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Reasonable evaluation and prediction of squeezing condition to avoid large deformation disaster in tunnels have been an important research issue. In order to accurately and rapidly predict the large deformation under complex geological conditions, this paper proposes a classification and prediction method for quick identification of large deformation in tunnel construction stage in a case study of Muzhailing Tunnel. Previous prediction methods of large deformation are usually based on the stages of geological survey and engineering design, and there are great difficulties in obtaining some prediction indexes in soft and fractured strata, such as uniaxial compressive strength. In this paper, the nonlinear deformation behaviors of surrounding rock were analyzed. The geo-stress condition, strata occurrence, rock strength, rock intactness and groundwater condition were chosen as evaluation indexes (including eight sub-indexes). The classification of large deformation was carried out based on the deformation statistics in Muzhailing Tunnel. And the fuzzy prediction was conducted and compared with other methods in engineering. The comparison results show that the new method has higher accuracy and applicability in predicting the large deformation of weak rock mass. This study provides a new approach for rapid identification and prediction of large deformation in tunnel construction stage. [ABSTRACT FROM AUTHOR]

The ascomycete Cordyceps genus has been used as valued traditional Chinese medicine and functional food. Solid-state fermentation (SSF) of soybean, chickpea, black bean, and mung bean with Cordyceps militaris was performed for 35 days at 22°C, and then the biomass, total phenolic content (TPC), and total flavonoid content (TFC) increased significantly with the extension of fermentation time. The cordycepin content in four SSF-beans was as high as 8.33, 11.12, 10.43, and 6.64 mg/g, respectively. Moreover, the fermentation improved the 1,1′-diphenyl-2- picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTs) radical scavenging capacity, ferric reducing antioxidant power (FRAP) and ACE inhibition ability. Overall, the findings of the study stated clearly that SSF of beans with C. militaris was a potentially promising way to enhance the nutritional, physico-chemical, and biological properties of the substrate. Cordyceps-fermented products may serve as a novel valuable nutritional and functional food in health industry. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the role of ribophorin II (RPN2) in nasopharyngeal cancer (NPC) cell survival and death. RPN2 expression was upregulated in 22 human NPC specimens and 5–8F and CNE1 cells compared with that in adjacent normal tissues and normal nasopharyngeal NP69 cells. CCK-8 and colony formation assays indicated that the silencing of RPN2 hindered the proliferation and growth of 5–8F and CNE1 cells. RPN2 expression was upregulated in 22 human NPC specimens as well as in 5–8F and CNE1 cells compared with that in adjacent normal tissues and NP69 cells. CCK-8 and colony formation assays indicated that the silencing of RPN2 reduced the proliferation and growth of 5–8F and CNE1 cells. Annexin V/PI flow cytometry and Bcl-2/Bax analysis showed that RPN2 silencing led to increased apoptosis. Moreover, JAK1 was found to interact with RPN2, and total JAK1, STAT3, and phosphorylated STAT3 levels were dramatically decreased in cells with RPN2 silencing. Furthermore, the nuclear localization of STAT3 was blocked by the silencing of RPN2. The administration of the STAT3 activator colivelin could offset the inhibitory effect of RPN2 silencing on the survival and apoptosis of NPC cells. RPN2 is upregulated in NPC tissues or cells, and RPN2 silencing repressed NPC cell proliferation and elicited apoptosis. RPN2 overexpression is possibly associated with JAK1/STAT3 silencing and activation. Finally, RPN2 represents a promising target for NPC treatment. [ABSTRACT FROM AUTHOR]

Evidence on how hot spot policing affects community members' views of police is very limited and inconclusive. Scholars have thus called for further study of community attitudes in hot spots to guide police in the formulation of hot spot strategies—an issue that is especially salient given recent public controversy surrounding policing, particularly in the United States. Using survey responses collected in 2018 from more than 1,000 community members living or working in more than 100 hot spots across 2 mid-sized cities in the United States, this study examines how community members' perceptions of police activities in hot spots relate to their wider attitudes about police. Bivariate and multivariate analyses indicate that community members in hot spots in both cities exhibit more positive attitudes towards police along several dimensions (e.g., trust and confidence in police, views of police legitimacy, and perceptions of police responsiveness and procedural justice) when they see more frequent patrol and when they see positive police-community interactions. They have more negative views of police when they witness higher levels of investigative and enforcement activity. The findings support hot spot policing strategies that emphasize regular, systematic patrol in hot spots, complemented by positive community engagement efforts and problem-solving work. In contrast, they imply that enhanced enforcement activity in hot spots should be used judiciously. [ABSTRACT FROM AUTHOR]

Type V collagen (collagen V) is one of the important components of extracellular matrix (ECM) in pancreas. We previously reported that pre-coating collagen V on the culture dishes enhanced insulin production in INS-1 rat pancreatic β cells. In this study, we investigate the underlying mechanism. Insulin biosynthesis and secretion are both increased in INS-1 cells cultured on collagen V-coated dishes, accompanied by the reduced nuclear translocation of Yes-associated protein (YAP), a transcriptional co-activator. YAP, the downstream effector of Hippo signaling pathway, plays an important role in the development and function of pancreas. Inhibition of YAP activation by verteporfin further up-regulates insulin biosynthesis and secretion. Silencing large tumor suppressor (LATS), a core component of Hippo pathway which inhibits activity of YAP by phosphorylation, by siRNA transfection inhibits both insulin biosynthesis and secretion. In the present study, the protein level of insulin-like growth factor 1 receptor (IGF-1 R), detected as the upstream molecule of YAP, is reduced in the INS-1 cells cultured on the dishes coated with collagen V. The silencing of IGF-1 R by siRNA transfection further enhances insulin biosynthesis and secretion. IGF-1 treatment reduces collagen V–induced up-regulation of insulin biosynthesis and secretion, accompanying the increased nuclear YAP. Inhibition of IGF-1 R/YAP signal pathway is involved in collagen V–induced insulin biosynthesis and secretion in INS-1 cells. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) plays an important role in tissue repair, cell proliferation, and differentiation. Our previous study showed that collagen I and collagen V differently regulate the proliferation of rat pancreatic β cells (INS-1 cells) through opposite influences on the nuclear translocation of β-catenin. In this study, we investigated the β-catenin pathway in INS-1 cells on dishes coated with collagen I or V. We found that nuclear translocation of the transcription factor Yes-associated protein (YAP) was enhanced by collagen I and suppressed by collagen V, but had no effect on INS-1 cell proliferation. Morphologically, INS-1 cells on collagen V-coated dishes showed stronger cell-to-cell adhesion, while the cells on collagen I-coated dishes showed weaker cell-to-cell adhesion in comparison with the cells on non-coated dishes. E-cadherin played an inhibitory role in the proliferation of INS-1 cells cultured on collagen I or collagen V coated dishes via regulation of the nuclear translocation of β-catenin. Integrin β1 was enhanced with collagen I, while it was repressed with collagen V. The integrin β1 pathway positively regulated the cell proliferation. Inhibition of integrin β1 pathway restored the protein level of E-cadherin and inhibited the nuclear translocation of β-catenin in the cells on collagen I-coated dishes, but no effect was observed in the cells on collagen V-coated dishes. In conclusion, collagen I enhances the proliferation of INS-1 cells via the integrin β1 and E-cadherin/β-catenin signaling pathway. In INS-1 cells on collagen V-coated dishes, both integrin β1 and E-cadherin/β-catenin signal pathways are involved in the inhibition of proliferation. [ABSTRACT FROM AUTHOR]

Besides comprising scaffolding, extracellular matrix components modulate many biological processes including inflammation and cell differentiation. We previously found precoating cell plates with extracellular matrix collagen I, or its denatured product gelatin, causes aggregation of macrophage-like human lymphoma U937 cells, which are induced to differentiation by phorbol myristate treatment. In the present study, we investigated the influence of gelatin or collagen I precoating on the bacteria phagocytosis in PMA-stimulated U937 cells. Colony forming units of phagocytosed bacteria, Giemsa-staining of cells with phagocytosed bacteria, confocal microscopic and flow cytometric analysis of cells with phagocytosed FITC-labeled bacteria and non-bioactive latex beats were conducted. Gelatin precoating enhances the phagocytosis of both Gram-negative and positive bacteria, as shown by the increased colony forming units of bacteria phagocytosed by cells, and increased intracellular bacteria observed after Giemsa-staining. But collagen I has no marked influence. Confocal microscopy reveals that both live and dead FITC-bacteria were phagocytosed more in the cells with gelatin-coating but not collagen-coating. Of note, both gelatin and collagen I coating had no influence on the phagocytosis of non-bioactive latex beads. Since gelatin-coating increases autophagy but collagen I has no such impact, we are curious about the role of autophagy. Inhibiting autophagy reduced the phagocytosis of bacteria, in cells with gelatin-coating, while stimulating autophagy enhanced phagocytosis. This study finds the bacteria-phagocytosis stimulatory effect of gelatin in PMA-treated U937 cells and reveals the positive regulatory role of autophagy, predicting the potential use of gelatin products in anti-bacterial therapy. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusions\nIMPLICATIONS FOR REHABILITATIONWe aimed to describe the facilitators and barriers of physical activity for patients with coronary heart disease.A qualitative descriptive study using semi-structured interviews was conducted with 15 participants with coronary heart disease. The interview guide was developed based on a multi-theory model. Interviews were audio-recorded, transcribed verbatim, and analyzed using a thematic analysis.Two main themes were identified: facilitators of initiation and maintenance of physical activity (behavioral motivation, perceived benefits, behavioral confidence, supportive physical environment, positive emotional experience, self-regulation, supportive social environment, illness perception, and excellent self-control), barriers of initiation and maintenance of physical activity (perceived barriers, restricted physical environment, psychological distress, insufficient social support, and poor self-control).This study presents an in-depth theory-based exploration of facilitators and barriers to initiating and maintaining physical activity among people with coronary heart disease. Relevant factors should be taken into account to increase their effectiveness when designing the target interventions to encourage a physically active lifestyle in this population.Before commencing cardiac rehabilitation, it is imperative to assess patients with coronary heart disease (CHD) to ascertain whether they have limited activity capacity, psychological distress, insufficient social support, and poor self-control.A customized cardiac rehabilitation plan should be meticulously devised for each patient with CHD.For patients in the early stage of initiating physical activity (PA), rehabilitation professionals should assist them in recognizing the severity of their condition and the advantages of engaging in PA.Rehabilitation professionals should also promote active utilization of social networks, stimulate CHD patients’ motivation, and enhance their behavioral confidence.When guiding patients during the maintenance stage of PA, it is essential to regularly evaluate their psychological well-being, assist them in self-regulation based on their physical condition, and foster the development of self-control.Rehabilitation professionals should consistently provide social support to reinforce the patients’ motivation to maintain their PA behavior.Before commencing cardiac rehabilitation, it is imperative to assess patients with coronary heart disease (CHD) to ascertain whether they have limited activity capacity, psychological distress, insufficient social support, and poor self-control.A customized cardiac rehabilitation plan should be meticulously devised for each patient with CHD.For patients in the early stage of initiating physical activity (PA), rehabilitation professionals should assist them in recognizing the severity of their condition and the advantages of engaging in PA.Rehabilitation professionals should also promote active utilization of social networks, stimulate CHD patients’ motivation, and enhance their behavioral confidence.When guiding patients during the maintenance stage of PA, it is essential to regularly evaluate their psychological well-being, assist them in self-regulation based on their physical condition, and foster the development of self-control.Rehabilitation professionals should consistently provide social support to reinforce the patients’ motivation to maintain their PA behavior. [ABSTRACT FROM AUTHOR]

The objective of this prospective cohort study was to investigate whether cryopreservation of cleavage or blastocyst stage embryos improves in vitro fertilization outcomes in recurrent implantation failure (RIF) patients. The study comprised 575 patients who were allocated to receive either single frozen/thawed blastocyst-stage transfer (SBT) or frozen/thawed double-cleavage-stage embryo transfer (DET). The clinical pregnancy rate, implantation rate, and ongoing pregnancy rate were higher in the SBT group compared with the DET group (41.15% vs. 27.11%, p < 0.001; 41.15% vs. 19.28%, p < 0.001; 40.03% vs. 25.9%, p < 0.001), but the miscarriage rate did not differ between the two groups. It was concluded that frozen/thawed SBT could be a preferred strategy for RIF patients. [ABSTRACT FROM AUTHOR]

At present, the country vigorously calls for the use of green, energy-saving and environmentally friendly materials in various fields, especially in electronic power systems that require the use of low-loss soft magnetic alloy materials. Amorphous nanocrystalline alloy materials that have received widespread attention have excellent high magnetic permeability and low loss performance. Therefore, this material has become a power system with energy saving, environmental protection and excellent efficiency. Among them, soft magnetic alloys have the most application prospects. In this paper, various amorphous/nanocrystalline samples have been successfully prepared by vacuum arc melting and rapid cooling. Using XRD, HV and SEM testing and analysis methods, the structure, hardness, mechanical properties, magnetic properties and other alloys were successfully prepared. Mo element improves the ability to form glass from amorphous nanocrystalline alloys, the alloy with alloy composition (F e 0.5 C o 0.5 ) 66 N b 6 B 26 M o 2 has the best glass forming ability. The addition of Mo deteriorates the soft magnetic properties of the alloy. The saturation magnetic flux density Ms of the alloy is reduced from 81 to 59 emu/g, but the coercive force is not significantly improved. By increasing the Fe content, the amorphous forming ability and heat the stability decreases, the Vickers hardness and corrosion resistance decrease, and the saturation magnetization and coercivity increase. It can reduce the cost of the alloy and improve the magnetic properties of the alloy. [ABSTRACT FROM AUTHOR]

Abstract This experiment was conducted to investigate the effects of JUNCAO Ganoderma lucidum polysaccharide peptide (JCGLPP) on slaughter performance and intestinal health of Minxinan black rabbits, which aimed to provide the basis for the application of JCGLPP in meat rabbits. One hundred male weaned Minxinan black rabbits of (33 ± 2) d [(initial body mass (655.65 ± 25.90) g] were randomly divided into four groups with five replicates per group and five rabbits per replicate. The diets were supplemented with 0 (control group), 50 (group I), 100 (group II) and 150 mg·kg−1 (group III) of JCGLPP, respectively. This experiment lasted for 56 days. The results are shown below: (1) The live weight before slaughter of groups I and III was significantly higher than that of control group (p < 0.05); The full net bore weight of group III was significantly higher than that of control group (p < 0.05). (2) pH value of group I was significantly higher than that of control group (p < 0.05); NH3–N content in experimental groups were significantly higher than that in control group(p < 0.05) while NH3-N content in group I was significantly higher than that in groups III and II (p < 0.05); The content of butyric acid in group II was significantly lower than that in control group (p < 0.05); There were no significant differences in acetic acid, isovaleric acid, isobutyric acid and propionic acid in experimental groups compared with control group (p > 0.05). (3) The Occludin content in duodenum, jejunum and ileum of groups I and II was significantly higher than that of control group (p < 0.05). (4) At the phylum level, Firmicutes and Bacteroidetes were the dominant phylum in each group. At the genus level, norank_f__norank_o__Clostridia_UCG-014 in group II were significantly higher than those in control group (p < 0.05). In conclusion, although dietary JCGLPP supplementation could not improve slaughter performance of Minxinan black rabbits, it could improve cecal fermentation parameters and intestinal flora structure and composition of Minxinan black rabbits to a certain extent. Our results revealed that 100 mg·kg−1 might be the optimal concentration obtained in dietary JCGLPP supplementation, which provided ideas and feasibility for drug combination. [ABSTRACT FROM AUTHOR]

This paper presents an experimental investigation into the effect of Z-pin on the low-velocity impact response and flexural properties after impact of the curved CFRP laminates. The Z-pinned specimens are produced using a low-damage pre-hole Z-pinning (PHZ) technique. Unpinned and Z-pinned [0/45/–45/90]4S specimens are both subjected to low-velocity impacts. Nondestructive inspection technique is used to evaluate the internal damage after impact. Subsequently, three-point bending tests are performed to characterize the flexural properties of the impacted specimens. Experimental results indicate that Z-pinned laminate, due to the bridging traction across the delamination cracks provided by pins, can provide an efficient crack arrest mechanism both in impact and bending after impact tests. Compared with the unpinned specimens, the delamination damage projection area (DDPA) is reduced by 28.5–63.5%, depending on the diameter and volume fraction of Z-pin. In addition, Z-pin could improve the residual flexural strength significantly. The specimens with a high Z-pin volume fraction have excellent damage tolerance, leading to an 18.1–76.1% improvement in the residual flexural strength compared with unpinned specimens. [ABSTRACT FROM AUTHOR]

In this study, the substrate design-based method of controlling the residual distortion in directed energy deposition additive manufacturing (DED AM) is proposed, in which the stiffness weakened interval is formed by designing long strip holes in the substrate. The effects of the designed substrates are studied using the sequentially coupled thermal-mechanical model. It is found that by rapidly releasing the thermal distortion through the designed stiffness-weakened substrate, the residual distortion of the DED AM product can be decreased by more than 60%. In the design of the stiffness weakened interval, a definition of the configuration ratio is adopted to study the design parameters of the long strip holes on the release of the thermal distortion. When the length coefficient and the spacing coefficient is designed between 0.25 and 0.35 and lower than 0.2, respectively, the residual distortion of the DED AM as-built sample can be decreased by 75%-85% without the extra distortion caused by the excessive decrease of the stiffness of the substrate. The simulated results were indirectly verified by the experimental data. This paper provides a new controlling method of the residual distortion in the laser DED AM product by designing the stiffness-weakened substrate. [ABSTRACT FROM AUTHOR]

Silibinin is a natural flavonoid with anti-diabetic activity. Glucagon-like peptide−1 (GLP−1), an intestinal hormone mainly secreted from L cells, which regulates insulin production and sensitivity, appears to be a potential therapeutic strategy for T2DM. The current study aims to determine the protective effect of silibinin against palmitic acid (PA)-induced damage in GLUTag cells. The results revealed that PA triggered endoplasmic reticulum (ER) stress and apoptosis in GLUTag cells, while silibinin attenuated PA-induced lipotoxicity. Based on the estrogen-like effects of silibinin and the role of estrogen receptors in regulating glycolipid metabolism, the involvement of estrogen receptors in the protective effects of silibinin in GLUTag cells was further investigated. The results showed that estrogen receptor α- and β-specific inhibitors reversed the inhibitory impact of silibinin on ER stress. Our study demonstrated that silibinin protects GLUTag cells from PA-induced injury by decreasing ER stress under the regulation of estrogen receptors α and β. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and it is characterized by mesangial IgA deposits. Proteinuria is a common clinical feature of IgAN, which has a critical connection to podocyte injury and has been used as a clinical prognostic factor for IgAN. Evidence has shown that TNF-α released from mesangial cells may lead to podocyte apoptosis. Forty male BALB/c mouse were randomly divided into the control group and IgAN group. A mice model of IgAN was developed by oral administration of bovine serum albumin (BSA) combined with Staphylococcus Enterotoxin B (SEB) tail vein injection. Urinary protein concentrations, renal function, renal morphological, IgA deposition, apoptosis situation, and the mRNA and protein expression of nephrin, podocin, TNF-α, TNFR1, caspase-8 and caspase-3, were detected after 12 weeks. BSA and SEB can successfully establish an IgAN mouse model, and the main pathological changes are the IgA immune complex deposition in the mesangial area. The gene and protein expression levels of nephrin and podocin were found to be downregulated, and death receptor pathway-related indicators were upregulated, and they were involved in TNF-α-activated podocyte injury and apoptosis in IgAN mice. TNF-α may play an important role in the pathogenesis of podocyte apoptosis in IgAN, and its effects may be mediated through the apoptotic death receptor pathway. [ABSTRACT FROM AUTHOR]

Protein engineering is an effective method to improve the thermal stability of biological macromolecules. Cytidine monophosphate kinase (CMK) is a key enzyme involved in nucleotide metabolism and participates in the production of cytidine triphosphate. It has previously been confirmed that CMK shows low thermal stability. This study aimed to enhance the thermal stability of CMK. Herein, we first analyzed native CMK using PoPMuSiC. Thereafter, we constructed single point mutants (Q30G, P62R, E85I, D148W and K165L) and multipoint mutants of CMK with higher thermal stability using site-directed mutagenesis. The thermal stability of the mutant Q30G/E85I/K165L was observed to be 1.2-fold higher than that of the wild type. The mutants were then allowed to catalyse 3′-sialyllactose (3′-SL) synthesis. After 51.72 mmol/L N-acetylneuraminic acid (sialic acid) was consumed in a 25 mL reaction system and 50.67 mmol/L 3′-SL was obtained, a decrease of 2 h was recorded in the reaction time, whereas the yield rate increased by 33.6%. The results suggest that the mutant Q30G/E85I/K165L can improve the thermal stability of CMK and its catalytic efficiency for 3′-SL synthesis. These findings are crucial for various applications involving enzyme conversion. [ABSTRACT FROM AUTHOR]

Changes in the intestinal microbiota indirectly impact the health of mucosa distal to the intestine, particularly the respiratory tract. However, the effects of intestinal microbiota dysbiosis on the regulation of respiratory syncytial virus (RSV) infection are not clear. In this study, we examined the effects of altering the intestinal microbiota on the pulmonary immune response against RSV infection. BALB/c mice were treated with streptomycin before infection with RSV to study the altered immune response. The ingestion of streptomycin led to a marked alteration in the intestinal microbiota with a reduced abundance of Lactobacillus and Clostridium genera, followed by greatly aggravated pulmonary inflammation in response to RSV infection. This aggravated inflammation was associated with a dysregulated immune response against RSV infection, characterized by the increased expression of IFN-γ and IL-17 and increased pulmonary M1-like macrophage polarization, and decreased expression of IL-5. Supplementation of Clostridium butyricum (CB) prevented aggravated inflammation and the dysregulated immune response characterized by greater M2 polarization of pulmonary macrophages and decreased release of IFN-γ and IL-17 as well as increased IL-5 levels. Furthermore, in vitro and in vivo experiments identified that butyrate, the main metabolite produced by CB, promoted M2 polarization of macrophages in RSV-infected mice exposed to streptomycin. Together, these results demonstrate the mechanism by which intestinal microbiota modulate the pulmonary immune response to RSV infection. [ABSTRACT FROM AUTHOR]