Asymmetrical large deformation problem of quartz mica schist is anticipated in a planning hydropower station. The objective of this study was to investigate the anisotropic mechanical properties of ...the schist under complex stress states. For this purpose, a series of true triaxial compression tests accompanied by acoustic emission monitoring were carried out on this schist with different loading angles with respect to inherent schistosity. The test results show that the orientation of schistosity and stress state have a significant impact on the deformation, strength and failure of this schist. More specifically, when the
σ
2
is parallel to the strike of the schistosity (
ω
= 0°), the failure of the specimen is mainly controlled by the schistosity structure, and the strength is lower compared with the case of
σ
2
perpendicular to the strike (
ω
= 90°). When
ω
= 90°, the deformation normal to schistosity is more restrained, and the acoustic emission impact mostly presents the phenomenon of concentration and sudden increase during the fracture. The test results indicate that the normal stress constraint effect on the schistosity can effectively improve the strength and inhibit the shear or splitting failure along the schistosity, hence, the tunnel axis should be at a large angle with the strike of schistosity, and support measures should be applied on schistosity as soon as possible after excavation.
Scytonemin is a promising UV-screen and antioxidant small molecule with commercial value in cosmetics and medicine. It is solely biosynthesized in some cyanobacteria. Recently, its biosynthesis ...mechanism has been elucidated in the model cyanobacterium
PCC 73102. The direct precursors for scytonemin biosynthesis are tryptophan and
-hydroxyphenylpyruvate, which are generated through the shikimate and aromatic amino acid biosynthesis pathway. More upstream substrates are the central carbon metabolism intermediates phosphoenolpyruvate and erythrose-4-phosphate. Thus, it is a long route to synthesize scytonemin from the fixed atmospheric CO
in cyanobacteria. Metabolic engineering has risen as an important biotechnological means for achieving sustainable high-efficiency and high-yield target metabolites. In this review, we summarized the biochemical properties of this molecule, its biosynthetic gene clusters and transcriptional regulations, the associated carbon flux-driving progresses, and the host selection and biosynthetic strategies, with the aim to expand our understanding on engineering suitable cyanobacteria for cost-effective production of scytonemin in future practices.
High glucose (HG)-induced podocyte injury contributes to the pathogenesis of diabetic nephropathy, a severe complication of diabetes. Bromodomain-containing protein 4 (BRD4) has emerged as a critical ...regulator for cell injury. However, whether BRD4 participates in HG-induced podocyte injury remains unclear. In this study, we aimed to explore the potential role of BRD4 in regulating HG-induced podocyte injury and its underlying molecular mechanism. HG exposure significantly upregulated BRD4 in podocytes. BRD4 inhibition by small interfering RNA or its chemical inhibitor (JQ1) markedly repressed HG-induced apoptosis and reactive oxygen species (ROS) production. By contrast, BRD4 overexpression exacerbated HG-induced podocyte injury. Moreover, BRD4 inhibition potentiated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling associated with suppression of Kelch-like ECH-associated protein (Keap1). BRD4 inhibition promoted Nrf2 nuclear translocation and upregulated the transcriptional activity of Nrf2/antioxidant response element (ARE). However, Nrf2 silencing partially reversed BRD4-inhibition-mediated protection against HG-induced podocyte injury. Overall, these results suggest that BRD4 inhibition confers cytoprotection against HG injury in podocytes through potentiation of Nrf2/ARE antioxidant signaling. This finding implicates BRD4/Nrf2/ARE signaling in the pathogenesis of diabetic nephropathy.
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•BRD4 is induced by HG in podocytes in vitro.•BRD4 inhibition protects podocytes from HG-induced injury.•BRD4 inhibition reinforces Nrf2 signaling by inhibiting Keap1.•Nrf2 inhibition reverses BRD4-inhibition-mediated protection effect.
Microalgae have high lipid accumulation capacity, high growth rate and high photosynthetic efficiency which are considered as one of the most promising alternative sustainable feedstocks for ...producing lipid-based biofuels. However, commercialization feasibility of microalgal biofuel production is still conditioned to the high production cost. Enhancement of lipid accumulation in microalgae play a significant role in boosting the economics of biofuel production based on microalgal lipid. The major challenge of enhancing microalgal lipid accumulation lies in overcoming the trade-off between microalgal cell growth and lipid accumulation. Substantial approaches including genetic modifications of microalgal strains by metabolic engineering and process regulations of microalgae cultivation by integrating multiple optimization strategies widely applied in industrial microbiology have been investigated. In the present review, we critically discuss recent trends in the application of multiple molecular strategies to construct high performance microalgal strains by metabolic engineering and synergistic strategies of process optimization and stress operation to enhance microalgal lipid accumulation for biofuel production. Additionally, this review aims to emphasize the opportunities and challenges regarding scaled application of the strategic integration and its viability to make microalgal biofuel production a commercial reality in the near future.
Deep underground engineering encounters substantial layered hard rock formations, and the engineering triaxial stress path involves an increase in maximum principal stress, constant intermediate ...principal stress, and a decrease in minimum principal stress. However, previous research has focused on rock layer angles under conventional triaxial stress conditions, disregarding the influence of foliation strike angles in engineering triaxial stress scenarios. This study experimentally investigates the effects of foliation strike angles on layered hard rock under an engineering triaxial stress path. To account for the brittleness of layered hard rock, we propose a specific small sample-processing method tailored to the foliation strike angle. True triaxial loading tests are conducted on steep, thin slate samples with two different loading orientations, accompanied by acoustic emission monitoring. Results indicate that the strength under a traditional true triaxial compression condition is similar for specimens with 90° and 0° strike angles. Stress–strain curves show that larger deformations occur perpendicular to bedding planes, while surface fractures propagate exclusively along the bedding planes. Mechanical responses differ significantly between specimens subjected to the engineering triaxial stress path at 0° and 90° strike angles compared to conventional true triaxial loading tests, with a lower bearing capacity and differentiated intermediate and minimum principal strains in the 0° case. Conversely, the 90° case exhibits a higher bearing capacity, consistent deformation, and more acoustic emission events. Numerical simulations comparing plastic zone sizes during actual underground excavation support these conclusions. These findings highlight the effects of foliation strike angles, favoring the 90° strike-angle configuration for excavation activities and providing enhanced stability in the surrounding rock mass.
Abstract
Background
Comorbidity between depressive and anxiety disorders is common. From network perspective, mental disorders arise from direct interactions between symptoms and comorbidity is due ...to direct interactions between depression and anxiety symptoms. The current study investigates the network structure of depression and anxiety symptoms in Chinese female nursing students and identifies the central and bridge symptoms as well as how other symptoms in present network are related to depression symptom “thoughts of death”.
Methods
To understand the full spectrum of depression and anxiety, we recruited 776 Chinese female nursing students with symptoms of depression and anxiety that span the full range of normal to abnormal. Depression symptoms were measured by Patient Health Questionnaire-9 while anxiety symptoms were measured by Generalized Anxiety Disorder 7-Item Questionnaire. Network analysis was used to construct networks. Specifically, we computed the predictability, expected influence and bridge expected influence for each symptom and showed a flow network of “thoughts of death”.
Results
Nine strongest edges existed in network were from the same disorder. Four were between depression symptoms, like “sleep difficulties” and “fatigue”, and “anhedonia” and “fatigue”. Five were between anxiety symptoms, like “nervousness or anxiety” and “worry too much”, and “restlessness” and “afraid something will happen”. The symptom “fatigue”, “feeling of worthlessness” and “irritable” had the highest expected influence centrality. Results also revealed two bridge symptoms: “depressed or sad mood” and “irritable”. As to “thoughts of death”, the direct relations between it and “psychomotor agitation/retardation” and “feeling of worthlessness” were the strongest direct relations.
Conclusions
The current study highlighted critical central symptoms “fatigue”, “feeling of worthlessness” and “irritable” and critical bridge symptoms “depressed or sad mood” and “irritable”. Particularly, “psychomotor agitation/retardation” and “feeling of worthlessness” were identified as key priorities due to their strongest associations with suicide ideation. Implications for clinical prevention and intervention based on these symptoms are discussed.
The concept design of the China Fusion Engineering Test Reactor (CFETR) was started in 2012 in two stages. For CFETR-Phase I, the major radius is 5.7 m, the minor radius is 1.6 m, and the magnetic ...field at the plasma region, B T , is 4-5 T. There were 16 toroidal field coils and six central solenoid coils designed by a Nb 3 Sn cable-in-conduit conductor (CICC) with the maximum operation current of 64 and 50 kA, respectively. Three types of plasma equilibrium configuration (ITER-like single null, super-X, and snowflake) were designed. The maximum flux provided by the central solenoid is set at 180 V·s. However, to get much higher operation parameters such as steady-state operation, particle and heat exhaust, disruption mitigation and avoidance, ELM control, and material damage by high heat flux and neutron, the superconducting magnet system of CFETR-phase II has been updated based on the larger machine with R = 6.7 m-7.0 m, a = 2.0 m, and B T = 6.5-7 T. Such a new design makes over 1-GW fusion power and better plasma performance possible. Hybrid TF coils are designed by a high-performance Nb 3 Sn conductor, since the maximum magnetic field can reach to 14-15 T. Besides, in order to save the space for the blanket system and get higher flux, a high-temperature superconducting Bi-2212 magnet with better current-carrying performance under high field is supposed to be employed for the CS coils of CFETR-phase II. The Bi-2212 CICC sample has been tested at 4.2 K with a critical current of 26.6 kA under its self-field.
The failure of layered surrounding rock tunnel is significantly related to bedding occurrence and in situ stress orientation, and often shows asymmetry. This is because the layered rock has a special ...bedding structure, resulting in its deformation and failure showing significant anisotropy. After excavation, the bedding loading angles of layered rock around the tunnel are different, resulting in different bearing capacity of each part of the tunnel. To reflect this characteristic, a three-dimensional equivalent continuous model considering the deformation and strength anisotropy of layered rock is developed, and the model is embedded in CASRock numerical software. The simulation of tunnel excavation in layered surrounding rock shows that the change of bedding dip angle will lead to the change of failure position of the tunnel, and with the increase of the angle between bedding strike and tunnel axis, the failure degree of surrounding rock will be greatly reduced. This model can be used to investigate the influence of in situ stress and bedding occurrence on the stability of layered surrounding rock tunnels.
Abstract Background Fish consumption may protect against colorectal cancer, but results from observational studies are inconsistent; therefore, a systematic review with a meta-analysis was conducted. ...Methods Relevant studies were identified by a search of MEDLINE and EMBASE databases to May 2011, with no restrictions. Reference lists from retrieved articles also were reviewed. Studies that reported odds ratio (OR) or relative risk estimates with 95% confidence intervals (CIs) for the association between the consumption of fish and the risk of colorectal, colon, or rectal cancer were included. Two authors independently extracted data and assessed study quality. The risk estimate (hazard ratio, relative risk, or OR) of the highest and lowest reported categories of fish intake were extracted from each study and analyzed using a random-effects model. Results Twenty-two prospective cohort and 19 case-control studies on fish consumption and colorectal cancer risk met the inclusion criteria and were included in the meta-analysis. Our analysis found that fish consumption decreased the risk of colorectal cancer by 12% (summary OR, 0.88; 95% CI, 0.80-0.95). The pooled ORs of colorectal cancer for the highest versus lowest fish consumption in case-control studies and cohort studies were 0.83 (95% CI, 0.72-0.95) and 0.93 (95% CI, 0.86-1.01), respectively. There was heterogeneity among case-control studies ( P < .001) but not among cohort studies. A significant inverse association was found between fish intake and rectal cancer (summary OR, 0.79; 95% CI, 0.65-0.97), and there was a modest trend seen between fish consumption and colon cancer (summary OR, 0.96; 95% CI, 0.81-1.14). This study had no publication bias. Conclusion Our findings from this meta-analysis suggest that fish consumption is inversely associated with colorectal cancer.
Hippocampal SIRT1 dysfunction and gene variation have previously been found potentially involved in depressive and anxiety disorders. However, the exact role of SIRT1 in post-traumatic stress ...disorder (PTSD) is not well understood. Here, we employed multiple genetic and pharmacological approaches targeting SIRT1 to verify the effects of SIRT1 on SPS-induced PTSD-like behaviors and its potential cellular and molecular mechanisms. We first demonstrated that Sirt1 knockout mice showed milder PTSD-like behavior after single prolonged stress (SPS) induction than wild type mice. Moreover, the expression of SIRT1 in the ventral CA1 (vCA1) region of hippocampus showed no significant changes following SPS induction, but the activity of SIRT1 enzyme was significantly increased post-SPS. Osmotic administration of EX527 in vCA1, a SIRT1 inhibitor, was shown to normalize the SIRT1 activity in SPS mice. Mechanically, EX527 rescued the acetylation of helix-loop-helix transcription factor 2 (NHLH2) and transcriptionally inhibited the increase of MAO-A expression in the vCA1, which thus suppressed the decomposition of the neurotransmitter serotonin into 5-hydroxydoleacetic acid (5-HIAA). Morphologically, Golgi staining showed that EX527 treatment improved the abnormal neuronal structure plasticity in the vCA1 region after SPS, including reversing the atrophic dendrites and the decreased dendritic spines. Finally, SIRT1 inhibitor effectively alleviated fear conditioning responses and anxiety-like behaviors. Our study first demonstrated that the development of PTSD-like behaviors was causatively related to the abnormal increase of SIRT1 activity in the ventral hippocampal CA1 region. And we also provided evidence that SIRT1 inhibition might exert therapeutic effects on PTSD by maintaining serotonin homeostasis through transcriptional inhibition of MAO-A, and thereby remodeled synaptic plasticity in the vCA1 region.
•Sirt1 deletion increased resistance to PTSD-like stress stimuli in mice.•SIRT1 activity in ventral CA1 was negatively involved with PTSD.•EX527 protected 5-HT homeostasis in ventral CA1 of PTSD mice via inhibiting MAO-A.•EX527 remodeled synaptic plasticity in the ventral CA1 of PTSD mice.•SIRT1 inhibition alleviated PTSD symptoms in mice.
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