mode B). In addition, the influence of the number of slices on the stability coefficients in the GHSM is studied and the stable value is obtained. Compared to the original method (Chen's method), the GHSM can acquire more precise results, which takes into account the energy dissipation in the inner sliding soil mass. Moreover, the GHSM, limit equilibrium method (LEM) and numerical simulation method (NSM) are applied to analyze the stability of a multi-layer slope with different slope angles and the results of the safety factor and failure mode are very close in each case. The ultimate failure modes are shown to be mode B when the slope angle is not more than 28°. It illustrates that the determination of the ultimate sliding surface requires comparison of multiple failure modes, not only mode A. [ABSTRACT FROM AUTHOR]

Granite is a heterogeneous material characterized by a significant population of mechanically distinct grain boundaries, which exert a substantial influence on crack propagation. An extended grain-based model was developed by integrating the geometric heterogeneity, represented by Voronoi tessellations, and the mechanical heterogeneity of grain boundary, as described by Weibull distribution. This study numerically investigates the influence of mechanical heterogeneity in grain boundary on the mechanical properties and microcracking behavior of semi-circular bend granite samples under mode I loading. The mechanical heterogeneity of grain boundary was assessed by independently varying the heterogeneity index, defined by the shape parameter m in the Weibull distribution. The findings indicate that the force–displacement curve and fracture toughness are primarily influenced by the parallel bond tensile strength and cohesion of grain boundary contacts. When the value of m in Weibull distribution is between 1.5 and 2, a compromise between failure patterns and diverse grain boundaries characterization can be reached. Considering the heterogeneous mechanical properties of grain boundary numerically is able to simulate the local stress concentration of the real rocks, thus accelerating the generation of microcracks and reflecting the brittleness of rock failure. Otherwise, the fracture toughness of the rock will may be overestimated. Generally speaking, models that consider grain boundary heterogeneity will produce larger fracture process zone and microscopically complex crack propagation patterns during loading, and these phenomena are more consistent with experimental observations than those models in which grain boundaries are homogeneous. Highlights: The mechanical heterogeneity of grain boundary in granite is quantitatively characterized by the Weibull distribution; The heterogeneous grain boundary could favor the local stress concentration, thus accelerating the generation of microcracks; Considering both geometric heterogeneity of granite and mechanical heterogeneity of grain boundary result in the generation of larger fracture process zone and microscopically complex crack propagation patterns under mode I loading. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we propose a micromechanical analysis of damage and related inelastic deformation in saturated porous quasi brittle materials. The materials are weakened by randomly distributed microcracks and saturated by interstitial fluid with drained and undrained conditions. The emphasis is put on the closed cracks under compression-dominated stresses. The material damage is related to the frictional sliding on crack surface and described by a local scalar variable. The effective properties of the materials are determined using a linear homogenization approach, based on the extension of Eshelby’s inclusion solution to penny shaped cracks. The inelastic behavior induced by microcracks is described in the framework of the irreversible thermodynamics. As an original contribution, the potential energy of the saturated materials weakened by closed frictional microcracks is determined and formulated as a sum of an elastic part and a plastic part, the latter entirely induced by frictional sliding of microcracks. The influence of fluid pressure is accounted for in the friction criterion through the concept of local effective stress at microcracks. We show that the Biot’s effective stress controls the evolution of total strain while the local Terzaghi’s effective stress controls the evolution of plastic strain. Further, the frictional sliding between crack lips generates volumetric dilatancy and reduction in fluid pressure. Applications of the proposed model to typical brittle rocks are presented with comparisons between numerical results and experimental data in both drained and undrained triaxial tests. [Copyright &y& Elsevier]

Abstract: Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined. In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex. Pregnant Sprague–Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n =4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5±41.9mg/dL) and on GD17 (mean=247.0±72.4mg/dL). PF (n =2) and CF (n =3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating ≤100μA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked. The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm2, standard error of the mean=±0.278) compared with the Ct offspring (8.03mm2 ±0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups. These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD. [Copyright &y& Elsevier]

Background: Cyclic-dependent kinase (CDK) 4/6 kinases, as the critical drivers of the cell cycle, are involved in the tumor progression of various malignancies. Pharmacologic inhibitors of CDK4/6 have shown significant clinical prospects in treating hormone receptor-positive and human epidermal growth factor receptor-negative (HR + /HER2-) breast cancer (BC) patients. However, acquired resistance to CDK4/6 inhibitors (CDK4/6i), as a common issue, has developed rapidly. It is of great significance that the identification of novel therapeutic targets facilitates overcoming the CDK4/6i resistance. PARP1, an amplified gene for CDK4/6i-resistant patients, was found to be significantly upregulated during the construction of CDK4/6i-resistant strains. Whether PARP1 drives CDK4/6i resistance in breast cancer is worth further study. Method: PARP1 and p-YB-1 protein levels in breast cancer cells and tissues were quantified using Western blot (WB) analysis, immunohistochemical staining (IHC) and immunofluorescence (IF) assays. Bioinformatics analyses of Gene Expression Profiling Interactive Analysis (GEPIA), Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) datasets were applied to explore the relationship between YB-1/PARP1 protein levels and CDK4/6i IC50. Cell Counting Kit-8 (CCK-8) and crystal violet staining assays were performed to evaluate cell proliferation rates and drug killing effects. Flow cytometry assays were conducted to assess apoptosis rates and the G1/S ratio in the cell cycle. An EdU proliferation assay was used to detect the DNA replication ratio after treatment with PARP1 and YB-1 inhibitors. A ChIP assay was performed to assess the interaction of the transcription factor YB-1 and associated DNA regions. A double fluorescein reporter gene assay was designed to assess the influence of WT/S102A/S102E YB-1 on the promoter region of PARP1. Subcutaneous implantation models were applied for in vivo tumor growth evaluations. Results: Here, we reported that PARP1 was amplified in breast cancer cells and CDK4/6i-resistant patients, and knockdown or inhibition of PARP1 reversed drug resistance in cell experiments and animal models. In addition, upregulation of transcription factor YB-1 also occurred in CDK4/6i-resistant breast cancer, and YB-1 inhibition can regulate PARP1 expression. p-YB-1 and PARP1 were upregulated when treated with CDK4/6i based on the WB and IF results, and elevated PARP1 and p-YB-1 were almost simultaneously observed during the construction of MCF7AR-resistant strains. Inhibition of YB-1 or PAPR1 can cause decreased DNA replication, G1/S cycle arrest, and increased apoptosis. We initially confirmed that YB-1 can bind to the promoter region of PARP1 through a ChIP assay. Furthermore, we found that YB-1 phosphorylated at S102 was crucial for PARP1 transcription according to the double fluorescein reporter gene assay. The combination therapy of YB-1 inhibitors and CDK4/6i exerted a synergistic antitumor effect in vitro and in vivo. The clinical data suggested that HR + /HER2- patients with low expression of p-YB-1/PARP1 may be sensitive to CDK4/6i in breast cancer. Conclusion: These findings indicated that a "YB-1/PARP1" loop conferred resistance to CDK4/6 inhibitors. Furthermore, interrupting the loop can enhance tumor killing in the xenograft tumor model, which provides a promising strategy against drug resistance in breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: Laser lithotripsy under fluoroscopic guidance is difficult to perform and risky due to its invisibility. In this study we aimed to investigate the efficacy and safety of a novel endoscopic auxiliary system (NEAS)‐assisted lithotripsy under fluoroscopy for treating difficult common bile duct (CBD) stones. Methods: Patients with difficult CBD stones who were treated with NEAS‐assisted laser lithotripsy (NEAS group) or conventional mechanical lithotripsy (ML) under fluoroscopy (ML group) were retrospectively evaluated. The primary outcome was the complete stone clearance rate and the secondary outcomes included operation time, complications, and medical cost. Results: Seventeen patients were treated with NEAS‐assisted laser lithotripsy and 144 patients underwent ML. Using the propensity score matching analysis, 17 pairs of cases treated with NEAS‐assisted lithotripsy and ML were included. Patients in the NEAS group showed a higher stone clearance rate than the ML group (94.1% vs 58.8%, P = 0.039), as well as shorter operation time (41.9 min vs 49.4 min, P < 0.001) and lower medical cost (USD 4607 vs USD 5014, P < 0.001). There was no significant difference in the complication rate between the two groups (5.9% vs 17.6%, P = 0.601). Conclusion: NEAS‐assisted fluoroscopy‐guided laser lithotripsy is feasible and safe, which may be a promising technique in fluoroscopy‐guided laser lithotripsy for difficult CBD stones. [ABSTRACT FROM AUTHOR]

Background: Abnormal metabolic pathways have been considered as one of the hallmarks of cancer. While numerous metabolic pathways have been studied in various cancers, the direct link between metabolic pathway gene expression and cancer prognosis has not been established. Results: Using two recently developed bioinformatics analysis methods, we evaluated the prognosis potential of metabolic pathway expression and tumor-vs-normal dysregulations for up to 29 metabolic pathways in 33 cancer types. Results show that increased metabolic gene expression within tumors corresponds to poor cancer prognosis. Meta differential co-expression analysis identified four metabolic pathways with significant global co-expression network disturbance between tumor and normal samples. Differential expression analysis of metabolic pathways also demonstrated strong gene expression disturbance between paired tumor and normal samples. Conclusion: Taken together, these results strongly suggested that metabolic pathway gene expressions are disturbed after tumorigenesis. Within tumors, many metabolic pathways are upregulated for tumor cells to activate corresponding metabolisms to sustain the required energy for cell division. [ABSTRACT FROM AUTHOR]

N7-Methylguanosine (m7G) modification holds significant importance in regulating posttranscriptional gene expression in epigenetics. Long non-coding RNAs (lncRNAs) have been demonstrated to play a crucial role in cancer progression. m7G-related lncRNA may be involved in the progression of pancreatic cancer (PC), although the underlying mechanism of regulation remains obscure. We obtained RNA sequence transcriptome data and relevant clinical information from the TCGA and GTEx databases. Univariate and multivariate Cox proportional risk analyses were performed to build a twelve-m7G-associated lncRNA risk model with prognostic value. The model was verified using receiver operating characteristic curve analysis and Kaplan–Meier analysis. The expression level of m7G-related lncRNAs in vitro was validated. Knockdown of SNHG8 increased the proliferation and migration of PC cells. Differentially expressed genes between high- and low-risk groups were identified for gene set enrichment analysis, immune infiltration, and potential drug exploration. We conducted an m7G-related lncRNA predictive risk model for PC patients. The model had independent prognostic significance and offered an exact survival prediction. The research provided us with better knowledge of the regulation of tumor-infiltrating lymphocytes in PC. The m7G-related lncRNA risk model may serve as a precise prognostic tool and indicate prospective therapeutic targets for PC patients. [ABSTRACT FROM AUTHOR]

Atractylodis Macrocephalae Rhizoma (AMR) is one of commonly used medicinal and edible herbs in China. It is often sulfur-fumigated during post-harvest processing. Carbohydrates are important active components of AMR. However, it is unknown whether sulfur-fumigation would induce changes on carbohydrates. Here, carbohydrates including polysaccharides, oligosaccharides and free monosaccharides were comprehensively analyzed to characterize the quality changes of sulfur-fumigated AMR. Determination of both homemade sulfur-fumigated AMR samples and commercial samples from market revealed that sulfur-fumigation did not affect molecular weight distribution of polysaccharides, but altered polysaccharides content and its ratios of constituent monosaccharides, especially glucose (Glc) and fructose (Fru), as well as the contents of oligosaccharides DP2–10 and free monosaccharide Fru. Moreover, the variations enhanced with the increasing of residual SO 2 content. The potential transformation mechanisms could be due to the hydrolysis of polysaccharides. The research outcomes could provide a chemical basis for the safety and efficacy evaluations of sulfur-fumigated AMR. [Display omitted] • Multi-chromatographic technology methods were integrated to characterize carbohydrates components of AMR. • Impact of sulfur-fumigation on carbohydrates of AMR was evaluated. • Sulfur-fumigation decreased the content of polysaccharides, whereas increased that of oligosaccharides and free fructose. • The variations of carbohydrates enhanced with the increase of SO 2 residual amounts. • The potential transformation mechanisms might be the hydrolysis of polysaccharides into oligosaccharides and monosaccharides. [ABSTRACT FROM AUTHOR]

There is increasing evidence that circular RNAs (circRNAs) can serve as microRNA (miRNA) sponges to regulate metastasis of multiple tumors, including pancreatic ductal adenocarcinoma (PDAC). However, the role of the circRNA/miRNA regulatory network in metastasis of PDAC has not been elucidated. The purpose of this study is to explore the role of circ_0047744/miR-21/SOCS5 in the metastasis of PDAC. We found that circRNA_0047744 was weakly expressed in PDAC tissues and cell lines. The expression of circ_0047744 was negatively correlated with lymph node metastasis and positively correlated with overall survival in PDAC patients. Functionally, the overexpression of circ_0047744 suppressed cell migration and invasion in vitro and in vivo. Mechanistically, circ_0047744 could regulate SOCS5 expression by acting as a sponge of miR-21 to inhibit migration and invasion of PDAC cells. Our study demonstrates that circ_0047744 acts as an anti-oncogene to inhibit PDAC metastasis by regulating the miR-21/SOCS5 axis, indicating that circ_0047744 may be a potential novel therapeutic target for PDAC patients. • circ_0047744 was downregulated in PDAC. • circ_0047744 suppressed metastasis of PDAC. • circ_0047744 served as a sponge for miR-21. • miR-21 promoted the metastasis of PDAC cells through targeting SOCS5. • circ_0047744 inhibited the metastasis of PDAC through the miR-21/SOCS5 axis. [ABSTRACT FROM AUTHOR]

Background: Transfer RNA-derived fragments (tRFs) are a new class of small non-coding RNAs. Recent studies suggest that tRFs participate in some pathological processes. However, the biological functions and mechanisms of tRFs in non-small cell lung cancer (NSCLC) are largely unknown. Methods: Differentially expressed tRFs were identified by tRF and tiRNA sequencing using 9 pairs of pre- and post-operation plasma from patients with NSCLC. Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to determine the levels of tRF in tissues, plasma, and cells. Gain- and loss-of-function experiments were implemented to investigate the oncogenic effects of tRF on NSCLC cells in vitro and in vivo. Chromatin immunoprecipitation (ChIP), luciferase reporter, RNA pulldown, mass spectrum, RNA immunoprecipitation (RIP), Western blot, co-immunoprecipitation (Co-IP) assays, and rescue experiments were performed to explore the regulatory mechanisms of tRF in NSCLC. Results: AS-tDR-007333 was an uncharacterized tRF and significantly up-regulated in NSCLC tissues, plasma, and cells. Clinically, AS-tDR-007333 overexpression could distinguish NSCLC patients from healthy controls and associated with poorer prognosis of NSCLC patients. Functionally, overexpression of AS-tDR-007333 enhanced proliferation and migration of NSCLC cells, whereas knockdown of AS-tDR-007333 resulted in opposite effects. Mechanistically, AS-tDR-007333 promoted the malignancy of NSCLC cells by activating MED29 through two distinct mechanisms. First, AS-tDR-007333 bound to and interacted with HSPB1, which activated MED29 expression by enhancing H3K4me1 and H3K27ac in MED29 promoter. Second, AS-tDR-007333 stimulated the expression of transcription factor ELK4, which bound to MED29 promoter and increased its transcription. Therapeutically, inhibition of AS-tDR-007333 suppressed NSCLC cell growth in vivo. Conclusions: Our study identifies a new oncogenic tRF and uncovers a novel mechanism that AS-tDR-007333 promotes NSCLC malignancy through the HSPB1-MED29 and ELK4-MED29 axes. AS-tDR-007333 is a potential diagnostic or prognostic marker and therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

• An extended grain-based phase field method (GB-PFM) is proposed to investigate the cracking behavior of brittle rocks at the grain scale. • This method can reproduce the material heterogeneities and microstructure heterogeneities of brittle rocks. • Validation studies are performed, both qualitatively and quantitatively. • Intergrain and intragrain cracks in granite with a single pre-existing flaw are captured. • This method can be generalized to more heterogeneous brittle rocks cracking behavior, such as branching. The cracking behavior and mechanical properties of brittle rocks is controlled by its microstructure. In this work, an extended grain-based phase field method (GB-PFM) based on Voronoi tessellation technology is proposed to investigate the mechanical properties and crack propagation in heterogeneous brittle rocks by considering material heterogeneities and microstructure heterogeneities at the grain scale. Then, a trial and error calibration procedure is developed after comprehensive study of uncertain parameters such as grain boundaries thickness and critical energy release rate. It is shown that greater grain boundaries thickness results in a lower tensile strength and lower Young's modulus, and greater number of intergrain cracks. Then, a group of models with single pre-existing flaw (flaw inclination angles: 0°, 30°, 45°, 60°, 90°) are built according to calibration parameters to study the mechanical properties and cracking behavior of heterogeneous granite under direct tension. The path of the macrocracks obtained from GB-PFM shows a more noticeable tortuous nature as compared with that results by others phase field methods. The variation of flaw inclination has an obviously influence on crack propagation. Failure patterns obtained by GB-PFM revealing the macrocracks are composed of intragrain and intergrain cracks at the microscopic view. Moreover, the stress field distribution obtained by GB-PFM is agree well with the theoretical analyses and other numerical simulations. The above simulated results prove that the GB-PFM provides an applicable numerical method for efficiently reproducing the microstructure and the related crack propagation of brittle crystalline rocks, which greatly expand the application of the phase field methods. [ABSTRACT FROM AUTHOR]

Purpose: Emerging evidence suggests that cytotoxic therapy may promote drug resistance and metastasis while inhibiting the growth of primary tumors. As yet, however, the underlying mechanisms remain unclear. Here, we aimed to investigate the pro-metastatic effects of adriamycin (ADR) therapy on breast cancer cells and to investigate the mechanisms underlying these effects. Methods: Differentially expressed genes between MCF-7 and ADR-resistant MCF-7 breast cancer cells were identified using high-throughput RNA-seq and differential gene expression analyses. In vitro transwell and scratch wound-healing assays, and an in vivo spontaneous metastasis model were used to study the metastatic potential of the breast cancer cells. The relationship between SIRT7 and TEK expression was studied using promoter activity, electrophoretic mobility shift (EMSA), CHIP-qPCR and Co-IP assays. Results: Using transcriptome sequencing, we identified two key genes (SIRT7 and TEK) that might contribute to the pro-metastatic effect of ADR on breast cancer cells. SIRT7 acted as a negative regulator for TEK by inducing deacetylation of H3K18 at the TEK promoter. Through transcription factor prediction and double fluorescence experiments, we found that EST-1 could bind to the TEK promoter. Knockdown of EST-1 removed the transcriptional inhibition of TEK that was mediated by up-regulation of SIRT7. Co-IP showed that SIRT7 interacts directly with EST-1 in breast cancer cells, indicating that SIRT7 may induce H3K18 deacetylation at the TEK promoter region by directly binding to EST-1. In vitro and in vivo results showed that overexpression of SIRT7 or inhibition of TIE2 significantly reduced ADR-dependent breast cancer cell invasion/metastasis. Conclusion: Our findings suggest that ADR therapy may accelerate breast cancer metastasis in a SIRT7/TEK(TIE2) dependent manner. [ABSTRACT FROM AUTHOR]

Most anticancer drugs with broad toxicities are systematically administrated to cancer patients and their distribution in tumors is extremely low owing to hypoxia, which compromises the therapeutic efficacies of these cancer drugs. Consequently, a preponderant proportion of cancer drugs is distributed in off-target-healthy tissues, which often causes severe adverse effects. Precision cancer therapy without overdosing patients with drugs remains one of the most challenging issues in cancer therapy. Here, a novel concept of nanopoxia is presented, which is a tumor-hypoxia-based photodynamic nanoplatform for the release of therapeutic agents to achieve precision cancer therapy. Under tumor hypoxia, exposure of tumors to laser irradiation induces the fracture of polymer outer shell and produces anticancer reactive oxygen species, and switches 2D antimonene (Sb) nanomaterials to cytotoxic trivalent antimony to synergistically kill tumors. In preclinical cancer models, delivery of Sb nanomaterials to mice virtually ablates tumor growth without producing any detectable adverse effects. Mechanistically, the tumor hypoxiatriggered generation of trivalent antimony displays direct damaging effects on cancer cells and suppression of tumor angiogenesis. Together, the study provides a proof-of-concept of hypoxia-based precision cancer therapy by developing a novel nanoplatform that offers multifarious mechanisms of cancer eradication. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been extensively investigated for decades for tumor treatment because of its non-invasiveness, spatiotemporal selectivity, lower side-effects, and immune activation ability. It can be a promising treatment modality in several medical fields, including oncology, immunology, urology, dermatology, ophthalmology, cardiology, pneumology, and dentistry. Nevertheless, the clinical application of PDT is largely restricted by the drawbacks of traditional photosensitizers, limited tissue penetrability of light, inefficient induction of tumor cell death, tumor resistance to the therapy, and the severe pain induced by the therapy. Recently, various photosensitizer formulations and therapy strategies have been developed to overcome these barriers. Significantly, the introduction of nanomaterials in PDT, as carriers or photosensitizers, may overcome the drawbacks of traditional photosensitizers. Based on this, nanocomposites excited by various light sources are applied in the PDT of deep-seated tumors. Modulation of cell death pathways with co-delivered reagents promotes PDT induced tumor cell death. Relief of tumor resistance to PDT with combined therapy strategies further promotes tumor inhibition. Also, the optimization of photosensitizer formulations and therapy procedures reduces pain in PDT. Here, a systematic summary of recent advances in the fabrication of photosensitizers and the design of therapy strategies to overcome barriers in PDT is presented. Several aspects important for the clinical application of PDT in cancer treatment are also discussed. [ABSTRACT FROM AUTHOR]

Non‐invasive cancer photothermal therapy (PTT) is a promising replacement for traditional cancer treatments. The second near‐infrared region induced PTT (NIR‐II PTT, 1000–1500 nm) with less energy dissipation has been developed for deeper‐seated tumor treatment in recent years compared with the traditional first near‐infrared light (750–1000 nm). In addition, the use of emerging inorganic 2D nanomaterials as photothermal agents (PTAs) further enhanced PTT efficiency due to their intrinsic photothermal properties. NIR‐II light stimulated inorganic 2D nanomaterials for PTT is becoming a hot topic in both academic and clinical fields. This review summarizes the categories, structures, and photothermal conversion properties of inorganic 2D nanomaterials for the first time. The recent synergistic strategies of NIR‐II responsive PTT combined with other treatment approaches including chemotherapy, chemodynamic therapy, photodynamic therapy, radiotherapy are summarized. The future challenges and perspectives on these 2D nanomaterials for NIR‐II responsive PTT systems construction are further discussed. [ABSTRACT FROM AUTHOR]

Abstract: Prenatal alcohol exposure (PAE) has been previously reported to result in behavioral and cognitive deficits that continue into adulthood. These deficits are often manifested by poor performance on higher-order cognitive motor tasks, difficulties in maintaining postural balance, slower reaction times, and deficits in fine motor performance. The central causes of these cognitive and motor deficits have been studied in human and animal models. Rats have been shown to be capable of performing skilled reaching and grasping movements with their forepaws that exhibit many components of skilled reaching also found in human and non-human primates. Whether PAE affects skilled reaching movements in rats is unknown. In the present study, we investigated the effect of PAE on skilled reaching and grasping behavior in rats. Pregnant Sprague–Dawley rats were intragastrically gavaged daily with alcohol at a dose of 6 g/kg body weight from gestation day one (G1) through G20 that yielded average blood alcohol levels between 265 and 343 mg/dL. Non-alcohol groups, pairfed (n =4) and chowfed (n =9), served as nutritionally-matched and normal controls, respectively to the alcohol treatment group (n =12). At 7 weeks of age, all rats were deprived of food for one day. The next day, rats were individually placed in test cages where food could only be accessed by reaching through a grid and grasping small food pellets (20 mg) on a tray. All rats were naive to the task. The major findings in this study are: a) PAE significantly increased the average number of minutes to make a successful skilled reach (Alc mean±SEM=97.3±16.9 min vs. non-Alc 52.3±9.6 min), b) once a successful skilled reach was learned, non-alcohol control rats were no better than Alc rats in using the skilled reach to acquire food, c) no significant differences between groups were observed in the amount of food consumption or changes in body weight during test sessions. These findings provide an important first step into the role that PAE plays for the learning of new skills and will lead to studies of central mechanisms underlying more complex skilled reaching behaviors. [Copyright &y& Elsevier]

Purpose: Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods: The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results: The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions: In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein–protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20–6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06–3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression. Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Targeting ubiquitin-dependent proteolysis is one of the strategies in cancer therapy. CRLCDT2 and CRLDDB2 are two key E3 ubiquitin ligases involved in DNA replication and DNA damage repair. But CDT2 and DDB2 are opposite prognostic factors in kinds of cancers, and the underlining mechanism needs to be elucidated. Methods: Small interfering RNAs were used to determine the function of target genes. Co-immunoprecipitation (Co-IP) was performed to detect the interaction between DDB2 and CDT2. Immunofluorescence assays and fluorescence activating cell sorting (FACS) were used to measure the change of DNA content. In vivo ubiquitination assay was carried out to clarify the ubiquitination of CDT2 mediated by DDB2. Cell synchronization was performed to arrest cells at G1/S and S phase. The mechanism involved in DDB2-mediated CDT2 degradation was investigated by constructing plasmids with mutant variants and measured by Western blot. Immunohistochemistry was performed to determine the relationship between DDB2 and CDT2. Paired two-side Student's t-test was used to measure the significance of the difference between control group and experimental group. Results: Knockdown of DDB2 stabilized CDT2, while over-expression of DDB2 enhanced ubiquitination of CDT2, and subsequentially degradation of CDT2. Although both DDB2 and CDT2 contain PIP (PCNA-interacting protein) box, PIP box is dispensable for DDB2-mediated CDT2 degradation. Knockdown of PCNA had negligible effects on the stability of CDT2, but promoted accumulation of CDT1, p21 and SET8. Silencing of DDB2 arrested cell cycle in G1 phase, destabilized CDT1 and reduced the chromatin loading of MCMs, thereby blocked the formation of polyploidy induced by ablation of CDT2. In breast cancer and ovarian teratoma tissues, high level of DDB2 was along with lower level of CDT2. Conclusions: We found that CRL4DDB2 is the novel E3 ubiquitin ligases of CDT2, and DDB2 regulates DNA replication through indirectly regulates CDT1 protein stability by degrading CDT2 and promotes the assembly of pre-replication complex. Our results broaden the horizon for understanding the opposite function of CDT2 and DDB2 in tumorigenesis, and may provide clues for drug discovery in cancer therapy. [ABSTRACT FROM AUTHOR]

The shear creep behavior of bolted rock joints is closely related to the long-term stability of bolt-reinforced high slopes and underground caverns. To investigate the controlling effect of bolts on rock joint shear creep, limestone samples from the Wudongde dam site area in southwest China were collected and processed, and multistep shear creep tests were conducted on both bolted an unbolted rock joints. The results show that the shear creep of bolted rock joints includes the instantaneous strain stage, transient creep stage and steady-state creep stage, yet the accelerating creep typically occurs instantaneously and is unobservable. By comparing the shear creep process of bolted and unbolted rock joints, it is observed that the presence of bolts decelerates the deterioration of joint surfaces, resulting in a shorter duration of transient creep and lower creep rate. Furthermore, the bolt alters the creep failure mode of the rock joint from brittle failure to plastic failure. Based on experimental results, the reinforcement effect of the bolt through joint creep is analyzed, and the stress evolution during creep is divided into three stages, i.e., the stress-compatibility stage, the stress-compensation stage, and the stress-limitation stage. We summarize how the bolt compensates for stress loss caused by joint surface deterioration through increased shear and axial forces, thereby reducing the creep rate and creep deformation of the rock joint. Based on the stress compensation mechanism of the bolt, a B-Q-N (Burgers-shear force Q o -axial force N o) creep constitutive model for bolted rock joints is proposed. When the creep behavior of the unbolted rock joint and the anchorage parameters are known, the B-Q-N model can describe the shear creep behavior of bolted rock joints without experimental data for parameter identification, as well verified by our tests. • The bolt decelerates the damaging of joint surfaces, resulting in a shorter duration of transient creep and lower creep rate of rock joint. • The bolt alters the creep failure mode of the rock joint from brittle failure to plastic failure. • The stress compensation mechanism of bolt on joint creep is proposed. • The proposed B-Q-N model can describe the creep behavior of bolted rock joints without experimental data for parameter identification. [ABSTRACT FROM AUTHOR]

Optical techniques using developed laser and optical devices have made a profound impact on modern medicine, with "biomedical optics" becoming an emerging field. Sophisticated technologies have been developed in cancer nanomedicine, such as photothermal therapy and photodynamic therapy, among others. However, single-mode phototherapy cannot completely treat persistent tumors, with the challenges of relapse or metastasis remaining; therefore, combinatorial strategies are being developed. In this review, the role of light in cancer therapy and the challenges of phototherapy are discussed. The development of combinatorial strategies with other therapeutic methods, including chemotherapy, immunotherapy, gene therapy, and radiotherapy, is presented and future directions are further discussed. This review aims to highlight the significance of light in cancer therapy and discuss the combinatorial strategies that show promise in addressing the challenges of phototherapy. [ABSTRACT FROM AUTHOR]

Nanomaterials‐based photothermal therapy (PTT) could efficiently eliminate cancer cells in a noninvasive manner. However, nanoscale photosensitizers still suffer from several drawbacks, limiting them from being an ideal PTT approach against cancer. These include unfavorable biodistribution and poor retention in tumor tissue. In this study, acid‐activatable smart self‐assembly of black phosphorous (BP) and polyoxometalates (POM) is carried out to yield POM@BP with prolonged tumor retention and enhanced efficacy of PTT. The as‐rationally designed POM@BP photosensitizers in acidic tumor microenvironments self‐assemble into nanoparticles with larger sizes, remarkably increasing the light absorption ability of BP nanosheets in PTT of cancer. The as‐obtained POM@BP endows prolonged retention and enhances the photothermal response in tumor tissue by smart self‐assembly of BP into larger nanoparticles. In summary, the proposed potent approach for the rational design and tailor photosensitizer for cancer treatment looks very promising for future scientific breakthroughs in nanomedicine. [ABSTRACT FROM AUTHOR]

Background. The microliposome maintenance (MCM) complex, MCM2-7, is revealed to be involved in multiple cellular processes and plays a key role in the development and progression of human cancers. However, the MCM complex remains poorly elaborated in hepatic carcinoma (HCC). Methods. In the study, we found the mRNA and protein level by bioinformatics. We also explored the prognostic value, genetic alteration, interaction network, and functional enrichment of MCM2-7. The MCM expression and correlation among these MCMs in HCC cell lines were identified by western blot. Results. MCM2-7 was significantly increased in HCC tissues compared to normal liver tissues. The high level of MCM2-7 had a positive correlation with poor prognosis. However, MCM2-7 alterations were not correlated with poor OS. MCMs were both increased in HCC cell lines compared to the normal hepatocyte cell line. Furthermore, the positive correlation was found among MCMs in HCC cell lines. Conclusions. The MCM complex was increased in HCC tissues and cell lines and negatively correlated with prognosis, which might be important biomarkers for HCC. [ABSTRACT FROM AUTHOR]

A rapid clinical diagnosis may efficiently improve the survival rate and prognosis of patients with ischemic heart disease (IHD). Therefore, a one-step, rapid and inexpensive analysis for the quick diagnosis of IHD was investigated in the present study. Consecutive patients who were subjected to myoglobin, cardiac troponin I and creatine kinase-MB isoenzyme assessment at the Emergency Department of Shenzhen Second People's Hospital (Shenzhen, China) between December 2017 and March 2018 prior to treatment were screened. Clinically applicable disposable strips were employed for quantification of the cardiac biomarkers. The analytical performance of the strips was evaluated by receiver operating characteristic (ROC) curves and compared with the traditional chemiluminescence immunoassay (CLIA) method. The data of 391 participants were collected. At the baseline, 57 patients were diagnosed with IHD and 334 patients were diagnosed with other diseases. The area under the ROC curve (AUC) of the CLIA model was 0.787 (95% CI, 0.709-0.865) with a specificity of 76.7% and a sensitivity of 71.9%. At the optimal cutoff value of -1.867, the negative and the positive predictive value were 94.1 and 34.5%, respectively. The AUC of the disposable strip model was 0.792 (95% CI, 0.729-0.855). At the cutoff value of -1.820 or below, the negative predictive value was 94.9%, the positive predictive value was 28.9%, the specificity was 66.8% and the sensitivity was 79.0%. The P-value of the ROCs was 0.858, indicating no statistically significant difference between the two assay methods. The cost of the disposable strip was 50% of that of the CLIA method and it took only 25% of the time that was required for the quantification of the three cardiac markers by CLIA. In conclusion, the disposable strip provides a platform for point-of-care testing and may be an easy, rapid, reliable and cost-saving method for the diagnosis of IHD. [ABSTRACT FROM AUTHOR]

Highlights: A comprehensive review of the recent development of two-dimensional (2D) PtSe2 synthesis strategies has been extensively surveyed. The applications of 2D PtSe2 materials in areas, including opto/electric devices, photocatalysis, hydrogen evolution reaction, and sensors, have been reviewed. Current challenges in the development of 2D PtSe2 materials are identified, and outlooks toward unexplored research areas are suggested.In recent years, emerging two-dimensional (2D) platinum diselenide (PtSe2) has quickly attracted the attention of the research community due to its novel physical and chemical properties. For the past few years, increasing research achievements on 2D PtSe2 have been reported toward the fundamental science and various potential applications of PtSe2. In this review, the properties and structure characteristics of 2D PtSe2 are discussed at first. Then, the recent advances in synthesis of PtSe2 as well as their applications are reviewed. At last, potential perspectives in exploring the application of 2D PtSe2 are reviewed. [ABSTRACT FROM AUTHOR]

Recently, emerging 2D material‐supported metal single‐atom catalysts (SACs) are receiving enormous attention in heterogeneous catalysis. Due to their well‐defined, precisely located metal centers, unique metal–support interaction and identical coordination environment, these catalysts serve as excellent models for understanding the fundamental issues in catalysis as well as exhibiting intriguing practical applications. Understanding the correlations between metal–support combinations and the catalytic performance at the atomic level can be achieved on the SACs@2D materials nanoplatforms. Herein, recent advances of metal SACs on various types of 2D materials are reviewed, especially their exciting applications in the fields of chemicals, energy, and the environment. Based on the summary and perspectives, this work should contribute to the rational design of perfect metal SACs with versatile properties. [ABSTRACT FROM AUTHOR]

The emergence of novel two-dimensional (2D) monoelemental materials (Xenes) has shown remarkable potential for their applications in different fields of technology, as well as addressing new discoveries in fundamental science. Xenes (e.g., borophene, silicene, germanene, stanene, phosphorene, arsenene, antimonene, bismuthene, and tellurene) are of particular interest because they are the most chemically tractable materials for synthetic exploration. Owing to their excellent physical, chemical, electronic and optical properties, Xenes have been regarded as promising agents for biosensors, bioimaging, therapeutic delivery, and theranostics, as well as in several other new bio-applications. In this tutorial review, we summarize their general properties including the classification of Xenes according to their bulk properties. The synthetic and modification methods of Xenes are also presented. Furthermore, the representative Xene nanoplatforms for various biomedical applications are highlighted. Finally, research progress, challenges, and perspectives for the future development of Xenes in biomedicines are discussed. [ABSTRACT FROM AUTHOR]

Abstract Glioma is the commonest malignant tumor in the central nervous system (CNS), characterized by rapid growth. However, the molecular mechanism underlying the growth remains unclear. Immunity-related GTPase family M protein (IRGM) participates in immune response to pathogen and tumorigenesis. Proliferation and autophagy are two crucial functions contributing to aggressive growth. Therefore, our aims were to probe whether IRGM regulates glioma proliferation and autophagy. In this study, we found that 47 glioma specimens had more IRGM expression than 11 non-cancerous brain tissues with immunohistochemistry. IRGM was also up-regulated in human glioma cell lines U87, U251 and A172 and so on compared with immortalized astrocytes. Importantly, overexpression of IRGM significantly increased the cell colonies formation, cell proliferation and Akt activation (Thr308 and Ser473 sites) than matched control. On another hand, all of IRGM, autophagy marker LC3II and autophagy adaptor p62 gradually increased after starvation 2 and 4 h. Furthermore, western blot and immunofluorescence results showed that knockdown of IRGM inhibited the formation of LC3-II and the expression of p62. Our data uncovered that IRGM acted in glioma proliferation and autophagy, providing a new target with dual roles for the future translation research. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Complementarity-determining region 3 (CDR3) of B-cell receptors (BCRs) and T-cell receptors are the major site of antigen recognition, which determines a unique clone type, and are considered to be the representative of the disease. In the present study, high-throughput sequencing was used to analyze the association of characteristics of the BCR immunoglobulin heavy chain (IGH) and the T-cell receptor β chain (TRB) CDR3 genes in PTC and corresponding pericarcinous tissues from patients. A difference of CDR3 length distributions of total IGH CDR3 sequences between the two groups was revealed. IGHV3-11/IGHJ6, TRBV2/TRBJ1-2 and TRBV2/TRBJ1-1 may be biomarkers for the development of PTC. Furthermore, it was revealed that the extent of the common clonotype expressions at the amino acid level was slightly higher compared with the nucleotide level. The Shannon entropy demonstrated a diversity reduction in PTC compared with the pericarcinous group, and the highly expended clone (HEC) expression of PTC was higher compared with that of the corresponding pericarcinous group. Additionally, the highest clone frequency percentage of IGH and TRB was at 0.1-1.0% degree of expansion, as HEC expression was higher in PTC compared with the matched group. There was no shared clone of HECs in the two groups either at the amino acid level or at the nucleotide expression level. The differential expression of CDR3 sequences of PTC have been identified in the present study. Further research is required for assessing the immune repertoire size, diversity, cloning tracking and finding public clones of T-cell and B-cell populations in the development of PTC. [ABSTRACT FROM AUTHOR]

• A micromechanical-based failure criterion incorporating temperature-dependent initial damage is proposed. • The failure criterion can predict strength evolution of rocks after high-temperature treatment under compressive loading. • The expression of failure criterion coincides with the classical Hoek-Brown failure criterion for intact rocks. The strength properties of rocks after high-temperature treatment are substantially impacted by thermally-induced cracks. In this work, a new parameter of temperature-dependent initial damage or crack density is proposed and a micromechanical-based failure criterion incorporating it is developed to characterize the strength properties of rocks after high-temperature treatment under compressive loading. The mathematical expression of the suggested nonlinear failure criterion coincides with the Hoek-Brown failure criterion for intact rocks. The micromechanical-based failure criterion is then verified using the experimental results of five sets of rocks (Macheng granite, Tournemire shale, red sandstone, coarse marble and veined marble) after high-temperature treatment. The results shown that the strength properties of rocks after high-temperature treatment can be well captured using the failure criterion incorporating temperature-dependent initial damage. Three evaluation indicators (root mean square error, correlation coefficient and mean absolute error) are indicated that the failure criterion incorporating temperature-dependent initial damage has a strong predictive capability. The parameter of temperature-dependent initial damage provides a great description of the effect of thermally-induced damage on the strength evolution of rocks after high-temperature treatment. The proposed failure criterion in this work will become an effective alternative for predicting the nonlinear strength evolution of pre-heated rocks under compressive loading due to its high reliability and easy-to-use. [ABSTRACT FROM AUTHOR]

Aim The mechanisms of non-alcoholic steatohepatitis (NASH) in hepatocytes are unknown. Our aim is to study the tissue metabolic profiling and pathways of NASH. Methods We built rat models for simple steatosis and NASH and analyzed the liver extract using a liquid chromatograph-mass spectrometer. The acquired data were processed by multivariate principal component analysis and partial least squares discriminant analysis (PLS-DA) to obtain metabolic profiling. Orthogonal projections to latent structures DA was used to obtain metabolites capable of distinguishing NASH and steatosis. The total differences in the metabolites between groups were analyzed to determine their metabolic pathways. Results Principal component analysis showed that the metabolic profiles of NASH and steatosis are different. The PLS-DA modeling revealed a clear separation between two groups with parameters R2Y and Q2Y all greater than 0.7. The orthogonal projections to latent structures DA model identified 171 metabolites capable of distinguishing NASH from steatosis. The identified metabolites are involved in fatty acid metabolism, tryptophan metabolism, the urea cycle, and the citric acid cycle in hepatocytes. Conclusions These metabolic profiles and pathways in rat hepatocytes will offer useful information when studying metabolic disorders in patients with NASH. [ABSTRACT FROM AUTHOR]

Electrode position after deep brain stimulation (DBS) for Parkinson's disease (PD) needs to be confirmed, but there are concerns about the risk of postoperative magnetic resonance imaging (MRI) after DBS. These issues could be avoided by fusion images obtained from preoperative MRI and postoperative computed tomography (CT). This study aimed to investigate image fusion technology for displaying the position of the electrodes compared with postoperative MRI. This was a retrospective study of 32 patients with PD treated with bilateral subthalamic nucleus (STN) DBS between April 2015 and March 2016. The postoperative (same day) CT and preoperative MRI were fused using the Elekta Leksell 10.1 planning workstation (Elekta Instruments, Stockholm, Sweden). The position of the electrodes was compared between the fusion images and postoperative 1–2-week MRI. The position of the electrodes was highly correlated between the fusion and postoperative MRI (all r between 0.865 and 0.996; all P < 0.001). The differences of the left electrode position in the lateral and vertical planes was significantly different between the two methods (0.30 and 0.24 mm, respectively, both P < 0.05), but there were no significant differences for the other electrode and planes (all P > 0.05). The position of the electrodes was highly correlated between the fusion and postoperative MRI. The CT-MRI fusion images could be used to avoid the potential risks of MRI after DBS in patients with PD. [ABSTRACT FROM AUTHOR]

Objective A key step in managing non-alcoholic fatty liver disease (NAFLD) is to differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis (SS). Method Serum samples were collected from three groups: NASH patients ( N = 21), SS patients ( N = 38) and healthy controls ( N = 31). High performance liquid chromatography-mass spectrometry (HPLC-MS) was used to analyse the metabolic profile of the serum samples. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) to identify novel metabolites. The potential biomarkers were quantitatively determined and their diagnostic power was further validated. Results A total of 56 metabolites were capable of distinguishing NASH from SS samples based on the OPLS-DA model. Pyroglutamate was found to be the most promising factor in distinguishing the NASH from SS groups. With an optimal cut-off value of 4.82 mmol/L, the sensitivity and specificity of the diagnosis of NASH were 72% and 85%, respectively. The area under the receiver operating characteristic (AUROC) of the pyroglutamate levels of NASH versus SS patients was more than those of tumor necrosis factor-α, adiponectin and interleukin-8. Conclusion These data suggest that pyroglutamate may be a new and useful biomarker for the diagnosis of NASH. [ABSTRACT FROM AUTHOR]

β-agonists are phenylethanolamines with different substituent groups on the aromatic ring and the terminal amino group which have the effect of nutrition redistribution and can accumulate in body tissues causing acute or chronic poisoning when consumed. Therefore, it is very important to establish a fast screening method for the detection of several kinds of β-agonists in food safety control. In this study, the aptamer-agonists (AP-Ago) has screened out by Isothermal Titration Calorimetric method. AP-Ago was a single-strand DNA with 22 base-pairs. The dissociation constant ( K d ) to phenylethanolamine (PHL) was 3.34×10 −5 mol L −1 . The AP-Ago based electrode was constructed by self-assembling on gold electrode. A label-free electrochemical aptasensor was then developed with AP-Ago-based gold electrode, which was sensitive to phenylethanolamine(PHL), clenbuterol (CLB), ractopamine (RAC), salbutamol (SAL) and procaterol (PRO). The detection limits were 0.04 ng/mL (RAC), 0.35 pg/mL (CLB), 1.0 pg/mL (PHL), 0.53 pg/mL (SAL) and 1.73 pg/mL(PRO), respectively, The detection time was 15 min. The reproductivity of the mentioned aptasensor is good with RSD of 2.09%. Comparing with ELISA and HPLC on β-agonists detection in actual sample, this aptasensor is advantage of fewer steps and fast screen-detection of these five β-agonists or their mixtures. This study suggests that the aptasensor can be developed to a rapid screening means with multi-β-agonists (may be one or more) in sample. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance is that the most important reason behind of carcinoma treatment failure but the underlying molecular mechanisms are unclear. Members of the tripartite motif containing protein (TRIM) family play crucial roles in the carcinogenesis and development of resistance against chemotherapy. Herein, we first confirmed that TRIM58 is highly expressed in triple-negative breast cancer tissues and drug-resistant MCF7/ADR cells. Furthermore, TRIM58 knockdown resulted in increased sensitivity of MCF7/ADR cells toward doxorubicin in vitro and in vivo. In contrast, TRIM58 overexpression in breast cancer cells increased doxorubicin resistance. TRIM58 was found to interact with DDX3, a protein recently reported to modulate resistance against chemotherapy. We found that TRIM58 negatively regulates DDX3 expression downstream of the P53/P21 pathway, and that DDX3 is degraded by TRIM58-mediated ubiquitination. Knockdown of DDX3 reversed doxorubicin chemotherapy sensitivity induced by TRIM58 knockdown via the P53/P21 pathway.Our study reveals that TRIM58 mediates a novel mechanism underlying the development of resistance against chemotherapy in breast cancer and provides potential targets for developing novel therapeutic targets for breast cancer. [ABSTRACT FROM AUTHOR]

Emissive electron donor–acceptor (D–A)conjugateshave a wide variety of applications in biophotonics, two-photon absorptionmaterials, organic lasers, long wavelength emitters, and so forth.However, it is still a challenge to synthesize high solid-state efficiencyD–A structured emitters due to the notorious aggregation-causedquenching (ACQ) effect. Though some D–A systems are reportedto show aggregation-induced emission (AIE) behaviors, most are onlyselectively AIE-active in highly polar solvents, showing decreasedsolid-sate emission efficiencies compared to those in nonpolar solvents.Here we report the triphenylamine (TPA) and 2,3,3-triphenylacrylonitrile(TPAN) based D–A architectures, namely, TPA3TPAN and DTPA4TPAN.Decoration of arylamines with TPAN changes their emission behaviorsfrom ACQ to AIE, making resulting TPA3TPAN and DTPA4TPAN nonluminescentin common solvents but highly emissive when aggregated as nanoparticles,solid powders, and thin films owing to their highly twisted configurations.Both compounds also display a bathochromic effect due to their intramolecularcharge transfer (ICT) attribute. Combined ICT and AIE features renderTPA3TPAN and DTPA4TPAN intense solid yellow emitters with quantumefficiencies of 33.2% and 38.2%, respectively. They are also thermallyand morphologically stable, with decomposition and glass transitiontemperatures (Td/Tg) being 365/127 and 377/141 °C, respectively. Multilayerelectroluminescence (EL) devices are constructed, which emit yellowEL with maximum luminance, current, power, and external quantum efficienciesup to 3101 cd/m2, 6.16 cd/A, 2.64 lm/W, and 2.18%, respectively.These results indicate that it is promising to fabricate high efficiencyAIE-ICT luminogens with tunable emissions through rational combinationand modulation of propeller-like donors and/or acceptors, thus pavingthe way for their biophotonic and optoelectronic applications. [ABSTRACT FROM AUTHOR]