Fabric-based jamming phase diagram for frictional granular materials.

A jamming phase diagram maps the phase states of granular materials to their intensive properties such as shear stress and density (or packing fraction). We investigate how different phases in a jamming phase diagram of granular materials are related to their fabric structure via three-dimensional discrete element method simulations. Constant-volume quasi-static simple shear tests ensuring uniform shear strain field are conducted on bi-disperse spherical frictional particles. Specimens with different initial solid fractions are sheared until reaching steady state at a large shear strain (200%). The jamming threshold in terms of stress, non-rattler fraction, and coordination numbers (Z's) of different contact networks is discussed. The evolution of fabric anisotropy (F) of each contact network during shearing is also examined. By plotting the fabric data in the F-Z space, a unique critical fabric surface (CFS) becomes apparent across all specimens, irrespective of their initial phase states. Through the correlation of this CFS with fabric signals corresponding to jamming transitions, we introduce a novel jamming phase diagram in the fabric F-Z space, offering a convenient approach to distinguish the various phases of granular materials solely through the direct observation of geometrical arrangements of particles. This jamming phase diagram underscores the importance of the microstructure underlying the conventional jamming phenomenon and introduces a novel standpoint for interpreting the phase transitions of granular materials that have been exposed to processes such as compaction, shearing, and other complex loading histories.

Synergy of Photogenerated Electrons and Holes toward Efficient Photocatalytic Urea Synthesis from CO2 and N2.

Directly coupling N2 and CO2 to synthesize urea by photocatalysis paves a sustainable route for urea synthesis, but its performance is limited by the competition of photogenerated electrons between N2 and CO2, as well as the underutilized photogenerated holes. Herein, we report an efficient urea synthesis process involving photogenerated electrons and holes in respectively converting CO2 and N2 over a redox heterojunction consisting of WO3 and Ni single-atom-decorated CdS (Ni1-CdS/WO3). For the photocatalytic urea synthesis from N2 and CO2 in pure water, Ni1-CdS/WO3 attained a urea yield rate of 78 µM h-1 and an apparent quantum yield of 0.15 % at 385 nm, which ranked among the best photocatalytic urea synthesis performance reported. Mechanistic studies reveal that the N2 was converted into NO species by ⋅OH radicals generated from photogenerated holes over the WO3 component, meanwhile, the CO2 was transformed into *CO species over the Ni site by photogenerated electrons. The generated NO and *CO species were further coupled to form *OCNO intermediate, then gradually transformed into urea. This work emphasizes the importance of reasonably utilizing photogenerated holes in photocatalytic reduction reactions.

Regional Variation of Splicing QTLs in Human Brain.

A major question in human genetics is how sequence variants of broadly expressed genes produce tissue- and cell type-specific molecular phenotypes. Genetic variation of alternative splicing is a prevalent source of transcriptomic and proteomic diversity in human populations. We investigated splicing quantitative trait loci (sQTLs) in 1,209 samples from 13 human brain regions, using RNA sequencing (RNA-seq) and genotype data from the Genotype-Tissue Expression (GTEx) project. Hundreds of sQTLs were identified in each brain region. Some sQTLs were shared across brain regions, whereas others displayed regional specificity. These "regionally ubiquitous" and "regionally specific" sQTLs showed distinct positional distributions of single-nucleotide polymorphisms (SNPs) within and outside essential splice sites, respectively, suggesting their regulation by distinct molecular mechanisms. Integrating the binding motifs and expression patterns of RNA binding proteins with exon splicing profiles, we uncovered likely causal variants underlying brain region-specific sQTLs. Notably, SNP rs17651213 created a putative binding site for the splicing factor RBFOX2 and was associated with increased splicing of MAPT exon 3 in cerebellar tissues, where RBFOX2 was highly expressed. Overall, our study reveals a more comprehensive spectrum and regional variation of sQTLs in human brain and demonstrates that such regional variation can be used to fine map potential causal variants of sQTLs and their associated neurological diseases.

Amorphous Vanadium Oxide Nanosheets with Alterable Polyhedron Configuration for Fast-Charging Lithium-Ion Batteries.

Transition metal oxides with high theoretical capacities are promising anode materials for lithium-ion batteries (LIBs). However, the sluggish reaction kinetics remain a bottleneck for fast-charging applications due to its slow Li+ migration rate. Herein, a strategy is reported of significantly reducing the Li+ diffusion barrier of amorphous vanadium oxide by constructing a specific ratio of the VO local polyhedron configuration in amorphous nanosheets. The optimized amorphous vanadium oxide nanosheets with a ratio ≈1:4 for octahedron sites (Oh ) to pyramidal sites (C4v ) revealed by Raman spectroscopy and X-ray absorption spectroscopy (XAS) demonstrate the highest rate capability (356.7 mA h g-1 at 10.0 A g-1 ) and long-term cycling life (455.6 mA h g-1 at 2.0 A g-1 over 1200 cycles). Density functional theory (DFT)calculations further verify that the local structure (Oh :C4v = 1:4) intrinsically changes the degree of orbital hybridization between V and O atoms and contributes to a higher intensity of electron occupied states near the Fermi level, thus resulting in a low Li+ diffusion barrier for favorable Li+ transport kinetics. Moreover, the amorphous vanadium oxide nanosheets possess a reversible VO vibration mode and volume expansion rate close to 0.3%, as determined through in situ Raman and in situ transmission electron microscopy.

Pathway-guided analysis identifies Myc-dependent alternative pre-mRNA splicing in aggressive prostate cancers.

We sought to define the landscape of alternative pre-mRNA splicing in prostate cancers and the relationship of exon choice to known cancer driver alterations. To do so, we compiled a metadataset composed of 876 RNA-sequencing (RNA-Seq) samples from five publicly available sources representing a range of prostate phenotypes from normal tissue to drug-resistant metastases. We subjected these samples to exon-level analysis with rMATS-turbo, purpose-built software designed for large-scale analyses of splicing, and identified 13,149 high-confidence cassette exon events with variable incorporation across samples. We then developed a computational framework, pathway enrichment-guided activity study of alternative splicing (PEGASAS), to correlate transcriptional signatures of 50 different cancer driver pathways with these alternative splicing events. We discovered that Myc signaling was correlated with incorporation of a set of 1,039 cassette exons enriched in genes encoding RNA binding proteins. Using a human prostate epithelial transformation assay, we confirmed the Myc regulation of 147 of these exons, many of which introduced frameshifts or encoded premature stop codons. Our results connect changes in alternative pre-mRNA splicing to oncogenic alterations common in prostate and many other cancers. We also establish a role for Myc in regulating RNA splicing by controlling the incorporation of nonsense-mediated decay-determinant exons in genes encoding RNA binding proteins.

Combination of chemical profiling and network pharmacology analysis to investigate the potential mechanism of Li-Zhong-Xiao-Pi granules in the treatment of gastric precancerous lesions.

Li-Zhong-Xiao-Pi granules (LZXP) are effective for treating gastric precancerous lesions (GPL) in traditional Chinese medicine. However, the active compounds of LZXP and their potential therapeutic mechanism in GPL remained unclarified. The purpose of this study is to investigate the chemical composition and potential targets of LZXP. Based on the accurate masses, ion fragments, and literature data, a total of 128 compounds were identified in the LZXP sample using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in both positive and negative ion modes, and 28 of these compounds were exactly determined by comparison with authentic reference standards. Meanwhile, 11 typical components were quantified via UPLC during a 24 min period. The linearity, accuracy, stability and recovery of the method were all proven. Through the network pharmacological analysis, six chemicals (quercetin, 4'-hydroxywogonin, sinensetin, 5, 7, 8, 3', 4'-pentamethoxyflavanone, 8-gingerdione and quercetin) were identified as the active ingredients, and five LZXP targets (AKT1, CYP1B1, PTGS2, MMP9 and EGFR) were found to be the crucial molecules in the treatment of GPL. This study provides a systematic and applicable method for the rapid screening and identification of the chemical constituents from LZXP, and an effective understanding the mechanism of LZXP in the treatment of GPL.

Monitoring Electron Flow in Nickel Single-Atom Catalysts during Nitrogen Photofixation.

An efficient catalytic system for nitrogen (N2) photofixation generally consists of light-harvesting units, active sites, and an electron-transfer bridge. In order to track photogenerated electron flow between different functional units, it is highly desired to develop in situ characterization techniques with element-specific capability, surface sensitivity, and detection of unoccupied states. In this work, we developed in situ synchrotron radiation soft X-ray absorption spectroscopy (in situ sXAS) to probe the variation of electronic structure for a reaction system during N2 photoreduction. Nickel single-atom and ceria nanoparticle comodified reduced graphene oxide (CeO2/Ni-G) was designed as a model catalyst. In situ sXAS directly reveals the dynamic interfacial charge transfer of photogenerated electrons under illumination and the consequent charge accumulation at the catalytic active sites for N2 activation. This work provides a powerful tool to monitor the electronic structure evolution of active sites under reaction conditions for photocatalysis and beyond.

Urinary Catheterization Induces Delirium-Like Behavior Through Glucose Metabolism Impairment in Mice.

BACKGROUND: Delirium, an acute confusion status, is associated with adverse effects, including the development of Alzheimer's disease. However, the etiology and underlying mechanisms of delirium remain largely to be determined. Many patients have urinary catheterization (UC), and UC is associated with delirium. However, the cause effects of UC-associated delirium and the underlying mechanisms remain largely unknown. We, therefore, established an animal model of UC, without urinary tract infection, in mice and determined whether UC could induce delirium-like behavior in the mice and the underlying mechanism of these effects. METHODS: Adult female mice (16 weeks old) had UC placement under brief isoflurane anesthesia. The delirium-like behavior was determined using our established mice model at 3, 6, 9, and 24 hours after UC placement. We measured the amounts of glucose in both blood and brain interstitial fluid, adenosine triphosphate (ATP) concentration in the cortex, and glucose transporter 1 in the cortex of mice using western blot, immunohistochemistry imaging, reverse transcriptase-polymerase chain reaction (RT-PCR), and fluorescence at 6 hours after the UC placement. Finally, we used vascular endothelial growth factor (VEGF) in the interaction studies. RESULTS: We found that UC induced delirium-like behavior in mice at 3, 6, 9, but not 24 hours after the UC placement. UC decreased glucose amounts in brain interstitial fluid (86.38% ± 4.99% vs 100% ± 6.26%, P = .003), but not blood of mice and reduced ATP amounts (84.49% ± 8.85% vs 100% ± 10.64%, P = .031) in the cortex of mice. Finally, UC reduced both protein amount (85.49% ± 6.83% vs 100% ± 11.93%, P = .040) and messenger ribonucleic acid (mRNA) expression (41.95% ± 6.48% vs 100% ± 19.80%, P = .017) of glucose transporter 1 in the cortex of mice. VEGF attenuated these UC-induced changes. CONCLUSIONS: These data demonstrated that UC decreased brain glucose and energy amounts via impairing the glucose transport from blood to brain, leading to delirium-like behavior in mice. These findings will promote more research to identify the etiologies and underlying mechanisms of delirium.

A pH-targeted and NIR-responsive NaCl-nanocarrier for photothermal therapy and ion-interference therapy.

Transport ions into cells through nanocarrier to achieve ion-interference therapy provides new inspiration for cancer treatment. In this work, a pH-targeted and NIR-responsive NaCl-nanocarrier is prepared using surfactant Vitamin E-O(EG2-Glu) and modified with polydopamine (PDA) and pH-sensitive zwitterionic chitosan (ZWC). The NaCl-nanocarrier is decorated with NH4HCO3 and IR-780 to introduce near-infrared (NIR)-responsive performance and imaging. Once the NaCl-nanocarrier is exposed to NIR laser, the temperature rises rapidly because of the excellent photothermal conversion ability of PDA, then NH4HCO3 is decomposed into NH3 and CO2, which burst the nanocarrier, resulting in Cl- and Na+ "bomb-like" release. This pH-targeted nanocarrier accumulates more at tumor site and when irradiating the site with NIR light, the temperature rises and excessive Cl- and Na+ are released to destroy the ion homeostasis and inhibit tumor growth effectively. Through this strategy, the unique combination of ion interference therapy and photothermal therapy is achieved.

Three-dimensional tree-like branched TiO2 nanorods for the highly selective enrichment and determination of lead.

Branched titanium dioxide nanorods (B-TiO2 NRs) grown on fluorine-doped tin oxide glass (FTO) were developed, which can be used as a solid-phase extractant for preconcentration and determination of trace Pb(II) combined with inductively coupled plasma optical emission spectrometry (ICP-OES). The B-TiO2 NR-based glass substrate displayed excellent adsorptive selectivity and capacity for Pb(II); the maximum adsorption capacity was found to be 168.4 mg⋅g-1 PB(II) at pH = 5.0. It proved that the primary extraction mechanism was attributed to soft acid/soft base interactions to form complexes for chemisorption. Investigating the adsorption kinetics and isotherms indicated that the pseudo-second-order and Langmuir models can better describe Pb(II) adsorption on the B-TiO2 NRs. The proposed method presented good linearity from 0.01 to 5 mg⋅L-1 with a correlation coefficient (R2) of 0.9989 and a low limit of detection (LOD) of 2.2 µg⋅L-1 for Pb(II) under optimal conditions. The method was successfully applied to Pb(II) determination in foodstuffs with desirable recoveries from 93.18 to 108.1% and good precision with an RSD of less than 12.2%. This work provides a new strategy for selective extraction and determination of Pb(II) in complicated matrix samples.

Rapid Controllable Synthesis of Atomically Dispersed Co on Carbon under High Voltage within One Minute.

Developing a rapid and low cost approach to access atomically dispersed metal catalysts (ADMCs) supported by carbon is important but still challenging. Here, an electric flash strategy using high voltage for the rapid fabrication of carbon-supported ADMCs within 1 min is reported. Continuous plasma arc results in nitrogen-doped carbon ultrathin nanosheets, while an intermittent spark pulse constructs carbon hollow nanospheres via blasting effect, and both structures are decorated with atomically dispersed cobalt. The latter catalyst shows a half-wave potential of 0.887 V versus RHE (47 mV higher than commercial Pt/C) in an oxygen reduction reaction (ORR) in alkaline media. The authors' work paves the way to rapid synthesis of carbon-supported ADMCs at both low cost and mass production.

Compressive Strain Modulation of Single Iron Sites on Helical Carbon Support Boosts Electrocatalytic Oxygen Reduction.

Designing and modulating the local structure of metal sites is the key to gain the unique selectivity and high activity of single metal site catalysts. Herein, we report strain engineering of curved single atomic iron-nitrogen sites to boost electrocatalytic activity. First, a helical carbon structure with abundant high-curvature surface is realized by carbonization of helical polypyrrole that is templated from self-assembled chiral surfactants. The high-curvature surface introduces compressive strain on the supported Fe-N4 sites. Consequently, the curved Fe-N4 sites with 1.5 % compressed Fe-N bonds exhibit downshifted d-band center than the planar sites. Such a change can weaken the bonding strength between the oxygenated intermediates and metal sites, resulting a much smaller energy barrier for oxygen reduction. Catalytic tests further demonstrate that a kinetic current density of 7.922 mA cm-2 at 0.9 V vs. RHE is obtained in alkaline media for curved Fe-N4 sites, which is 31 times higher than that for planar ones. Our findings shed light on modulating the local three-dimensional structure of single metal sites and boosting the catalytic activity via strain engineering.

Atomically Dispersed Pt on Screw-like Pd/Au Core-shell Nanowires for Enhanced Electrocatalysis.

Engineering noble metal nanostructures at the atomic level can significantly optimize their electrocatalytic performance and remarkably reduce their usage. We report the synthesis of atomically dispersed Pt on screw-like Pd/Au nanowires by using ultrafine Pd nanowires as seeds. Au can selectively grow on the surface of Pd nanowires by an island growth pattern to fabricate surface defect sites to load atomically dispersed Pt, which can be confirmed by X-ray absorption fine structure measurements and aberration corrected HRTEM images. The nanowires with 2.74 at % Pt exhibit superior HER properties in acidic solution with an overpotential of 20.6 mV at 10 mA cm-2 and enhanced alkaline ORR performance with a mass activity over 15 times greater than the commercial platinum/carbon (Pt/C) catalysts.

Integrated Proteomics, Biological Functional Assessments, and Metabolomics Reveal Toosendanin-Induced Hepatic Energy Metabolic Disorders.

Toosendanin (TSN), a compound from Melia toosendan, exhibits severe hepatotoxicity, which restricts its clinical application. However, the mechanism is not clear. Our previous research found that covalent modification of TSN for proteins might be a possible reason using human liver microsomes, and the glycolytic enzymes, triosephosphate isomerase 1 (TPIS) and α-enolase (ENOA), were responsible for the hepatotoxicity. In this study, we tried to prove these findings in cell and animal models by integration of proteomics, metabolomics, and biological methods. Proteomics analysis in rats showed that TPIS and ENOA were covalently modified by TSN reactive metabolites. The biological functional assessments revealed that the modifications inhibited the activity of TPIS and induced the activity of ENOA, in vitro and in vivo, followed by an increase in the level of cellular methylglyoxal, advanced glycation end products, and reactive oxygen species/superoxide, and the induction of mitochondrial dysfunction, which further inhibited oxidative phosphorylation and stimulated glycolysis. Furthermore, metabolomics demonstrated the decrease in the level of metabolites in the tricarboxylic acid cycle, fatty acid ß-oxidation, and amino acid metabolism; i.e., TSN induced hepatocyte energy metabolism disorder. In conclusion, these data suggest novel mechanistic insights into TSN-induced liver injury on the upstream level and provide valuable proteins and energy metabolic targets for diagnosis and therapy in the clinic.

Transmembrane and Ubiquitin-Like Domain Containing 1 Protein (TMUB1) Negatively Regulates Hepatocellular Carcinoma Proliferation via Regulating Signal Transducer and Activator of Transcription 1 (STAT1).

BACKGROUND Hepatocellular carcinoma (HCC) is a common malignancy, but the pathogenesis of HCC is unclear. TMUB1 has an inhibitory effect on normal hepatocytes, but its role in HCC has not been reported. MATERIAL AND METHODS We used immunohistochemistry to observe the expression of transmembrane and ubiquitin-like domain containing 1 protein (TMUB1) and signal transducer and activator of transcription 1 (STAT1) in 132 HCC tissue specimens. The expression of TMUB1, STAT1, and CCND1 in HCC cells were detected by quantitative polymerase chain reaction (qPCR) and western blotting. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used for detecting HCC cells proliferation, and Transwell assays were used for observing the invasion and migration of HCC cells. RESULTS TMUB1 was negatively correlated with HCC pathological malignancy; low expression of TMUB1 indicated poor prognosis. TMUB1 inhibited proliferation but not metastasis in HCC cells. TMUB1 expression was positively correlated with STAT1 in 132 HCC tissues, TMUB1 promoted the expression of STAT1, and suppressed the expression of CCND1 in HCC cells. CONCLUSIONS TMUB1 negatively regulates hepatocellular carcinoma proliferation via regulating STAT1.

Molecularly imprinted gelatin nanoparticles for DNA delivery and in-situ fluorescence imaging of telomerase activity.

DNA-loaded molecularly imprinted gelatin nanoparticles (GDMI-NPs) were prepared to deliver the Cy3- and Cy5-labelled DNA probe to a tumor region. This allows the activity of telomerase can be detected over 3-400 cells with a low detection limit (3 cells). Fluorescence images were acquired at an excitation wavelength of 535 nm and the emission from the green channel (550-580 nm; label Cy3) and the red channel (650-680 nm; label Cy5). HeLa cells and HepG2 cells were both used to test the performance of GDMI-NPs. Experimental results confirmed the GDMI-NPs has hardly retained in liver and spleen tissue, and its circulated time was longer than that of non-imprinted nanoparticles in blood. The ability of GDMI-NPs to resist immuno stress and anti-macrophage phagocytosis shows great potential for cancer diagnosis and as a drug carrier. Graphical abstract Highly DNA-loaded molecularly imprinted gelatin nanoparticles (GDMI-NPs) were prepared to deliver the Cy3-labelled DNA probe to a cancer region, and realization of telomerase in situ fluorescence imaging at the tumor site.

Transcriptome sequencing reveals aberrant alternative splicing in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion in the gene-encoding Huntingtin (HTT). Transcriptome dysregulation is a major feature of HD pathogenesis, as revealed by a large body of work on gene expression profiling of tissues from human HD patients and mouse models. These studies were primarily focused on transcriptional changes affecting steady-state overall gene expression levels using microarray based approaches. A major missing component, however, has been the study of transcriptome changes at the post-transcriptional level, such as alternative splicing. Alternative splicing is a critical mechanism for expanding regulatory and functional diversity from a limited number of genes, and is particularly complex in the mammalian brain. Here we carried out a deep RNA-seq analysis of the BA4 (Brodmann area 4) motor cortex from seven human HD brains and seven controls to systematically discover aberrant alternative splicing events and characterize potential associated splicing factors in HD. We identified 593 differential alternative splicing events between HD and control brains. Using two expanded panels with a total of 108 BA4 tissues from patients and controls, we identified four splicing factors exhibiting significantly altered expression levels in HD patient brains. Moreover, follow-up molecular analyses of one splicing factor PTBP1 revealed its impact on disease-associated splicing patterns in HD. Collectively, our data provide genomic evidence for widespread splicing dysregulation in HD brains, and suggest the role of aberrant alternative splicing in the pathogenesis of HD.

Isolation of transferrin by imprinted nanoparticles with magnetic deep eutectic solvents as monomer.

Transferrin (TrF) is a very important human body glycoprotein and a clinical biomarker which controls the body's iron ion channels and iron ion balance. Any change in TrF concentration and isoform also reflects the emergence of some diseases. In this work, we prepared magnetic molecularly imprinted nanoparticles (deep eutectic solvent-molecular imprinting polymers [DES-MIPs]) with a deep eutectic solvent (DES) as a functional monomer to separate TrF in human serum. The DES dosage for MIP, pH value, and time for adsorption have been optimized, and these materials show special adsorption properties for TrF. The maximum adsorption capacity (Qmax) and dissociation constant KL of the MIP by the Langmuir adsorption curve (R2 = 0.9949) were 37.5 mg/g and 0.015 g/L, respectively. The imprinting factor of the MIP is 3.50 with relative standard deviation (5.63%). In summary, the use of DES as a functional monomer in molecular imprinting technology provides a novel, efficient, and biocompatible method for the isolation and purification of proteins. Graphical abstract ᅟ.

Modulation of platelet functions by crude rice (Oryza sativa) bran policosanol extract.

BACKGROUND: Rice bran is bioactive-rich and has proven health benefits for humans. Moreover, its source, the brown rice has antioxidant, hypolipidemic and other functional properties that are increasingly making it a nutritional staple especially in Asian countries. This study investigated the antiplatelet aggregation mechanisms of crude hexane/methanolic rice bran extract, in which policosanol was the targeted bioactive. Platelets play a vital role in pathogenesis of atherosclerosis and cardiovascular diseases, and their increased activities could potentially cause arterial thrombus formation or severe bleeding disorders. Thus, in this study, platelet aggregation and adhesion of platelets to major components of basal lamina were examined in vitro. In addition, cellular protein secretion was quantified as a measurement of platelet activation. METHODS: Adenosine diphosphate (ADP), collagen, and arachidonic acid (AA)-induced aggregation were studied using the microtiter technique. Rat platelets were pre-treated with various concentrations of policosanol extract, and the adhesion of platelets onto collagen- and laminin-coated surface (extracellular matrix) was studied using the acid phosphatase assay. The effect of crude policosanol extract on released proteins from activated platelets was measured using modified Lowry determination method. RESULTS: Rice bran policosanol extract significantly inhibited in vitro platelet aggregation induced by different agonists in a dose dependent manner. The IC50 of ADP-, collagen-, and AA-induced platelet aggregation were 533.37 ± 112.16, 635.94 ± 78.45 and 693.86 ± 70.57 µg/mL, respectively. The present study showed that crude rice bran policosanol extract significantly inhibited platelet adhesion to collagen in a dose dependent manner. Conversely, at a low concentration of 15.625 µg/mL, the extract significantly inhibited platelet adhesion to laminin stimulated by different platelet agonists. In addition to the alteration of cell adhesive properties, cellular protein secretion of the treated platelets towards different stimulants were decreased upon crude extract treatment. CONCLUSION: Our results showed that crude rice bran policosanol extract could inhibit in vitro platelet adhesion, aggregation and secretion upon activation using agonists. These findings serve as a scientific platform to further explore alternative therapies in cardiovascular diseases related to platelet malfunction.

Seismic stability of subsea tunnels subjected to seepage.

Strength reduction method and ADINA software are adopted to study the stability of submarine tunnel structures subjected to seepage and earthquake under different seawater depths and overlying rock strata thicknesses. First, the excess pore water pressure in the rock mass is eliminated through consolidation calculation. Second, dynamic time-history analysis is performed by inputting the seismic wave to obtain the maximum horizontal displacement at the model top. Finally, static analysis is conducted by inputting the gravity and the lateral border node horizontal displacement when the horizontal displacement is the largest on the top border. The safety factor of a subsea tunnel structure subjected to seepage and earthquake is obtained by continuously reducing the shear strength parameters until the calculation is not convergent. The results show that the plastic zone initially appears at a small scope on the arch feet close to the lining structure and at both sides of the vault. Moreover, the safety factor decreases with increasing seawater depth and overlying rock strata thickness. With increasing seawater depth and overlying rock strata thickness, maximum main stress, effective stress, and maximum displacement increase, whereas displacement amplitude slightly decreases.