Search

ObjectiveThis study aims to analyze the application and clinical translation value of the self-evolving machine learning methods in predicting diabetic retinopathy and visualizing clinical outcomes.MethodsA retrospective study was conducted on 300 diabetic patients admitted to our hospital between January 2022 and October 2023. The patients were divided into a diabetic retinopathy group (n=150) and a non-diabetic retinopathy group (n=150). The improved Beetle Antennae Search (IBAS) was used for hyperparameter optimization in machine learning, and a self-evolving machine learning model based on XGBoost was developed. Value analysis was performed on the predictive features for diabetic retinopathy selected through multifactor logistic regression analysis, followed by the construction of a visualization system to calculate the risk of diabetic retinopathy occurrence.ResultsMultifactor logistic regression analysis revealed that being male, having a longer disease duration, higher systolic blood pressure, fasting blood glucose, glycosylated hemoglobin, low-density lipoprotein cholesterol, and urine albumin-to-creatinine ratio were risk factors for the development of diabetic retinopathy, while non-pharmacological treatment was a protective factor. The self-evolving machine learning model demonstrated significant performance advantages in early diagnosis and prediction of diabetic retinopathy occurrence.ConclusionThe application of the self-evolving machine learning models can assist in identifying features associated with diabetic retinopathy in clinical settings, enabling early prediction of disease occurrence and aiding in the formulation of treatment plans to improve patient prognosis.

The Voronoi grain-based breakable block model (VGBBM) based on the combined finite-discrete element method (FDEM) was proposed to explicitly characterize the failure mechanism and predict the deformation behavior of hard-rock mine pillars. The influence of the microscopic parameters on the macroscopic mechanical behavior was investigated using laboratory-scale models. The field-scale pillar models (width-to-height, W/H=1, 2 and 3) were calibrated based on the empirically predicted stress-strain curves of Creighton mine pillars. The results indicated that as the W/H ratios increased, the VGBBM effectively predicted the transition from strain-softening to pseudo-ductile behavior in pillars, and explicitly captured the separated rock slabs and the V-shaped damage zones on both sides of pillars and conjugate shear bands in core zones of pillars. The volumetric strain field revealed significant compressional deformation in core zones of pillars. While the peak strains of W/H=1 and 2 pillars were relatively consistent, there were significant differences in the strain energy storage and release mechanism. W/H was the primary factor influencing the deformation and strain energy in the pillar core. The friction coefficient of the structural plane was also an important factor affecting the pillar strength and the weakest discontinuity angle. The fracture surface was controlled by the discontinuity angle and the friction coefficient. This study demonstrated the capability of the VGBBM in predicting the strengths and deformation behavior of hard-rock pillars in deep mine design.

Imaging the wave velocity field surrounding a borehole while drilling is a promising and urgently needed approach for extending the exploration range of the borehole point. This paper develops a drilling process detection (DPD) system consisting of a multifunctional sensor and a pilot geophone installed at the top of the drilling rod, geophones at the tunnel face, a laser rangefinder, and an onsite computer. A weighted adjoint-state first arrival travel time tomography method is used to invert the P-wave velocity field of rock mass while borehole drilling. A field experiment in the ongoing construction of a deep buried tunnel in southwestern China demonstrated the DPD system and the tomography method. Time-frequency analysis of typical borehole drilling detection data shows that the impact drilling source is a pulse-like seismic exploration wavelet. A velocity field of the rock mass in a triangular area defined by the borehole trajectory and geophone receiving line can be obtained. Both the borehole core and optical image validate the inverted P-wave velocity field. A numerical simulation of a checkerboard benchmark model is used to test the tomography method. The rapid convergence of the misfits and consistent agreement between the inverted and observed travel times validate the P-wave velocity imaging.

Abstract Background Glucocorticoids and sclerostin act as inhibitors of the Wnt signaling pathway, thereby hindering bone formation. Given the pathway's intricate association with mesenchymal stem cells, the hypothesis suggests that heightened sclerostin levels may be intricately linked to an augmentation in marrow adiposity induced by glucocorticoids. This study endeavored to delve into the nuanced relationship between circulating sclerostin and bone marrow adipose tissue in postmenopausal women grappling with glucocorticoid-induced osteoporosis (GIO). Methods In this cross-sectional study, 103 patients with autoimmune-associated diseases underwent glucocorticoid treatment, boasting an average age of 61.3 years (standard deviation 7.1 years). The investigation encompassed a thorough assessment, incorporating medical history, anthropometric data, biochemical analysis, and dual-energy X-ray absorptiometry measurements of lumbar and femoral bone mineral density (BMD). Osteoporosis criteria were established at a T-score of -2.5 or lower. Additionally, MR spectroscopy quantified the vertebral marrow fat fraction. Results BMD at the femoral neck, total hip, and lumbar spine showcased an inverse correlation with marrow fat fraction (r = –0.511 to – 0.647, P

The far-field microdynamic disturbance caused by the excavation of deep mineral resources and underground engineering can induce surrounding rock damage in high-stress conditions and even lead to disasters. However, the mechanical properties and damage/fracture evolution mechanisms of deep rock induced by microdynamic disturbance under three-dimensional stress states are unclear. Therefore, a true triaxial multilevel disturbance test method is proposed, which can completely simulate natural geostress, excavation stress redistribution (such as stress unloading, concentration and rotation), and subsequently the microdynamic disturbance triggering damaged rock failure. Based on a dynamic true triaxial test platform, true triaxial microdynamic disturbance tests under different frequency and amplitudes were carried out on monzogabbro. The results show that increasing amplitude or decreasing frequency diminishes the failure strength of monzogabbro. Deformation modulus gradually decreases during disturbance failure. As frequency and amplitude increase, the degradation rate of deformation modulus decreases slightly, disturbance dissipated energy increases significantly, and disturbance deformation anisotropy strengthens obviously. A damage model has been proposed to quantitatively characterize the disturbance-induced damage evolution at different frequency and amplitude under true triaxial stress. Before disturbance failure, the micro-tensile crack mechanism is dominant, and the micro-shear crack mechanism increases significantly at failure. With the increase of amplitude and frequency, the micro-shear crack mechanism increases. When approaching disturbance failure, the acoustic emission fractal dimension changes from a stable value to local large oscillation, and finally increases sharply to a high value at failure. Finally, the disturbance-induced failure mechanism of surrounding rock in deep engineering is clearly elucidated.

Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering. The inverse analysis is commonly utilized to determine the physico-mechanical parameters. However, conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems. In this study, a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model (ROM) and probabilistic programming. The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems. Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering. A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution. The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty. Then, a slope case was employed to demonstrate the performance of the developed framework. The results prove that the proposed framework provides a scientific, feasible, and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.

The Industrial Internet of Things integrates modern technologies such as intelligent terminals, computer technology, and big data, achieving low cost and high applicability in industrial production processes, and improving industrial production efficiency. The offloading of IoT data traffic requires significant energy consumption due to limited mobile terminal device resources. For this reason, the author designs a method of IoT data traffic unloading based on mobile edge computing. The initialization simulation parameters include the number of mobile users, the number of base stations equipped with edge servers, fixed bandwidth, base station height, etc. Calculate the distance and channel power gain from each base station to mobile users, and optimize power allocation through algorithms such as simulated annealing and PSO. The binary PSO algorithm is used to maximize the welfare in edge computing. Finally, by comparing with local offloading, utilizing layered offloading methods, and collaborative computing offloading methods based on fiber wireless networks. Simulation results: The energy consumption of SAPA is generally higher than that of PSO, and with the increase of mobile users, the energy consumption of both algorithms shows a significant growth trend. Especially, SAPA's energy consumption is significantly higher than PSO when the number of users is 40 and 60. This indicates that in the mobile network environment, PSO algorithm has more advantages in energy consumption than SAPA, By using particle swarm optimization algorithm to further optimize energy consumption, it greatly saves energy consumption. In comparison to local execution, the proposed offloading method yields substantial energy savings of nearly 62.5 %. The maximum difference in energy consumption between the proposed method and the collaborative computing offloading method based on fiber optic wireless networks is 268 J, while the maximum difference compared to the layered offloading method is 150 J. These results highlight the strategy's ability to enhance the computational efficiency of high-priority tasks on edge servers, concurrently reducing latency and energy consumption for task completion. This underscores the effectiveness of the proposed offloading method in conserving energy and emphasizes its practical significance.

Abstract Objective Acute pancreatitis (AP) stands as a frequent cause for clinical emergency hospital admissions. The X‐box binding protein 1 (XBP1) was found to be implicated in pancreatic acinar cell apoptosis. The objective is to unveil the potential mechanisms governed by XBP1 and SIRT6 in the context of AP. Methods Caerulein‐treated human pancreatic duct epithelial (HPDE) cells to establish an in vitro research model. The levels and regulatory role of SIRT6 in the treated cells were evaluated, including its effects on inflammatory responses, oxidative stress, apoptosis, and endoplasmic reticulum stress. The relationship between XBP1 and SIRT6 was explored by luciferase and ChIP experiments. Furthermore, the effect of XBP1 overexpression on the regulatory function of SIRT6 on cells was evaluated. Results Caerulein promoted the decrease of SIRT6 and the increase of XBP1 in HPDE cells. Overexpression of SIRT6 slowed down the secretion of inflammatory factors, oxidative stress, apoptosis level, and endoplasmic reticulum stress in HPDE cells. However, XBP1 negatively regulated SIRT6, and XBP1 overexpression partially reversed the regulation of SIRT6 on the above aspects. Conclusion Our study illuminates the role of XBP1 in downregulating SIRT6 in HPDE cells, thereby promoting cellular injury. Inhibiting XBP1 or augmenting SIRT6 levels holds promise in preserving cell function and represents a potential therapeutic avenue in the management of AP.

In deep hard rock excavation, stress plays a pivotal role in inducing stress-controlled failure. While the impact of excavation-induced stress disturbance on rock failure and tunnel stability has undergone comprehensive examination through laboratory tests and numerical simulations, its validation through in-situ stress tests remains unexplored. This study analyzes the three-dimensional stress changes in the surrounding rock at various depths, monitored during the excavation of B2 Lab in China Jinping Underground Laboratory Phase II (CJPL-II). The investigation delves into the three-dimensional stress variation characteristics in deep hard rock, encompassing stress components and principal stress. The results indicate changes in both the magnitude and direction of the principal stress during tunnel excavation. To quantitatively describe the degree of stress disturbance, a series of stress evaluation indexes are established based on the distances between stress tensors, including the stress disturbance index (SDI), the principal stress magnitude disturbance index (SDIm), and the principal stress direction disturbance index (SDId). The SDI indicates the greatest stress disturbance in the surrounding rock is 4.5 m from the tunnel wall in B2 Lab. SDIm shows that the principal stress magnitude disturbance peaks at 2.5 m from the tunnel wall. SDId reveals that the largest change in principal stress direction does not necessarily occur near the tunnel wall but at a specific depth from it. The established relationship between SDI and the depth of the excavation damaged zone (EDZ) can serve as a criterion for determining the depth of the EDZ in deep hard rock engineering. Additionally, it provides a reference for future construction and support considerations.

PurposeTo determine whether there are alterations in marrow fat content in individuals first-time diagnosed with type 1 diabetes mellitus (T1DM) and to explore the associations between marrow fat fraction and MRI-based findings in trabecular bone microarchitecture.MethodA case-control study was conducted, involving adults with first-time diagnosed T1DM (n=35) and age- and sex-matched healthy adults (n=46). Dual-energy X-ray absorptiometry and 3 Tesla-MRI of the proximal tibia were performed to assess trabecular microarchitecture and vertebral marrow fat fraction. Multiple linear regression analysis was used to test the associations of marrow fat fraction with trabecular microarchitecture and bone density while adjusting for potential confounding factors.ResultsIn individuals first-time diagnosed with T1DM, the marrow fat fraction was significantly higher (p < 0.001) compared to healthy controls. T1DM patients also exhibited higher trabecular separation [median (IQR): 2.19 (1.70, 2.68) vs 1.81 (1.62, 2.10), p < 0.001], lower trabecular volume [0.45 (0.30, 0.56) vs 0.53 (0.38, 0.60), p = 0.013], and lower trabecular number [0.37 (0.26, 0.44) vs 0.41 (0.32, 0.47), p = 0.020] compared to controls. However, bone density was similar between the two groups (p = 0.815). In individuals with T1DM, there was an inverse association between marrow fat fraction and trabecular volume (r = -0.69, p < 0.001) as well as trabecular number (r = -0.55, p < 0.001), and a positive association with trabecular separation (r = 0.75, p < 0.001). Marrow fat fraction was independently associated with total trabecular volume (standardized β = -0.21), trabecular number (β = -0.12), and trabecular separation (β = 0.57) of the proximal tibia after adjusting for various factors including age, gender, body mass index, physical activity, smoking status, alcohol consumption, blood glucose, plasma glycated hemoglobin, lipid profile, and bone turnover biomarkers.ConclusionsIndividuals first-time diagnosed with T1DM experience expansion of marrow adiposity, and elevated marrow fat content is associated with MRI-based trabecular microstructure.

The investigation of the fluorescence mechanism of carbon dots (CDs) has attracted significant attention, particularly the role of the oxygen-containing groups. Dual-CDs exhibiting blue and green emissions are synthesized from glucose via a simple ultrasonic treatment, and the oxidation degree of the CDs is softly modified through a slow natural oxidation approach, which is in stark contrast to that aggressively altering CDs’ surface configurations through chemical oxidation methods. It is interesting to find that the intensity of the blue fluorescence gradually increases, eventually becoming the dominant emission after prolonging the oxidation periods, with the quantum yield (QY) of the CDs being enhanced from ~0.61% to ~4.26%. Combining the microstructure characterizations, optical measurements, and ultrafiltration experiments, we hypothesize that the blue emission could be ascribed to the surface states induced by the C–O and C=O groups, while the green luminescence may originate from the deep energy levels associated with the O–C=O groups. The distinct emission states and energy distributions could result in the blue and the green luminescence exhibiting distinct excitation and emission behaviors. Our findings could provide new insights into the fluorescence mechanism of CDs.

Abstract Background Brainstem stroke causes severe and persistent neurological impairment. Due to the limited spontaneous recovery and regeneration of the disrupted neural circuits, transplantation of exogenous neural stem cells (NSCs) was an alternative, while there were limitations for primitive NSCs. Methods We established a mouse model of brainstem stroke by injecting endothelin in the right pons. Brain-derived neurotrophic factor (BDNF)- and distal-less homeobox 2 (Dlx2)-modified NSCs were transplanted to treat brainstem stroke. Transsynaptic viral tracking, immunostaining, magnetic resonance imaging, behavioral testing, and whole-cell patch clamp recordings were applied to probe the pathophysiology and therapeutic prospects of BDNF- and Dlx2-modified NSCs. Results GABAergic neurons were predominantly lost after the brainstem stroke. No endogenous NSCs were generated in situ or migrated from the neurogenesis niches within the brainstem infarct region. Co-overexpressions of BDNF and Dlx2 not only promoted the survival of NSCs, but also boosted the differentiation of NSCs into GABAergic neurons. Results from transsynaptic virus tracking, immunostaining, and evidence from whole-cell patch clamping revealed the morphological and functional integration of the grafted BDNF- and Dlx2-modified NSCs-derived neurons with the host neural circuits. Neurological function was improved by transplantation of BDNF- and Dlx2-modified NSCs in brainstem stroke. Conclusions These findings demonstrated that BDNF- and Dlx2-modified NSCs differentiated into GABAergic neurons, integrated into and reconstituted the host neural networks, and alleviated the ischemic injury. It thus provided a potential therapeutic strategy for brainstem stroke.

The damage-fracture evolution of deep rock mass has obvious particularity, which is revealed in 2400-m-deep tunnels by field tests. The evolution of the excavation damaged zone depth is consistent with that of the fractured zone depth. The ratio of the excavation damaged zone depth to the excavation fractured zone depth is greater than 2.0 in a rock mass with both high strength and good integrity, but less than 1.5 in a rock mass with lower strength or poor integrity. Zonal disintegration in a rock mass with high strength and fair integrity is more likely to occur when it contains more than two groups of primary fractures in damaged zones. Fractures develop outward in zonal disintegration but are totally different from the single-zone fracture, in which the fractures develop inward, and it is the starting position of the fractured zone when the excavation surface of the middle pilot is 7–9 m close to the pre-set borehole and it stops after the excavation surface of the baseplate is 11–14 m away. The most intense evolution occurs around 2–4 m from the pre-set borehole in the sidewall expansion stage. The research results provide a reference for the monitoring scheme and support design of CJPL-III in its future construction.

Disturbance stress assessment is crucial for ensuring the safety of deep engineering projects. Currently, the primary technique for continuously monitoring three-dimensional disturbance stress is the stress relief method, but its accuracy can be compromised by rock damage that occurs after excavation. To mitigate this issue, grouting is employed to repair damaged rock masses and enhance their mechanical properties. However, the impact of grouting techniques on improving the accuracy of disturbance stress testing is challenging to evaluate through laboratory and in situ experiments. To address this problem, numerical simulation technology is employed to investigate disturbance stress testing after the repair of damaged surrounding rock through grouting. The simulation results indicate that grouting repair significantly enhances the accuracy of stress testing. As the depth of damaged rock mass repair increases, the error in stress testing decreases. Achieving complete repair of the initial damage zone during grouting is essential to eliminate errors in stress testing. Expanding on the positive effects of grouting repair on stress testing, a segmented testing method for disturbance stress is proposed. The method involves separately testing the initial stress and stress changes, thereby reducing the stress level within the rock, minimizing rock failure, and enhancing the accuracy of disturbance stress testing. This study provides valuable reference methods, and the outcomes of this research will serve as a foundation for enhancing the accuracy of disturbance stress testing in deep hard rock engineering.

Ectopic mammary gland tissue in the vulva is an exceptionally rare disease. We present a case of a 62-year-old woman with a left vulvar mass of 30 years duration that progressively increased in size. The patient reported having pressure and discomfort, especially during movement. Surgical excision was performed, and a histopathological examination revealed a well-differentiated ectopic breast. We also review other cases of vulvar ectopic breast to further comprehend the characteristics of this rare disease. Clinicians and pathologists should always consider it as a differential diagnosis when presented with a vulvar mass.

IntroductionSepsis is a vitally serious disease leading to high mortality. Nucleated red blood cells (NRBCs) are present in some noninfectious diseases, but the relationship between NRBCs and sepsis in children remains unknown. The purpose of this study was to compare the clinical characteristics and outcomes of sepsis with positive NRBCs and negative NRBCs in children, and to further explore whether the count of NRBCs has a relationship with the severity of sepsis.MethodsWe enrolled children with sepsis who were admitted to the Children’s Hospital of Chongqing Medical University between January 2020 and December 2022. The children’s clinical data, laboratory data and outcomes were recorded and analyzed.ResultsOne hundred and fifteen children met the inclusion criteria in our study. Compared to negative NRBCs patients, the C-reactive protein, alanine transaminase, urea nitrogen values, mortality rate and length of hospitalization were found to be significantly increased, while platelet counts, and hemoglobin were significantly decreased in sepsis patients with positive NRBC (P < 0.05). Receiver operating characteristic (ROC) curves analysis showed that the optimal cutoff value of the NRBC count in the diagnosis of severe sepsis was 3, with a sensitivity of 87.5% and specificity of 94.9%. The area under the ROC curve was 0.877 (95% CI: 0.798-0.957).DiscussionThese findings demonstrated that NRBC count has the potential to be a biomarker for the diagnosis of sepsis in children, especially an NRBC count greater than 3, which may predict the severity and poor prognosis in children suffering from sepsis.

Objective This study aimed to analyse the burden and temporal trends of tuberculosis (TB) incidence and mortality globally, as well as the association between mortality-to-incidence ratio (MIR) and Socio-Demographic Index (SDI).Design A retrospective analysis of TB data from 1990 to 2019 was conducted using the Global Burden of Disease Study database.Results Between 1990 and 2019, there was a declining trend in the global incidence and mortality of TB. High SDI regions experienced a higher declining rate than in low SDI regions during the same period. Nearly half of the new patients occurred in South Asia. In addition, there is a sex–age imbalance in the overall burden of TB, with young males having higher incidence and mortality than females. In terms of the three subtypes of TB, drug-sensitive (DS)-TB accounted for more than 90% of the incidents and deaths and experienced a decline over the past 30 years. However, drug-resistant TB (multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB) showed an overall increasing trend in age-standardised incidence rates and age-standardised mortality rates, with an inflection point after the year 2000. At the regional level, South Asia and Eastern Europe remained a high burden of drug-resistant TB incidence and mortality. Interestingly, a negative correlation was found between the MIR and SDI for TB, including DS-TB, MDR-TB and XDR-TB. Notably, central sub-Saharan Africa had the highest MIR, which indicated a higher-than-expected burden given its level of sociodemographic development.Conclusion This study provides comprehensive insights into the global burden and temporal trends of TB incidence and mortality, as well as the relationship between MIR and SDI. These findings contribute to our understanding of TB epidemiology and can inform public health strategies for prevention and management.

Dynamic failure of rock masses around deep tunnels, such as fault-slip rockburst and seismic-induced collapse, can pose a significant threat to tunnel construction safety. One of the most significant factors that control the accuracy of its risk assessment is the estimation of the ground motion around a tunnel caused by seismicity events. In general, the characteristic parameters of ground motion are estimated in terms of empirical scaling laws. However, these scaling laws make it difficult to accurately estimate the near-field ground motion parameters because the roles of control factors, such as tunnel geometry, damage zone distribution, and seismic source parameters, are not considered. For this, the finite fracturing seismic source model (FFSSM) proposed in this study is used to simulate the near-field ground motion characteristics around deep tunnels. Then, the amplification effects of ground motion caused by the interaction between seismic waves and deep tunnels and corresponding control factors are studied. The control effects of four factors on the near-field ground motion amplification effect are analyzed, including the main seismic source wavelength, tunnel span, tunnel shape, and range of damage zones. An empirical formula for the maximum amplification factor (αm) of the near-field ground motion around deep tunnels is proposed, which consists of four control factors, i.e. the wavelength control factor (Fλ), tunnel span factor (FD), tunnel shape factor (Fs) and excavation damage factor (Fd). This empirical formula provides an easy approach for accurately estimating the ground motion parameters in seismicity-prone regimes and the rock support design of deep tunnels under dynamic loads.

Abstract Purpose Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids. Methods The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I 2 with the inspection level of 0.1 and 50%, respectively. Results Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70–0.87; P

Fully grouted bolts are a key component of the support system for underground openings. Although considerable effort has been made in the simulation of the reinforcement effect of the fully grouted bolts on the rock masses surrounding underground openings, most of the work has limited significance since the structural element approach is used. This study proposes a local homogenization approach (L-H approach) that integrates elastoplastic mechanics, composite mechanics, and analytical approaches with numerical simulation to effectively simulate the reinforcement effect of the fully grouted bolt on deep surrounding rock masses. In the L-H approach, the representative volume of bolted rock mass (RVBRM) with a fully grouted bolt is established based on the original mesh model utilized in the rockbolt element approach. The RVBRM is a regular quadrangular prism with a cross-sectional size equal to the bolt spacing and a length equal to the bolt length. The RVBRM is homogenized by the L-H approach from a unidirectional bolt-reinforced composite into a homogeneous transversely isotropic medium whose mechanical properties are described by a new transversely isotropic elastoplastic model. The L-H parameters for the RVBRM are obtained using analytical approaches, composite mechanics, and known parameters of the rock mass and bolt. Using the L-H approach, the reinforcement effect of the fully grouted bolt on the bolted rock specimen and the surrounding rock mass in Jinping II Diversion Tunnel #2 with a depth greater than 2000 m is simulated. The results show that the predictions of the L-H approach are more in agreement with the physical model results of bolted rock specimen and provide a more realistic response of the bolted surrounding rock mass. The L-H approach demonstrates that fully grouted bolts with common bolt spacings and diameters substantially enhance the elastic modulus, shear strength, and tensile strength of the rock mass in the direction of the bolt axis.

BackgroundSpatial transcriptomics (STs) simultaneously obtains the location and amount of gene expression within a tissue section. However, current methods like FindMarkers calculated the differentially expressed genes (DEGs) based on the classical statistics, which should abolish the spatial information.Materials and methodsA new method named spatial analysis of spatial transcriptomics (saSpatial) was developed for both the location and the amount of gene expression. Then saSpatial was applied to detect DEGs in both inter- and intra-cross sections. DEGs detected by saSpatial were compared with those detected by FindMarkers.ResultsSpatial analysis of spatial transcriptomics was founded on the basis of spatial statistics. It was able to detect DEGs in different regions in the normal brain section. As for the brain with ischemic stroke, saSpatial revealed the DEGs for the ischemic core and penumbra. In addition, saSpatial characterized the genetic heterogeneity in the normal and ischemic cortex. Compared to FindMarkers, a larger number of valuable DEGs were found by saSpatial.ConclusionSpatial analysis of spatial transcriptomics was able to effectively detect DEGs in STs data. It was a simple and valuable tool that could help potential researchers to find more valuable genes in the future research.

BackgroundEpilepsy is one of the leading neurological diseases. Our study is aimed to determine whether there is a focal region of high epilepsy prevalence in China.MethodsAll studies published between 1981 and 2020 investigating the prevalence of epilepsy in China were systematically reviewed. The geographical location, sample size, number of cases, urbanization rate, gross domestic product (GDP) per capita, percentage of

IntroductionHigh-resolution magnetic resonance imaging (HR-MRI) is used to characterize atherosclerotic plaque. The present study aimed to determine the high-risk features of the basilar artery (BA) atherosclerotic plaque.MethodsPatients with advanced BA stenosis were screened. The features including the ruptured fibrous cap (RFC), lipid core, intraplaque hemorrhage (IPH), plaque enhancement, and calcification were assessed by using high-resolution MRI. The relationship between the features and acute infarction was analyzed.ResultsFrom 1 June 2014 to 31 December 2018, a total of 143 patients with 76 new strokes were included. RFC was identified in 25% of symptomatic and 10.4% of asymptomatic patients. IPH was identified in 48.7% of symptomatic and 25.4% of asymptomatic patients. RFC (3.157, 95% CI 1.062 to 9.382, p = 0.039) and IPH (2.78, 95% CI 1.127 to 6.505, p = 0.026) were independent risk factors for acute infarction.ConclusionOur study showed that RFC and IPH of BA plaque were independent risk factors for acute infarction.

Lymphatic metastasis influences clinical treatment and prognosis of patients with non-small-cell lung cancer (NSCLC). There is an urgency to understand the molecular features and mechanisms of lymph node metastasis. We analyzed the molecular features on pairs of the primary tumor and lymphatic metastasis tissue samples from 15 NSCLC patients using targeted next-generation sequencing. The potential metastasis-related genes were screened from our cohort based on cancer cell fraction. After filtering with gene functions, candidate metastasis-related events were validated in the MSK cohort with Fisher’s exact test. The molecular signature and tumor mutational burden were similar in paired samples, and the average mutational concordance was 42.0% ± 28.9%. Its metastatic mechanism is potentially a linear progression based on the metastatic seeding theory. Furthermore, mutated ataxia telangiectasia mutated and Rad3-related (ATR) and tet methylcytosine dioxygenase 2 (TET2) genes were significantly enriched in lymphatic metastases (p ≤ 0.05). Alterations in these two genes could be considered metastasis-related driving events. Mutated ATR and TET2 might play an active role in the metastasis of lymph nodes with NSCLC. More case enrollment and long-term follow-up will further verify the clinical significance of these two genes.

Bone marrow adipocytes may be responsible for cancer progression. Although marrow adipogenesis is suspected to be involved in prostate carcinogenesis, an association between marrow adiposity and prostate cancer risk has not been clearly established in vivo. This work included 115 newly diagnosed cases of histologically confirmed prostate cancer (range, 48–79 years) and 87 age-matched healthy controls. Marrow proton density fat fraction (PDFF) was measured by 3.0-T MR spectroscopy at the spine lumbar. Associations between marrow PDFF and risk of prostate cancer by stage of disease and grade sub-types were performed using multivariable polytomous logistic regression. There were no significant group differences in the vertebral marrow PDFF, despite prostate cancer patients having 6.6% higher marrow PDFF compared to the healthy controls (61.7 ± 9.8% vs. 57.9 ± 6.5%; t = 1.429, p = 0.161). After adjusting for various clinical and demographic characteristics, we found that elevated marrow PDFF was related to an increased risk of high-grade prostate cancer [odds ratios (OR) = 1.31; 95% confidence interval (CI), 1.08–1.57; p = 0.003]. Likewise, increased marrow PDFF had a significantly positive correlation with aggressive prostate cancer risk (OR = 1.54; 95% CI, 1.13–1.92; p

Abstract Background The activation of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent pyroptosis has been shown to play a vital role in the pathology of manganese (Mn)-induced neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has a positive effect on the treatment of manganism. However, the mechanism is still unclear. We hypothesized that PAS-Na might act through NLRP3. Methods The microglial cell line BV2 and male Sprague-Dawley rats were used to investigate the impacts of PAS-Na on Mn-induced NLRP3 inflammasome-dependent pyroptosis. The related protein of the NF-κB pathway and NLRP3-inflammasome-dependent pyroptosis was detected by western blot. The reactive oxygen species and mitochondrial membrane potential were detected by immunofluorescence staining and flow cytometry. The activation of microglia and the gasdermin D (GSDMD) were detected by immunofluorescence staining. Results Our results showed that Mn treatment induced oxidative stress and activated the NF-κB pathway by increasing the phosphorylation of p65 and IkB-α in BV2 cells and in the basal ganglia of rats. PAS-Na could alleviate Mn-induced oxidative stress damage by inhibiting ROS generation, increasing mitochondrial membrane potential and ATP levels, thereby reducing the phosphorylation of p65 and IkB-α. Besides, Mn treatment could activate the NLRP3 pathway and promote the secretion of IL-18 and IL-1β, mediating pyroptosis in BV2 cells and in the basal ganglia and hippocampus of rats. But an inhibitor of NF-κb (JSH-23) treatment could significantly reduce LDH release, the expression of NLRP3 and Cleaved CASP1 protein and IL-1β and IL-18 mRNA level in BV2 cells. Interestingly, the effect of PAS-Na treatment in Mn-treated BV2 cells is similar to those of JSH-23. Besides, immunofluorescence results showed that PAS-Na reduced the increase number of activated microglia, which stained positively for GSDMD. Conclusion PAS-Na antagonized Mn-induced NLRP3 inflammasome dependent pyroptosis through inhibiting NF-κB pathway activation and oxidative stress.

Objective: Acute poisoning in children is characterized by regional differences. This study described the basic situation of childhood poisoning in southwest China based on hospitalized cases.Data and Methods: A total of 1,076 acute poisoning cases among hospitalized children admitted to Children's Hospital of Chongqing Medical University from January 2012 to December 2020 were included in this study. Clinical data such as gender, age, living environment, poisonous substance, and cause of poisoning were statistically described. Trends of length of hospital stay, population distribution, poisonous substances, and causes of acute poisoning in the hospitalized children were compared over time.Results: The cohort comprised 588 males and 488 females; 811 cases lived in rural areas and the rest resided in urban areas. Most cases were between early childhood and school age. Poisoning usually occurred at home (973 cases, 90.4%). Pesticides (381 cases, 35.4%) and drugs (275 cases, 25.6%) were the two most common poisonous substances. Two main causes of poisoning were accidental taking (755 cases, 70.2%) and suicide (177 cases, 16.4%). The results of univariate analysis of suicide showed significant correlations among gender, place of residence, age, poisonous substance, and place of suicide (P < 0.001), while living environment (town), age (adolescence), and poisonous substance (pesticide, drug) were independent risk factors (P < 0.05). There was no significant change in the length of hospital stay for poisoning over time. The overall number of hospitalizations presented a decreasing trend, while the number of urban children gradually increased. The proportion of adolescent poisoned children and suicidal children increased in the last 3 years.Conclusion: Optimizing the package and distribution channels of pesticides and drugs, raising safety awareness of children to avoid accidental injuries, and paying attention to children's mental health are measures that are necessary to prevent poisoning in children.

Noninvasive prenatal diagnosis (NIPD) of single-gene disorders has recently become the focus of clinical laboratories. However, reports on the clinical application of NIPD of Duchenne muscular dystrophy (DMD) are limited. This study aimed to evaluate the detection performance of haplotype-based NIPD of DMD in a real clinical environment. Twenty-one DMD families at 7–12 weeks of gestation were prospectively recruited. DNA libraries of cell-free DNA from the pregnant and genomic DNA from family members were captured using a custom assay for the enrichment of DMD gene exons and spanning single-nucleotide polymorphisms, followed by next-generation sequencing. Parental haplotype phasing was based on family linkage analysis, and fetal genotyping was inferred using the Bayes factor through target maternal plasma sequencing. Finally, the entire experimental process was promoted in the local clinical laboratory. We recruited 13 complete families, 6 families without paternal samples, and 2 families without probands in which daughter samples were collected. Two different maternal haplotypes were constructed based on family members in all 21 pedigrees at as early as 7 gestational weeks. Among the included families, the fetal genotypes of 20 families were identified at the first blood collection, and a second blood collection was performed for another family due to low fetal concentration. The NIPD result of each family was reported within 1 week. The fetal fraction in maternal cfDNA ranged from 1.87 to 11.68%. In addition, recombination events were assessed in two fetuses. All NIPD results were concordant with the findings of invasive prenatal diagnosis (chorionic villus sampling or amniocentesis). Exon capture and haplotype-based NIPD of DMD are regularly used for DMD genetic diagnosis, carrier screening, and noninvasive prenatal diagnosis in the clinic. Our method, haplotype-based early screening for DMD fetal genotyping via cfDNA sequencing, has high feasibility and accuracy, a short turnaround time, and is inexpensive in a real clinical environment.

Abstract Background Parkinson's disease is a progressive degenerative nervous system disease. Recent studies have shown that secondary changes in the GABA system play directly affect the pathogenesis of PD. There is still much debate about GABA concentrations because currently, GABA concentrations in the brain tissue are obtained indirectly by measuring its concentration in the blood and cerebrospinal fluid. These results are unreliable. Magnetic resonance spectroscopy (MRS) is the only noninvasive method for evaluating the concentration of metabolites in living brain tissue and has been widely applied in research and clinical practice. In addition, combining MEGA-PRESS technology with LCModel software for quantitative GABA measurements is largely recognized. At present, the PD monkeys model in primates has been increasingly proficient. Primates are more similar to humans in terms of brain structure and function than other animals. However, 3.0 T MRS studies involving the PD monkey model to measure metabolites in living subjects with PD are still rare. The study was performed at 3.0 T MRI with control monkeys and PD monkeys that were injected methyl-phenyl-tetrahydropyridine (MPTP) in one side of common carotid artery before and 3 months after successful model establishment to measure GABA concentrations in the bilateral striatum. Behavioral observations were performed for all animals, and the behavioral score was recorded. After 3 months, the GABA concentration in the bilateral striatum was measured in both groups by high-performance liquid chromatography (HPLC). The data obtained from magnetic resonance spectroscopy (MRS) were compared with the actual measured GABA concentrations in tissues isolated from the corresponding regions, and their correlations with the behavior score were analyzed. The research objectives are to investigate the changes of γ-aminobutyric acid (GABA) concentration in the bilateral striatum of monkeys with Parkinson's disease (PD) and the value of quantitatively measuring its concentration by noninvasive 3.0 T spectroscopy. Results (1) The MRS results showed that the GABA concentration in the injured side of the striatum of the PD monkeys was higher than in the contralateral side, but the difference was not statistically significant (P = 0.154). Compared with that the blank control group, the GABA concentration in the striatum of the PD monkeys increased, but there was no difference between the groups (P = 0.381; P = 0.425). (2) The GABA concentration that determined from the isolated specimens by HPLC in the injured side of the striatum of the PD monkeys was significantly higher than that in the contralateral side (P

Background: Ghrelin is the endogenous ligand of growth hormone secretagogue receptor 1a, which plays a role in regulating immunity and inflammation. The aim of this study is to assess the diagnostic value of plasma ghrelin in sepsis-associated pediatric acute respiratory distress syndrome (PARDS).Methods: We recruited patients who were admitted to the pediatric ICU (PICU) of the Children's Hospital of Chongqing Medical University between January 2019 and January 2020 and met the diagnostic criteria for sepsis. Data on clinical variables, laboratory indicators, plasma ghrelin concentrations, and inflammatory factors were collected and evaluated, and patients were followed up for 28 days. The area under the receiver-operating characteristic curves (AUROC) were determined using logistic regression to calculate and test cut-off values for ghrelin as a diagnostic indicator of sepsis-associated PARDS. The log-rank test was used to compare survival according to ghrelin levels.Main results: Sixty-six PICU patients (30 with ARDS and 36 without ARDS) who met the diagnostic criteria of sepsis were recruited. The ghrelin level was significantly higher in the ARDS group than in the non-ARDS group. The AUROC of ghrelin was 0.708 (95% confidence interval: 0.584–0.833) and the positivity cutoff value was 445 pg/mL. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of plasma ghrelin for the diagnosis of PARDS-associated sepsis were 86.7, 50.0, 59.1, 81.8, 1.734, and 0.266%, respectively. The survival rate of sepsis patients were significantly improved when the ghrelin level was >445 pg/mL.Conclusions: Ghrelin plasma levels were higher in sepsis-associated PARDS, and accompanied by increased levels of inflammatory factors. High ghrelin levels are a positive predictor of ICU survival in sepsis patients. Yet, there is no evidence to prove that elevated ghrelin is a promising diagnostic indicator of sepsis-associated PARDS.Trial registration: Clinicaltrials, ChiCTR1900023254. Registered 1 December 2018 - Retrospectively registered, http://www.clinicaltrials.gov/ChiCTR1900023254.

Uncertainty is critical to the tunnel design. In this study, a novel reliability-based design (RBD) method was developed by integrating the rock-support interaction and its uncertainties for rock tunnels. In this method, the rock-support interactions were analyzed based on a convergence-confinement method. Uncertainties were estimated by reliability analysis using Excel Solver. Chaotic particle swarm optimization (CPSO) was adopted to search the optimal tunnel design parameters based on the rock-support interaction analysis. The proposed method for estimating the reliability index and determining the tunnel support parameters was introduced in detail. To illustrate the proposed method, it was applied to two tunnels with rock-bolt and combined support systems. The results indicated that the method could obtain accurate solutions with a dramatically improved computing efficiency, guaranteeing the tunnel stability at the same time. The developed method provides an excellent way to deal with the uncertainty in tunnel design. It was proved to be an efficient and effective method for the support designs of rock tunnels.

Background and objective Previous studies have found the lincRNAs play important roles in the occurrence and development of lung adenocarcinoma, but their regulated mechanims are still unclear. The aim of this study is to evaluate the relationship between DNA methylation and lincRNA expression, and the effect of prognosis in lung adenocarcinoma. Methods The whole genome Illumina Methylation 450 DNA methylatiuon data and RNAseq for lung adenocarcinoma were download from TCGA. DNA methylation around lincRNA and their relationship to gene expression were analyzed. Their contribution to lung adenocarcinoma were further analyzed by comparing DNA methylation and lincRNA expression in tumor and adjacent tissues. Results The methylation level in promoter region was lower than other positions in lincRNA, and was negatively correlated with gene expression. There were 427 lincRNA genes showed differential DNA methylation in their promoter regions in tumor and adjacent tissues. Among these, 15 lincRNA genes showed differential gene expression and negatively correlated with DNA methylation, including FENDRR (a tumor progression and metastasis gene) whose high methylation in its promoter showed poor survival in lung adenocarcinoma. Conclusion The expression of lincRNA can be regulated by DNA methylation in their promoter regions, and the level of DNA methylation is related to patient prognosis in lung adenocarcinoma.

Granite exhibits obvious meso-geometric heterogeneity. To study the influence of grain size and preferred grain orientation on the damage evolution and mechanical properties of granite, as well as to reveal the inner link between grain size‚ preferred orientation, uniaxial tensile strength (UTS) and damage evolution, a series of Brazilian splitting tests were carried out based on the combined finite-discrete element method (FDEM), grain-based model (GBM) and inverse Monte Carlo (IMC) algorithm. The main conclusions are as follows: (1) Mineral grain significantly influences the crack propagation paths, and the GBM can capture the location of fracture section more accurately than the conventional model. (2) Shear cracks occur near the loading area, while tensile and tensile-shear mixed cracks occur far from the loading area. The applied stress must overcome the tensile strength of the grain interface contacts. (3) The UTS and the ratio of the number of intergrain tensile cracks to the number of intragrain tensile cracks are negatively related to the grain size. (4) With the increase of the preferred grain orientation, the UTS presents a “V-shaped” characteristic distribution. (5) During the whole process of splitting simulation, shear microcracks play the dominant role in energy release; particularly, they occur in later stage. This novel framework, which can reveal the control mechanism of brittle rock heterogeneity on continuous-discontinuous trans-scale fracture process and microscopic rock behaviour, provides an effective technology and numerical analysis method for characterizing rock meso-structure. Accordingly, the research results can provide a useful reference for the prediction of heterogeneous rock mechanical properties and the stability control of engineering rock masses.

Metals are actively involved in multiple catalytic physiological activities. However, metal overload may result in neurotoxicity as it increases formation of reactive oxygen species (ROS) and elevates oxidative stress in the nervous system. Mitochondria are a key target of metal-induced toxicity, given their role in energy production. As the brain consumes a large amount of energy, mitochondrial dysfunction and the subsequent decrease in levels of ATP may significantly disrupt brain function, resulting in neuronal cell death and ensuing neurological disorders. Here, we address contemporary studies on metal-induced mitochondrial dysfunction and its impact on the nervous system.

Abstract Background Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by enteroviruses, and HFMD complicated by cardiopulmonary failure has a high mortality. B type natriuretic peptide (BNP) is widely applied in monitoring cardiovascular disorders, and thus, we investigated whether this index was associated with the severity of HFMD and the outcome in severe HFMD. Methods Serum BNP, lactate, and glucose levels as well as white blood cell (WBC) count, PaO2/FiO2, and cardiac output (CO) were analyzed in the 83 enrolled HFMD patients according to different conditions (common, severe, and critical; with and without complication; and survivors and non-survivors). The control group consisted of 29 patients with respiratory tract infections. Results No significant differences in CO were observed between the groups. Serum lactate, glucose, BNP, and WBC levels in the critical group were significantly higher than those in the severe, common, and control groups (p

Abstract The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus. Further study indicated that inhibition of calcineurin by cyclosporine A or knockdown of NFATc4 using small interfering RNA suppressed ET-1-induced TRPC6 up-regulation. In addition, luciferase reporter assay showed that NFATc4 directly regulated the expression of TRPC6 in PASMCs. Inhibition of PDE5 by sildenafil suppressed ET-1-induced activation of calcineurin/NFATc4 signaling pathway and consequent TRPC6 up-regulation in PASMCs, while these inhibitory effects of sildenafil were abolished by PKG inhibitor Rp-8Br-cGMPs. Taken together, our study indicates that ET-1 stimulates TRPC6 expression by activation of calcineurin/NFATc4 signaling pathway, and inhibition of PDE5 suppresses calcineurin/NFATc4- mediated TRPC6 expression in PASMCs in a cGMP-PKG-dependent manner.

Sclerostin knock-out mice or sclerostin antibody (Scl-Ab) treated wild-type mice displayed decreased marrow adiposity. But the effects of Scl-Ab on estrogen deficiency-induced marrow fat expansion remain elusive. In this work, 45 female New Zealand rabbits were equally divided into sham-operation, ovariectomy controls, and ovariectomy treated with Scl-Ab for 5 months. MR spectroscopy was performed to longitudinally assess marrow fat fraction at baseline conditions, 2.5 and 5 months post-operatively, respectively. We evaluated bone mineral density (BMD), bone structural parameters, serum bone biomarkers, and quantitative parameters of marrow adipocytes. Ovariectomized rabbits markedly exhibited expansion of marrow fat in a time-dependent manner, with a variation of marrow fat fraction (+17.8%) at 2.5 months relative to baseline and it was maintained until 5 months (+30.4%, all P < 0.001), which was accompanied by diminished BMD and deterioration of trabecular microstructure. Compared to sham controls, adipocyte mean diameter, adipocyte density and adipocytes area percentage was increased by 42.9, 68.3, and 108.6% in ovariectomized rabbits, respectively. Scl-Ab treatment increased serum bone formation marker and alleviated the ovariectomy escalation of serum bone resorption marker. It remarkably lessened the ovariectomy-mediated deterioration of BMD, and morphometric characteristics of trabecular bone. Marrow fat fraction was decreased significantly with Scl-Ab to levels matching that of sham-operated controls and correlated positively with reductions in adipocyte mean diameter, percentage adipocyte volume per marrow volume, and adipocyte density. Taken together, early Scl-Ab treatment reverts marrow fat expansion seen in ovariectomized rabbits in addition to having a beneficial effect on bone mass and microstructural properties.

The upregulation of Sphingosine kinase 1 (SphK1) expression and accompanied sphingosine-1-phosphate (S1P) production have been reported to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMC) and pulmonary arterial remodeling. However, the molecular mechanisms of SphK1/S1P upregulation in PASMC and the specific mechanisms of how SphK1/S1P pathway promotes PASMC proliferation remain largely unclear. This study aims to address these issues. Here, we demonstrated that TGF-β1 significantly upregulated SphK1 expression and S1P production by promoting the phosphorylation of Smad2/3 in PASMC. Further study indicated that SphK1/S1P pathway mediated TGF-β1-induced Notch3 activation in PASMC. In addition, we showed that TGF-β1 significantly induced proliferation of PASMC, while pre-inhibition of Smad2/3 phosphorylation with SB431542 or silencing SphK1 using small interfering RNA in advance, or pre-blocking Notch3 pathway with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), attenuated TGF-β1-induced PASMC proliferation. Taken together, our study indicates that Smad2/3/SphK1/S1P/Notch3 pathway mediates TGF-β1-induced PASMC proliferation and suggests this pathway as a potential therapeutic target in the prevention and treatment of pulmonary hypertension.

Numerous deep underground projects have been designed and constructed in China, which are beyond the current specifications in terms of scale and construction difficulty. The severe failure problems induced by high in situ stress, such as rockburst, spalling, damage of deep surrounding rocks, and time-dependent damage, were observed during construction of these projects. To address these problems, the dynamic design method for deep hard rock tunnels is proposed based on the disintegration process of surrounding rocks using associated dynamic control theories and technologies. Seven steps are basically employed: (i) determination of design objective, (ii) characteristics of site, rock mass and project, and identification of constraint conditions, (iii) selection or development of global design strategy, (iv) determination of modeling method and software, (v) preliminary design, (vi) comprehensive integrated method and dynamic feedback analysis, and (vii) final design. This dynamic method was applied to the construction of the headrace tunnels at Jinping II hydropower station. The key technical issues encountered during the construction of deep hard rock tunnels, such as in situ stress distribution along the tunnels, mechanical properties and constitutive model of deep hard rocks, determination of mechanical parameters of surrounding rocks, stability evaluation of surrounding rocks, and optimization design of rock support and lining, have been adequately addressed. The proposed method and its application can provide guidance for deep underground projects characterized with similar geological conditions.

Background and objective To detect the expression of neutrophil gelatinase-assoeiated lipocalin (NGAL) in the different differentiations of lung cancer tissues and to study the mechanism of invasion of A549 cells affected by NGAL. Methods The expression of NGAL was detected by immunochemistry in lung cancer tissue and the tissue around edge of the cancer. The effect of NGAL expression on A549 cells was observed by using qRT-PCR and Western blot. The abilities of invasion and metastasis were evaluated by transwell invasion and migration assay, and cell scratch assay in vitro. The protein expression of E-cadherin, Vimentin was measured by immunofluoresence and Western blot. Results The positive expression rate of NGAL was 76.32% (58/76) in the lung cancer, 13.3% (4/30) in adjacent tissue by immunochemistry. NGAL expression levels in the lung cancer tissues were significantly higher than that in adjacent tissues. The rate of migration and invasion in NGAL-siRNA group was 60.4%±6.4% compared to 50.5%±4.4% in the control group, there was a significant difference (P

Hydraulic fracturing is widely used to determine in situ stress of rock engineering. In this paper we propose a new method for simultaneously determining the in situ stress and elastic parameters of rock. The method utilizing the hydraulic fracturing numerical model and a computational intelligent method is proposed and verified. The hydraulic fracturing numerical model provides the samples which include borehole pressure, in situ stress, and elastic parameters. A computational intelligent method is applied in back analysis. A multioutput support vector machine is used to map the complex, nonlinear relationship between the in situ stress, elastic parameters, and borehole pressure. The artificial bee colony algorithm is applied in back analysis to find the optimal in situ stress and elastic parameters. The in situ stress is determined using the proposed method and the results are compared with those of the classic breakdown formula. The proposed method provides a good estimate of the relationship between the in situ stress and borehole pressure and predicts the maximum horizontal in situ stress with high precision while considering the influence of pore pressure without the need to estimate Biot’s coefficient and other parameters.

The crystal structure development of jojoba-like esters incorporating either 1-decenoic acid and/or 1-decenol, namely octadec-9-enyl dec-9-enoate (JLE-281), and its isomer dec-9-enyl oleate (JLE-282) was investigated to reveal the effect of symmetry about the ester group on crystallization of aliphatic fatty monoesters. The phase transformation path was investigated with temperature-time resolved X-ray diffraction during stepped isothermal crystallization, and while cooling from the melt at a fixed rate. Startling differences in phase behavior were uncovered between the isomers. When stepped isothermals were used, selective extinctions occurred at a transition temperature for JLE-281 but not for JLE-282. The extinctions, which are due to dramatic changes in the electronic density of certain families of planes, indicate a phase transition attributed to a brusque rearrangement of the oxygen atoms in the crystal subcell. The phase transition did not occur when the JLEs were cooled continuously. The crucial role played by the position of the alkyl chain and its orientation relative to the easy rotation site of the C–O bond in the phase trajectories of the JLEs was particularly highlighted.

Cytokinins (CKs) are a family of evolutionarily conserved growth regulating hormones. While CKs are well-characterized in plant systems, these N6-substituted adenine derivatives are found in a variety of organisms beyond plants, including bacteria, fungi, mammals, and the social amoeba, Dictyostelium discoideum. Within Dictyostelium, CKs have only been studied in the late developmental stages of the life cycle, where they promote spore encapsulation and dormancy. In this study, we used ultra high-performance liquid chromatography-positive electrospray ionization-high resolution tandem mass spectrometry (UHPLC-(ESI+)-HRMS/MS) to profile CKs during the Dictyostelium life cycle: growth, aggregation, mound, slug, fruiting body, and germination. Comprehensive profiling revealed that Dictyostelium produces 6 CK forms (cis-Zeatin (cZ), discadenine (DA), N6-isopentenyladenine (iP), N6-isopentenyladenine-9-riboside (iPR), N6-isopentenyladenine-9-riboside-5′ phosphate (iPRP), and 2-methylthio-N6-isopentenyladenine (2MeSiP)) in varying abundance across the sampled life cycle stages, thus laying the foundation for the CK biosynthesis pathway to be defined in this organism. Interestingly, iP-type CKs were the most dominant CK analytes detected during growth and aggregation. Exogenous treatment of AX3 cells with various CK types revealed that iP was the only CK to promote the proliferation of cells in culture. In support of previous studies, metabolomics data revealed that DA is one of the most significantly upregulated small molecules during Dictyostelium development, and our data indicates that total CK levels are highest during germination. While much remains to be explored in Dictyostelium, this research offers new insight into the nature of CK biosynthesis, secretion, and function during Dictyostelium growth, development, and spore germination.

The most dangerous landslide disasters always cause serious economic losses and human deaths. The contribution of this work is to present an integrated landslide modelling framework, in which an adaptive neuro-fuzzy inference system (ANFIS) is combined with the two optimization algorithms of whale optimization algorithm (WOA) and grey wolf optimizer (GWO) at Anyuan County, China. It means that WOA and GWO are used as two meta-heuristic algorithms to improve the prediction performance of the ANFIS-based methods. In addition, the step-wise weight assessment ratio analysis (SWARA) method is used to obtain the initial weight of each class of landslide influencing factors. To validate the effectiveness of the proposed framework, 315 landslide events in history were selected for our experiments and were randomly divided into the training and verification sets. To perform landslide susceptibility mapping, fifteen geological, hydrological, geomorphological, land cover, and other factors are considered for the modelling construction. The landslide susceptibility maps by SWARA, SWARA-ANFIS, SWARA-ANFIS-PSO, SWARA-ANFIS-WOA, and SWARA-ANFIS-GWO models are assessed using the measures of the receiver operating characteristic (ROC) curve and root-mean-square error (RMSE). The experiments demonstrated that the obtained results of modelling process from the SWARA to the SAWRA-ANFIS-GWO model were more accurate and that the proposed methods have satisfactory prediction ability. Specifically, prediction accuracy by area under the curve (AUC) of SWARA, SWARA-ANFIS, SWARA-ANFIS-PSO, SWARA-ANFIS-GWO, and SWARA-ANFIS-WOA models were 0.831, 0.831, 0.850, 0.856, and 0.869, respectively. Due to adaptability and usability, the proposed prediction methods can be applied to other areas for landslide management and mitigation as well as prevention throughout the world.

Landslides are a major geological hazard worldwide. Landslide susceptibility assessments are useful to mitigate human casualties, loss of property, and damage to natural resources, ecosystems, and infrastructures. This study aims to evaluate landslide susceptibility using a novel hybrid intelligence approach with the rotation forest-based credal decision tree (RF-CDT) classifier. First, 152 landslide locations and 15 landslide conditioning factors were collected from the study area. Then, these conditioning factors were assigned values using an entropy method and subsequently optimized using correlation attribute evaluation (CAE). Finally, the performance of the proposed hybrid model was validated using the receiver operating characteristic (ROC) curve and compared with two well-known ensemble models, bagging (bag-CDT) and MultiBoostAB (MB-CDT). Results show that the proposed RF-CDT model had better performance than the single CDT model and hybrid bag-CDT and MB-CDT models. The findings in the present study overall confirm that a combination of the meta model with a decision tree classifier could enhance the prediction power of the single landslide model. The resulting susceptibility maps could be effective for enforcement of land management regulations to reduce landslide hazards in the study area and other similar areas in the world.

Floods are considered one of the most disastrous hazards all over the world and cause serious casualties and property damage. Therefore, the assessment and regionalization of flood disasters are becoming increasingly important and urgent. To predict the probability of a flood, an essential step is to map flood susceptibility. The main objective of this work is to investigate the use a novel hybrid technique by integrating multi-criteria decision analysis and geographic information system to evaluate flood susceptibility mapping (FSM), which is constructed by ensemble of decision making trial and evaluation laboratory (DEMATEL), analytic network process, weighted linear combinations (WLC) and interval rough numbers (IRN) techniques in the case study at Shangyou County, China. Specifically, we improve the DEMATEL method by applying IRN to determine connections in the network structure based on criteria and to accept imprecisions during collective decision making. The application of IRN can eliminate the necessity of additional information to define uncertain number intervals. Therefore, the quality of the existing data during collective decision making and experts’ perceptions that are expressed through an aggregation matrix can be retained. In this work, eleven conditioning factors associated with flooding were considered and historical flood locations were randomly divided into the training (70% of the total) and validation (30%) sets. The flood susceptibility map validates a satisfactory consistency between the flood-susceptible areas and the spatial distribution of the previous flood events. The accuracy of the map was evaluated by using objective measures of receiver operating characteristic (ROC) curve and area under the curve (AUC). The AUC values of the proposed method coupling with the WLC fuzzy technique for aggregation and flood susceptibility index are 0.988 and 0.964, respectively, which proves that the WLC fuzzy method is more effective for FSM in the study area. The proposed method can be helpful in predicting accurate flood occurrence locations with similar geographic environments and can be effectively used for flood management and prevention.

Purpureocillium lilacinum is a promising nematophagous ascomycete able to adapt diverse environments and it is also an opportunistic fungus that infects humans. A microbial inoculant of P. lilacinum has been registered to control plant parasitic nematodes. However, the molecular mechanism of the toxicological processes is still unclear because of the relatively few reports on the subject. In this study, using Illumina paired-end sequencing, the draft genome sequence and the transcriptome of P. lilacinum strain 36-1 infecting nematode-eggs were determined. Whole genome alignment indicated that P. lilacinum 36-1 possessed a more dynamic genome in comparison with P. lilacinum India strain. Moreover, a phylogenetic analysis showed that the P. lilacinum 36-1 had a closer relation to entomophagous fungi. The protein-coding genes in P. lilacinum 36-1 occurred much more frequently than they did in other fungi, which was a result of the depletion of repeat-induced point mutations (RIP). Comparative genome and transcriptome analyses revealed the genes that were involved in pathogenicity, particularly in the recognition, adhesion of nematode-eggs, downstream signal transduction pathways and hydrolase genes. By contrast, certain numbers of cellulose and xylan degradation genes and a lack of polysaccharide lyase genes showed the potential of P. lilacinum 36-1 as an endophyte. Notably, the expression of appressorium-formation and antioxidants-related genes exhibited similar infection patterns in P. lilacinum strain 36-1 to those of the model entomophagous fungi Metarhizium spp. These results uncovered the specific parasitism of P. lilacinum and presented the genes responsible for the infection of nematode-eggs.

OBJECTIVE:This meta-analysis aimed to investigate the efficacy and safety of plastic wrap applied after birth and during NICU in preterm infants for prevention of heat loss in preterm infants. STUDY METHODS:The Medline (1950 to August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7, 2015), CINAHL (1982 to August 2015) and the Embase (1974 to August 2015) databases were searched for randomized controlled trials (RCTs) or quasi-RCTs with main outcomes related to the core temperature (baseline temperature and/or post-stabilization temperature), hypothermia, mortality rate and hyperthermia. RESULT:The included studies were of low to moderate quality. Compared with unwrapped infants, plastic wrap was associated with a significantly higher baseline temperature and post-stabilization temperature both in infants < 28 weeks of gestation (mean difference [MD] = 0.62, 95% CI 0.38 to 0.85; MD = 0.41, 95% CI 0.33 to 0.50, respectively), and in infants between 28 to 34 weeks of gestation (MD = 0.54, 95% CI 0.21 to 0.87; MD = 0.64, 95% CI 0.45 to 0.82, respectively). Use of plastic wrap was associated with lower incidence of hypothermia (relative risk [RR] = 0.70, 95% CI 0.63 to 0.78). However, use of plastic wrap in preterm infants was not associated with decrease in mortality (RR: 0.88, 95% CI 0.70 to 1.12, P = 0.31). Incidence of hyperthermia was significantly higher in the plastic wrap group as compared to that in the control group (RR = 2.55, 95% CI: 1.56 to 4.15, P = 0.0002). Hyperthermia in the plastic wrap group was resolved within one or two hours after unwrapping the babies. CONCLUSION:Plastic wrap can be considered an effective and safe additional intervention to prevent hypothermia in preterm infants. However, its cost-effectiveness and long-term effect on mortality needs to be ascertained by conducting well-designed studies with longer follow-up period.