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In this study, we aim to assess dynamical downscaling simulations by utilizing a novel bias-corrected global climate model (GCM) data to drive a regional climate model (RCM) over the Asia-western North Pacific region. Three simulations were conducted with a 25-km grid spacing for the period 1980–2014. The first simulation (WRF_ERA5) was driven by the European Centre for Medium-Range Weather Forecasts Reanalysis 5 (ERA5) dataset and served as the validation dataset. The original GCM dataset (MPI-ESM1-2-HR model) was used to drive the second simulation (WRF_GCM), while the third simulation (WRF_GCMbc) was driven by the bias-corrected GCM dataset. The bias-corrected GCM data has an ERA5-based mean and interannual variance and long-term trends derived from the ensemble mean of 18 CMIP6 models. Results demonstrate that the WRFGCMbc significantly reduced the root-mean-square errors (RMSEs) of the climatological mean of downscaled variables, including temperature, precipitation, snow, wind, relative humidity, and planetary boundary layer height by 50%–90% compared to the WRF_GCM. Similarly, the RMSEs of interannual-to-interdecadal variances of downscaled variables were reduced by 30%–60%. Furthermore, the WRFGCMbc better captured the annual cycle of the monsoon circulation and intraseasonal and day-to-day variabilities. The leading empirical orthogonal function (EOF) shows a monopole precipitation mode in the WRFGCM. In contrast, the WRF_GCMbc successfully reproduced the observed tri-pole mode of summer precipitation over eastern China. This improvement could be attributed to a better-simulated location of the western North Pacific subtropical high in the WRF_GCMbc after GCM bias correction. [ABSTRACT FROM AUTHOR]

Background: The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan–amoxicillin (VA) and 14-day rabeprazole–amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. Methods: This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. Results: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). Conclusions: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication. [ABSTRACT FROM AUTHOR]

In this paper, we focus on the partially linear varying-coefficient quantile regression with missing observations under ultra-high dimension, where the missing observations include either responses or covariates or the responses and part of the covariates are missing at random, and the ultra-high dimension implies that the dimension of parameter is much larger than sample size. Based on the B-spline method for the varying coefficient functions, we study the consistency of the oracle estimator which is obtained only using active covariates whose coefficients are nonzero. At the same time, we discuss the asymptotic normality of the oracle estimator for the linear parameter. Note that the active covariates are unknown in practice, non-convex penalized estimator is investigated for simultaneous variable selection and estimation, whose oracle property is also established. Finite sample behavior of the proposed methods is investigated via simulations and real data analysis. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative diseases are a common group of neurological disorders characterized by progressive loss of neuronal structure and function leading to cognitive impairment. Recent studies have shown that neuronal pyroptosis mediated by the NLRP3 inflammasome plays a crucial role in the pathogenesis of neurodegenerative diseases. Objective and method: The NLRP3 inflammasome is a multiprotein complex that, when activated within cells, triggers an inflammatory response, ultimately leading to pyroptotic cell death of neurons. Pyroptosis is a typical pro-inflammatory programmed cell death process occurring downstream of NLRP3 inflammasome activation, characterized by the formation of pores on the cell membrane by the GSDMD protein, leading to cell lysis and the release of inflammatory factors. It has been found that NLRP3 inflammasome-mediated neuronal pyroptosis is closely associated with the development of various neurodegenerative diseases, such as Alzheimer's disease, traumatic brain injury, and Parkinson's disease. Therefore, inhibiting NLRP3 inflammasome activation and attenuating neuronal pyroptosis could potentially serve as novel strategies for the treatment of neurodegenerative diseases. Results: The aim of this review is to explore the role of NLRP3 activation-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases. Firstly, we extensively discuss the relationship between NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in various neurodegenerative diseases. Subsequently, we further explore the mechanisms driving NLRP3 activation and assembly, as well as the post-translational modifications regulating NLRP3 inflammasome activation. Conclusion: Understanding these mechanisms will contribute to a deeper understanding of the link between neuronal pyroptosis and neurodegenerative diseases, and hold significant implications for the treatment and prevention of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The way in which moist convection interacts with large scale flows is a major contemporary research issue. Organized mesoscale systems are, in particular, important for the interactions between convection and the ambient shear. Here we present numerical simulations of mesoscale systems evolving in a background shear using the Research and Weather Forecasting model. We are particularly interested in the long time integration, allowing the systems to repeatedly develop and die and effectively interact with the background shear. Starting with a typical African and equatorial jet-shear, the simulated solution goes through various phases or stages. First, a transient state, consisting of scattered squall-like systems that are aligned perpendicular to the background shear, develops and then evolves into a regime of multiscale mesoscale systems with large stratiform anvils. During the latter period the background wind changes substantially through the effect of both up scale and down scale convective momentum transport. At this stage, the systems become aligned parallel to the wind shear, with elongated stratiform anvils in which meso-beta scale convective cells evolve and propagate in the shear direction, relative to the stratiform anvils. These results are reminiscent of the development of shear parallel mesoscale convective systems observed for instance in the Eastern Pacific ITCZ and corroborate recent theoretical results obtained with a simple multi-cloud model. As such they have important implications for the parameterization of CMT in climate models. [ABSTRACT FROM AUTHOR]

Sea surface temperature is an important parameter of ocean hydrology. Accurate prediction of sea surface temperature is of great significance for ocean economic development and extreme weather prevention. Application of deep learning-based method in sea surface temperature prediction has significantly increased due to its high analytical power. Nevertheless, sea surface temperature time series are so volatile and stochastic, leading to the fact that in-depth analysis and accurate prediction of sea surface temperature are still challenging. Considering non-stationary and nonlinear characteristics in sea surface temperature sequence, variational mode decomposition is adopted as the de-noising module to reduce the influence of noise. Furthermore, the convolutional neural network is combined with the gated recurrent unit network to extract both spatial and temporal features in sea surface temperature sequence, simultaneously. Finally, a sea surface temperature prediction model based on deep learning model with frequency analysis module is proposed in this paper. The sea surface temperature of East China Sea is selected for empirical study. Comparative analysis demonstrated that the proposed model significantly outperforms the existing sea surface temperature prediction models. Especially, even to the mesoscale level, mean absolute error and root mean squared error of the proposed method are still 0.2038 and 0.2481, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Peptides are an important class of therapeutics. Their quality is evaluated using a series of analytical tests, many of which depend on well-characterized reference standards to determine identity, purity, and strength. Objective: Discuss approaches to producing peptide reference standards, including vialing, lyophilization, analytical testing and stability studies. Methods: Case studies are used to illustrate analytical approaches to characterize reference standards, including methods for value assignment, content uniformity, and identity testing. Methods described include NMR, mass spectrometry, and chromatography techniques for identity testing and HPLC and GC methods for assessing peptide content and impurities. Results: This report describes the analytical strategy used to establish peptide reference standard and illustrates how results from multiple labs are integrated to assign a value to the final lyophilized vial. A two-step process for value assignment is described, which uses a mass balance approach to assign a quantitative value to a bulk peptide material. The bulk material is then used as a standard to assign a final value to the vialed material. Testing to confirm peptide identity and to ensure consistency of the vialed material is also described. Considerations for addressing variability, identifying outliers, and implementing stability studies are also presented. Conclusion: The methods and case studies described provide a benchmark for best practices in establishing the preparation, analytical testing, handling, and storage of peptide reference standards for the pharmaceutical industry. Some peptide features, such as chiral or isobaric amino acids, may require additional techniques to ensure a full characterization of the peptide reference standard. [ABSTRACT FROM AUTHOR]

In this paper, we focus on partially linear varying coefficient quantile regression with observations missing at random, which allows the responses or responses and covariates simultaneously missing. By means of empirical likelihood method, we construct posterior distributions of the parameter in the model, and investigate their large sample properties under fixed prior. Meanwhile, we use a Bayesian hierarchical model based on empirical likelihood, spike and slab Gaussian priors to discuss variable selection. By using MCMC algorithm, finite sample performance of the proposed methods is investigated via simulations, and real data analysis is discussed too. [ABSTRACT FROM AUTHOR]

In the paper (Han et al. in IEEE Trans Fuzzy Syst 23:2358–2370, 2015), we proposed the bipolar-valued rough fuzzy set in one universe, which is an inevitable improvement by introducing inconsistentbipolarity to rough set. However, the bipolar-valued rough fuzzy set in one universe still has the limitations to complex practical problems. This motives us to propose the generalized concept of bipolar-valued fuzzy rough set in two universes, in which, inconsistentbipolarity is introduced into the crisp approximation space for the first time, and furthermore, two universes are considered to reflect the interrelations among different sources' inconsistentbipolarity information. Comparing with other existing fuzzy rough set models, in syntax, the new one generalizes the existing ones. And most importantly, in semantics, the new one firstly considering the inconsistentbipolarity information, which is important in practice. Based on the new concept, two methods to the decision-making problems with inconsistent fuzzy bipolarity information are proposed, together with their applications. The comparison study with other existing rough set related methods highlights the necessity of our study, which provides a new inconsistent fuzzy bipolarity perspective to rough set theory and related applications. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 5 (FGF5), which is a well-established causative factor for blood pressure, has been identified as a susceptibility gene for preeclampsia (PE) in European and Central Asian women. Here, we examined whether polymorphism rs16998073 in FGF5 confer a significant risk to PE in Chinese Han population by case–control association analysis. FGF5 rs16998073 was genotyped by Sanger sequencing in women with preeclampsia (n = 187) and healthy controls (n = 229) of Han Chinese. We found the frequency of rs16998073T allele was significantly higher in PE patients than that in controls. Next, we utilized dual-luciferase reporter assays and electrophoretic mobility shift assay (EMSA) reactions to investigate whether rs16998073 different alleles could affect the transcriptional activity of FGF5. The dual luciferase reporter assay showed that T allele increased the transcriptional efficiency by 1.5-fold compared with the G allele. Similarly, EMSA revealed that the T allele had a strong transcription factor binding strength compared with the G allele. We then examined the mRNA and protein expression levels of FGF5 in placental tissues by real-time PCR and Western blot assays. We found FGF5 were significantly upregulated in placental tissues from PE patients or PE mouse model than their corresponding controls. In addition, in vitro cell experiments confirmed that FGF5 could promote cell apoptosis of HTR8/SVneo and inhibit cell invasion. Taken together, our data provide evidence implicating rs16998073 of FGF5 as a functional genetic risk variant for PE disease and FGF5 might participate in development of PE disease. [ABSTRACT FROM AUTHOR]

To assess associations between infants with macrosomia and placental expression levels of lipid activated/transport-related factors and umbilical cord blood lipid concentrations in healthy pregnancy. We conducted a case-control study of 38 macrosomic neonates (MS group) and 39 normal-birth-weight newborns (NC group) in a healthy pregnancy. Cord blood lipid levels were measured by automatic biochemical analyzer, mRNA and protein expression levels of placental lipid activated/transport-related factors were determined by real-time polymerase chain reaction and western blot, respectively. Compared with NC group, cord blood total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and non-esterified fatty acid (NEFA) concentrations were decreased in the MS group. The mRNA and protein expression levels of placental peroxisome proliferator-activated receptors (PPARα, PPARγ), plasma membrane fatty acid-binding protein (FABPpm), and fatty acid translocase (FAT/CD36) were significantly higher in the MS group than the NC group. And there was a weak positive correlation between the expression of PPARγ, FABP4, and FABP3 mRNA in the placenta and the HDLC (rs = 0.439; P = 0.005), NEFA (rs = 0.342; P = 0.041), and TG (rs = 0.349; P = 0.034) levels in the cord blood in the MS group, respectively. After multivariate adjustment, the logistic regression analysis showed that high placental PPARα (adjusted odds ratio [AOR] = 3.022; 95% confidence interval [CI] 1.032–8.853) and FAT/CD36 (AOR=2.989; 95%CI 1.029–8.679) and low LDLC concentration in the cord blood (AOR=0.246; 95%CI 0.080–0.759) increased the risk of macrosomia. The increased PPARα and FAT/CD36 expression levels may influence the occurrence of fetal macrosomia through regulating placental lipid transport. [ABSTRACT FROM AUTHOR]

General circulation model (GCM) biases are one of the important sources of biases and uncertainty in dynamic downscaling–based simulations. The ability of regional climate models to simulate tropical cyclones (TCs) is strongly affected by the ability of GCMs to simulate the large-scale environmental field. Thus, in this work, we employ a recently developed multivariable integrated evaluation method to assess the performance of 33 CMIP6 (phase 6 of the Coupled Model Intercomparison Project) models in simulating multiple fields in terms of their climatology. The CMIP6 models are quantitatively evaluated against two reanalysis datasets over five ocean areas. The results show that most of the CMIP6 models overestimate the mid-level humidity in almost all tropical oceans. The multi-model ensemble mean overestimates the vertical shear of the horizontal winds in the Northeast Pacific and North Atlantic. An increase in model horizontal resolution appears to be helpful in improving the model simulations. For example, there are 6–8 models with higher resolution among the top 10 models in terms of overall model performance in simulating the climatology and interannual variability of multiple variables. Similarly, there are 7–8 models with lower resolution among the bottom 10 models. The model skill varies depending on the region and variable being evaluated. Although no model performs best in all regions and for all variables, some models do show relatively good capability in simulating the large-scale environmental field of TCs. [ABSTRACT FROM AUTHOR]

Perfluorinated compounds (PFCs) cause environmental pollution and serious health issues. Therefore, magnetic fluorinated porous carbons (M-FPCs) derived from the carbonization and further fluorination of Fe-Zr MOFs were used as novel adsorbents to investigate the possibility of PFC removal from wastewater. Investigation of the adsorption behavior of PFCs on M-FPCs revealed that the isotherms conformed to the Langmuir model and kinetics fit the pseudo-second-order model. Simulations using the Weber–Morris and Boyd diffusion models indicated that the adsorption of PFCs on M-FPCs involved external mass transfer first, followed by intraparticle diffusion, where film diffusion was the primary controlling process. M-FPCs with maximum adsorption ranging from 518.1 to 919.3 mg g− 1 for studied PFCs were adopted to remove PFCs from simulated wastewaters of textile mill and leather factory. Up to 98.1–100.0% of PFCs were removed within 15 min, and the residual levels of PFCs reached drinking water standards after treatment, which suggests the promising application of M-FPCs in the removal of PFCs from wastewater. [ABSTRACT FROM AUTHOR]

We, in this paper, investigate two-sample quantile difference by empirical likelihood method when the responses with high-dimensional covariates of the two populations are missing at random. In particular, based on sufficient dimension reduction technique, we construct three empirical log-likelihood ratios for the quantile difference between two samples by using inverse probability weighting imputation, regression imputation as well as augmented inverse probability weighting imputation, respectively, and prove their asymptotic distributions. At the same time, we give a test to check whether two populations have the same distribution. A simulation study is carried out to investigate finite sample behavior of the proposed methods too. [ABSTRACT FROM AUTHOR]

Both long non-coding RNA (lncRNA) RMRP and heat shock protein (HSP) 70 have been known to play crucial roles in inflammation. The present study investigated the roles of lncRNA RMRP and HSP70 protein 4 (HSPA4) in lipopolysaccharide (LPS)-induced sepsis. The C57BL/6 mice were treated with LPS, following which the cardiomyocytes were isolated for in vitro experiments. Further, a cardiac muscle cell line, HL-1 was transfected with plasmids expressing RMRP and HSPA4, si-NC, si-HSPA4, miR-1-5p mimic, and controls in vitro. Cell apoptosis, mitochondrial membrane potential (MMP), and levels of intracellular reactive oxygen species (ROS), mRNAs, and proteins were detected in the transfected mice tissues and cells. The LPS treatment significantly reduced the expression levels of RMRP, MMP, and mitochondrial cytochrome C. Moreover, it enhanced the cardiomyocyte apoptosis, intracellular ROS levels, cytoplasm cytochrome C levels, and the expression of caspase-3 and caspase-9 and nuclear factor κB (NF-κB) p65 subunit. The predicted RMRP-miR-1-5p-HSPA4 network was validated by co-transfection experiments in vitro in HL-1 cells. The transfection of miR-1-5p-treated cells with pcDNA-RMRP enhanced the levels of the protein HSPA4; however, no change at the mRNA level was observed. Moreover, miR-1-5p mimic attenuated the protective effect of pcDNA-HSPA4 against LPS-induced mitochondrial damage and apoptosis. In addition, we observed that silencing of HSPA4 increased the expression of nuclear p65; however, this effect could be reversed by co-transfection with pcDNA-RMRP. The lncRNA RMRP axis acts as a sponge for miR-1-5p. RMRP inhibits LPS-induced apoptosis of cardiomyocytes and mitochondrial damage by suppressing the post-transcriptional regulatory function of miR-1-5p on HSPA4. We believe that RMRP exhibits therapeutic potential for LPS-induced myocardial dysfunction both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is applied in a number of medical applications and HA of different molecular weight (Mw) are used in different pharmaceutical preparations. In determination of Mw by muti-angle laser light-scattering (MALS), refractive index increment (dn/dc) is an important parameter for accuracy. Herein, the influence of dn/dc on the Mw of HA in stroke-physiological saline solution is investigated by MALS in this work. Additionally, the Mw variation of HA in the manufacturing process of preparations is measured. It is shown that each HA sample corresponds to a specific value of dn/dc, which is varied from 1.38 to 1.74 L/g with the Mw increasing from 13.5 to 2840 kDa in solution. It is indicated by the results from both MALS approach and viscometry that appropriate dn/dc should be selected for Mw determination. In steam sterilization process of preparations at 121 °C, the Mw and conformation of HA can be accurately and rapidly determined by MALS. This work provides a precise method to determine the Mw of HA in the medical applications and preparation industries. [ABSTRACT FROM AUTHOR]

This ecological study examined the individual and joint impacts of natural–human factors on the spatial patterns of maternal and child health status in China at the provincial scale in 2020. We considered natural factors (forest coverage, average temperature, and total sulfur dioxide and particulate matter emissions) and human factors (economic development, urbanization, healthcare access, and education level). We combined maternal, infant, and under-five mortality rates into a composite maternal and child health index using the entropy method. The spatial autocorrelation analysis of this index highlighted distinct health patterns across provinces, whereas the geodetector method assessed the effects of natural–human factors on the patterns. A notable east–central–west stepwise decline in health status was observed. Global Moran's I showed positive spatial clustering, with high–high clustering areas in the Yangtze River Delta and low–low clustering areas in western regions. Factor detection identified eight significant natural–human factors impacting maternal and child health, with total sulfur dioxide emission density having the greatest impact. The interaction between average schooling years and total sulfur dioxide emission notably affected maternal and child health patterns. The study concludes that natural–human factors critically affect the spatial distribution of maternal and child health. [ABSTRACT FROM AUTHOR]

Purpose: To compare the anatomical effects on anterior segment by lens extraction (LE, phacoemulsification with posterior chamber intraocular lens implantation) and laser peripheral iridotomy (LPI) in primary angle closure suspect (PACS) eyes. Methods: This prospective comparative cohort trial included a total of 122 consecutive patients identified as PACS aged 52 to 80 years. LE or LPI was performed based on each patient's choice. The anterior segment optical coherence tomography (ASOCT) and gonioscopy were conducted at baseline and 4 weeks post-operation. Outcome measures include percentage of residual angle closure, mean angle width (modified Shaffer grade), angle opening distance (AOD), trabecular iris angle (TIA), trabecular iris space area (TISA), anterior chamber depth (ACD), iris curvature (I-Curve), lens vault (LV), intraocular pressure (IOP), and best-corrected visual acuity (BCVA). Results: All anterior angle parameters (AOD, TIA, and TISA) were significantly greater after LE than LPI (P < 0.001 for all). ACD (P < 0.001) increased, LV (P < 0.001) decreased, IOP (P < 0.001) decreased, and BCVA (P < 0.001) increased after LE. However, no significant changes were found in ACD (P = 0.782), LV (P = 0.616), IOP (P = 0.112), and BCVA (P = 0.131) after LPI. In both groups, I-Curve decreased after the operation, but the iris was flatter after LE than LPI (P < 0.001). Gonioscopically, the LE group achieved a larger post-operative angle width (modified Shaffer grade) than LPI (P < 0.001) and all anterior chamber angles were open (defined as posterior pigmented trabecular meshwork (PTM) visible with static gonioscopy) after operation. Nevertheless, after LPI, 12 eyes (20.0%) still had two or more quadrants and 32 eyes (53.3%) still had at least one quadrant in which the posterior PTM could not be observed. Conclusions: Compared with LPI, LE resulted in a wider anterior chamber angle, a deeper anterior chamber, and a lower IOP in PACS eyes. Moreover, no residual angle closure was observed after LE, which could morphologically prevent the progress of angle closure. Trial registration: ChiCTR1800016511 [ABSTRACT FROM AUTHOR]

The traditional dynamical downscaling (TDD) method employs continuous integration of regional climate models (RCM) with the general circulation model (GCM) providing the initial and lateral boundary conditions. Dynamical downscaling simulations are constrained by physical principles and can generate a full set of climate information, providing one of the important approaches to projecting fine spatial-scale future climate information. However, the systematic biases of climate models often degrade the TDD simulations and hinder the application of dynamical downscaling in the climate-change related studies. New methods developed over past decades improve the performance of dynamical downscaling simulations. These methods can be divided into four groups: the TDD method, the pseudo global warming method, dynamical downscaling with GCM bias corrections, and dynamical downscaling with both GCM and RCM bias corrections. These dynamical downscaling methods are reviewed and compared in this paper. The merits and limitations of each dynamical downscaling method are also discussed. In addition, the challenges and potential directions in progressing dynamical downscaling methods are stated. [ABSTRACT FROM AUTHOR]

Three standalone tetrahedral copper hydride clusters, [Cu4(μ4-H)(μ2-X)2(PPh2Py)4]+ (X = Cl, Br; Py = pyridyl), containing a tetrahedral [Cu4(μ4-H)] unit have been synthesized and structurally characterized. The six Cu-Cu distances of the [Cu4(μ4-H)] unit can be divided into three groups (2.65, 2.85, and 2.95 Å), lowering the idealized point group of the Cu4 core to D2 symmetry, thereby resulting in intrinsically chiral metal clusters which exist as racemic pairs of enantiomers in the centrosymmetric crystal structures. Strong photoluminescence (attributable to the existence of the two short Cu-Cu distances of 2.65 Å) was observed in solution and in the solid state upon near-UV irradiation. According to the Jellium model, the title clusters can be considered as two-shell Jelliumatic systems with superatomic electron counts of 2e@0e corresponding to the two shells of H−@[Cu4X2(PPh2Py)4]2+. The four-coordinated hydride in the tetrahedral Cu4 cavity adopts the superatomic electronic configuration of 1S2. [ABSTRACT FROM AUTHOR]

Based on empirical likelihood method, we construct new weighted estimators of conditional density and conditional survival functions when the interest random variable is subject to random left-truncation; further, we define a plug-in weighted estimator of the conditional hazard rate. Under strong mixing assumptions, we derive asymptotic normality of the proposed estimators which permit to built a confidence interval for the conditional hazard rate. The finite sample behavior of the estimators is investigated via simulations too. [ABSTRACT FROM AUTHOR]

Epilepsy is among the most common neurological disorders. Recurrent seizures result in neuronal death, cognitive deficits and intellectual disabilities in children. Currently, recombinant human erythropoietin (rhEPO) is considered to play a neuroprotective role in nervous system disorders. However, the precise mechanisms through which rhEPO modulates epilepsy remain unknown. Based on results from numerous studies, we hypothesized that rhEPO protects against hippocampal damage in developing rats with seizures probably by modulating autophagy via the ribosomal protein S6 (S6) in a time-dependent manner. First, we observed that rats with recurrent seizures displayed neuronal loss in the hippocampal CA1 region. Second, rhEPO injection reduced neuronal loss and decreased the number of apoptotic cells in the hippocampal CA1 region. Moreover, rhEPO increased the Bcl-2 protein expression levels and decreased the ratio of cleaved caspase-3/caspase-3 in the hippocampus. Finally, rhEPO modulated autophagy in the hippocampus in a time-dependent manner, probably via the S6 protein. In summary, rhEPO protects against hippocampal damage in developing rats with seizures by modulating autophagy in a time-dependent manner, probably via the S6 protein. Consequently, rhEPO is a likely drug candidate that is capable of attenuating brain injury. [ABSTRACT FROM AUTHOR]

Flexible job shop scheduling in uncertain environments plays an important part in real-world manufacturing systems. With the aim of capturing the uncertain and multi-objective nature of flexible job shop scheduling, a mathematical model for the multi-objective stochastic flexible job shop scheduling problem (MOSFJSSP) is constructed, where three objectives of make-span, maximal machine workload, and robustness to uncertainties are considered simultaneously under a variety of practical constraints. Two new scenario-based robustness measures are defined based on statistical tools. To solve MOSFJSSP appropriately, a modified multi-objective evolutionary algorithm based on decomposition (m-MOEA/D) is developed for robust scheduling. The novelty of our approach is that it adopts a new subproblem update method which exploits the global information, allows the elitists kept in an archive to participate in the child generation, employs a subproblem selection and suspension strategy to focus more computational efforts on promising subproblems, and incorporates problem-specific genetic operators for variation. Extensive experimental results on 18 problem instances, including 8 total flexible and 10 partial flexible instances, show that the two new robustness measures are more effective than the existing scenario-based measures, in improving the schedule robustness to uncertainties and maintaining a small variance of disrupted objective values. Compared to the state-of-the-art multi-objective optimization evolutionary algorithms (MOEAs), our proposed m-MOEA/D-based robust scheduling approach achieves a much better convergence performance. Different trade-offs among the three objectives are also analyzed. [ABSTRACT FROM AUTHOR]

In this paper, we construct the nonlinear wavelet estimator of a density with data missing at random when covariables are present, and provide an asymptotic expression for the mean integrated squared error (MISE) of the estimator. Unlike for kernel estimators, the MISE expression of the wavelet-based estimator still holds when the density function is piecewise smooth. Also, the asymptotic normality of the estimator is established. [ABSTRACT FROM AUTHOR]

The preparation of SA508 Grade 3 steel was innovatively realized based on laser powder bed fusion (LPBF). On this basis, the influence of processing parameters on the microstructure as well as the mechanical properties of SA508 Grade 3 steel was studied. The effect of the high cooling rate brought about by LPBF on the microstructure and mechanical properties of the specimens was investigated. Defects such as unfused powders and lack-of-fusion defects were observed in specimens prepared at excessively low volumetric energy density. Defects in specimens prepared at excessively high volumetric energy density were predominantly keyhole-shaped defects. The range of the volumetric energy density for obtaining defect-free specimens with a high relative density (99.4 ± 0.3%) was determined to be 111–133 J/mm3. The cooling rate provided by LPBF is much higher than the critical cooling rate for martensitic transformation, resulting in a uniform distribution of fine martensite with an average grain size of about 3 μm in the specimens. The strength of the specimens reached 1.041 GPa, which was much higher than that of the specimens prepared by the traditional process. The high strength of the specimens can be attributed to the Hall–Petch relationship provided by the fine grains. The proposed strategy in this work provides a new technical approach for the additive manufacturing of a high-performance low-carbon and low-alloy steel. [ABSTRACT FROM AUTHOR]

The mechanical properties of coal containing fluid are an important factor affecting the safe mining of soft coal seams. In particular, for class III–V coal, coal and gas outbursts and other dynamic phenomena are prone to occur due to the influences of gas pressure and groundwater, which seriously threaten the safety and lives of field workers. However, briquette samples are usually used in place of raw coal in laboratory tests conducted on class III–V coal samples. Whether the research conclusions for briquette and raw coal are consistent and whether briquette coal can replace raw coal in research on strength characteristics need to be further verified. In this paper, the evolution of the strength characteristics of fluid-bearing briquette coal and raw coal is studied. The strength characteristics, instability failure characteristics, and acoustic emission characteristics of raw coal and briquette coal under uniaxial and triaxial compression are analyzed in detail. In addition, the influence of the water content and pore pressure on the strength characteristics of class III–V raw coal and briquette coal is further studied. The results show that the failure characteristic of raw coal is overall brittle failure, mainly axial splitting failure, whereas that of briquette is overall ductile failure, mainly cone-shaped continuous spalling. The strength parameters of the raw coal and briquette coal improve under confining pressure, but the internal difference in the raw coal is significantly reduced. The cohesion of the raw coal sample initially increases and then decreases with increasing water content, and the internal friction angle increases with increasing water content. In addition, it is verified that the strength, cohesion, elastic modulus, and deformation modulus of the briquette decrease with increasing pore pressure under different pore pressures, but the strength difference of the class III–V coal decreases under increasing pore pressure. Based on the abovementioned results, the strength parameters of a coal body are estimated using the Hoek–Brown (H–B) criterion. Based on a comparison of the strength parameters of the coal sample and coal body, the estimated strength parameters of the coal body are closer to the actual values on site. [ABSTRACT FROM AUTHOR]

Introduction: Various fusion techniques have been used to treat lumbar spine isthmic spondylolisthesis (IS) in adults, including anterior lumbar interbody fusion (ALIF), posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), posterolateral fusion (PLF), and circumferential fusion. The objective of this study was to evaluate which fusion technique provides the best clinical and radiological outcome for adult lumbar IS. Materials and methods: A systematic review was performed. MEDLINE databases and reference lists of selected articles were searched. Inclusion criteria stated that the studies had to be controlled and that they compared clinical and radiological outcomes of various fusion techniques for treating adult IS. Exclusion criteria were use of only one treatment and non-English language articles. Two reviewers independently extracted relevant data from each included study. Statistical comparisons were made when appropriate. Results: Nine studies that compared two surgical approaches to IS were included in this systematic review. Three were prospective studies, and six were retrospective studies. Two studies compared ALIF with instrumented PLF and ALIF with percutaneous pedicle screw fixation, two studies compared ALIF and TLIF, and five studies compared PLIF and PLF. ALIF was superior to other techniques regarding restoration of disc height, segmental lordosis, and whole lumbar lordosis. TLIF had lower complication rates. ALIF combined with PLF showed lower nonfusion rates than other techniques. However, there were no significant differences in clinical outcomes between any two techniques. Conclusion: Compared to other fusion techniques, TLIF shows fewer complications, ALIF shows better sagittal alignment, and circumferential fusion showed better fusion rates. It was difficult to make recommendations about the optimal approach because of the methodological variance in the publications. [ABSTRACT FROM AUTHOR]

Purpose: Traditionally, lumbar spinal surgery is performed with bilateral pedicle screw fixation to provide stability as the fusion heals. However, many studies have reported that unilateral pedicle screw fixation is as effective as bilateral constructs. To compare the clinical outcomes, complications, and surgical trauma between the two techniques for treatment of degenerative lumbar diseases, we conducted a meta-analysis. Methods: We searched MEDLINE, EMBASE, PubMed, Google Scholar, and Cochrane databases for relevant controlled studies up to August 2013 that compared unilateral with bilateral fixation for the treatment of degenerative lumbar diseases. We independently performed title/abstract screening and full-text screening. A random effects model was used for heterogeneous data; otherwise, a fixed effect model was used, pooling data using mean difference (MD) for continuous outcomes and odds ratio (OR) for dichotomous outcomes. Results: A total of 12 articles (865 participants) were eligible. Overall, there were significant differences between the two groups for blood loss (MD = −171.73, 95 % CI = −281.70 to −61.76; p = 0.002), operation time (MD = −66.02, 95 % CI = −115.52 to −16.51; p = 0.009), and fusion rate (OR = 0.50, 95 % CI = 0.26-0.96; p = 0.004). However, there were no significant differences in hospital stay (MD = −4.44, 95 % CI = −13.37 to 4.50), ODI (MD = −0.09, 95 % CI = −0.59 to 0.42; p = 0.74), JOA (MD = 0.18, 95 % CI = −0.77 to 1.14; p = 0.71), VAS (MD = −0.04, 95 % CI = −0.16 to 0.08; p = 0.49), SF-36 (PF: MD = −1.11, 95 % CI = −4.38 to 2.17, p = 0.51; GH: MD = 1.22, 95 % CI = −2.17 to 4.60, p = 0.48; MH: MD = −0.22, 95 % CI = −3.83 to 3.38, p = 0.90) and complications (OR = 1.15, 95 % CI = 0.72-1.85; p = 0.56). Conclusions: This meta-analysis shows that there was significantly less blood loss in unilateral group and less operating time; however, the fusion rate was significantly higher in the bilateral group. The outcomes of hospital stay, ODI, JOA, VAS, SF-36 score, and complications are similar in the two groups. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with a high morbidity in patients with impaired fasting glucose (IFG). Bicyclol is a synthetic compound known to protect the liver against oxidation and lipid injuries. Objective: The objective of this study was to evaluate the efficacy and safety of metformin and bicyclol in the treatment of NAFLD patients with IFG. Methods: After lifestyle changes and metformin treatment (500 mg orally three times daily), the 248 patients enrolled with NAFLD and IFG were equally randomized to two 24-week treatment groups: bicyclol 25 mg three times daily or vitamin E (α-tocopherol) 100 mg three times daily (control). Anthropometric measurements, serum biochemistry, liver/spleen computed tomography ratio, and changes in liver histological parameters were compared before and after treatments. Results: A total of 223 patients completed the treatment, and there were significant improvements in body mass index, waist-to-hip ratio, and biochemical parameters in both groups ( P < 0.01). Compared with the control group, the improvement in serum alanine aminotransferase levels in the bicyclol group was statistically significant ( P < 0.01). Liver histological assessments revealed that steatosis, inflammation, hepatocellular ballooning, and NAFLD activity scores (NAS) were all decreased in both groups after treatment ( P < 0.01). However, decreases in inflammation and NAS in the bicyclol group were statistically significant compared with the vitamin E group ( P < 0.01). Adverse events in the bicyclol and control groups occurred in 1.79 and 1.80 %, respectively. Conclusion: Metformin combined with bicyclol is effective and safe in the treatment of patients with NAFLD and IFG. However, further studies with a larger sample size are needed to confirm the efficacy and safety of the combination. [ABSTRACT FROM AUTHOR]

Engineering accumulation of triacylglycerol (TAG) in vegetative tissues has been recently proposed as a promising strategy for increasing plant oil production. However, little is known about regulatory mechanisms involved in increasing oil production in plant vegetative tissues. In this study, expression of NtMGD1 encoding a major biosynthetic enzyme for the chloroplast membrane lipid was inhibited by RNAi interference in tobacco. Furthermore, AtDGAT1, a rate-regulating gene involved in TAG biosynthesis, was ectopically overexpressed. Results showed that leaf TAG accumulations were significantly increased both by NtMGD1 RNAi and AtDGAT1 overexpression. However, combination of AtDGAT1 overexpression with NtMGD1 RNAi did not result in additive increase in TAG accumulation in leaves than AtDGAT1 overexpression or NtMGD1 RNAi alone. In addition, reduction of monogalactosyldiacylglycerol (MGDG) biosynthesis by NtMGD1 RNAi was relieved by AtDGAT1 overexpression. Expression of lipid transfer protein (LTP) was upregulated both by AtDGAT1 overexpression and NtMGD1 RNAi and correlated with increased oil accumulation in leaves. Our results indicated that fatty acids deesterified from chloroplast membrane galactolipids could be redirected into TAG. TAG is an energy-dense molecule that might act as a storage pool for carbohydrate. This membrane lipid remodeling may represent an adaptive response that enables plant cells to avoid toxic effects of free fatty acids. [ABSTRACT FROM AUTHOR]

As an autoimmune disease, up to 73% of patients with primary biliary cholangitis (PBC) have a combination of extrahepatic autoimmune diseases (EHAIDs); however, the causal relationship between PBC and EHAIDs is unclear. The genome-wide association analyses provided 14 GWAS data for PBC and EHAIDs, and bidirectional, two-sample MR analyses were performed to examine the relationship between PBC and EHAIDs. The analysis using MR provides a strong and meaningful estimation of the bidirectional correlation between PBC and 7 EHAIDs: rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, autoimmune hypothyroidism, inflammatory bowel disease and ulcerative colitis of its types. In addition, PBC increases the risk of autoimmune thyroid diseases such as autoimmune hyperthyroidism and Graves' disease, as well as multiple sclerosis and psoriasis. Additionally, PBC is identified as a risk factor for Crohn's disease and Celiac disease. Based on genetic evidence, there may be connections between PBC and specific EHAIDs: not all coexisting EHAIDs induce PBC, and vice versa. This underscores the significance of prioritizing PBC in clinical practice. Additionally, if any liver function abnormalities are observed during treatment or with EHAIDs, it is crucial to consider the possibility of comorbid PBC. [ABSTRACT FROM AUTHOR]

The atmospheric variability in the tropics is primarily driven by convective heating. Observations revealed that convection in the tropics is organized into a hierarchy of multiscale convective systems ranging from the individual cloud cells to planetary scale disturbances that are nested within each other like Russian dolls. Current global climate models simulate very poorly these convectively coupled waves due in part to inadequate treatment of organized convection by the underlying cumulus parameterizations. Here, we present idealized simulations of convectively coupled equatorial waves (CCWs) using the weather research and forecast model in a horizontally limited domain consisting of a 4,500 km-wide square centered at the equator at moderate horizontal resolution of 10 km. We attempted and compared various configuration options, including switching on and off the cumulus parameterization (CP) and nesting a fine resolution 3.33 km domain, a 2,000 km-wide square, in the middle of the domain. It turns out that the results without a CP are much superior than those using a CP. While the cases without a CP resulted in a coherent eastward propagating CCW, which has many common features with observed convectively coupled Kelvin waves, the cumulus parameterization tends to destroy both the coherence of the propagating waves, even in the case with a nested domain, and reduces dramatically the variability. A primary demonstration on how such results could be used to show evidence of energy exchange, through momentum transport, between small-scale circulation due to mesoscale convection and the propagating synoptic scale wave will be reported is also presented. [ABSTRACT FROM AUTHOR]

In this paper, we employ the method of empirical likelihood to construct confidence intervals for a conditional quantile in the presence and absence of auxiliary information, respectively, for the left-truncation model. It is proved that the empirical likelihood ratio admits a limiting chi-square distribution with one degree of freedom when the lifetime observations with multivariate covariates form a stationary α-mixing sequence. For the problem of testing a hypothesis on the conditional quantile, it is shown that the asymptotic power of the test statistic based on the empirical likelihood ratio with the auxiliary information is larger than that of the one based on the standard empirical likelihood ratio. The finite sample performance of the empirical likelihood confidence intervals in the presence and absence of auxiliary information is investigated through simulations. [ABSTRACT FROM AUTHOR]

Water-soluble quantum dots (QDs) have shown potential as tumor diagnostic agents. However, little is known about their biological behaviors in vivo. Male ICR mice were intravenously given a single dose (2.5 μmol kg body weight) of water-soluble cadmium-telluride (CdTe) QDs (the QDs are approximately 4 nm in diameter and have maximal emission at 630 nm). Inductively coupled plasma mass spectrometry (ICP-MS) was used for measuring the kinetic action of Cd and Te for 7 days. The plasma kinetics of Cd and Te followed a two-compartment model, in which Cd exhibited greater apparent volume of distribution, greater clearance, faster distribution half-life, and significantly slower elimination half-life compared to Te. Contrary to its relatively transient fate in the plasma, high levels of Cd persisted in the liver and kidneys. Te accumulated primarily in the spleen. The different plasma kinetics and distribution patterns of Cd and Te imply that CdTe QDs have been part of the degradation or aggregation in vivo. [ABSTRACT FROM AUTHOR]

In this paper, we establish strong uniform convergence and asymptotic normality of the conditional quantile estimator for the censorship model when the data exhibit some kind of dependence. It is assumed that the observations form a stationary α-mixing sequence. The strong uniform convergence in iid framework has recently been discussed by Ould-Saïd (Stat Probab Lett 76:579-586, 2006). As a by-product, we also obtain a uniform weak convergence rate for the product-limit estimator of the lifetime and censoring distributions under dependence, which is interesting independently. [ABSTRACT FROM AUTHOR]

Enhanced cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation in renovascular hypertension. The study was to determine whether c-Src in paraventricular nucleus (PVN) is involved in the enhanced CSAR and sympathetic activation in hypertensive rats induced by two-kidney one-clip (2K1C). At the end of the fourth week after 2K1C surgery, renal sympathetic nerve activity (RSNA) was recorded in anesthetized rats with baroreceptor denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin. In the PVN, c-Src activity was higher in 2K1C rats than sham-operated (Sham) rats while c-Src expression was not. Epicardial application of capsaicin or PVN microinjection of angiotensin II (Ang II) increased c-Src activity more in 2K1C than Sham rats. PVN microinjection of selective Src family kinase inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazol [3,4-D] pyrimidine (PP2) or 2,3-Dihydro-N,N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1 H-indol-2-yl)methylene]-1 H-indole-5-sulfonamide (SU6656) abolished the CSAR and decreased RSNA more in 2K1C than Sham rats. The Ang II-induced RSNA and CSAR enhancement was abolished by PP2 or SU6656 pretreatment in 2K1C and Sham rats. NAD(P)H oxidase activity and superoxide anion level in PVN were higher in 2K1C rats, which was attenuated by PP2 but increased by epicardial application of capsaicin or PVN microinjection of Ang II. The effects of capsaicin or Ang II were abolished by PP2. These results indicate that c-Src in the PVN is involved in the enhanced CSAR and sympathetic activation in renovascular hypertension, and mediates the excitatory effects of Ang II in the PVN on the CSAR and sympathetic activity via NAD(P)H oxidase-derived generation of superoxide anions. [ABSTRACT FROM AUTHOR]

In this paper, we establish asymptotic normality of a new kernel estimator of the conditional mode function introduced by Ould-Saïd and Tatachak (C R Acad Sci Paris Ser I 344:651–656, 2007) for the left-truncation model when the data exhibit some kind of dependence. It is assumed that the lifetime observations with multivariate covariates form a stationary α-mixing sequence. [ABSTRACT FROM AUTHOR]

Abstract  Let {X j } be a strictly stationary sequence of negatively associated random variables with the marginal probability density function f(x). The recursive kernel estimators of f(x) are defined by $$\hat{f_n}(x)=\frac{1}{n\sqrt{b_n}}\sum^n_{j=1}b_j^{-\frac{1}{2}}K \left(\frac{x-X_j}{b_j}\right),\quad \tilde{f_n}(x)=\frac{1}{n}\sum^n_{j=1}\frac{1}{b_j}K \left(\frac{x-X_j}{b_j}\right)$$ and the Rosenblatt–Parzen’s kernel estimator of f(x) is defined by $${{f_n}(x)=\frac{1}{nb_n}\sum^n_{j=1} K(\frac{x-X_j}{b_n}), }$$ , where 0  b n → 0 are bandwidths and K is some kernel function. In this paper, we study the uniformly Berry–Esseen bounds for these estimators of f(x). In particular, by choice of the bandwidths, the Berry–Esseen bounds of the estimators attain $${O\left((\log n/n)^{1/6}\right)}$$ . [ABSTRACT FROM AUTHOR]

We present the general form of equations that generate a volume-preserving flow on a symplectic manifold ($\{\backslash cal\; M\}$,ω) via the highest Euler–Lagrange cohomology. It is shown that for every volume-preserving flow there are some 2-forms that play a similar role to the Hamiltonian in Hamilton mechanics. The ordinary canonical equations are included as a special case with a 2-form 1/(n - 1)Hω, where H is the corresponding Hamiltonian. [ABSTRACT FROM AUTHOR]

Introduction: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by inflammatory infiltration, and dysfunction of the salivary and lacrimal glands. This research aimed to explore the disease pathogenesis and improve the diagnosis and treatment of pSS by mining inflammation-associated biomarkers. Methods: Five pSS-related datasets were retrieved from the Gene Expression Omnibus (GEO) database. Inflammation-associated biomarkers were determined by the least absolute shrinkage and selection operator (LASSO) and support vector machines recursive feature elimination (SVM-RFE). Single sample gene set enrichment analysis (ssGSEA) was implemented to profile the infiltration levels of immune cells. Real-time quantitative PCR (RT-qPCR) verified the expression of biomarkers in clinical samples. Results: Four genes (LY6E, EIF2AK2, IL15, and CXCL10) were screened as inflammation-associated biomarkers in pSS, the predictive performance of which were determined among three pSS-related datasets (AUC > 0.7). Functional enrichment results suggested that the biomarkers were involved in immune and inflammation-related pathways. Immune infiltration analysis revealed that biomarkers were notably connected with type 2 T helper cells, regulatory T cells which were significantly expressed between pSS and control. TESTOSTERONE and CYCLOSPORINE were predicted to take effect by targeting CXCL10 and IL15 in pSS, respectively. Conclusion: Four inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were explored, and the underlying regulatory mechanisms and targeted drugs associated with these biomarkers were preliminarily investigated according to a series of bioinformatics methods based on the online datasets of pSS, which provided a reference for understanding the pathogenesis of pSS. Key Points • Inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were firstly identified in Sjögren's syndrome based on LASSO and SVM-RFE analyses. • CXCL10, EIF2AK2 and LY6E were prominently positively correlated with immature B cells, while IL15 were significantly negatively correlated with memory B cells in Sjögren's syndrome. • LY6E, EIF2AK2, IL15, and CXCL10 were significantly more highly expressed in clinical Sjögren's syndrome samples compared to healthy control samples, which was consistent with the analysis results of the GEO database. •LY6E, EIF2AK2, IL15, and CXCL10 might be used as the biomarkers for the treatment and diagnosis of Sjögren's syndrome. [ABSTRACT FROM AUTHOR]

Background: Developing biomarkers for early stage AD patients is crucial. Glucose metabolism measured by 18F-FDG PET is the most common biomarker for evaluating cellular energy metabolism to diagnose AD. Arterial spin labeling (ASL) MRI can potentially provide comparable diagnostic information to 18F-FDG PET in patients with neurodegenerative disorders. However, the conclusions about the diagnostic performance of AD are still controversial between 18F-FDG PET and ASL. This study aims to compare quantitative cerebral blood flow (CBF) and glucose metabolism measured by 18F-FDG PET diagnostic values in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using integrated PET/MR. Results: Analyses revealed overlapping between decreased regional rCBF and 18F-FDG PET SUVR in patients with AD compared with NC participants in the bilateral parietotemporal regions, frontal cortex, and cingulate cortex. Compared with NC participants, patients with aMCI exclusively demonstrated lower 18F-FDG PET SUVR in the bilateral temporal cortex, insula cortex, and inferior frontal cortex. Comparison of the rCBF in patients with aMCI and NC participants revealed no significant difference (P > 0.05). The ROC analysis of rCBF in the meta-ROI could diagnose patients with AD (AUC, 0.87) but not aMCI (AUC, 0.61). The specificity of diagnosing aMCI has been improved to 75.56% when combining rCBF and 18F-FDG PET SUVR. Conclusion: ASL could detect similar aberrant patterns of abnormalities compared to 18F-FDG PET in patients with AD compared with NC participants but not in aMCI. The diagnostic efficiency of 18F-FDG-PET for AD and aMCI patients remained higher to ASL. Our findings support that applying 18F-FDG PET may be preferable for diagnosing AD and aMCI. Key points: Hypometabolic brain areas are more widespread in patients with AD and aMCI than hypoperfused brain areas. 18F-FDG PET provides superior diagnostic performance over ASL for patients with AD and aMCI. After comprehensive consideration, PET alone is recommended for the diagnosis of AD and aMCI patients. [ABSTRACT FROM AUTHOR]

Background: The pink-color sign (PCS) has been widely used for diagnosing esophageal squamous cell carcinoma (ESCC) during Lugol's iodine chromoendoscopy. However, the identification of the PCS only relies on the subjective assessments made by the endoscopist, which could lead to bias and disagreement. Previous research has indicated that the V′ variable can, as an objective index, define the PCS in the LU′V′ color space. We aimed to validate the diagnostic performance of the PCS defined by the V′ variable alone and attempt to improve the diagnostic performance by combining the V′ and U′ variables. Methods: We re-examined 231 subjects with Lugol's unstained lesions (LULs) from a previously reported prospective trial. The diagnostic performance of the method using V′ variable alone (V′ alone method), the combination method using V′ and U′ variables (V′ + U′ method), and the endoscopists were calculated and compared. Results: A total of 236 LULs were included, among which 46 were histologically confirmed to be cancerous lesions. The sensitivity, specificity, and accuracy of the V′ alone method were 73.91% (95% CI 58.87–85.73%), 79.47% (95% CI 73.03–84.98%), and 78.39% (95% CI 72.59–83.47%) in the external validation cohort, respectively. It is inferior to endoscopists in terms of specificity and accuracy. The V′ + U′ method demonstrated a diagnostic performance comparable to the experienced endoscopists, with sensitivity, specificity, and accuracy of 76.74% (95% CI 61.37–88.25%), 88.64% (95% CI 83.00–92.92%), and 86.30% (95% CI 81.03–90.56%), respectively. Conclusion: The V′ alone method exhibited lower specificity and accuracy than the experienced endoscopist and the V′ + U′ method. However, the modified V′ + U′ method demonstrated a diagnostic performance comparable to experienced endoscopists. Utilizing the objective index of the PCS could provide valuable support in clinical decision-making. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) can be decomposed into various fragments, including negative/positive charges, Zn+ or Cu2+ when used as drug delivery materials. To evaluate the safety of MOFs, different mechanisms of intermolecular proton-transfer in guanine-cytosine (GC) base pair under the influence of such fragments were investigated by density functional theory methods. In a vacuum, calculation results show that an excess electron assists proton transfer in the anionic GC radical, and a hole assists proton transfer in the cationic GC radical with small energy barriers. The mechanism for Zn+-GC transfer is that the located hole assists proton transfer from G to C. All proton-transfers of Cu2+-GC become spontaneous with stable proton-transferred structures, and the driving force is the Cu2+ due to its electrostatic and oxidative effects. However, in a micro-water environment, the average energy barrier of all proton-transfer processes increases by 2.8 kcal mol−1 because of the redistribution of charges. Water molecules play a very important role in buffering, and the influence of fragments on intermolecular proton-transfer processes of GC is reduced. [ABSTRACT FROM AUTHOR]

As part of our ongoing search for novel therapeutic structures from microorganism, the chemical examination of marine fungus Phoma sp. resulted in the isolation of ergosterol, ergosterol peroxide (EP), and 9,11-dehydroergosterol peroxide (DEP). The bioassay results demonstrated that the three isolates reduced the viability of various cancer cells, with EP being highest in human lung cancer cell line A549 cells. EP induced caspase-dependent apoptosis through mitochondrial damage in A549 cells. Additionally, EP-induced ROS generation and apoptosis were attenuated by ROS-generating enzymes inhibitors and antioxidant N-acetylcysteine, indicated that ROS played an important role in EP-mediated apoptosis in A549 cells. Furthermore, it was observed that EP induced ROS-dependent autophagy, which attenuated apoptosis in A549 cells. On the other hand, EP reduced the LPS/ATP-induced proliferation and migration of A549 cells through attenuated NLRP3 inflammasome activity. Additionally, EP showed synergistic cytotoxic effect with antitumor drug Sorafenib in A549 cell viability inhibition. Furthermore, Micro-Western Array and Western blot analyses demonstrated that the protein levels of EGFR, HSP27, MEK5, AKT1, mTOR, Smad2, Smad3, TAB1, NF-κB, and HIF1-α decreased, while the levels of p-p38α, p-ERK1/2, p-JNK, fibronectin and p27 increased. Collectively, the results of this study demonstrated that EP might be useful to develop a therapeutic candidate for lung cancer complications. [ABSTRACT FROM AUTHOR]

We developed a dual-modal colorimetric and photothermal assay for glutathione (GSH) using MnO2 nanosheets prepared with environmentally friendly materials. The nanosheets were synthesized by using ascorbic acid present abundantly in lemon and orange juices to reduce KMnO4. The as-prepared MnO2 nanosheets display oxidase-like activity and can catalyze the oxidation reaction of 3,3′,5,5′-tetramethylbenzidine (TMB), yielding a blue oxidative product (oxTMB) that exhibits a UV–Vis absorption peak at 652 nm. In the presence of GSH, the MnO2 nanosheets are reduced and decomposed, resulting in a decrease in the peak intensity. The colorimetric assay offers a wide dynamic range (0.1–100 μM) and a detection limit of 100 nM. The MnO2 nanosheets are also efficient in converting photoenergy to thermal energy, with a photothermal conversion efficiency of 23.3%. The temperature change, after near-infrared (NIR) irradiation at 808 nm, can be easily measured by an inexpensive pen-type thermometer. This effect can also be used for GSH quantification and expands the GSH concentration detection to the range from 6.0 to 200 μM. The viability of our dual-modal assay for clinical applications was demonstrated with successful analyses of GSH in human serum samples. [ABSTRACT FROM AUTHOR]

Small cell base stations (SBSs) are being developed as a way of expanding the coverage of cellular networks. However, the power consumption of small cell networks has become an acute problem. To mitigate this problem, we propose a new power-saving scheme based on coordinate multi-point (CoMP) transmission for densely deployed small cell networks. This scheme turns off lightly loaded SBSs and switches their users to the cooperative clusters formed by their neighbor SBSs. The cooperative clusters adopt the virtual multiple-input multiple-output (MIMO) technology to serve the users in the switched-off SBSs. To achieve high power-efficiency, we first model the power consumption of all the SBSs by considering the quality of service of users in the switched-off SBSs and then provide in-depth proofs and analysis according to characteristics of small cell networks. Our extensive simulation results show that the proposed algorithm improves system power-saving efficiency significantly. [ABSTRACT FROM AUTHOR]

Complex brain circuitry with feedforward and feedback systems regulates neuronal activity, enabling neural networks to process and drive the entire spectrum of cognitive, behavioral, sensory, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits is underpinned by hundreds of synaptic adhesion molecules that span synaptic junctions. Dysfunction of a single molecule or molecular interaction at synapses can lead to disrupted circuit activity and brain disorders. Neuroligins, a family of cell adhesion molecules, were first identified as postsynaptic-binding partners of presynaptic neurexins and are essential for synapse specification and maturation. Here, we review recent advances in our understanding of how this family of adhesion molecules controls neuronal circuit assembly by acting in a synapse-specific manner. [ABSTRACT FROM AUTHOR]

Minimal hepatic encephalopathy (MHE), which shows mild cognitive impairment, is a subtle complication of cirrhosis that has been shown to affect daily functioning and quality of life. However, until 2014, relevant guidelines do not give much attention to the diagnosis and treatment of MHE, resulting in patients being ignored and denied the benefits of treatment. In this review, we summarize recent cognition-based research about (1) alteration of nerve cells, including astrocytes, microglial cells and neurons, in mild cognitive impairment in MHE; (2) comparison of methods in detecting cognitive impairment in MHE; and (3) comparison of methods for therapy of cognitive impairment in MHE. We hope to provide information about diagnosis and treatment of cognitive impairment in patients with MHE. [ABSTRACT FROM AUTHOR]

Background: Endoscopic resection (ER) is widely applied to treat early colorectal cancer (CRC). Predicting the invasion depth of early CRC is critical in determining treatment strategies. The use of computer-aided diagnosis (CAD) algorithms could theoretically make accurate and objective predictions regarding the suitability of lesions for ER indication based on invasion depth. This study aimed to assess diagnostic test accuracy of CAD algorithms in predicting the invasion depth of early CRC and to compare the performance between the CAD algorithms and endoscopists. Methods: Multiple databases were searched until June 30, 2022 for studies that evaluated the diagnostic performance of CAD algorithms for invasion depth of CRC. Meta-analysis of diagnostic test accuracy using a bivariate mixed-effects model was performed. Results: Ten studies consisting of 13 arms (13,918 images from 1472 lesions) were included. Due to significant heterogeneity, studies were stratified into Japan/Korea-based or China-based studies. For the former, the area under the curve (AUC), sensitivity, and specificity of the CAD algorithms were 0.89 (95% CI 0.86–0.91), 62% (95% CI 50–72%), and 96% (95% CI 93–98%), respectively. For the latter, AUC, sensitivity, and specificity were 0.94 (95% CI 0.92–0.96), 88% (95% CI 78–94%), and 88% (95% CI 80–93%), respectively. The performance of the CAD algorithms in Japan/Korea-based studies was not significantly different from that of all endoscopists (0.88 vs. 0.91, P = 0.10) but was inferior to that of expert endoscopists (0.88 vs. 0.92, P = 0.03). The performance of the CAD algorithms in China-based studies was better than that of all endoscopists (0.94 vs. 0.90, P = 0.01). Conclusion: The CAD algorithms showed comparable accuracy for prediction of invasion depth of early CRC compared to all endoscopists, which was still lower than expert endoscopists in diagnostic accuracy; more improvements should be achieved before it can be extensively applied to clinical practice. [ABSTRACT FROM AUTHOR]