Search

This study aimed to determine whether the prevalence of thyroid nodules (TNs) increased due to modern lifestyles or other factors, despite the advances in screening and diagnostic tools.This study included 3474 pairs of participants, who were matched by gender and age (±3 years) from two cross-sectional sampling surveys: (1) the program on the iodine nutritional status and related health status of residents in Shanghai in 2009; (2) the thyroid disease screening program for adults in Shanghai between 2017 and 2018. The prevalence of TNs and thyroid diseases in 2009 and 2017-2018 were compared, and the potential risk factors of TNs were detected.The prevalence of TNs in 2009 was 28.9%: 22.5% in males and 34.5% in females. In 2017, this increased to 43.8%: 37.9% in males and 49.1% in females. The prevalence of TNs significantly increased from 2009 to 2017 (odds ratio, 1.486; 95% confidence interval, 1.238-1.786). In addition, female gender, thyroid disease history, and age were the main risk factors for TNs after adjusting for confounders in the logistic regression across the time period.The prevalence of TNs significantly increased across nearly 10 years in Shanghai.

Traditional denitrification often produces high operating costs and excessive sludge disposal expenses due to conventional carbon sources. A novel electric-magnetic field (MF) 48 mT with Fe

To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS).The relevant studies were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Collaboration Database up to May 2022. Cardiovascular and cerebrovascular events were chosen to evaluate the efficacy of antiplatelet therapy for secondary prevention. Loop-specific approach and node-splitting analysis were used to evaluate consistency and inconsistency, respectively. The value of the surface under the cumulative ranking (SUCRA) was calculated and ranked. Funnel-plot symmetry was used to evaluate publication bias. The meta-analysis was performed by using STATA 16.0.Thirteen studies with a total of 33,011 subjects were included in this network meta-analysis. Compared with placebo, aspirin, clopidogrel, cilostazol, ticlopidine, aspirin plus dipyridamole, and aspirin plus clopidogrel were associated with reducing cardiovascular and cerebrovascular events. The SUCRA estimated relative ranking of treatments showed that cilostazol may be the most effective (RR 0.56, 95% CI 0.42-0.74, SUCRA 95.8). No significant inconsistency or publication bias was found in the study.This meta-analysis suggests that cilostazol may be a priority option for secondary prevention of patients with LS. These findings still need further study in the future.

Saline-alkalisation of the soil environment and microorganism is a global challenge. However, relevant studies on the effects of saline-alkali stress on soil bacterial communities are limited. In this study, we investigated the effects of saline-alkali stress on the carbon source metabolic utilisation of the microbial community, bacterial diversity, and composition in soil using Biolog Ecoplate and 16S rRNA gene amplicon sequencing. Biolog Ecoplate results showed that saline-alkali stress decreased the metabolic activity and functional diversity, and changed the utilisation characteristics of carbon sources in soil microorganisms. Particularly, high level of saline-alkali stress significantly decreased the utilisation of carbohydrates and amino acids carbon sources. The results of 16S rRNA gene amplicon sequencing showed that high level of saline-alkali stress significantly reduced the diversity of soil bacterial communities. In addition, high level of saline-alkali stress significantly decreased the relative abundances of some key bacterial taxa, such as Gemmatimonas, Sphingomonas, and Bradyrhizobium. Furthermore, as saline-alkali content increased, the soil catalase, protease, urease, and sucrase activities also significantly decreased. Collectively, these results provide new insight for studies on the changes in the soil bacterial community and soil enzyme activity under saline-alkali stress.

Pathogenic large inversions are rarely reported on DMD gene due to the lack of effective detection methods. Here we report two DMD pedigrees and proposed a reliable pipeline to define large inversions in DMD patients. In the first pedigree, conventional approaches including multiplex ligation-dependent probe amplification, and whole-exome sequencing by next generation sequencing were failed to detect any pathologic variant. Then an advanced analysis pipeline which consists of RNA-seq, cDNA array capture sequencing, optical mapping, long-read sequencing was built. RNA-seq and cDNA capture sequencing showed a complete absence of transcripts of exons 3-55. Optical mapping identified a 55 Mb pericentric inversion between Xp21 and Xq21. Subsequently, long-read sequencing and Sanger sequencing determined the inversion breakpoints at 32,915,769 and 87,989,324 of the X chromosomes. In the second pedigree, long-read sequencing was directly conducted and Sanger sequencing was performed to verify the mutation. Long-read sequencing and Sanger sequencing found breakpoints at 32,581,576 and 127,797,236 on DMD gene directly. In conclusion, large inversion might be a rare but important mutation type in DMD gene. An effective pipeline was built in detecting large inversion mutations based on long-read sequencing platforms.

Long non-coding RNAs (lncRNAs) have been confirmed to be involved in epilepsy development. It has been reported that lncRNA ZFAS1 plays a vital regulatory role in epilepsy progression. Therefore, the role and molecular mechanism of ZFAS1 in epilepsy progression deserve further investigation. Mice status epilepticus (SE) model was constructed, and hippocampal neurons were isolated from mice hippocampus tissues. The expression of ZFAS1, miR-15a-5p and oxidative stress responsive 1 (OXSR1) were determined by quantitative real-time PCR. ELISA assay was used to detect the concentrations of inflammation factors. Cell viability and apoptosis were examined by MTT assay, EdU staining and flow cytometry. Western blot analysis was conducted to measure protein levels, and the productions of SOD and MDA were measured to assess cell oxidative stress. Dual-luciferase reporter assay and RIP assay were employed to validate the relationship between miR-15a-5p and ZFAS1 or OXSR1. LncRNA ZFAS1 was highly expressed in SE mice and SE-stimulated hippocampal neurons. Silenced ZFAS1 promoted viability, while inhibited inflammation, apoptosis and oxidative stress in SE-induced hippocampal neurons. MiR-15a-5p could be targeted by ZFAS1, and its inhibitor also reversed the suppressive effect of ZFAS1 knockdown on SE-induced hippocampal neurons injury. In addition, OXSR1 was a target of miR-15a-5p, and its silencing also could relieve SE-induced hippocampal neurons injury. OXSR1 overexpression reversed the inhibition effect of miR-15a-5p on SE-induced hippocampal neurons injury. Moreover, ZFAS1 positively regulated OXSR1 expression by sponging miR-15a-5p, thereby activating the NF-κB pathway. LncRNA ZFAS1 might contribute to the progression of epilepsy by regulating the miR-15a-5p/OXSR1/NF-κB pathway.

This paper studies several solution paths of sparse quadratic minimization problems as a function of the weighing parameter of the bi-objective of estimation loss versus solution sparsity. Three such paths are considered: the “$$\ell _0$$ ℓ 0 -path” where the discontinuous $$\ell _0$$ ℓ 0 -function provides the exact sparsity count; the “$$\ell _1$$ ℓ 1 -path” where the $$\ell _1$$ ℓ 1 -function provides a convex surrogate of sparsity count; and the “capped $$\ell _1$$ ℓ 1 -path” where the nonconvex nondifferentiable capped $$\ell _1$$ ℓ 1 -function aims to enhance the $$\ell _1$$ ℓ 1 -approximation. Serving different purposes, each of these three formulations is different from each other, both analytically and computationally. Our results deepen the understanding of (old and new) properties of the associated paths, highlight the pros, cons, and tradeoffs of these sparse optimization models, and provide numerical evidence to support the practical superiority of the capped $$\ell _1$$ ℓ 1 -path. Our study of the capped $$\ell _1$$ ℓ 1 -path is interesting in its own right as the path pertains to computable directionally stationary (= strongly locally minimizing in this context, as opposed to globally optimal) solutions of a parametric nonconvex nondifferentiable optimization problem. Motivated by classical parametric quadratic programming theory and reinforced by modern statistical learning studies, both casting an exponential perspective in fully describing such solution paths, we also aim to address the question of whether some of them can be fully traced in strongly polynomial time in the problem dimensions. A major conclusion of this paper is that a path of directional stationary solutions of the capped $$\ell _1$$ ℓ 1 -regularized problem offers interesting theoretical properties and practical compromise between the $$\ell _0$$ ℓ 0 -path and the $$\ell _1$$ ℓ 1 -path. Indeed, while the $$\ell _0$$ ℓ 0 -path is computationally prohibitive and greatly handicapped by the repeated solution of mixed-integer nonlinear programs, the quality of $$\ell _1$$ ℓ 1 -path, in terms of the two criteria—loss and sparsity—in the estimation objective, is inferior to the capped $$\ell _1$$ ℓ 1 -path; the latter can be obtained efficiently by a combination of a parametric pivoting-like scheme supplemented by an algorithm that takes advantage of the Z-matrix structure of the loss function.

When granular assemblies are subject to external loads or displacements, particles interact with each other through contact and may exhibit translations and rotations. From a micromechanical perspective, particle rotations are an essential mechanism influencing the macroscopic behavior of granular materials. In this study, biaxial shearing tests were conducted on assemblies of dual-sized circular particles at different confining pressures. A high-precision image analysis method was developed to extract the particle-level motion of all the particles, including the rotational behavior. Experimental results showed that most of the particles exhibited rotations. Particles within the shear band exhibited more significant rotations and were characterized by low connectivity (number of contacts per particle). In contrast, the particles outside the shear band rotated lesser, only in the beginning stage of shearing. Every rotation in either direction is accompanied by an opposite rotation of almost the same magnitude in the neighboring region, and rotation clusters have been observed. Rotations in both directions are normally distributed within the assembly, and the average particle rotation is zero. The average rotations in both directions evolve symmetrically with major principal strain. Generally, the rotation rate (degrees per incremental strain) is observed to be maximum at the start of the shearing, and gradually it becomes constant toward the end of the shearing. The average value of the absolute cumulative rotation observed for whole particles is 18.6° at the end of shearing, i.e., 20% deviatoric strain. Smaller size particles tend to exhibit 67% higher rotations than bigger particles. Confining pressures have no significant effect on the rotational behavior of circular particles.

Visual tracking of generic objects is one of the fundamental but challenging problems in computer vision. Here, we propose a novel fully convolutional Siamese network to solve visual tracking by directly predicting the target bounding box in an end-to-end manner. We first reformulate the visual tracking task as two subproblems: a classification problem for pixel category prediction and a regression task for object status estimation at this pixel. With this decomposition, we design a simple yet effective Siamese architecture based classification and regression framework, termed SiamCAR, which consists of two subnetworks: a Siamese subnetwork for feature extraction and a classification-regression subnetwork for direct bounding box prediction. Since the proposed framework is both proposal- and anchor-free, SiamCAR can avoid the tedious hyper-parameter tuning of anchors, considerably simplifying the training. To demonstrate that a much simpler tracking framework can achieve superior tracking results, we conduct extensive experiments and comparisons with state-of-the-art trackers on a few challenging benchmarks. Without bells and whistles, SiamCAR achieves leading performance with a real-time speed. Furthermore, the ablation study validates that the proposed framework is effective with various backbone networks, and can benefit from deeper networks. Code is available at https://github.com/ohhhyeahhh/SiamCAR.

Nanomaterials-based photoluminescence thermometry (PLT) is a new contact-free photonic approach for temperature sensing, important for applications ranging from quantum technology to biomedical imaging and diagnostics. Even though numerous new materials have been explored, great challenges and deficiencies remain that hamper many applications. In contrast to most of the existing approaches that use large ensembles of rare-earth-doped nanomaterials with large volumes and unavoidable inhomogeneity, we demonstrate the ultimate size reduction and simplicity of PLT by using only a single erbium-chloride-silicate (ECS) nanowire. Importantly, we propose and demonstrate a novel strategy that contains a self-optimization or “smart” procedure to automatically identify the best PL intensity ratio for temperature sensing. The automated procedure is used to self-optimize key sensing metrics, such as sensitivity, precision, or resolution to achieve an all-around superior PLT including several record-setting metrics including the first sensitivity exceeding 100% K−1 (~138% K−1), the highest resolution of 0.01 K, and the largest range of sensible temperatures 4–500 K operating completely within 1500–1800 nm (an important biological window). The high-quality ECS nanowire enables the use of well-resolved Stark-sublevels to construct a series of PL intensity ratios for optimization in infrared, allowing the completely Boltzmann-based sensing at cryogenic temperature for the first time. Our single-nanowire PLT and the proposed optimization strategy overcome many existing challenges and could fundamentally impact PL nano-thermometry and related applications such as single-cell thermometry.

Background To compare the intraocular lens (IOL) tilt and decentration and visual outcomes of transscleral sutured IOL fixation and sutureless flanged IOL fixation. To investigate the influence of IOL tilt and decentration on internal higher-order aberrations (HOAs) in these two techniques. Methods Patients who received transscleral sutured or sutureless flanged IOL fixation procedures were included in this prospective, non-randomized, comparative study. Corrected distance visual acuity (CDVA) was measured at baseline and at every postoperative visit for 12 months. IOL tilt and decentration were measured using a second-generation anterior segment optical coherence tomography (Casia2) and internal HOAs were measured using iTrace Visual Function Analyzer at 3 months postoperatively. Results The study included 27 eyes from the transscleral sutured IOL fixation group and 26 eyes from the sutureless flanged IOL fixation group. There was no significant difference in CDVA between the two groups at all time points. The two groups did not differ in refractive difference from the predicted value, corneal endothelial cell loss, IOL tilt, IOL decentration, internal astigmatism or internal HOAs. Vertical IOL decentration significantly correlated with total internal optical aberration (r = 0.288, P = 0.036), total internal HOA (r = 0.440, P = 0.001), internal coma (r = 0.348, P = 0.001), vertical internal coma (r = 0.388, P = 0.004), average height of modulation transfer function (r = − 0.364, P = 0.007) and Strehl ratio (r = − 0.297, P = 0.031). Horizontal IOL decentration significantly correlated with horizontal internal coma (r = 0.312, P = 0.023). Conclusions Transscleral sutured IOL fixation and sutureless flanged IOL fixation had similar IOL positions and visual outcomes. IOL decentrations correlated with internal HOAs and thus should be avoided.

MicroRNA-1290 (miR-1290) has been reported to be involved in many diseases and play a key role during the development process. However, the role of miR-1290 in atherosclerosis (AS) is still unclear. The current study showed that the expressions of miR-1290 were high in serum of patients with hyperlipidemia. The functional role of miR-1290 were then investigated in human umbilical vein endothelial cells (HUVECs). Here, we found that miR-1290 expressions were notably enhanced in HUVECs mediated by IL-8. miR-1290 inhibitor repressed monocytic THP-1 cells adhesion to HUVECs by regulating ICAM-1 and VCAM-1, inhibited proliferation through regulating cyclinD1 and PCNA, and inhibited inflammatory response by regulating IL-1β. Mechanistically, we verified that miR-1290 mimic was able to directly target the 3′-UTR of GSK-3β mRNA using luciferase reporter assay. Knockdown of GSK-3β (si-GSK-3β) promoted HUVECs adhesion and the expression of IL-1β, and partially restore the depression effect of miR-1290 inhibitor on HUVECs adhesion and inflammation. In contrast, si-GSK-3β inhibited the proliferation of HUVECs and the expression of cyclinD1 and PCNA. In summary, our study revealed that miR-1290 promotes IL-8-mediated the adhesion of HUVECs by targeting GSK-3β. However, GSK-3β is not the target protein for miR-1290 to regulate the proliferation of HUVECs. Our findings may provide potential target in atherosclerosis treatment.

OBJECTIVE We aim to investigate blood-brain barrier (BBB) dysfunction and myelin basic protein (MBP) in amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD) and further determine the effect of these factors on the survival of ALS. METHODS This was a retrospective study of 113 ALS patients, 12 ALS-FTD patients, and 40 disease controls hospitalized between September 2013 and October 2020. CSF parameters including total protein (TP), albumin (Alb), immunoglobulin-G (IgG), and MBP were collected and compared between groups. The CSF-TP, CSF-Alb, CSF-IgG, and CSF/serum quotients of Alb and IgG (QAlb, QIgG) were used to reflect the BBB status. Patients were followed up until December 2020. Cox regression and Kaplan-Meier method were used for survival analysis. RESULTS The CSF-TP, CSF-Alb, and CSF-IgG concentrations were significantly higher in patients than controls (p

This paper re-validates middle school students’ learning progression of the concept of buoyancy (Gao et al., 2020) by using two-time point data. The previous study developed a four-level learning progression based on data collected at a single time point using cross-sectional design. This single-time-point model of learning progression calls for a further validation through a longitudinal design focusing on changes in individual students as a result of targeted instruction. In this study, 91 eighth-grade students first learned buoyancy under a traditional pedagogy and took test A of buoyancy. Based on results of test A, the teacher provided a targeted remediation instruction to students. Students then took a second test B which was designed as a parallel instrument to test A. Latent class analysis was conducted to locate students’ levels in the learning progression, and a rule space model was employed to diagnose students’ concept mastery patterns at each level. The test A data provide evidence to support the original learning progression of buoyancy developed by Gao et al. (2020), but the test B data suggest two more additional progression sub-levels for the prior study. Together, our findings indicate that one-time point data under the current status quo of teaching might be insufficient to accurately depict pathways of scientific thinking for how students progress from the lower anchor to the upper anchor. We thus argue that it is essential to involve well-designed instruction and collect multi-time-point data that could portray alternative pathways in students’ learning progression.

Deoxynivalenol (DON) is synthesized by Fusarium species that frequently infect crops during storage, and it’s harm risk to human is reflected in the consumption of infected food crops or indirectly through foods of animal origin. In this study, Hela and Chang liver cells were used to research the cellular apoptosis induced by deoxynivalenol. Cells were treated by DON toxin with a series of concentration and incubated for different time. MTT, fluorescence microscope, flow cytometer and Western blot methods were used to analyze the effect of DON on the cell apoptosis in vitro and in vivo systematically. The results showed that DON was toxic to the cells tested. After being treated by DON, the morphology of Chang livers and Hela cells changed significantly. The DON promoted apoptosis in a dose- and time-dependent manner. The activity of Caspase 3 was significantly increased in DON-induced apoptosis. Moreover, endogenous Glutathione (GSH) level in these cell lines was gradually decreased. In the early apoptosis progress, oxidative stress was induced by DON. When DON reached 10 µg/mL, a markedly increased content of Malondialdehyde (MDA) was detected in both Hela and Chang liver cells. Furthermore, an in vivo test indicated that DON had toxicity to mice by causing weight loss and swollen spleen, and significantly increased expression of AST and ALT. In conclusion, the DON was toxic to mice and could induce the apoptosis of tested cells undergoing a Caspase-3 related pathway.

In this paper, we provide some gentle introductions to the recent advance in augmented Lagrangian methods for solving large-scale convex matrix optimization problems (cMOP). Specifically, we reviewed two types of sufficient conditions for ensuring the quadratic growth conditions of a class of constrained convex matrix optimization problems regularized by nonsmooth spectral functions. Under a mild quadratic growth condition on the dual of cMOP, we further discussed the R-superlinear convergence of the Karush–Kuhn–Tucker (KKT) residuals of the sequence generated by the augmented Lagrangian methods (ALM) for solving convex matrix optimization problems. Implementation details of the ALM for solving core convex matrix optimization problems are also provided.

Convex programming based robust optimization is an active research topic in the past two decades, partially because of its computational tractability for many classes of optimization problems and uncertainty sets. However, many problems arising from modern operations research and statistical learning applications are nonconvex even in the nominal case, let alone their robust counterpart. In this paper, we introduce a systematic approach for tackling the nonconvexity of the robust optimization problems that is usually coupled with the nonsmoothness of the objective function brought by the worst-case value function. A majorization-minimization algorithm is presented to solve the penalized min-max formulation of the robustified problem that deterministically generates a “better” solution compared with the starting point (that is usually chosen as an unrobustfied optimal solution). A generalized saddle-point theorem regarding the directional stationarity is established and a game-theoretic interpretation of the computed solutions is provided. Numerical experiments show that the computed solutions of the nonconvex robust optimization problems are less sensitive to the data perturbation compared with the unrobustfied ones.

The purpose of this case study is to demonstrate how to utilize machine learning approaches to analyze student process data for validating and informing digital game-based assessments (DGBAs) with an evidence-centered game design (ECgD). The first analysis was conducted to examine whether students’ mastery of the overall skill required by the game can be well predicted by task-related behavioral features and if the selected key features map onto the evidence model of the ECgD. Specifically, we extracted 27 behavioral features as the indicators of students’ gameplay activities from the evidence trace files and modelled them using a machine learning algorithm—support vector machine with recursive feature elimination—to identify the key features for prediction. The key features were in turn used to predict students’ mastery of the overall skill. Results showed that students’ retry attempts on two assessment tasks were found to be most influential for prediction with a moderate to high training and testing accuracy. The second analysis was conducted to examine whether the number of learning opportunities is sufficient for evaluating students’ mastery of the overall skill as well as determine the optimal number of learning opportunities for evaluation. The approach of long short-term memory networks was used to model students’ time-series behavioral features across multiple learning opportunities for predicting their acquisition of the overall skill. Results suggested that five learning opportunities were a good balance between evaluation accuracy and practical feasibility, and they were sufficient for evaluating students’ mastery of the overall skill given the DGGA tasks.

The biological function of miRNA (miR)-424-5p in glioma has not been clarified. This study was to explore the roles of miR-424-5p/Bifunctional apoptosis regulator (BFAR) axis in glioma. Ninety-six pairs of human glioma tissues and their adjacent non-cancer tissues were collected. The levels of BFAR and miR-424-5p were detected by quantitative polymerase chain reaction (qPCR) in glioma tissues and cell lines. Moreover, the biological roles of miR-424-5p and BFAR in glioma cells were assessed. We found a miR-424-5p binding site in the 3’UTR of BFAR by using TargetScan 7.2 online database. The miR-424-5p level was dramatically decreased in glioma tissues and cell lines, and the BFAR expression was significantly increased. The BFAR expression was negatively related to the miR-424-5p level in glioma tissues. Compared to patients with high miR-424-5p levels in glioma tissues, patients with low miR-424-5p levels had significantly lower survival rate (χ2 = 13.728 and P

The present study aimed to investigate the effects of miR-504 in cervical cancer. Normal and cervical cancer tissue specimens derived from TCGA and GTEx databases were employed to analyze the miR-504 and PAICS (one of potential target gene of miR-504) expression. Kaplan–Meier strategy was applied to analyze the prognostic powers of miR-504 and PAICS. The proliferation, clonogenic ability, invasion, and migration of cervical cancer cells (C-33A and HeLa) were detected using Cell Counting Kit 8, colony formation, and transwell assays. Pearson correlation analysis was used to assess the correlation between miR-504 and PAICS, which was confirmed using luciferase reporter assay. The mRNA and protein levels were detected by qRT-PCR and western blot, respectively. TCGA data revealed that miR-504 expression might be decreased in cervical cancer, which was correlated with unfavorable prognosis. Further experiments exhibited that abnormal miR-504 expression negatively affected malignant cellular behaviors in cervical cancer, including proliferation, colony formation, invasion, and migration. PAICS was identified as a putative target of miR-504, and negatively related with miR-504 expression. PAICS expression was increased in cervical cancer and its high-regulation-induced worse outcomes of patients with cervical cancer. Rescue experiments indicated that PAICS restricted the impacts of miR-504 in cervical cancer cells. Analysis of western blot suggested that overexpression of PAICS overturned the miR-504-induced EMT inactivation. Our observations elucidated that miR-504, acting as a suppressor for the progression of cervical cancer, inhibits cell proliferation, invasion and migration, and mediates EMT via negatively regulating PAICS.

Cancer recurrence after surgery remains an unresolved clinical problem1–3. Myeloid cells derived from bone marrow contribute to the formation of the premetastatic microenvironment, which is required for disseminating tumour cells to engraft distant sites4–6. There are currently no effective interventions that prevent the formation of the premetastatic microenvironment6,7. Here we show that, after surgical removal of primary lung, breast and oesophageal cancers, low-dose adjuvant epigenetic therapy disrupts the premetastatic microenvironment and inhibits both the formation and growth of lung metastases through its selective effect on myeloid-derived suppressor cells (MDSCs). In mouse models of pulmonary metastases, MDSCs are key factors in the formation of the premetastatic microenvironment after resection of primary tumours. Adjuvant epigenetic therapy that uses low-dose DNA methyltransferase and histone deacetylase inhibitors, 5-azacytidine and entinostat, disrupts the premetastatic niche by inhibiting the trafficking of MDSCs through the downregulation of CCR2 and CXCR2, and by promoting MDSC differentiation into a more-interstitial macrophage-like phenotype. A decreased accumulation of MDSCs in the premetastatic lung produces longer periods of disease-free survival and increased overall survival, compared with chemotherapy. Our data demonstrate that, even after removal of the primary tumour, MDSCs contribute to the development of premetastatic niches and settlement of residual tumour cells. A combination of low-dose adjuvant epigenetic modifiers that disrupts this premetastatic microenvironment and inhibits metastases may permit an adjuvant approach to cancer therapy. In mouse models of pulmonary metastasis, adjuvant epigenetic therapy targeting myeloid-derived suppressor cells disrupts the premetastatic microenvironment after resection of primary tumours and inhibits the dissemination of residual tumour cells.

This study aimed at developing a radiomics signature (R score) as prognostic biomarkers based on penumbra quantification and to validate the radiomics nomogram to predict the clinical outcomes for thrombolysis for acute ischemic stroke (AIS) patients. In total, 168 patients collected from seven centers were retrospectively included. A score of mismatch was defined as MIS. Based on a short-term clinical label, 456 radiomics features were evaluated with feature selection methods. R score was constructed with the selected features. To compare the predictive capabilities of the clinical factors, MIS, and R score, three nomograms were developed and evaluated, according to the short-term clinical assessment on day 7. Finally, the radiomics nomogram was validated by predicting the 3-month clinical outcomes of AIS patients, in an external cohort. R scores were found to be significantly higher in patients with favorable clinical outcomes in both training and validation datasets. The predictive value of the radiomics nomogram estimating favorable clinical outcomes was modest, with a concordance index (C-index) of 0.695 [95% confidence interval (CI) 0.667–0.723) in an external validation dataset. In addition, the area under curve (AUC) of the radiomics nomogram predicting favorable clinical outcome reached 0.886 (95% CI 0.809–0.963) on day 7 and 0.777 (95% CI 0.666–0.888) at 3 months. The radiomics signature is an independent biomarker for estimating the clinical outcomes in AIS patients. By improving the individualized prediction of the clinical outcome for AIS patients 3 months after onset, the radiomics nomogram adds more value to the current clinical decision-making process.

Pulmonary manifestations are common in patients with primary immunodeficiency disorders (PIDs) but the prevalence, specific diseases, and their patterns are not well characterized. We conducted a retrospective analysis of pulmonary diseases reported in the database of the United States Immunodeficiency Network (USIDNET), a program of the Immune Deficiency Foundation. PIDs were categorized into 10 groups and their demographics, pulmonary diagnoses and procedures, infections, prophylaxis regimens, and laboratory findings were analyzed. A total of 1937 patients with various PIDs (39.3% of total patients, 49.6% male, average age 37.9 years (SD = 22.4 years)) were noted to have a pulmonary disease comorbidity. Pulmonary diseases were categorized into broad categories: airway (86.8%), parenchymal (18.5%), pleural (4.6%), vascular (4.3%), and other (13.9%) disorders. Common variable immune deficiency (CVID) accounted for almost half of PIDs associated with airway, parenchymal, and other pulmonary disorders. Pulmonary procedures performed in 392 patients were mostly diagnostic (77.3%) or therapeutic (16.3%). These patients were receiving a wide variety of treatments, which included immunoglobulin replacement (82.1%), immunosuppressive (32.2%), anti-inflammatory (12.7%), biologic (9.3%), and cytokine (7.6%)-based therapies. Prophylactic therapy was being given with antibiotics (18.1%), antifungal (3.3%), and antiviral (2.2%) medications, and 7.1% of patients were on long-term oxygen therapy due to advanced lung disease. Pulmonary manifestations are common in individuals with PID, but long-term pulmonary outcomes are not well known in this group of patients. Further longitudinal follow-up will help to define long-term prognosis of respiratory comorbidities and optimal treatment modalities.

BackgroundStudies increasingly show that positive psychological constructs affect the mental health of cancer patients. However, most scales that measure hope, resilience, optimism and self-efficacy have been developed based on general populations. The aim of our study was to develop a psychological capital (PsyCap) questionnaire for patients with cancer (PCQ-C) to gauge their mental state more accurately.MethodsThe items for the scale were selected by comprehensive literature review and semi-structured interviews, and the relevant terms were screened by an expert panel. A pilot study was then conducted on 202 patients to reduce the item pool, and the reliability and validity of the scale were evaluated using 500 completed questionnaires. The test-retest reliability was then assessed using a subsample of 100 patients. Finally, the completed questionnaires of 229 patients with breast cancer were used to assess the criterion validity of the PCQ-C, including measures of depression and anxiety.ResultsItem reduction and exploratory factory analysis resulted in 24 items for self-efficacy, hope, resilience and optimism, accounting for 56.72% of the variance. The Cronbach’s alpha for the scale was 0.886, and the test-retest reliability was 0.825. PsyCap showed a significant negative correlation with both depression (r = − 0.631,P r = − 0.601,P ConclusionThe PCQ-C can objectively evaluate PsyCap in cancer patients and exhibits good psychometric properties.

The accurate measurement of characteristic parameters of fracture structures and fluid flow is an essential prerequisite for understanding the seepage mechanism of complex fracture systems. This paper discusses the research progress on the characteristic parameters measured in seepage tests of the real rock, the transparent rock and the digital rock from the perspective of visualisation. Firstly, the studies on the measurement of rock permeability without considering fractures, the seepage experiment with single fractures, the characterisation of complex fracture structures and the auxiliary visualisation of seepage experiments are reviewed. Secondly, the preparation method of transparent rocks and the measuring method of the fluid flow process in transparent rocks are summarised. Thirdly, digital modelling methods for complex fractured rocks and numerical simulation methods for seepage tests in fractures are reviewed. Finally, this paper proposes recommendations for revealing the seepage mechanism of complex fracture systems through the visual measurement method.

A sulfonated lignin-derived mesoporous carbon (LDMC-SO3H) was prepared from kraft lignin (KL) using phenolation and soft-template method followed by sulfonation. LDMC-SO3H bearing a sulfonic acid density of 0.65 mmol/g possessed a well-ordered 2D hexagonal mesoporous characteristics with mesopore volume of 0.067 cm3/g and specific surface area of 262 m2/g as well as mesopore size of 3.42 nm. A high 5-hydroxymethylfurfural (5-HMF) yield of 98.0% with a full fructose conversion was obtained using LDMC-SO3H as catalyst under the optimized reaction conditions of reaction temperature and time of 140 °C and 120 min, initial fructose concentration of 100 g/L, catalyst load of 0.1 mg/mg in DMSO. Furthermore, there was no obvious decrease in 5-HMF yield (≥95.0%) within the five-cycle experiment, highlighting the superior reusability and stability of LDMC-SO3H in fructose-to-5-HMF transformation.

The main focus of this paper is to investigate synchronization of delayed impulsive switched coupled neural networks, in which both synchronizing and desynchronizing impulses are taken into account simultaneously in a distributed way. In addition, both cooperative and competitive interactions are considered. In view of the impulsive strength-dependent average impulsive interval (ISDAII) and the Lyapunov function approach, exponential synchronization problem was investigated for the considered coupled impulsive switched neural networks, where, it is assumed that the average impulsive intervals for different impulsive sequences are distinct. Thus, the proposed ISDAII approach is more general and of a wider application than the usual AII approach. The theoretical results have been verified via a numerical example.

The long-term temperature response to a given change in CO2 forcing, or Earth-system sensitivity (ESS), is a key parameter quantifying our understanding about the relationship between changes in Earth’s radiative forcing and the resulting long-term Earth-system response. Current ESS estimates are subject to sizable uncertainties. Long-term carbon cycle models can provide a useful avenue to constrain ESS, but previous efforts either use rather informal statistical approaches or focus on discrete paleoevents. Here, we improve on previous ESS estimates by using a Bayesian approach to fuse deep-time CO2 and temperature data over the last 420 Myrs with a long-term carbon cycle model. Our median ESS estimate of 3.4 °C (2.6-4.7 °C; 5-95% range) shows a narrower range than previous assessments. We show that weaker chemical weathering relative to the a priori model configuration via reduced weatherable land area yields better agreement with temperature records during the Cretaceous. Research into improving the understanding about these weathering mechanisms hence provides potentially powerful avenues to further constrain this fundamental Earth-system property., Earth-system sensitivity (ESS) describes the long-term temperature response for a given change in atmospheric CO2 and, as such, is a crucial parameter to assess future climate change. Here, the authors use a Bayesian model with data from the last 420 Myrs to reduce uncertainties and estimate ESS to be around 3.4 °C.

Background Antimicrobial resistance (AMR) is a global healthcare problem, including in China where high rates of resistance to common bacterial infections have been documented. In 2016, the National Health and Family Planning Commission (NHFPC) in China established a comprehensive strategic plan to increase awareness about AMR through education programs. Methods We conducted an online survey to assess changes in public knowledge, awareness and practices related to AMR in China since 2016. The survey was administered using China’s national and provincial level 12320 Health Hotline Weibo (micro-blog site) and WeChat (text messaging service) social media accounts from April 12, 2019 to May 7, 2019. All persons ≥16 years of age able to read Chinese were eligible to participate. Results A total of 2773 respondents completed the survey. Of the 2633 respondents indicating recent use of antibiotics, 84% (2223) reported obtaining their course of antibiotics from a hospital or pharmacy, 9% (246) of respondents reported using antibiotics saved from a previous prescription or treatment course, and 42% (1115) of respondents reported that they had stopped taking antibiotics as soon as they started feeling better. Most respondents correctly indicated that antibiotics can effectively treat urinary tract infections (86% [2388]) and skin infections (76% [2119]), but many incorrectly indicated that antibiotics can also treat viral infections such as measles (32% [889]) or a cold or flu (26% [726]). Of all respondents, 95% (2634) had heard of ‘antibiotic resistance’. Almost half (47% [1315]) reported using antibiotics within the last 6 months. Conclusion While awareness of AMR was high in this survey of social media users in China, inappropriate antibiotic use remains common, including the believe that antibiotics can effectively treat viral infections. Multiple interventions targeting the correct use of antibiotics and information on the cause AMR are likely needed. The 12320 Health Hotline provides a platform for conducting routine surveys to monitor antibiotic use and knowledge about AMR.

In this study, microbial fuel cells (MFCs) were explored to promote the nitrogen removal performance of combined anaerobic ammonium oxidation (anammox) and Fe-C micro-electrolysis (CAE) systems. The average total nitrogen (TN) removal efficiency of the modified MFC system was 85.00%, while that of the anammox system was 62.16%. Additionally, the effective operation time of this system increased from six (CAE system alone) to over 50 days, significantly promoting TN removal. The enhanced performance could be attributed to the electron transferred from the anode to the cathode, which aided in reducing nitrate/nitrite in denitrification. The H+ released through the proton exchange membrane caused a decrease in the pH, facilitating Fe corrosion. The pyrolyzed waste tire used as the cathode could immobilize microorganisms, enhance electron transport, and produce a natural Fe-C micro-electrolysis system. According to the microbial community analysis, Candidatus kuenenia was the major genus involved in the anammox process. Furthermore, the SM1A02 genus exhibited the highest abundance and was enriched the fastest, and could be a novel potential strain that aids the anammox process.

A novel hybrid with three-dimensional (3D) hierarchical CuS@Pd core-shell cauliflowers decorated on nitrogen-doped reduced graphene oxide (CuS@Pd/N-RGO) has been prepared by a facile wet-chemical route without utilizing any template molecules and surfactants. The characterization results reveal that the 3D flower-like structure of CuS "core" is composed of interconnecting nanoplates, which is conductive to the loading of Pd nanoparticles' "shell" and results in the robust interaction between the core and shell for the formation of CuS@Pd cauliflowers. Anchoring such appealing CuS@Pd cauliflowers on the two-dimensional N-RGO can efficaciously inhibit the aggregation of CuS@Pd cauliflowers and accelerate the kinetics of xanthine oxidation. Benefiting from the multi-functional properties and unique morphology, the sensor constructed by CuS@Pd/N-RGO exhibits excellent performance for non-enzymatic detection of xanthine including a wide detection range of 0.7-200.0 μM (0.94 V vs. SCE), a low detection limit of 28 nM (S/N = 3), high reproducibility (relative standard deviation (RSD) = 4.1%), and commendable stability (retained 90% of the initial electrochemical responses after storage for 30 days), which is amongst the best of various electrochemical sensors reported for xanthine assays till date. Reliable and satisfying recoveries (95-105%, RSD ≤ 4.1%) are achieved for xanthine detection in real samples. The inspiring results make the uniquely structural CuS@Pd/N-RGO greatly promising in non-enzymatic electrochemical sensing applications. Graphical abstract A high-performance non-enzymatic xanthine sensor has been constructed by the three-dimensional hierarchical CuS@Pd core-shell cauliflowers decorated on nitrogen-doped reduced graphene oxide.

Urban wastewater is one of main sources for the introduction of antibiotics into the environment. Monitoring the concentrations of antibiotics in wastewater is necessary for estimating the amount of antibiotics discharged into the environment through urban wastewater treatment systems. In this study, we report a novel diffusive gradient in thin films (DGT) method based on molecularly imprinted polymers (MIPs) for in situ measurement of two typical antibiotics, fluoroquinolones (FQs) and sulfonamides (SAs) in urban wastewater. MIPs show specific adsorption toward their templates and their structural analogs, resulting in the selective uptake of the two target antibiotics during MIP-DGT deployment. The uptake performance of the MIP-DGTs was evaluated in the laboratory and was relatively independent of solution pH (4.0–9.0), ionic strength (1–750 mmol/L), and dissolved organic matter (DOM, 0–20 mg/L). MIP-DGT samplers were tested in the effluent of an urban wastewater treatment plant for field trials, where three SA (sulfamethoxazole, sulfapyridine, and trimethoprim) and one FQ (ofloxacin) antibiotics were detected, with concentrations ranging from 25.50 to 117.58 ng/L, which are consistent with the results measured by grab sampling. The total removal efficiency of the antibiotics was 80.1% by the treatment plant. This study demonstrates that MIP-DGT is an effective tool for in situ monitoring of trace antibiotics in complex urban wastewaters.

Hybrid rice breeding offers an important strategy to improve rice production, and therefore is crucial for ensuring worldwide food security. Purity of hybrids is a key factor in keeping the high production of hybrid rice. While another important thing is mechanical weeding of hybrid rice, which could greatly release labor from laborious work and cut the production cost. Both of these two problems could be partly resolved by developing glyphosate-tolerant restorer lines. In this study, a novel glyphosate-tolerant gene I.variabilis-EPSPS* was transferred into elite indica restorer line Minghui 86 (MH86) by Agrobacterium-mediated transformation. By Southern blot and inverse PCR analysis, 3 transgenic restorer lines (MY28, MY50, and MY51) with a single copy of I.variabilis-EPSPS* integrated into the intergenic regions were selected from 72 regenerated transgenic plants. The inheritance of I.variabilis-EPSPS* in the 3 transgenic restorer lines was proved to follow Mendelian inheritance by germinating test. In the following generations, according to Southern blot, Northern blot, 3’RACE, and Western blot, I.variabilis-EPSPS* were proved to stably inherit and express in the candidate transgenic restorer lines. At the same time, glyphosate tolerance assay was performed in the field, in which the candidate transgenic restorer lines kept normal agronomic traits under glyphosate treatments with a dosage as high as 8400 g/ha. Therefore, the candidate transgenic restorer lines were highly tolerant to glyphosate. The 3 candidate transgenic restorer lines were respectively hybridized with the male sterile line II-32A, and their hybrids were respectively named as MY28H, MY50H, and MY51H. According to Southern blot and Western blot analysis, I.variabilis-EPSPS* could stably inherit to F1 hybrids and express in these hybrids, which indicated that the true hybrids could be distinguished by I.variabilis-EPSPS*. In the field test, the transgenic hybrids with I.variabilis-EPSPS* could suffer 3360 g/ha glyphosate without the damage of agronomic traits, which indicated the application potential of these hybrids in direct seeding. Collectively, the transgenic glyphosate-tolerant restore lines developed in this study were highly tolerant to glyphosate, and they had potential to be used in commercial production of hybrid rice.

Leigh syndrome (LS) is an early onset progressive neurodegenerative disorder with considerable clinical and genetic heterogeneities. Late-onset Leigh syndrome, i.e., onset after age of 2 years, is considered rare and often presents with atypical clinical features. We review the clinical features and imaging studies in a cohort of late-onset Leigh syndrome caused by mtDNA mutations. A total of 16 patients, 6 males and 10 females, were enrolled. The age at presentation was between 2 and 27 years of age. The first three clinical presentations found in our case series were ataxia, bulbar palsy, and pyramidal tract involvement, while disturbance of cognition and consciousness was less common. Six patients had both stroke-like episodes and seizures corresponding to the cortical lesions revealed on MRI. The most common lesion sites of basal ganglia and brainstem were putamen and midbrain, respectively. Dorsal aspects of the midbrain were the most vulnerable, especially periaqueductal region, and superior and inferior colliculus. Substantia nigra and red nuclei were involved less commonly. In our cohort, mutations of mtDNA in complex I were the commonest. In order of frequency, they were MT-ND3 (7/16), ND5 (3/16), ND6 (2/16), and ND1 (1/16). Causative mutations of MT-ATP6 were detected in the remaining three cases including 8993T>C, 9176 T>C, and 9185 T>C. Our study helps to define the types of clinical and neuroimaging finding in late-onset LS with the mutations of mtDNA. We expect to shed light on the identification of genotype–phenotype and genotype–neuroimaging correlations. On the other hand, our study highlights the importance of mtDNA mutations as a cause for LS, especially for late-onset cases.

Bisphenol A (BPA), a known endocrine disruptor, is of global concern because it poses serious threats to the ecological environment and human health. In this work, hydrophilic polydopamine-coated Fe3O4/oxide graphene (IPDA@MGO) magnetic imprinted nanocomposites were prepared by the self-polymerization of dopamine on the surface of Fe3O4/GO in Tris-HCl buffer using BPA as a template for selective adsorption of BPA in water. IPDA@MGO showed specific recognition toward BPA with a high imprinting factor of 3.2 compared with nonimprinted polymer. The capacity of IPDA@MGO toward BPA was 41.2 mg/g and the adsorption reached equilibrium within 30 min. The adsorption agreed well with the Freundlich and pseudo-second order kinetic models. The good adsorption performance was attributed to the abundant binding sites and good dispersibility of IPDA@MGO nanocomposites derived from its excellent hydrophilicity. The nanocomposites could be removed rapidly by an external magnet and regenerated for repeated adsorption of BPA in water. The proposed method has potential applications for efficient removal of BPA in environmental waters.

PURPOSE: The purpose of this study is to explore the differences in ocular symptoms and signs between Sjögren’s syndrome (SS) and non-SS aqueous-deficient dry eye (ADDE) patients. METHODS: Twenty-two eyes of 22 SS patients (Group 1) and 22 eyes of 22 non-SS ADDE patients (Group 2) were enrolled. The evaluated variables included the Standard Patient Evaluation of Eye Dryness (SPEED), the Ocular Surface Disease Index (OSDI), tear meniscus height, first and average non-invasive keratographic breakup time (fNIKBUT and avNIKBUT), Schirmer I test, lipid layer thickness (LLT), meibomian gland expressibility, Marx line, corneal staining, conjunctival congestion, incomplete blinking, and meibomian gland dropout using two novel, non-invasive instruments, the Keratograph and LipiView II. RESULTS: Ocular signs of the NIKBUT (fNIKBUT: 3.8 (2.7, 5.2)s and 6.3 (3.7, 8.9)s, P = 0.024; avNIKBUT: 5.4 (4.5, 8.9)s and 7.6 (5.8, 13.7)s, P = 0.041), meibomian gland dropout of the upper eyelid (35.5% (29.1%, 54.8%) and 21.9% (16.7%, 24.9%), P = 0.000), and corneal staining (P = 0.050) were more severe but were associated with less severe symptoms, i.e., a lower SPEED score (P = 0.001), in SS subjects than in non-SS subjects. CONCLUSION: SS patients exhibit more severe meibomian gland destruction of the upper eyelid than non-SS patients. Meibomian gland dysfunction is another key cause of SS-associated dry eye.

Due to the possible lack of primal-dual-type error bounds, it was not clear whether the Karush–Kuhn–Tucker (KKT) residuals of the sequence generated by the augmented Lagrangian method (ALM) for solving convex composite conic programming (CCCP) problems converge superlinearly. In this paper, we resolve this issue by establishing the R-superlinear convergence of the KKT residuals generated by the ALM under only a mild quadratic growth condition on the dual of CCCP, with easy-to-implement stopping criteria for the augmented Lagrangian subproblems. This discovery may help to explain the good numerical performance of several recently developed semismooth Newton-CG based ALM solvers for linear and convex quadratic semidefinite programming.

The dried roots of Rehmannia glutinosa Libosch. (Scrophulariaceae) are of both medicinal and nutritional importance. Our previous study has found that the 80% ethanol extract of R. glutinosa (RGEE) produced antidepressant-like activities in mouse behavioral despair depression models. However, its mechanisms are still unclear. The present study aimed to observe the antidepressant-like mechanisms of RGEE on a rat chronic unpredictable mild stress (CUMS) model by involving monoaminergic neurotransmitters and brain-derived neurotrophic factor (BDNF). CUMS-stressed rats were orally given RGEE daily (150, 300, and 600 mg/kg) or fluoxetine hydrochloride (FH) for 3 weeks after starting the CUMS procedure. Sucrose preference test was carried out to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. Results demonstrated that CUMS induced depression-like behavior, whereas RGEE and FH administration inhibited this symptom. Furthermore, CUMS caused excessively elevated levels of serum corticosterone (CORT), an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, in a manner attenuated by RGEE and FH administration. RGEE administration also further elevated monoamine neurotransmitters and BDNF levels, up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB) in hippocampus of rats suffering CUMS. Together, our findings suggest that RGEE can improve CUMS-evoked depression-like behavior, and indicate its mechanisms may partially be associated with restoring HPA axis dysfunctions, enhancing monoamineergic nervous systems, and up-regulating BDNF and TrkB expression.

In this paper, stochastic stability is analyzed for a class of discrete-time switched neural networks, in which time-varying mixed delays and stochastic noise are considered. Specifically, benefitting from the triple summation term included in a new Lyapunov functional, time-varying distributed delays are tackled and a criterion of decay estimation for a non-switched neural network is firstly obtained. Subsequently, in view of average dwell time methodology and stochastic analysis, several sufficient conditions are obtained to ensure that the stochastic stability problem is solvable. Furthermore, the derived sufficient conditions reflect that the decay rate of the considered neural networks has a close relationship with average dwell time, upper and lower bounds of delays and intensity of stochastic noise. Finally, validity of the inferred conclusions is given by a simulated example.

Two ruthenium complexes [Ru(MeIm)4(bpy)]2+ (Ru1, MeIm = 1-methylimidazole, bpy = 2,2′-bipyridine) and [Ru(Im)4(bpy)]2+ (Ru2, Im = imidazole) with the same PF 6 − counter-ion but different lipophilicities were synthesized and characterized and as potent anticancer agents. The relationships between cellular uptake, localization and molecular action mechanisms of these complexes were elucidated. The results showed that Ru1 with higher logPo/w exhibited faster cellular uptake rates, but lower anticancer activity than Ru2. In addition, Ru1 predominantly accumulated in the mitochondria and cytoplasm, and induced G0/G1 cell cycle arrest, whereas the more hydrophilic Ru2 tended to localize and accumulate in the cell nucleus and mitochondria. Further mechanism studies indicated that Ru2 caused cell cycle arrest at S phase by regulating cell cycle related proteins and induced apoptosis in A549 cells through DNA damage, cellular ROS accumulation, activation of the caspase pathway and mitochondrial dysfunction.

Background Early recurrent spontaneous abortion (ERSA) is a common condition in pregnant women. To prevent ERSA is necessary to look for abortion indicators, such as hormones and proteins, in an early stage. Methods Thirty patients with ERSA were enrolled in the case group. In the control group, we recruited 30 healthy women without a history of miscarriage undergoing voluntary pregnancy termination. The differentially expressed proteins in the serum were identified between the two groups using PRM and iTRAQ. Results Seventy-eight differentially expressed proteins were identified. Using GO functional annotation and KEGG pathway analysis, we detected that the most significant changes occurred in the pathway of Fc gamma R-mediated phagocytosis. Meanwhile, using PRM, we identified three proteins that were closely related to abortion, B4DTF1 (highly similar to PSG1), P11464 (PSG1), and B4DF70 (highly similar to Prdx-2). The levels of B4DTF1 and P11464 were down-regulated, while the level of B4DF70 was up-regulated. Conclusions CD45, PSG1, and Prdx-2, were significantly dysregulated in the samples of ERSA and could become important biomarkers for the prediction and diagnosis of ERSA. Larger‑scale studies are required to confirm the diagnostic value of these biomarkers.

To explore the effect of T2DM on cerebral perfusion, and the relationship between cerebral perfusion changes and cognitive impairment as well as diabetic variables, by using a whole-brain arterial spin-labeling (ASL) MRI technique. This prospective study was approved by the local institutional review board and was performed between November 2012 and October 2013. All subjects provided informed consent. Forty T2DM patients and 41 age-, sex- and education-matched healthy controls were included. Cerebral blood flow (CBF) map was obtained by pulsed ASL perfusion imaging at 3 T MRI. Voxel-wise comparisons on CBF maps with and without partial volume effects (PVEs) correction were performed between groups. Associations between CBF and cognitive functioning, and between CBF and diabetic variables were investigated by using voxel-wise, whole-brain correlation analyses. In T2DM patients, PVEs uncorrected CBF was decreased in the posterior cingulate cortex (PCC), precuneus and bilateral occipital lobe, and increased in the anterior cingulate cortex (corrected P

Clinical and preclinical data suggest that diabetes is often psychological complications such as depression. Geniposide (GP), a major compound in Gardenia jasminoides Ellis with both medicinal and nutritional values, has been previously confirmed to exert anti-diabetic and anti-depressive activities. The present study attempted to observe anti-depressive mechanisms of GP in streptozotocin (STZ) evoked diabetic mice by involving brain-derived neurotrophic factor (BDNF), for the first time. Mice were given GP daily (50, and 100 mg/kg, ig) or reference drugs FHMH [fluoxetine hydrochloride (FH, 10 mg/kg, ig) combined with metformin hydrochloride (MH, 100 mg/kg, ig)] for 3 weeks. The forced swimming test (FST) was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analyses. STZ induced excessively increased blood sugar and immobility time in FST, in a manner attenuated by GP and FHMH administration. GP administration further elevated BDNF levels, and up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB) in hippocampus of diabetic mice. In addition, STZ induced the excessive level of serum corticosterone (CORT), while GP did not influence on it in diabetic mice. Taken together, these findings indicate that GP can alleviate depression-like behavior in STZ-evoked diabetic mice, and suggest its mechanisms may partially be ascribed to up-regulating BDNF expression in brain.