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In order to obtain the optimum fatigue performance, 35CrMo steel was processed by different heat treatment procedures. The microstructure, tensile properties, fatigue properties, and fatigue cracking mechanisms were compared and analyzed. The results show that fatigue strength and yield strength slowly increase at first and then rapidly decrease with the increase of tempering temperature, and both reach the maximum values at a tempering temperature of 200 °C. The yield strength affects the ratio of crack initiation site, fatigue strength coefficient, and fatigue strength exponent to a certain extent. Based on Basquin equation and fatigue crack initiation mechanism, a fatigue strength prediction method for 35CrMo steel was established.

Background Waardenburg syndrome type 2 (WS2) has been reported to be a rare hereditary disorder, which is distinguished by vivid blue eyes, varying degrees of hearing impairment, and abnormal pigment deposition in the skin and hair. Variants in the sex-determining region Y-box containing gene 10 ( SOXl0 ) gene may cause congenital deafness and have been demonstrated to be important during the development of WS2. Methods Complete clinical data of the proband and her family members (her parents and 2 sisters) was collected and physical examinations were performed in the hospital. The laboratory examination including hemoglobin, Coomb’s test, urine protein, ENA, autoimmune hepatitis-related autoantibodies and ultrasonography were all conducted. We obtained the peripheral blood samples from all the participants and performed whole exome sequencing and sanger sequencing validation. Results The present study identified a family of 5 members, and only the proband exhibited typical WS2. Beyond the characteristics of WS2, the proband also manifested absence of puberty. The proband and her younger sister manifested systemic lupus erythematosus (SLE). Whole exome sequencing revealed a de novo variant in the SOX10 gene. The variant c.175 C > T was located in exon 2 of the SOX10 gene, which is anticipated to result in early termination of protein translation. Conclusion The present study is the first to report a case of both WS2 and SLE, and the present findings may provide a new insight into WS2.

Age of first exposure (AoFE) is an important factor that influences the quality of L2 acquisition. This study aims to investigate the AoFE effect on the contextual learning of L2 novel words at the neural level, as measured by the N400 component from event-related potentials (ERPs). Eighty-eight participants were recruited for the experiment of L2 pseudoword learning, which includes a learning session and a testing session. The participants’ EEG data were recorded from the testing session, and the N400 effect was derived from target words that were either congruous or incongruous with the context. The linear mixed model and multiple regression model revealed a positive AoFE effect on the N400 effect in discourses that were designed for testing retrieval of episodic and semantic memory even after accounting for the variance contributed by several confounding factors. In addition to AoFE, the effects of total L2 exposure, L2 proficiency and personality on the L2 novel word learning performance indicated by the N400 effect were also confirmed in the statistical results.

The stability of slopes and tunnels is controlled by rock discontinuities, and the rock discontinuities roughness and the sliding direction play a significant role in shear failure. However, three-dimensional roughness evaluation considering shear directions is scare, and the internal shear fracturing processes, micromechanical mechanisms and failure precursor of rock discontinuities are not well understood. Therefore, this study proposes a novel roughness evaluation index to quantitatively analyze the anisotropic characteristics of rock discontinuities. In conjunction with shear tests, a novel 3D-GBM modelling method considering the micromineral constituent and particle size distribution characteristics of granite as well as the geometric shape of discontinuities was realized. The strength, macro and micro-fracture characteristics, visual anisotropic shear evolution process and microfailure mechanism of granite discontinuities at different roughness and shear direction were investigated. Finally, the spatial and temporal evolutions of AE parameter b -value and magnitude M were further analyzed to reveal the shear fracture precursor of granite discontinuities. Highlights A novel anisotropic roughness evaluation method for rock discontinuities based on 3D scanning was proposed and computer implemented. A novel 3D-GBM modelling with mesomineral composition, particle size distribution and geometric characteristics of rock discontinuities was realized. The visual anisotropic shear fracture evolution and tensile-shear mechanisms of rock discontinuities were investigated at different roughness and shear direction. Shear fracture precursor of rock discontinuities was further revealed based on spatial and temporal evolutions of AE parameter b- value and magnitude M .

Background In the postpartum period, postpartum women experience numerous brain structural and functional changes. Functional neuroimaging studies have focused on the responses of the maternal brain to infant stimuli ; however, the connectivity of the maternal brain remains to be explored. We aimed to examine the differences in functional connectivity patterns between postpartum women and nulliparous women. Methods Resting-state functional magnetic resonance imaging data from 38 postpartum women and 25 nulliparous women were used to analyze functional connectivity. Moreover, we also collected Interpersonal Reactivity Index-C scores. The group functional connectivity differences were analyzed by a two-sample T test. Results Compared to nulliparous women, postpartum women exhibited increased functional connectivity in regions associated with emotional processes (insula, hippocampus, posterior cingulate gyrus, and medial frontal gyrus), while functional connectivity in the default mode network (inferior parietal lobule and precuneus) decreased significantly. Conclusion These results suggest that the maternal brain shows altered connectivity patterns, which may reveal the neuroanatomical basis for processing emotional and cognitive information in postpartum women.

The leaves of is a traditional Chinese medicine widely applied in lung diseases. Moracin N (MAN), a secondary metabolite extracted form the leaves of L, is a potent anticancer agent. But its molecular mechanism remains unveiled. In this study, we aimed to examine the effect of MAN on human lung cancer and reveal the underlying molecular mechanism. MTT assay was conducted to measure cell viability. Annexin V-FITC/PI staining was used to detect cell apoptosis. Confocal microscope was performed to determine the formation of autophagosomes and autolysosomes. Flow cytometry was performed to quantify cell death. Western blotting was used to determine the related-signaling pathway. In the present study, we demonstrated for the first time that MAN inhibitd cell proliferation and induced cell apoptosis in human non-small-cell lung carcinoma (NSCLC) cells. We found that MAN treatment dysregulated mitochondrial function and led to mitochondrial apoptosis in A549 and PC9 cells. Meanwhile, MAN enhanced autophagy flux by the increase of autophagosome formation, the fusion of autophagsomes and lysosomes and lysosomal function. Moreover, mTOR signaling pathway, a classical pathway regualting autophagy, was inhibited by MAN in a time- and dose-dependent mannner, resulting in autophagy induction. Interestingly, autophagy inhibition by CQ or Atg5 knockdown attenuated cell apoptosis by MAN, indicating that autophagy serves as cell death. Furthermore, autophagy-mediated cell death by MAN can be blocked by reactive oxygen species (ROS) scavenger NAC, indicating that ROS accumulation is the inducing factor of apoptosis and autophagy. In summary, we revealed the molecular mechanism of MAN against lung cancer through apoptosis and autophagy, suggesting that MAN might be a novel therapeutic agent for NSCLC treatment.

Background Free-range cattle are common in the Northeast China area, which have close contact with farmers and may carry virus threatening to cattle and farmers. Methods Using viral metagenomics we analyzed the virome in plasma samples collected from 80 cattle from the forested region of Northeast China. Results The virome of cattle plasma is composed of the viruses belonging to the families including Parvoviridae, Papillomaviridae, Picobirnaviridae, and divergent viral genomes showing sequence similarity to circular Rep-encoding single stranded (CRESS) DNA viruses. Five such CRESS-DNA genomes were full characterized, with Rep sequences related to circovirus and gemycircularvirus. Three bovine parvoviruses belonging to two different genera were also characterized. Conclusion The virome in plasma samples of cattle from the forested region of Northeast China was revealed, which further characterized the diversity of viruses in cattle plasma.

To establish a point-scoring diagnostic system for Sjögren's syndrome (SS) based on quantified SPECT imaging of salivary gland, and evaluate its feasibility and performance compared with 2002 AECG criteria and 2012 ACR criteria. 213 patients with suspected SS enrolled in this study. The related clinical data of all patients were collected. All patients were evaluated and grouped on a clinical basis and posttreatment follow-up by rheumatology specialists as the unified standard (SS group with 149 cases and nSS group with 64 cases). From SPECT imaging of salivary gland, Tmax, UImax, Ts and EFs were derived for bilateral parotid and submandibular glands, and compared between the groups. A point-scoring diagnostic system for SS was established based on the quantified SPECT imaging of salivary gland. We estimated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the new diagnostic system, compared with 2002 AECG criteria and 2012 ACR criteria. When 7.0 was used as the cut-off point, the sensitivity, specificity, PPV, NPV and accuracy for the new point-scoring system in diagnosing SS were 89.93% (134/149), 93.75% (60/64), 97.10% (134/138), 80.00% (60/75) and 91.08% (194/213), respectively. The new point-scoring diagnostic system based on quantified SPECT imaging of salivary gland keeps the specificity comparatively to 2002 AECG criteria and 2012 ACR criteria, but improves the sensitivity significantly (P<0.01). The new point-scoring diagnostic system for SS based on quantified SPECT imaging of salivary gland may be superior to 2002 AECG criteria and 2012 ACR criteria, with higher sensitivity and similar specificity in the diagnosis of SS. Additionally, it also has good feasibility in the clinical settings.

DHOK (14,15β-dihydroxyklaineanone) is a novel diterpene isolated from roots of Eurycoma longifolia Jack , a traditional herb widely applied in Southeast Asia. It is reported that DHOK has cytotoxic effect on cancer cells, but its anti-cancer mechanism has still been not clear. In our study, we first observed that DHOK inhibits cell proliferation of colorectal cancer cells in a time- and dose-dependent manner. Next, we performed transcriptome sequencing to identify the targets of DHOK and found that autophagy-related signaling pathways are involved under DHOK treatment. Indeed, in DHOK-treated cells, the level of autophagosome marker LC3 and the formation of GFP-LC3 puncta were decreased, indicating the reduction of autophagy. Moreover, confocal microscopy results revealed the lysosomal activity and the formation of autolysosomes are also inhibited. Our western blotting results demonstrated the activation of mammalian target of rapamycin (mTOR) signaling pathway by DHOK, which may be attributed to the enhancement of ERK and AKT activity. Functionally, activation of autophagy attenuated DHOK-caused cell death, indicating that autophagy serves as cell survival. In xenograft mouse model, our results also showed that DHOK activates the mTOR signaling pathway, decreases autophagy level and inhibits the tumorigenesis of colon cancer. Taken together, we revealed the molecular mechanism of DHOK against cancer and our results also demonstrate great potential of DHOK in the treatment of colorectal cancer.

The excavation of deep underground engineering causes a sophisticated three-dimensional stress redistribution in the surrounding rock, leading to the damage and rupture of the surrounding rock. It is difficult to reveal the fracture mechanism of rocks under complex stress loading path changes through conventional uniaxial or triaxial stress tests. In this study, a marble dual-scale 3DEC-GBM (grain-based modeling) discrete element model was established. The model was according to the practical mineral component of marble and its particle size distribution characteristics. Through laboratory true triaxial tests and numerical simulations, investigations were conducted on the deformation and strength characteristics of marble under true triaxial stress states. The evolution process and characteristics of anisotropic fracture and its microscopic tensile and shear fracture mechanism were also thoroughly investigated. Subsequently, the effects of intermediate principal stress σ2 and minimum principal stress σ3 on the intergranular and transgranular failures of marble as well as cracked anisotropy were analyzed, and the tensile–shear failure mechanism and crack anisotropy evolution law of the marble fracture evolution were determined under different true triaxial stress conditions. Finally, the effects of mineral crystal micromechanical parameters on the mechanical characteristics of marble under true triaxial conditions were examined.HighlightsMacro-meso failure mechanisms of anisotropic deformation and failure of marble induced by true triaxial stresses were revealed through tests and simulations.Pre- and post-peak microcrack anisotropic propagation processes and tensile‒shear mechanisms of marble under true triaxial stresses (σ2, σ3) were investigated.Effects of 3DEC-GBM model meso parameters on mechanical behavior of rock were explored.