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Objective: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status. Methods: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI. Results: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status. Conclusion: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population. [ABSTRACT FROM AUTHOR]

Internet of Things (IoT) devices will generate massive fragmented data that requires real-time computing and intelligent analysis, which makes it facing the challenge of insufficient computing resources and limited battery energy. With the assistance of mobile edge computing (MEC), IoT devices can offload computing tasks to the MEC server to reduce their computing pressure. Cooperation between devices and wireless power transmission technology (WPT) can be used to solve the problem of limited battery energy. Moreover, the use of unmanned aerial vehicles (UAVs) in the WPT-MEC system can improve signal coverage and energy collection efficiency. In this paper, we propose an UAV-based wireless power transmission and collaborative MEC scheme for IoT networks, in which IoT devices utilize different subcarriers to transmit the information. We aim to minimize UAV's transmitting power via optimizing the transmitting power of IoT devices with the constraints of delay and offloading task size. The performance of the proposed scheme is verified by simulation results. [ABSTRACT FROM AUTHOR]

Tea plant [Camellia sinensis (L.) O. Kuntze] is one of the important foliar cash crops in China, and its root system absorbs heavy metal (HM) elements enriched in the soil and transports them to the over ground part. In order to ensure the safety of the soil ecological environment and tea raw materials in the tea production area, the HM contents of soil and tea plant leaves in Suzhou tea plantations were detected, the relationship between HMs and soil physicochemical properties was analyzed, and the ecological risk of HMs in tea plantation soils was evaluated by using relevant detection techniques and evaluation models. The results showed that the average pH of tea plantation soils around Tai Lake in Suzhou was within the range suitable for the growth of tea plants. The pH, soil organic matter, total nitrogen, available phosphorus and available potassium of tea plantation soil satisfying the requirements of high quality, high efficiency and high yield ('3H') tea plantation accounted for 47.06%, 26.47%, 8.82%, 79.41% and 67.65%, respectively. Site 2 fully met the requirements of '3H' tea plantation. In addition, the contents of cadmium (Cd) and mercury (Hg) were extremely variable, and the average contents exceeded the background value of soil in Jiangsu Province, but the HM contents of tea leaves all met the pollution-free standard, and the HM contents of tea leaves around Tai Lake in Suzhou were generally at a safe level. The composite ecological risk index ranged from 0.05 to 0.60, and 32 of the 34 sample sites (except site 21 and site 23) are the most suitable agricultural land for tea plantations. [ABSTRACT FROM AUTHOR]

With the development of economic and technologies, the trend of annual Gross Domestic Product (GDP) and carbon dioxide (CO2) emission changes with time passes. The relationship between economic growth and carbon dioxide emissions is considered as one of the most important empirical relationships. In this study, we focus on the member of Shanghai Cooperation Organization, including China, Russia, India, and Pakistan and collect CO2 emission and annual GDP from 1969 to 2014. The statistical methods and tests are used to find the relationship between annual GDP and CO2 emission in these countries. Based on relationship between annual and CO2 emission, a novel multi-step prediction algorithm called Extreme Learning Machine with Artificial Bee Colony (ELM-ABC) is proposed for forecasting annual GDP based on CO2 emission and historical GDP features. According to the experimental results, it proved that the proposed model had a super forecasting ability in GDP prediction and it could predict ten-year future annual GDP for the corresponding countries. Moreover, the forecasting results showed that the annual GDP of China and Pakistan will continue to grow but growth will slow after 2025. The annual GDP in India will exhibit unstable growth. The trend of Russia will follow the pattern between 2010 and 2016. [ABSTRACT FROM AUTHOR]

Background: Gadolinium-based nanoparticles (GdNPs) are clinically used agents to increase the radiosensitivity of tumor cells. However, studies on the mechanisms and biological modeling of GdNP radio-enhancement are still preliminary. This study aims to investigate the mechanism of radio-enhancement of GdNPs for kilovoltage photons using Monte Carlo (MC) simulations, and to establish local effect model (LEM)-based biological model of GdNP radiosensitization. Methods: The spectrum and yield of secondary electrons and dose enhancement around a single GdNP and clustered GdNPs were calculated in a water cube phantom by MC track-structure simulations using TOPAS code. We constructed a partial shell-like cell geometry model of pancreatic cancer cell based on transmission electron microscope (TEM) observations. LEM-based biological modeling of GdNP radiosensitization was established based on the MC-calculated nano-scale dose distributions in the cell model to predict the cell surviving fractions after irradiation. Results: The yield of secondary electrons for GdNP was 0.16% of the yield for gold nanoparticle (GNP), whereas the average electron energy was 12% higher. The majority of the dose enhancement came from the contribution of Auger electrons. GdNP clusters had a larger range and extent of dose enhancement than single GdNPs, although GdNP clustering reduced radial dose per interacting photon significantly. For the dose range between 0 and 8 Gy, the surviving fraction predicted using LEM-based biological model laid within one standard deviation of the published experimental results, and the deviations between them were all within 25%. Conclusions: The mechanism of radio-enhancement of GdNPs for kilovoltage photons was investigated using MC simulations. The prediction results of the established LEM-based biological model for GdNP radiosensitization showed good agreement with published experimental results, although the deviation of simulation parameters can lead to large disparity in the results. To our knowledge, this was the first LEM-based biological model for GdNP radiosensitization. [ABSTRACT FROM AUTHOR]

Chromium(III) is extensively used as a supplement for muscle development and the treatment of diabetes mellitus. However, its mode of action, essentiality, and physiological/pharmacological effects have been a subject of scientific debate for over half a century owing to the failure in identifying the molecular targets of Cr(III). Herein, by integrating fluorescence imaging with a proteomic approach, we visualized the Cr(III) proteome being mainly localized in the mitochondria, and subsequently identified and validated eight Cr(III)-binding proteins, which are predominately associated with ATP synthesis. We show that Cr(III) binds to ATP synthase at its beta subunit via the catalytic residues of Thr213/Glu242 and the nucleotide in the active site. Such a binding suppresses ATP synthase activity, leading to the activation of AMPK, improving glucose metabolism, and rescuing mitochondria from hyperglycaemia-induced fragmentation. The mode of action of Cr(III) in cells also holds true in type II diabetic male mice. Through this study, we resolve the long-standing question of how Cr(III) ameliorates hyperglycaemia stress at the molecular level, opening a new horizon for further exploration of the pharmacological effects of Cr(III). Despite common use as a diabetes mellitus supplement, chromium(III)'s pharmacological effects remain unknown. We identified the Cr(III)-proteome in cells with a metalloproteomic approach and uncovered ATP synthase as a vital target to relieve hyperglycaemia stress. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress initiates the unfolded protein response (UPR) and is decisive for tumor cell growth and tumor microenvironment (TME) maintenance. Tumor cells persistently undergo ER stress and could transmit it to the neighboring macrophages and surroundings. Tumor infiltrating macrophages can also adapt to the microenvironment variations to fulfill their highly energy-demanding and biological functions via ER stress. However, whether the different macrophage populations differentially sense ER stress and transmit ER stress to surrounding tumor cells has not yet been elucidated. Here, we aimed to investigate the role of transmissible ER stress, a novel regulator of intercellular communication in the TME. Murine bone marrow-derived macrophage (BMDM) can be polarized toward distinct functional endpoints termed classical (M1) and alternative (M2) activation, and their polarization status has been shown to be tightly correlated with their functional significance. We showed that tumor cells could receive the transmissible ER stress from two differentially polarized macrophage populations with different extent of ER stress activation. The proinflammatory M1-like macrophages respond to ER stress with less extent, however they could transmit more ER stress to tumor cells. Moreover, by analyzing the secreted components of two ER-stressed macrophage populations, we identified certain damage-associated molecular patterns (DAMPs), including S100A8 and S100A9, which are dominantly secreted by M1-like macrophages could lead to significant recipient tumor cells death in synergy with transferred ER stress. [ABSTRACT FROM AUTHOR]

Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. We demonstrate that dynamic changes in O-GlcNAcylation are required for osteoclastogenesis. Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. TNFα fosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory arthritis. Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the common causes of neurological injury in full-term neonates following perinatal asphyxia. The conventional magnetic resonance technique has low sensitivity in detecting variations in cerebral blood flow in patients with HIE. Objective: This article evaluates the clinical diagnostic value of three-dimensional pseudo-continuous arterial spin labelling (3-D pcASL) perfusion magnetic resonance imaging (MRI) for early prediction of neurobehavioral outcomes in full-term neonates with HIE. Materials and methods: All neonates diagnosed with HIE underwent MRI (conventional and 3-D pcASL perfusion MRI). Cerebral blood flow values were measured in the basal ganglia (caudate nuclei, lenticular nuclei), thalami and white matter regions (frontal lobes, corona radiata). After 1-month follow-up, the Neonatal Behavioral Neurological Assessment scores were used to divide patients into favourable outcome group versus adverse outcome group. Results: Twenty-three patients were enrolled in this study. There were no statistical differences between the symmetrical cerebral blood flow values of bilateral basal ganglia, thalami and white matter regions. However, the cerebral blood flow values of grey matter nuclei were higher than the white matter regions. The average value of cerebral blood flow in the basal ganglia and thalami in the adverse outcome group was 37.28±6.42 ml/100 g/min, which is greater than the favourable outcome group (22.55 ± 3.21 ml/100 g/min) (P<0.01). The area under the curve (AUC) of 3-D pcASL perfusion MRI was 0.992 with a cutoff value of 28.75 ml/100 g/min, with a Youden's index of 0.9231. The sensitivity and specificity were 92.3% and 100%, respectively. Conclusion: The 3-D pcASL demonstrated higher perfusion alteration in the basal ganglia and thalami of neonatal HIE with adverse outcomes. The 3-D pcASL perfusion MRI has the potential to predict neurobehavioral outcomes of neonates with HIE. [ABSTRACT FROM AUTHOR]

Mobile edge computing (MEC) meets the high-bandwidth and ultra-low-latency requirements of mobile networks and improves communication reliability by reducing the networks’ load. In this study, we study a wireless powered MEC system, which includes an access point (AP) and two mobile devices. The endurance of mobile devices can be effectively enhanced using the wireless power transfer technology and user cooperation. However, during user cooperation, a closer user assists a farther user with forwarding tasks by sharing the same bandwidth, which causes interference. To overcome the interference issue, the closer user can instead assist other users in forwarding tasks by using a different bandwidth. We aim to minimize the power of the AP by joint power and bandwidth optimization while satisfying the delay and users’ computational tasks. Simulation results show that the proposed user collaboration method can overcome user interference, reduce energy consumption, and improve user performance compared with the baseline policies. [ABSTRACT FROM AUTHOR]

The rapid emergence of drug resistant Staphylococcus aureus (S. aureus) poses a serious threat to public health globally. Silver (Ag)-based antimicrobials are promising to combat antibiotic resistant S. aureus, yet their molecular targets are largely elusive. Herein, we separate and identify 38 authentic Ag+-binding proteins in S. aureus at the whole-cell scale. We then capture the molecular snapshot on the dynamic action of Ag+ against S. aureus and further validate that Ag+ could inhibit a key target 6-phosphogluconate dehydrogenase through binding to catalytic His185 by X-ray crystallography. Significantly, the multi-target mode of action of Ag+ (and nanosilver) endows its sustainable antimicrobial efficacy, leading to enhanced efficacy of conventional antibiotics and resensitization of MRSA to antibiotics. Our study resolves the long-standing question of the molecular targets of silver in S. aureus and offers insights into the sustainable bacterial susceptibility of silver, providing a potential approach for combating antimicrobial resistance. Silver (Ag) has been used as an antimicrobial agent since a long time, but its molecular mechanism of action was not elucidated due to technical challenges. Here, the authors develop a mass spectrometric approach to identify the Ag-proteome in Staphylococcus aureus, and capture a molecular snapshot of the dynamic bactericidal mode of action of Ag through targeting multiple biological pathways. [ABSTRACT FROM AUTHOR]

Cervical cancer is a common gynecological malignancy with high incidence and mortality. Somatic copy number alterations (CNAs) play an important role in identifying tumor suppressor genes and oncogenes and are a useful diagnostic indicator for many cancer types. However, the genomic landscape of CNAs in cervical cancer has not yet been comprehensively characterized. In the present study, we collected 974 cervical cancer samples from different data sources. All samples were analyzed by genomic arrays to obtain high-resolution CNAs. Focal genomic regions with CNA events and potential cancer driver genes were identified by GISTIC2.0. Meanwhile, we constructed a comprehensive cervical cancer database by PHP and self-written Perl and R scripts. In total, 54 recurrent regions of amplification and deletion were detected. Frequently altered tumor suppressor genes were found in these regions, including PIK3CA, ERBB2, EP300 and FBXW7. CNA hotspots and related enriched functional categories were also identified. The incidence of chromothripsis in cervical cancer was estimated to be 6.06%, and the chromosome pulverization hotspot regions were detected. Based on the curated data, we developed CNAdbCC (http://cailab.labshare.cn/CNAdbCC/), a comprehensive database for copy number alterations in cervical cancer. We provide a user-friendly Web interface for data mining and visualization. It is the most comprehensive public database devoted exclusively to genomic alterations in cervical cancer. These results extend our molecular understanding of cervical cancer. The database will enable researchers to explore specific CNA patterns in this lethal cancer and facilitate the discovery of therapeutic candidates. [ABSTRACT FROM AUTHOR]

Summary: The Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays central roles in cancer cell growth and survival. Drug repurposing strategies have provided a valuable approach for developing antitumor drugs. Zelnorm (tegaserod maleate) was originally designed as an agonist of 5-hydroxytryptamine 4 receptor (5-HT4R) and approved by the FDA for treating irritable bowel syndrome with constipation (IBS-C). Through the use of a high-throughput drug screening system, Zelnorm was identified as a JAK/STAT3 signaling inhibitor. Moreover, the inhibition of STAT3 phosphorylation by Zelnorm was independent of its original target 5-HT4R. Zelnorm could cause G1 cell cycle arrest, induce cell apoptosis and inhibit the growth of a variety of cancer cells. The present study identifies Zelnorm as a novel JAK/STAT3 signaling inhibitor and reveals a new clinical application of Zelnorm upon market reintroduction. [ABSTRACT FROM AUTHOR]

Objective: During an oral glucose tolerance test (OGTT), typically fasting plasma glucose is lower than 2-h postprandial plasma glucose. However, postprandial plasma glucose (PPG) levels lower than fasting plasma glucose (FPG) levels may also occur. This study aims to describe the prevalence, clinical characteristics and contributing risk factors for PPG ≤ FPG in a large diverse Chinese population.We conducted a cross-sectional analysis of baseline data from a nationwide cohort study conducted in China. In addition to sociodemographic and anthropometric data collection, individuals had OGTT and blood chemistry tests. We determined the prevalence of PPG ≤ FPG (‘Low Post Load’ group) and PPG > FPG (‘High Post Load’ group) and used logistic regression to evaluate the association of risk factors with the occurrence of Low Post Load.The prevalence of Low Post Load was 26.04% (n = 3773) and High Post Load was 73.96% (n = 10,714). Low Post Load was found to be related to younger age, male, lower BMI, lower blood pressure, higher HDL cholesterol levels and lower triglycerides levels. Compared with participants in the High Post Load group, participants in Low Post Load group had lower PPG (4.59 ± 0.83 mmol/L vs 7.15 ± 1.41 mmol/L) and HbA1c (5.30 ± 0.43% vs 5.39 ± 0.45%). People in Low Post Load group were more likely to have hypoglycaemic episodes (2.12% vs 0.01%) and impaired fasting glucose (12.30% vs 4.81%) compared with people with High Post Load, all p < 0.001.We found a high prevalence of people with Low Post Load glucose (26.04%) in a Chinese population cohort. The relationship between Low Post Load and the progression to or protection from diabetes and related complications and future incidence of cardiovascular disease needs further exploration in longitudinal analyses.Methods: During an oral glucose tolerance test (OGTT), typically fasting plasma glucose is lower than 2-h postprandial plasma glucose. However, postprandial plasma glucose (PPG) levels lower than fasting plasma glucose (FPG) levels may also occur. This study aims to describe the prevalence, clinical characteristics and contributing risk factors for PPG ≤ FPG in a large diverse Chinese population.We conducted a cross-sectional analysis of baseline data from a nationwide cohort study conducted in China. In addition to sociodemographic and anthropometric data collection, individuals had OGTT and blood chemistry tests. We determined the prevalence of PPG ≤ FPG (‘Low Post Load’ group) and PPG > FPG (‘High Post Load’ group) and used logistic regression to evaluate the association of risk factors with the occurrence of Low Post Load.The prevalence of Low Post Load was 26.04% (n = 3773) and High Post Load was 73.96% (n = 10,714). Low Post Load was found to be related to younger age, male, lower BMI, lower blood pressure, higher HDL cholesterol levels and lower triglycerides levels. Compared with participants in the High Post Load group, participants in Low Post Load group had lower PPG (4.59 ± 0.83 mmol/L vs 7.15 ± 1.41 mmol/L) and HbA1c (5.30 ± 0.43% vs 5.39 ± 0.45%). People in Low Post Load group were more likely to have hypoglycaemic episodes (2.12% vs 0.01%) and impaired fasting glucose (12.30% vs 4.81%) compared with people with High Post Load, all p < 0.001.We found a high prevalence of people with Low Post Load glucose (26.04%) in a Chinese population cohort. The relationship between Low Post Load and the progression to or protection from diabetes and related complications and future incidence of cardiovascular disease needs further exploration in longitudinal analyses.Results: During an oral glucose tolerance test (OGTT), typically fasting plasma glucose is lower than 2-h postprandial plasma glucose. However, postprandial plasma glucose (PPG) levels lower than fasting plasma glucose (FPG) levels may also occur. This study aims to describe the prevalence, clinical characteristics and contributing risk factors for PPG ≤ FPG in a large diverse Chinese population.We conducted a cross-sectional analysis of baseline data from a nationwide cohort study conducted in China. In addition to sociodemographic and anthropometric data collection, individuals had OGTT and blood chemistry tests. We determined the prevalence of PPG ≤ FPG (‘Low Post Load’ group) and PPG > FPG (‘High Post Load’ group) and used logistic regression to evaluate the association of risk factors with the occurrence of Low Post Load.The prevalence of Low Post Load was 26.04% (n = 3773) and High Post Load was 73.96% (n = 10,714). Low Post Load was found to be related to younger age, male, lower BMI, lower blood pressure, higher HDL cholesterol levels and lower triglycerides levels. Compared with participants in the High Post Load group, participants in Low Post Load group had lower PPG (4.59 ± 0.83 mmol/L vs 7.15 ± 1.41 mmol/L) and HbA1c (5.30 ± 0.43% vs 5.39 ± 0.45%). People in Low Post Load group were more likely to have hypoglycaemic episodes (2.12% vs 0.01%) and impaired fasting glucose (12.30% vs 4.81%) compared with people with High Post Load, all p < 0.001.We found a high prevalence of people with Low Post Load glucose (26.04%) in a Chinese population cohort. The relationship between Low Post Load and the progression to or protection from diabetes and related complications and future incidence of cardiovascular disease needs further exploration in longitudinal analyses.Conclusions: During an oral glucose tolerance test (OGTT), typically fasting plasma glucose is lower than 2-h postprandial plasma glucose. However, postprandial plasma glucose (PPG) levels lower than fasting plasma glucose (FPG) levels may also occur. This study aims to describe the prevalence, clinical characteristics and contributing risk factors for PPG ≤ FPG in a large diverse Chinese population.We conducted a cross-sectional analysis of baseline data from a nationwide cohort study conducted in China. In addition to sociodemographic and anthropometric data collection, individuals had OGTT and blood chemistry tests. We determined the prevalence of PPG ≤ FPG (‘Low Post Load’ group) and PPG > FPG (‘High Post Load’ group) and used logistic regression to evaluate the association of risk factors with the occurrence of Low Post Load.The prevalence of Low Post Load was 26.04% (n = 3773) and High Post Load was 73.96% (n = 10,714). Low Post Load was found to be related to younger age, male, lower BMI, lower blood pressure, higher HDL cholesterol levels and lower triglycerides levels. Compared with participants in the High Post Load group, participants in Low Post Load group had lower PPG (4.59 ± 0.83 mmol/L vs 7.15 ± 1.41 mmol/L) and HbA1c (5.30 ± 0.43% vs 5.39 ± 0.45%). People in Low Post Load group were more likely to have hypoglycaemic episodes (2.12% vs 0.01%) and impaired fasting glucose (12.30% vs 4.81%) compared with people with High Post Load, all p < 0.001.We found a high prevalence of people with Low Post Load glucose (26.04%) in a Chinese population cohort. The relationship between Low Post Load and the progression to or protection from diabetes and related complications and future incidence of cardiovascular disease needs further exploration in longitudinal analyses. [ABSTRACT FROM AUTHOR]

Cd and Pb are a toxic environmental pollutant, and their elevated concentrations in the waters and soils could exert detriment effects on human health by food chain. In order to evaluate the capacity to heavy metal accumulation and the physiochemical responses of two Salix genotypes, a 35-day hydroponic seedling experiment was implemented with Salix matsudana Koidz. 'Shidi1' (A42) and Salix psammophila C. 'Huangpi1' (A94) under different concentrations of Cd (15 and 30 μM) or Pb (250 and 300 μM). The results showed that the biomass of A94 severely reduced more than that of A42. The accumulation ability of Cd in different plant organs followed the sequence of leaves > roots > stems. Pb primarily accumulated in the roots for both Salix genotypes (54.27 mg g−1 for A42 and 54.52 mg g−1 for A94). Translocation factors based on accumulation (TF′) for Cd were more than 8.0, while TF′s for Pb were less than 1.0 in both A42 and A94, implying they could be applied in the phytoremediation of Cd-contaminated sites due to their stronger ability to Cd phytoextraction. The stress of Cd or Pb significantly increased malondialdehyde (MDA) contents and increased photosynthetic rates in leaves of two Salix genotypes. Transpiration rates of willow were positively correlated with its Cd translocation. Both catalase (CAT) and peroxidase (POD) activities were suppressed, while the superoxide dismutase (SOD) was boosted with increasing Cd and Pb levels in the leaves and roots of the two willow genotypes, suggesting SOD plays an important role in the removal of ROS. The inconsistency of the changes in enzyme activity suggests that the integrated antioxidative mechanisms regulate the tolerance to Cd and Pb stress. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is a potentially lethal multisystem disorder which could be caused by autoimmune diseases. However, the concomitant occurrence of TTP and Sjögren’s syndrome (SS) is an extremely uncommon scenario, especially in male patients. A 56-year-old Chinese male was admitted for the appearance of diffuse ecchymosis. Then he gradually developed transient slurred speech, progressive confusion, agitation, extremity weakness, and fever. Laboratory investigations suggested anemia, thrombocytopenia, significantly increased lactic dehydrogenase, schistocytes in peripheral blood smear, and a disintegrin-like metalloproteinase with thrombospondin motif type 1 member 13 (ADAMTS13) activity deficiency with high inhibitor titers. TTP was thus diagnosed. The patient also had positive anti-nuclear antibody, anti-SSA, and anti-SSB; however, anti-double stranded DNA (dsDNA) was negative. These drove us to perform ocular and dental sicca evaluation and the finial diagnosis was TTP secondary to SS. Plasma exchange and corticosteroid therapy were effective to control TTP. Cyclophosphamide was subsequently added when the platelet count was stable. The total duration of corticosteroid and cyclophosphamide was 8 and 6 months, respectively. The patient recovered without relapse at 1-year follow-up. To our knowledge, this was the first case of SS initially presented as TTP in a male patient. The case also elucidated the importance of autoantibody screen in the workup of TTP and the benefits of adjunctive immunosuppressive therapy in relapse prevention. [ABSTRACT FROM AUTHOR]

Neutrophil chemotaxis plays an essential role in recruiting neutrophils to sites of inflammation. Neutrophil chemotaxis is suppressed both after exposure to lipopolysaccharide (LPS) in vitro and during clinical and experimental endotoxemia, leading to serious consequences. Adenosine (ADO) is a potent anti-inflammatory agent that acts on a variety of neutrophil functions. However, its effects on human neutrophil chemotaxis during infection have been less well characterized. In the present study, we investigated the effect of ADO and its receptor-specific antagonist and agonist on neutrophil chemotaxis in an in vitro LPS-stimulated model. The results showed that increasing the concentration of ADO effectively restored the LPS-inhibited neutrophil chemotaxis to IL-8. A similar phenomenon occurred after intervention with a selective A1 receptor agonist but not with a selective antagonist. Pre-treatment with cAMP antagonist failed to restore LPS-inhibited chemotaxis. Furthermore, protein array and western blot analysis showed that the activation of A1 receptor significantly decreased LPS-induced p38 MAPK phosphorylation. However, the surface expression of the A1 receptor in LPS-stimulated neutrophils was not significantly changed. Taken together, these data indicated that ADO restored the LPS-inhibited chemotaxis via the A1 receptor, which downregulated the phosphorylation level of p38 MAPK, making this a promising new therapeutic strategy for infectious diseases. [ABSTRACT FROM AUTHOR]

Methylmercury is a toxic pollutant and is generated by microbial methylation of elemental or inorganic mercury in the environment. Previous study found decreased hepatic MDA levels and urinary mercury levels in methylmercury poisoned rats after sodium selenite treatment. This study further found increased mercury levels in serum samples from methylmercury poisoned rats after selenium treatment. By using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, three Hg- binding protein fractions and two Se-binding protein fractions were identified with the molecular weight of approximately 21, 40, and 75 kDa and of 40 and 75 kDa, respectively. Elevated mercury level in the 75 kDa protein fraction was found binding with both Hg and Se, which may explain the decreased urinary Hg excretion in MeHg poisoned rats after Se treatment. MALDI-TOF-MS analysis of the serum found that the 75 kDa protein fractions were albumin binding with both Hg and Se and the 21 kDa fraction was Hg- binding metallothionein. [ABSTRACT FROM AUTHOR]

Background and aims: Iron plaque can affect the absorption and accumulation of metal(loid)s in plants. However, it is still unclear whether iron plaque plays different roles in the accumulation of different mercury species in rice plants. The aims of this study are 1) to explore the adsorption of IHg and MeHg onto iron plaque, 2) to investigate the influence of iron plaque on the absorption, translocation of IHg and MeHg in rice plants, 3) to explore whether the process of methylation and demethylation of Hg in vivo occurs in rice plants, and 4) to investigate the effects of iron plaque on the IHg and MeHg transformation in rice. Methods: The seedlings were cultivated in an Fe solution for 24 h to induce the iron plaque and then transferred into a nutrient solution containing 500 μg/L HgCl or MeHgCl for 72 h. The Hg content in the iron plaque and rice seedlings was measured by ICP-MS. The chemical forms of Hg in the rice seedlings were determined with HPLC-ICP-MS and XANES. Results: Both IHg and MeHg, particularly MeHg, could be adsorbed by iron plaque. The IHg content of the root and the MeHg content in both the roots and shoots decreased markedly with the increase in iron plaque. The Hg in the root was mainly in the form of RS-Hg-SR with the exposure to HgCl and in the form of CH-Hg-SR and RS-Hg-SR (4:1) with the exposure to MeHgCl. The iron plaque did not change the chemical forms of Hg in the rice plants. Conclusions: Iron plaque greatly decreased the absorption and translocation of both IHg and MeHg in rice seedlings. The demethylation of MeHg occurred in rice plants (in vivo) regardless the formation of iron plaque. This work sheds some light on the understanding of different pathways between IHg and MeHg in rice plants. [ABSTRACT FROM AUTHOR]

Background and Objective: Trimetazidine has been shown to improve angina pectoris and left ventricular (LV) function in diabetic patients with ischaemic cardiomyopathy. The objective of this study was to evaluate the effects of trimetazidine on recurrent angina pectoris and LV structure after drug-eluting stent (DES) implantation in elderly multivessel coronary heart disease (CHD) patients with diabetes mellitus (DM) and a left ventricular ejection fraction (LVEF) of ≥50 %. Methods: This was a single-centre, prospective, randomized, double-blind evaluation study. Between January 2010 and September 2010, 700 CHD patients with DM who were aged ≥65 years and undergoing coronary angiography at An Zhen Hospital (Beijing, China) were recruited and prospectively randomized to receive trimetazidine (20 mg three times daily) or placebo after DES implantation as an addition to conventional CHD treatment. The primary end points were the incidence of recurrent angina pectoris and measures of various echocardiographic parameters, which included LVEF. Results: At 2-year follow-up, patients in the trimetazidine group ( n = 255) showed significant improvements in the incidence ( P = 0.024) and severity of angina pectoris, compared with the control group, as well as silent myocardial ischaemia ( P = 0.009) and angina pectoris-free survival ( P = 0.011). LV function and structure in trimetazidine-treated patients were relatively stable at 2-year follow-up, while they deteriorated in the control group ( n = 255) with a significant difference between groups (all P < 0.01). The E peak to A peak ( E/A) ratio in trimetazidine-treated patients and in the control group decreased after 2 years; the E/ A ratio in trimetazidine-treated patients was slightly better than that in the control group, without a significant difference ( P = 0.170). There was no significant difference in event-free survival for the composite end point including death, myocardial infarction, cerebrovascular accident ( P = 0.422) and subsequent revascularization ( P = 0.073). Conclusion: Adjunctive therapy with trimetazidine after DES implantation can have a beneficial effect on recurrent angina pectoris as well as LV function and structure in elderly multivessel CHD patients with DM. [ABSTRACT FROM AUTHOR]

A spontaneously restored sinus rhythm in permanent atrial fibrillation patients has been often observed after mitral valve (MV) surgery, but persisting duration in sinus rhythm varies from patient to patient. Heat shock proteins (Hsps) may be involved in pathogenesis of atrial fibrillation. We hypothesized that stabilization of restored sinus rhythm is associated with expression of Hsps in the atria. To test this hypothesis, clinical data, biopsies of right atrial appendage, and blood samples were collected from 135 atrial fibrillation patients who spontaneously restored sinus rhythm after conventional isolated MV replacement. Comparison was made between patients who had recurrence of atrial fibrillation within 7 days (AF) vs. patients with persisted sinus rhythm for more than 7 days (SR). Results showed that SR patients had higher activity of heat shock transcription factor 1 (HSF1) as well as upregulated expressions of heat shock cognate 70, Hsp70, and Hsp27 in the tissues. The activation of HSF1-Hsps pathway was associated with less-aggressive pathogenesis as reflected by lower rates of myolysis, apoptosis, interstitial fibrosis, and inflammation in SR patients. However, Hsp60 was lower in both tissue and plasma in SR patients, and was positively correlated with apoptosis, interstitial fibrosis, and inflammation. These findings suggest that the Hsps play important roles in stabilization of restored sinus rhythm after MV surgery by inhibiting AF-related atrial remodeling and arrhythmogenic substrates in atrial fibrillation patients. Low circulating Hsp60 levels preoperatively might predict a stable spontaneously restored sinus rhythm postoperatively. [ABSTRACT FROM AUTHOR]

Affiliation 1 incorrectly read "Department of Chemistry, The University of Hong Kong, Hong Kong S.A.R., People's Republic of China". This has now been corrected to "Department of Chemistry, State Key Laboratory of Synthetic Chemistry, CAS-HKU Joint Laboratory of Metallomics on Health and Environment, The University of Hong Kong, Hong Kong S.A.R., People's Republic of China". in both the PDF and HTML versions of the Article. [Extracted from the article]

Ankylosing spondylitis (AS) is a common chronic progressive inflammatory autoimmune disease. T helper 17 (Th17) cells are the major effector cells mediating AS inflammation. Histone 3 Lys 27 trimethylation (H3K27me3) is an inhibitory histone modification that silences gene transcription and plays an important role in Th17 differentiation. The objective of this study was to investigate the expression of H3K27me3 in patients with AS and to explore its epigenetic regulation mechanism of Th17 differentiation during AS inflammation. We collected serum samples from 45 patients with AS at various stages and 10 healthy controls to measure their Interleukin-17 (IL-17) levels using ELISA. A quantitative polymerase chain reaction was used to quantify the mRNA levels of RORc and the signaling molecules of the JAK2/STAT3 pathway, JMJD3, and EZH2. Additionally, Western blot analysis was performed to quantify the protein levels of H3K27me3, RORγt, JAK2, STAT3, JMJD3, and EZH2 in cell protein extracts. The results showed that H3K27me3 expression in peripheral blood mononuclear cells (PBMCs) was significantly lower in patients with active AS compared to both the normal control groups and those with stable AS. Moreover, a significant negative correlation was observed between H3K27me3 expression and the characteristic transcription factor of Th17 differentiation, RORγt. We also discovered that patients with active AS exhibited significantly higher levels of JMJD3, an inhibitor of H3K27 demethylase, compared to the normal control group and patients with stable AS, while the expression of H3K27 methyltransferase (EZH2) was significantly lower. These findings suggest that H3K27me3 may be a dynamic and important epigenetic modification in AS inflammation, and JMJD3/EZH2 regulates the methylation level of H3K27me3, which may be one of the key regulatory factors in the pathogenesis of AS. These findings contribute to our understanding of the role of epigenetics in AS and may have implications for the development of novel therapeutic strategies for AS. [ABSTRACT FROM AUTHOR]

Uncontrolled activation of TGFβ signaling is a common denominator of fibrotic tissue remodeling. Here we characterize the tyrosine phosphatase SHP2 as a molecular checkpoint for TGFβ-induced JAK2/STAT3 signaling and as a potential target for the treatment of fibrosis. TGFβ stimulates the phosphatase activity of SHP2, although this effect is in part counterbalanced by inhibitory effects on SHP2 expression. Stimulation with TGFβ promotes recruitment of SHP2 to JAK2 in fibroblasts with subsequent dephosphorylation of JAK2 at Y570 and activation of STAT3. The effects of SHP2 on STAT3 activation translate into major regulatory effects of SHP2 on fibroblast activation and tissue fibrosis. Genetic or pharmacologic inactivation of SHP2 promotes accumulation of JAK2 phosphorylated at Y570, reduces JAK2/STAT3 signaling, inhibits TGFβ-induced fibroblast activation and ameliorates dermal and pulmonary fibrosis. Given the availability of potent SHP2 inhibitors, SHP2 might thus be a potential target for the treatment of fibrosis. Hyperactivation of TGFβ signaling is a common feature of fibrotic diseases. Here the authors show that genetic or pharmacologic inactivation of the tyrosine phosphatase SHP2 prevents TGFβ-induced JAK2/STAT3 signaling, inhibits fibroblast activation and exerts potent anti-fibrotic effects. [ABSTRACT FROM AUTHOR]