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Summary: T helper (Th)17 cells mediate both protective anti-bacterial immune responses and autoimmune pathogenesis, but the distinct pathways regulating these Th17 responses remain unclear. Retinoid-related orphan receptor γ t (RORγt) is a master transcription factor that governs Th17 cell generation and effector functions. We found that a K256R mutation in RORγt impairs Th17-mediated experimental autoimmune encephalomyelitis (EAE) without affecting the clearance of Citrobacter rodentium. This indicates distinct RORγt roles in central nervous system pathogenesis versus gut-associated protective Th17 responses. Mechanically, RORγt/Runx1-dependent upregulation of galectin-3 (Lgals3) and chemokine receptor Ccr6 in CD4+ T cells is essential for EAE development but not for bacterial clearance. Moreover, Lgals3 is selectively required for recruiting macrophages to produce interleukin (IL)-1β, which in turn promotes Ccr6 expression on CD4+ T cells during EAE pathogenesis. Our findings highlight different RORγt-regulated Th17 pathways in autoimmunity and anti-bacterial immunity, with implications for therapies targeting Th17-mediated autoimmunity while preserving effective anti-bacterial responses.

Choristoneura metasequoiacola Liu, 1983 is an important caterpillar species that specifically infests the leaves and branches of Metasequoia glyptostroboides Hu & W. C. Cheng 1948 with short larval infestations, long-term dormancy, and has a limited distribution in Lichuan, Hubei, China. The complete mitochondria genome of C. metasequoiacola was determined by using Illumina NovaSeq, and analyzed based on previously annotated sibling species. In total, we obtained mitochondria genome with 15,128 bp in length, circular in shape with a double-stranded closed ring structure, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and an AT-rich region. Of which the nucleotide composition was highly A + T biased, accounting for 81.98% of the whole mitogenome. Thirteen protein-coding genes (PCGs) were 11,142 bp; Twenty-two tRNA genes and AT-rich region were 1,472 and 199 bp, respectively. Phylogenetically, the relationship between Choristoneura spp. (containing C. metasequoiacola) and Adoxophyes spp. was closer than any other two genera from Tortricidae, and the relationship between C. metasequoiacola and C.murinana was the closest among nine sibling species from that genus, which helps to explain species evolution within the family Tortricidae.

Highlights Kevlar polyanionic chains induced the formation of highly ordered porous thermoplastic polyurethane foams with adjustable pore sizes. A tiny amount of Ti3C2Tx MXene was performed as reducing agent for the electroless deposition of copper nanoparticles. The conductive foam reinforced by aramid nanofibers exhibited excellent piezoresistive sensing and electromagnetic interference shielding performance.

Background: Nicotinamide adenine dinucleotide (NAD+), a coenzyme that plays crucial roles in many cellular processes, is a potential therapeutic target for various diseases. Dihydronicotinamide riboside (NRH), a novel reduced form of nicotinamide riboside, has emerged as a potent NAD+ precursor. Here, we studied the protective effects and underlying mechanism of NRH on aminoglycoside-induced ototoxicity. Methods: Auditory function and hair-cell (HC) morphology were examined to assess the effects of NRH on kanamycin-induced hearing loss. The pharmacokinetic parameters of NRH were measured in plasma and the cochlea using liquid chromatography tandem mass spectrometry. NAD+ levels in organ explant cultures were assessed to compare NRH with known NAD+ precursors. Immunofluorescence analysis was performed to detect reactive oxygen species (ROS) and apoptosis. We analyzed SIRT1 and 14–3–3 protein expression. EX527 and resveratrol were used to investigate the role of SIRT1 in the protective effect of NRH against kanamycin-induced ototoxicity. Results: NRH alleviated kanamycin-induced HC damage and attenuated hearing loss in mice. NRH reduced gentamicin-induced vestibular HC loss. Compared with NAD and NR, NRH produced more NAD+ in cochlear HCs and significantly ameliorated kanamycin-induced oxidative stress and apoptosis. NRH rescued the aminoglycoside-induced decreases in SIRT1 and 14–3–3 protein expression. Moreover, EX527 antagonized the protective effect of NRH on kanamycin-induced HC loss by inhibition of SIRT1, while resveratrol alleviated HC damage caused by EX527. Conclusions: NRH ameliorates aminoglycoside-induced ototoxicity by inhibiting HC apoptosis by activating SIRT1 and decreasing ROS. NRH is an effective therapeutic option for aminoglycoside-induced ototoxicity.

Otosclerosis is caused by abnormal bone remodeling in the middle ear, resulting in progressive hearing loss, dizziness, balance problems, and tinnitus. Previous infection, stress fractures of the bony tissue surrounding the inner ear, immune disorders, and genetic factors are believed to contribute to this disease. Currently, no effective drug treatment for otosclerosis is known. Herein, we generated an induced pluripotent stem cell line from the peripheral blood mononuclear cells of an otosclerosis patient. The cell line exhibited normal morphology, karyotype, and pluripotency marker expression. A teratoma assay revealed successful differentiation into all three germ layers.

Robotic bin-picking is a common process in modern manufacturing, logistics, and warehousing that aims to pick-up known or unknown objects with random poses out of a bin by using a robot-camera system. Rapid and accurate object pose estimation pipelines have become an escalating issue for robot picking in recent years. In this paper, a fast 6-DoF (degrees of freedom) pose estimation pipeline for random bin-picking is proposed in which the pipeline is capable of recognizing different types of objects in various cluttered scenarios and uses an adaptive threshold segment strategy to accelerate estimation and matching for the robot picking task. Particularly, our proposed method can be effectively trained with fewer samples by introducing the geometric properties of objects such as contour, normal distribution, and curvature. An experimental setup is designed with a Kinova 6-Dof robot and an Ensenso industrial 3D camera for evaluating our proposed methods with respect to four different objects. The results indicate that our proposed method achieves a 91.25% average success rate and a 0.265s average estimation time, which sufficiently demonstrates that our approach provides competitive results for fast objects pose estimation and can be applied to robotic random bin-picking tasks.

In this study, we investigate the problem of cooperative kinematic control for multiple redundant manipulators under partially known information using recurrent neural network (RNN). The communication among manipulators is modeled as a graph topology network with the information exchange that only occurs at the neighbouring robot nodes. Under partially known information, four objectives are simultaneously achieved, i.e, global cooperation and synchronization among manipulators, joint physical limits compliance, neighbor-to-neighbor communication among robots, and optimality of cost function. We develop a velocity observer for each individual manipulator to help them to obtain the desired motion velocity information. Moreover, a negative feedback term is introduced with a higher tracking precision. Minimizing the joint velocity norm as cost function, the considered cooperative kinematic control is built as a quadratic programming (QP) optimization problem integrating with both joint angle and joint speed limitations, and is solved online by constructing a dynamic RNN. Moreover, global convergence of the developed velocity observer, RNN controller and cooperative tracking error are theoretically derived. Finally, under a fixed and variable communication topology, respectively, application in using a group of iiwa R800 redundant manipulators to transport a payload and comparison with the existing method are conducted. Among the simulative results, the robot group synchronously achieves the desired circle and rhodonea trajectory tracking, with higher tracking precision reaching to zero. When joint angles and joint velocities tend to exceed the setting constraints, respectively, they are constrained into the upper and lower bounds owing to the designed RNN controller.

Learning movement primitive from unstructured demonstrations has become a popular topic in recent years, which provides a natural way to endow human-inspired skills to robots. The main idea of movement primitives is that should suffice to reconstruct a large set of complex manipulation tasks. However, conventional learning methods mostly focus on the kinesthetic variables and ignore those critical introspective capacities in manipulation such as movement generalization and assessment of the sensory signals. In this paper, we investigate the association of generalization, fault detection, fault diagnoses, and task exploration during manipulation task, and call such movement primitives augmented with introspective capacities Introspective Movement Primitives (IMP). With our previous work, this paper mainly addresses how IMPs can be acquired by assessing the quality of multimodal sensory data of unstructured demonstrations and how they can incrementally create manipulation task by reverse execution and human interaction. Experimental evaluation on a human-robot collaborative packaging task with a Rethink Baxter robot, results indicate that our proposed method can effectively increase robustness towards external perturbations and adaptive exploration during robot manipulation task.

Waardenburg syndrome (WS) is an inherited auditory-pigmentary syndrome characterized by deafness and pigment abnormalities. Here, we generated an induced pluripotent stem cell (iPSC) line using episomal plasmid vectors from the fibroblasts of an 8-year-old boy affected with WS, caused by a novel mutation in the SOX10 gene (NM_006941.3: c.937_947del; p.Tyr313Argfs*85), with a concurrent hotspot mutation in the GJB2 gene (NM_004004.5:c.235delC; p.Leu79Cysfs*3). The expression of pluripotency markers of the iPSC cell line was verified at both the mRNA and protein levels and the pluripotency state of the cell line was demonstrated by the capability to differentiate into all three germ layers.

A persistent increase in the number of lung fibroblasts (LFs) is found in the interstitium of the lungs of infants with bronchopulmonary dysplasia (BPD), which leads to lung fibrosis. P16 methylation plays an important role in the pathogenesis of BPD. 5-aza-2′-deoxycytidine (5-aza-CdR) is a major methyltransferase-specific inhibitor. This study investigated the effects of 5-aza-CdR on LFs in vitro from a hyperoxia-induced lung fibrosis model in newborn rats. Methods: Methylation-specific polymerase chain reaction (PCR) and Western blotting were performed to determine P16 gene methylation status and protein expression after LFs were treated with 0 μmol/L, 0.5 μmol/L, 1.0 μmol/L, and 5.0 μmol/L 5-aza-CdR for 120 hours. Proliferation was assessed by an MTT assay after LFs were treated with 0 μmol/L, 0.5 μmol/L, 1.0 μmol/L, and 5.0 μmol/L 5-aza-CdR for 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours. At the final time point, cells were also analyzed by flow cytometry to identify any change in their cell cycle profiles. Results: A methylated P16 gene promoter was detected in hyperoxia LFs. Following treatment with 5-aza-CdR, partial methylation and demethylation was detected. The expression protein's level of the P16 gene was significantly higher in the 5.0 μmol/L 5-aza-CdR-treated group compared with that in the control group (p

Robot introspection aids robots to understand what they do and how they do it. Previous robot introspection techniques have often used parametric hidden Markov models or supervised learning techniques, implying that the number of hidden states or classes is defined a priori and fixed through the entire modeling process. Fixed parameterizations limit the modeling power of a process to properly encode the data. Furthermore, first-order Markov models are limited in their ability to model complex data sequences that represent highly dynamic behaviors as they assume observations are conditionally independent given the state. In this work, we contribute a Bayesian nonparametric autoregressive Hidden Markov model for the monitoring of robot contact tasks, which are characterized by complex dynamical data that are hard to model. We used a nonparametric prior that endows our hidden Markov models with an unbounded number of hidden states for a given robot skill (or subtask). We use a hierarchical Dirichlet stochastic process prior to learn an hidden Markov model with a switching vector autoregressive observation model of wrench signatures and end-effector pose for the manipulation contact tasks. The proposed scheme monitors both nominal skill execution and anomalous behaviors. Two contact tasks are used to measure the effectiveness of our approach: (i) a traditional pick-and-place task composed of four skills and (ii) a cantilever snap assembly task (also composed of four skills). The modeling performance or our approach was compared with other methods, and classification accuracy measures were computed for skill and anomaly identification. The hierarchical Dirichlet stochastic process prior to learn an hidden Markov model with a switching vector autoregressive observation model was shown to have excellent process monitoring performance with higher identification rates and monitoring ability.

Robot introspection is expected to greatly aid longer-term autonomy of autonomous manipulation systems. By equipping robots with abilities that allow them to assess the quality of their sensory data, robots can detect and classify anomalies and recover appropriately from common anomalies. This work builds on our previous Sense-Plan-Act-Introspect-Recover (SPAIR) system. We introduce an improved anomaly detector that exploits latent states to monitor anomaly occurrence when robots collaborate with humans in shared workspaces, but also present a multiclass classifier that is activated with anomaly detection. Both implementations are derived from Bayesian non-parametric methods with strong modeling capabilities for learning and inference of multivariate time series with complex and uncertain behavior patterns. In particular, we explore the use of a hierarchical Dirichlet stochastic process prior to learning a Hidden Markov Model (HMM) with a switching vector auto-regressive observation model (sHDP-VAR-HMM). The detector uses a dynamic log-likelihood threshold that varies by latent state for anomaly detection and the anomaly classifier is implemented by calculating the cumulative log-likelihood of testing observation based on trained models. The purpose of our work is to equip the robot with anomaly detection and anomaly classification for the full set of skills associated with a given manipulation task. We consider a human–robot cooperation task to verify our work and measure the robustness and accuracy of each skill. Our improved detector succeeded in detecting 136 common anomalies and 368 nominal executions with a total accuracy of 91.0%. An overall anomaly classification accuracy of 97.1% is derived by performing the anomaly classification on an anomaly dataset that consists of 7 kinds of detected anomalies from a total of 136 anomalies samples.

Background: Depression and smoking decrease health status in Chronic Obstructive Pulmonary Disease (COPD), but the combined effect of the two factors is unknown. This study aimed to assess the interactive effects of depression and smoking on the severity of patients with COPD. Methods: A prospective cohort study including 2,268 patients with COPD was conducted in seven rural communities from May 2008 to May 2012. The relationships between the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and depression and nicotine addiction were assessed. The product of depression and smoking was added to the logistic regression model to evaluate the multiplicative interaction and relative excess risk of interaction (RERI). The Attributable Proportion (AP) of interaction and the synergy index (S) was applied to evaluate the additive interaction of two factors. Results: The severity of COPD in patients with depressive symptoms who never smoked was increased 1.74-fold and in smoking patients it increased by 6.08-fold. Highly addicted smokers with depressive symptoms had a nearly 40-fold increase in severity (all P

Repetitive Transcranial Magnetic Stimulation (rTMS) is a novel therapeutic tool to induce a suppression of tinnitus. However, the optimal target sites are unknown. We aimed to determine whether low-frequency rTMS induced lasting suppression of tinnitus by decreasing neural activity in the cortex, navigated by high-density electroencephalogram (EEG) source analysis, and the utility of EEG for targeting treatment.In this controlled three-armed trial, seven normal hearing patients with tonal tinnitus received a 10-day course of 1-Hz rTMS to the cortex, navigated by high-density EEG source analysis, to the left temporoparietal cortex region, and to the left temporoparietal with sham stimulation. The Tinnitus handicap inventory (THI) and a visual analog scale (VAS) were used to assess tinnitus severity and loudness. Measurements were taken before, and immediately, 2 weeks, and 4 weeks after the end of the interventions.Low-frequency rTMS decreased tinnitus significantly after active, but not sham, treatment. Responders in the EEG source analysis-based rTMS group, 71.4% (5/7) patients, experienced a significant reduction in tinnitus loudness, as evidenced by VAS scores. The target site of neuronal generators most consistently associated with a positive response was the frontal lobe in the right hemisphere, sourced using high-density EEG equipment, in the tinnitus patients. After left temporoparietal rTMS stimulation, 42.8% (3/7) patients experienced a decrease in tinnitus loudness.Active EEG source analysis based rTMS resulted in significant suppression in tinnitus loudness, showing the superiority of neuronavigation-guided coil positioning in dealing with tinnitus. Non-auditory areas should be considered in the pathophysiology of tinnitus. This knowledge in turn can contribute to investigate the pathophysiology of tinnitus.

T cell activation stimulates substantially increased protein synthesis activity to accumulate sufficient biomass for cell proliferation. The protein synthesis is fueled by the amino acids transported from the environment. Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. Here, we show that SRC2 recruited by c-Myc enhances CD4+ T cell activation to stimulate immune responses via upregulation of amino acid transporter Slc7a5. Mice deficient of SRC2 in T cells (SRC2fl/fl/CD4Cre) are resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and susceptible to Citrobacter rodentium (C. rodentium) infection. Adoptive transfer of naive CD4+ T cells from SRC2fl/fl/CD4Cre mice fails to elicit EAE and colitis in Rag1/recipients. Further, CD4+ T cells from SRC2fl/fl/CD4Cre mice display defective T cell proliferation, cytokine production, and differentiation both in vitro and in vivo. Mechanically, SRC2 functions as a coactivator to work together with c-Myc to stimulate the expression of amino acid transporter Slc7a5 required for T cell activation. Slc7a5 fails to be up-regulated in CD4+ T cells from SRC2fl/fl/CD4Cre mice, and forced expression of Slc7a5 rescues proliferation, cytokine production, and the ability of SRC2fl/fl/CD4Cre CD4+ T cells to induce EAE. Therefore, SRC2 is essential for CD4+ T cell activation and, thus, a potential drug target for controlling CD4+ T cell-mediated autoimmunity. [ABSTRACT FROM AUTHOR]

Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic studywide significant loci (P,2.63 x 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 x 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 x 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent. [ABSTRACT FROM AUTHOR]

Human-Robot Collaboration (HRC) has been widely used in daily life and industry for maximizing the advantages of humans and robots, respectively. However, the internal modeling errors or external perturbations still affect robotic systems such as human collisions and environmental changes. Multimodal anomaly detection plays an increasingly important role in HRC applications, which detects unexpected anomalies from multimodal signals. Due to the complex temporal dependence and stochasticity, it is still difficult to choose a common model applicable to all collaborative tasks, and lack of comparative analysis of existing methods and verification of specific application cases. In this paper, six representative deep learning-based methods are evaluated and the comparing metrics including detection accuracy, multi-modality combinations, and anomaly time bias. For a fair comparison, each detector models multimodal signals from non-anomalous samples and then determines an anomaly using a predefined threshold. We evaluate the detectors with force, torque, velocity, tactile, and kinematic sensing during a human-robot kitting experiment that consists of six individual skills, results indicate that the LSTM-DAGMM based detector outperformed the others, which yielding higher accuracy and efficiency. The metrics are measured with the RUC and ROC by changing the settings of multi-modality combinations and various anomaly biases, which aim to obtain the best performance of multimodal anomaly detection. [ABSTRACT FROM AUTHOR]

Overnight polysomnography (PSG) is currently the gold standard for diagnosing obstructive sleep apnea (OSA); however, it is time-consuming, expensive and uncomfortable for the patient. A micromovement sensitive mattress (MSM) sleep-monitoring system was developed as an alternative to PSG, however, there has yet to be a study verifying the accuracy of diagnosing OSA with this device. Therefore, the present study assessed the validity of the MSM sleep-monitoring system. Chinese Han participants who were suspected of having OSA were recruited between June 2013 and June 2014. The MSM sleep-monitoring system and PSG were utilized simultaneously overnight on each subject. The apnea-hypopnea index (AHI) was measured by the MSM sleep-monitoring system (AHIMSM) and compared with that determined by PSG (AHIPSG), revealing a significant correlation between the two values (r=0.97, P<0.001). Bland-Altman plots also indicated good agreement (97%) between MSM and PSG. Using an AHIPSG cut-off of ≥5, ≥15 and ≥30 events/h, the sensitivity (specificity) of detecting an AHIMSM of ≥5, ≥15, and ≥30 events/h were 94.9 (100%), 89.9 (96.9%) and 90.3% (94.9%), respectively. The areas under the receiver operating characteristic curve, which were used to differentiate an AHIPSG of ≥5, ≥15 and ≥30 events/h in clinically diagnosed OSA, were 0.984, 0.982 and 0.980, respectively. Thus, the MSM sleeping system may accurately diagnose OSA in the Chinese Han population. Further community-based studies with larger sample sizes are warranted to confirm the validity of this MSM sleeping system. [ABSTRACT FROM AUTHOR]

BACKGROUND: A number of effective strategies have been developed to improve the quality of life in patients with COPD. However, few have been implemented in patients with COPD at all stages in a community setting. This study evaluated the efficacy of a complex COPD health management intervention in rural communities in China. METHODS: A randomized controlled trial including 8,217 subjects with COPD was implemented from May 2008 to May 2012 in 14 community health-care centers. The control group of subjects received usual care, whereas the management group of subjects participated in a health management program that included assessing the subjects’ health status, giving regular health lectures, smoking cessation counseling, encouraging regular exercise, providing rehabilitative training and psychological counseling, and regular followup. As a primary outcome, we examined the changes in the BODE index. Secondary outcomes included depression and anxiety rates, current smoking rate, awareness of COPD, mortality, risk factors, respiratory medication use, hospital admissions, and emergency department visits. RESULTS: After 4 y, the mean cumulative value of the BODE index increased by 0.7 per subject in the control group and decreased by 0.4 per subject in the health management group (difference of 1.1, 95% CI 0.2–2.0, P < .001). Health management reduced anxiety symptoms by 4.8%, depression symptoms by 6.6%, current smoking by 14.3%, mortality due to all causes by 9.0%, hospitalizations due to all causes by 16.1%, and emergency department visits due to all causes by 18.1% (P < .05 for all). However, it increased immunomodulator use by 58.9%, respiratory medication use by 14.1–21.9%, and awareness scores for COPD by 57.2% (P < .05 for all). CONCLUSIONS: The health management program is an effective community-based strategy for the prevention and management of COPD in China, increasing awareness and knowledge among patients and practitioners and improving management within the limitations of access to pharmacotherapy. [ABSTRACT FROM AUTHOR]

Hemi-ordered nanoporous carbon (HONC) was obtained from a mesoporous silica template through a nano-replication method using furfuryl alcohol as the carbon source. The structure and morphology of HONC were characterized and analyzed in detail by X-ray diffraction, N2-sorption, Raman spectroscopy and transmission electron microscopy. HONC was then demonstrated as active electrode material for selective determination of nitrite in either physiological or environmental system. Well separated oxidation peaks of ascorbic acid, dopamine, uric acid and nitrite were observed in physiological system, and simultaneous discrimination of catechol, hydroquinone, resorcinol and nitrite in environmental system was also accomplished. Distinctly improved performances for selective determination of nitrite (such as significantly fast and sensitive current response with especially high selectivity) coexisted with ascorbic acid, dopamine and uric acid in the physiological system, as well as with catechol, hydroquinone and resorcinol in the environmental system were achieved at HONC electrode material. The excellent discriminating ability and high selectivity for NO2- determination were ascribed to the good electronic conductivity, unique hemi-ordered porous structure, large surface area and large number of edge plane defect sites contained on the surface of nanopore walls of HONC. Results in this work demonstrated that HONC is one of the promising catalytic electrode materials for nitrite sensor fabrication. [ABSTRACT FROM AUTHOR]

BACKGROUND: Smoking, depression, and anxiety increase the risk of death in patients with COPD, but the combined effect of these factors is unknown. We assessed the interactive effects of smoking, depression, and anxiety on mortality in patients with COPD. METHODS: We collected and analyzed data from 7,787 subjects with COPD, in 14 rural communities, from May 2008 to May 2012, and used logistic regression to evaluate the interactions and relative excess risk due to interaction (RERI). We applied the attributable proportion of interaction and the synergy index to evaluate the additive interactions of the factors. RESULTS: In our COPD subjects the interaction of current smoking and depression symptoms increased the death risk by 3.8-fold (odds ratio 3.78, 95% CI 2.51-5.05), with significant biological interactions (RERI 1.74, 95% CI 0.51_2.99, attributable proportion 0.48, 95% CI 0.13- 0.85, synergy index 2.98, 95% CI 1.44-4.56). The biological interactions increased with increasing years or pack-years of smoking: for subjects with ≥ 30 years of smoking: RERI 1.80, 95% CI 1.05-2.75, attributable proportion 0.48, 95% CI 0.15- 0.82, synergy index 2.85, 95% CI 1.75-3.96; for subjects with ≥ 40 pack-years of smoking: RERI 3.11, 95% CI 1.54-4.71, attributable proportion 0.60, 95% CI 0.31- 0.91, synergy index 4.00, 95% CI 2.84 -5.26. Similarly, the combined effect of current smoking and anxiety symptoms increased the death risk by 4.3-fold (odds ratio 4.27, 95% CI 95% CI 2.96 -5.59), with significant biological interactions (RERI 1.51, 95% CI 0.31-2.74, attributable proportion 0.46, 95% CI 0.11- 0.87, synergy index 2.89, 95% CI 1.31- 4.51). The biological interactions also increased with increasing years or pack-years of smoking: for subjects with ≥ 30 years of smoking: RERI 1.41, 95% CI 0.45-2.43, attributable proportion 0.45, 95% CI 0.12- 0.81, synergy index 2.88, 95% CI 1.24 -5.98; for subjects with ≥ 40 pack-years of smoking: RERI 3.15, 95% CI 2.07- 4.61, attributable proportion 0.55, 95% CI 0.21- 0.94, synergy index 3.00, 95% CI 1.45- 4.75. CONCLUSIONS: Smoking, depression, and anxiety are associated with higher risk of death in patients with COPD. The risk of death, depression, and anxiety increases with increasing duration of smoking (years) and cigarette pack-years. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) often have organ dysfunction and resulting poor quality of life; however, in China little information is available regarding factors that affect their health. Here, the relationship between risk factors, activities and psychological disorders and health of patients with COPD in rural areas of Xuzhou, China was assessed. Methods: A cross-sectional study of 7597 COPD patients randomly selected by place of residence from 24,641 COPD patients who had been identified by screening of the 1.10 million health records of all residents of the target area was carried out to evaluate the relationships between risk factors, activities, psychological disorders and the ADO index (age, dyspnea, and airflow obstruction). The participants were assessed by spirometry and by administering a newly designed face-to-face questionnaire, which included items on general factors, risk factors, activities and psychological disorders. Correlations between the ADO index and the items addressed by the questionnaire were calculated. Results: The mean score of the ADO index was 3.7 ± 1.6. The ADO indices of current smokers, ex-smokers, and non-smokers were 3.9 ± 2.1, 3.7 ± 1.9, and 3.2 ± 1.5, respectively (P < 0.001). The ADO indices of cooks and non-cooks were 4.0 ± 2.2 and 3.5 ± 1.7, respectively (P < 0.001). The correlation coefficient between self-assessment of health status and ADO index was 0.976 (P < 0.001). Only 5.7% of patients reported no limitation of their daily living activities. The correlation coefficient between daily living activities and ADO index was 0.981 (P < 0.001). Only 5.5% of patients reported no limitation of social activities. The correlation coefficient between social activities and ADO index was 0.989 (P < 0.001), between the assessed anxiety score and ADO index 0.972 (P < 0.001), and between the assessed depression score and ADO index 0.989 (P < 0.001). Conclusions: COPD severity was significantly correlated with behavior (especially regarding smoking and cooking with biofuel in confined spaces), physical strength, daily living activities, social activities, anxiety and depression. Comprehensive approaches are required for the prevention and treatment of COPD. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). But a fewer smoking cessation measures were conducted in communities for smokers with COPD in China. The aim of our study was to assess the preventive effects of behavioral interventions for smoking cessation and potential impact factors in smokers with COPD in China. Methods: In a randomised controlled smoking cessation trial 3562 patients with COPD who were current smoker were allocated to intervention group received behavioral intervention and control group received the usual care for two years. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of month 24 to the end of month 30. Participants were followed up at month 48. Results: Continuous smoking abstinence rates from month 24 to 30 were significantly higher in participants receiving behavioral intervention than in those receiving usual care (46.4% vs 3.4%, p < 0.001). Continuous abstinence rates from months 24 to 36 (45.8% vs 4.0%) and months 24 to 48 (44.3% vs 5.1%) were also higher in participants receiving behavioral intervention than in those control group. Family members or family physicians/ nurses smoking were first identified to influence smoking cessation. Conclusions: Behavioral intervention doubled the smoking cessation rate in patients with COPD and was complied well by the general practitioners. The family members and family physicians/nurses smoking were the main risk factors for smoking cessation. [ABSTRACT FROM AUTHOR]

Background: The incidence of chronic obstructive pulmonary disease (COPD) in China is very high. This study aimed to assess the vulnerability of COPD patients in rural areas outside Xuzhou City, Jiangsu province, in order to provide helpful guidance for future research and public policies. Methods: The vulnerability of 8,217 COPD patients was evaluated using a face-to-face questionnaire to obtain information on general characteristics, awareness, beliefs, medication usage, acute exacerbation of the disease, and economic burdens. Direct economic burdens were calculated based on the questionnaire, and indirect economic burdens were estimated using local per capita income and life expectancy in 2008. The years of potential life lost were calculated using loss of life years for each age group and multiplying by the number of deaths in a given age group. Results: Of the 8,217 patients, 7,921 (96.4%) had not heard of COPD, and 2,638 (32.1%) did not understand that smoking was a risk factor for COPD. No patients had used inhalers, nebulizer drugs or oxygen therapy, either regularly or sporadically. No patients had undergone pulmonary rehabilitation or surgical treatment, while 4,215 (51.3%) took theophylline to relieve dyspnea, and 3,418 (41.6%) used antibiotics to treat exacerbations. A total of 2,925 (35.6%) patients had been admitted to hospital during the past year because of respiratory symptoms. The average direct and indirect economic burdens on COPD patients were 1,090 and 20,605 yuan, respectively. Conclusions: The vulnerability of patients in rural Xuzhou to COPD was high. Their awareness of COPD was poor, their treatment during both the stable and acute exacerbation stages did not meet standards, and the economic burdens were large. Interventions are therefore needed to improve the prevention and management of COPD in this population. Further studies are required to verify these findings. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) often experience depression and anxiety, but little information is available regarding Chinese patients with these conditions. The present study assessed depression and anxiety in Chinese patients with COPD. Methods: A case-controlled study was designed with 1100 patients with COPD enrolled in the case group and1100 residents without COPD and respiratory symptoms selected as the control group. Anxiety and depression in both groups were evaluated using the Hospital Anxiety and Depression Scale (HADS). The body mass index, degree of airflow obstruction, dyspnea, and exercise capacity (BODE ) index was used to assess COPD severity. Binary logistic regression models were used to test the association between anxiety and depression. Results: The patients with COPD were more likely than controls to experience depression (cases, HADS 10.5 ± 3.6, prevalence 35.7%; controls, HADS 8.7 ± 2.7, prevalence 7.2%) and anxiety (cases, HADS 10.4 ± 3.1, prevalence 18.3%; controls, HADS 8.6 ± 2.1, prevalence 5.3%). Subjects with anxious and depressive symptoms had poorer health outcomes including a higher BODE index, a shorter 6-minute-walk distance (6MWD), more dyspnea, and a higher St George's respiratory questionnaire (SGRQ) score. The prevalence of anxious and depressive symptoms increased with increasing BODE scores. On the basis of binary logistic regression, the BODE index was significantly correlated with anxiety (OR = 1.47, p < 0.001) and depression (OR = 1.51, p < 0.001). Anxious and depressive symptoms were also associated with several factors including younger age, female sex, higher education level, lower household income and history of smoking. Conclusions: This study confirmed the high prevalence of anxiety and depression in Chinese outpatients with COPD. Patients with COPD who had anxiety and/or depression had a poorer health-related quality of life. [ABSTRACT FROM AUTHOR]

A novel method for the determination of Pb2+ has been developed based on quenching of the fluorescence of thiol-capped CdTe quantum dots (QDs) by Pb2+ in aqueous solutions. Under optimum conditions, the relative fluorescence intensity was linearly proportional to the concentration of Pb2+ between 2.0 × 10−6 and 1.0 × 10−4 mol L−1 with a detection limit of 2.7 × 10−7 mol L−1. The relative standard deviation (RSD) was 4.6% for a 4.0 × 10−5 mol L−1 Pb2+ solution ( N = 5). As an application, the proposed method was successfully applied to the analysis of Pb2+ in food samples, and the results were satisfactory, i.e. consistent with those of flame atomic absorption spectrometry (FAAS). [ABSTRACT FROM AUTHOR]

Recurrent somatic mutations in spliceosome factor 3b subunit 1 (SF3B1) are identified in hematopoietic malignancies, with SF3B1-K700E being the most common one. Here, we show that regulatory T cell (Treg)-specific expression of SF3B1-K700E (Sf3b1K700Efl/+/Foxp3YFP-Cre) results in spontaneous autoimmune phenotypes. CD4+ T cells from Sf3b1K700Efl/+/Foxp3YFP-Cre mice display defective Treg differentiation and inhibitory function, which is demonstrated by failed prevention of adoptive transfer colitis by Sf3b1K700Efl/+/Foxp3YFP-Cre Tregs. Mechanically, SF3B1-K700E induces an aberrant splicing event that results in reduced expression of a cell proliferation regulator Anapc13 due to the insertion of a 231-base pair DNA fragment to the 5' untranslated region. Forced expression of the Anapc13 gene restores the differentiation and ability of Sf3b1K700Efl/+/Foxp3YFP-Cre Tregs to prevent adoptive transfer colitis. In addition, acute myeloid leukemia grows faster in aged, but not young, Sf3b1K700Efl/+/Foxp3YFP-Cre mice compared to Foxp3YFP-Cre mice. Our results highlight the impact of cancer-associated SF3B1 mutation on immune responses, which affect cancer development. [ABSTRACT FROM AUTHOR]

The article presents a study which explores about steroid nuclear receptor coactivator 2 controls immune tolerance by promoting induced Treg differentiation via up-regulating Nr4a2. It mentions that Regulatory T cells (Tregs) are essential to protect against autoimmune responses, maintain homeostasis, and damp immune responses after clearance of infection.

The 1,815,783-bp genome of a serotype M49 strain of Streptococcus pyogenes (group A streptococcus [GAS]), strain NZ131, has been determined. This GAS strain (FCT type 3; emm pattern E), originally isolated from a case of acute post-streptococcal glomerulonephritis, is unusually competent for electrotransformation and has been used extensively as a model organism for both basic genetic and pathogenesis investigations. As with the previously sequenced S. pyogenes genomes, three unique prophages are a major source of genetic diversity. Two clustered regularly interspaced short palindromic repeat (CRISPR) regions were present in the genome, providing genetic information on previous prophage encounters. A unique cluster of genes was found in the pathogenicity island-like emm region that included a novel Nudix hydrolase, and, further, this cluster appears to be specific for serotype M49 and M82 strains. Nudix hydrolases eliminate potentially hazardous materials or prevent the unbalanced accumulation of normal metabolites; in bacteria, these enzymes may play a role in host cell invasion. Since M49 S. pyogenes strains have been known to be associated with skin infections, the Nudix hydrolase and its associated genes may have a role in facilitating survival in an environment that is more variable and unpredictable than the uniform warmth and moisture of the throat. The genome of NZ131 continues to shed light upon the evolutionary history of this human pathogen. Apparent horizontal transfer of genetic material has led to the existence of highly variable virulence-associated regions that are marked by multiple rearrangements and genetic diversification while other regions, even those associated with virulence, vary little between genomes. The genome regions that encode surface gene products that will interact with host targets or aid in immune avoidance are the ones that display the most sequence diversity. Thus, while natural selection favors stability in much of the genome, it favors diversity in these regions. [ABSTRACT FROM AUTHOR]