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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., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 (T reg )-specific expression of SF3B1-K700E ( Sf3b1 K700Efl/+ /Foxp3 YFP-Cre ) results in spontaneous autoimmune phenotypes. CD4 + T cells from Sf3b1 K700Efl/+ /Foxp3 YFP-Cre mice display defective T reg differentiation and inhibitory function, which is demonstrated by failed prevention of adoptive transfer colitis by Sf3b1 K700Efl/+ /Foxp3 YFP-Cre T regs . 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 Sf3b1 K700Efl/+ /Foxp3 YFP-Cre T regs to prevent adoptive transfer colitis. In addition, acute myeloid leukemia grows faster in aged, but not young, Sf3b1 K700Efl/+ /Foxp3 YFP-Cre mice compared to Foxp3 YFP-Cre mice. Our results highlight the impact of cancer-associated SF3B1 mutation on immune responses, which affect cancer development.

Objectives: The study aimed to develop a deep learning-based edge AI model deployed on electrocardiograph (ECG) devices for the real-time detection of atrial fibrillation (AF) risk during sinus rhythm (SR) using standard 10 s, 12-lead electrocardiograms (ECGs). Methods: A novel approach was used to convert standard 12-lead ECGs into binary images for model input, and a lightweight convolutional neural network (CNN)-based model was trained using data collected by the Japan Agency for Medical and Research Development (AMED) between 2019 and 2022. Patients over 40 years old with digital, SR ECGs were retrospectively enrolled and divided into AF and non-AF groups. The data labeling was supervised by cardiologists. The dataset was randomly allocated into training, validation, and internal testing datasets. External testing was conducted on data collected from other hospitals. Results: The best-trained model achieved an AUC of 0.82 and 0.80, sensitivity of 79.5% and 72.3%, specificity of 77.8% and 77.7%, precision of 78.2% and 76.4%, and overall accuracy of 78.6% and 75.0% in the internal and external testing datasets, respectively. The deployed model and app package utilized 2.5 MB and 40 MB of the available ROM and RAM capacity on the edge ECG device, correspondingly. The processing time for AF risk detection was approximately 2 s. Conclusions: The model maintains comparable performance and improves its suitability for deployment on resource-constrained ECG devices, thereby expanding its potential impact to a wide range of healthcare settings. Its successful deployment enables real-time AF risk detection during SR, allowing for timely intervention to prevent AF-related serious consequences like stroke and premature death.

Steroid receptor coactivator (SRC) family members (SRC1, SRC2 and SRC3) are transcriptional co-regulators. SRCs orchestrate gene transcription by inducing transactivation of nuclear receptors and other transcription factors. Overexpression of SRCs is widely implicated in a range of cancers, especially hormone-related cancers. As coactivators, SRCs regulate multiple metabolic pathways involved in tumor growth, invasion, metastasis, and chemo-resistance. Emerging evidence in recent years suggest that SRCs also regulate maturation, differentiation, and cytotoxicity of T cells by controlling metabolic activities. In this review, we summarize the current understanding of the function of SRCs in T cells as well as cancer cells. Importantly, the controversies of targeting SRCs for cancer immunotherapy as well as possible reconciliation strategies are also discussed.

Nuclear receptor coactivator 2 (Ncoa2) is a member of the Ncoa family of coactivators, and we previously showed that Ncoa2 regulates the differentiation of induced regulatory T cells. However, it remains unknown if Ncoa2 plays a role in CD8+ T-cell function. Here, we show that Ncoa2 promotes CD8+ T cell-mediated immune responses against tumors by stimulating T-cell activation via upregulating PGC-1α expression to enhance mitochondrial function. Mice deficient in Ncoa2 in T cells (Ncoa2fl/fl/CD4Cre) displayed defective immune responses against implanted MC38 tumors, which associated with significantly reduced tumor-infiltrating CD8+ T cells and decreased IFNγ production. Consistently, CD8+ T cells from Ncoa2fl/fl/CD4Cre mice failed to reject tumors after adoptive transfer into Rag1-/- mice. Further, in response to TCR stimulation, Ncoa2fl/fl/CD4Cre CD8+ T cells failed to increase mitochondrial mass, showed impaired oxidative phosphorylation, and had lower expression of PGC-1α, a master regulator of mitochondrial biogenesis and function. Mechanically, T-cell activation-induced phosphorylation of CREB triggered the recruitment of Ncoa2 to bind to enhancers, thus, stimulating PGC-1α expression. Forced expression of PGC-1α in Ncoa2fl/fl/CD4Cre CD8+ T cells restored mitochondrial function, T-cell activation, IFNγ production, and antitumor immunity. This work informs the development of Ncoa2-based therapies that modulate CD8+ T cell-mediated antitumor immune responses., (©2023 American Association for Cancer Research.)

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., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

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 ( SRC2 fl/fl /CD4 Cre ) 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 SRC2 fl/fl /CD4 Cre mice fails to elicit EAE and colitis in Rag1 /  recipients. Further, CD4 + T cells from SRC2 fl/fl /CD4 Cre 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 SRC2 fl/fl /CD4 Cre mice, and forced expression of Slc7a5 rescues proliferation, cytokine production, and the ability of SRC2 fl/fl /CD4 Cre 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.

Highly ordered and uniformly porous structure of conductive foams is a vital issue for various functional purposes such as piezoresistive sensing and electromagnetic interference (EMI) shielding. With the aids of Kevlar polyanionic chains, thermoplastic polyurethane (TPU) foams reinforced by aramid nanofibers (ANF) with adjustable pore-size distribution were successfully obtained via a non-solvent-induced phase separation. In this regard, the most outstanding result is the in situ formation of ANF in TPU foams after protonation of Kevlar polyanion during the NIPS process. Furthermore, in situ growth of copper nanoparticles (Cu NPs) on TPU/ANF foams was performed according to the electroless deposition by using the tiny amount of pre-blended Ti 3 C 2 T x MXene as reducing agents. Particularly, the existence of Cu NPs layers significantly promoted the storage modulus in 2,932% increments, and the well-designed TPU/ANF/Ti 3 C 2 T x MXene (PAM-Cu) composite foams showed distinguished compressive cycle stability. Taking virtues of the highly ordered and elastic porous architectures, the PAM-Cu foams were utilized as piezoresistive sensor exhibiting board compressive interval of 0-344.5 kPa (50% strain) with good sensitivity at 0.46 kPa -1 . Meanwhile, the PAM-Cu foams displayed remarkable EMI shielding effectiveness at 79.09 dB in X band. This work provides an ideal strategy to fabricate highly ordered TPU foams with outstanding elastic recovery and excellent EMI shielding performance, which can be used as a promising candidate in integration of satisfactory piezoresistive sensor and EMI shielding applications for human-machine interfaces., (© 2023. The Author(s).)

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 study-wide significant loci ( P  < 2.63 × 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 × 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 × 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.

Introduction: This study investigated the effect of sound therapy combined with drug therapy (SDT) on gap detection threshold and speech recognition scores in patients with sudden sensorineural hearing loss (SSNHL)., Methods: Patients with SSNHL were grouped randomly into SDT and drug therapy (DT) groups. All patients received standard drug treatment and patients in the SDT group additionally received sound stimulation for the affected ears for 6 days. Pure tone audiogram, speech recognition scores at normal and time-compressed rates under quiet and noisy conditions, and the gap detection threshold of the SDT and DT groups before treatment and on day 6 and 30 after treatment were compared., Results: There were 20 patients in the SDT group and 24 in the DT group. The pure tone thresholds of affected ears were significantly lower in the SDT group on day 6 after treatment than those in the DT group at 125 and 250 Hz. Significantly lower gap detection thresholds and higher speech recognition scores under noisy conditions were observed at the normal and time-compressed rates in the SDT group than those in the DT group on day 6 and 30 after treatment. Significant correlations were observed between the gap thresholds and speech recognition scores in a noisy environment at normal and time-compressed rates on day 6 and 30., Conclusions: SDT may improve the recovery of hearing abilities, such as the gap in noise thresholds and speech recognition in noise, in the case of SSNHL., Trial Registration Number: ChiCTR-IOR-17012262., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

RORγt is known to instruct the differentiation of T helper 17 (T H 17) cells that mediate the pathogenesis of autoimmune diseases. However, it remains unknown whether RORγt plays a distinct role in the differentiation and effector function of T H 17 cells. Here, we show that mutation of RORγt lysine-256, a ubiquitination site, to arginine (K256R) separates the RORγt role in these two functions. Preventing ubiquitination at K256 via arginine substitution does not affect RORγt-dependent thymocyte development, and T H 17 differentiation in vitro and in vivo, however, greatly impaired the pathogenesis of T H 17 cell-mediated experimental autoimmune encephalomyelitis (EAE). Mechanistically, K256R mutation impairs RORγt to bind to and activate Runx1 expression critical for T H 17-mediated EAE. Thus, RORγt regulates the effector function of T H 17 cells in addition to T H 17 differentiation. This work informs the development of RORγt-based therapies that specifically target the effector function of T H 17 cells responsible for autoimmunity.

Grain size is a key agronomic trait that determines the yield in plants. Regulation of grain size by brassinosteroids (BRs) in rice has been widely reported. However, the relationship between the BR signaling pathway and grain size still requires further study. Here, we isolated a rice mutant, named small grain2 (sg2), which displayed smaller grain and a semi-dwarf phenotype. The decreased grain size was caused by repressed cell expansion in spikelet hulls of the sg2 mutant. Using map-based cloning combined with a MutMap approach, we cloned SG2, which encodes a plant-specific protein with a ribonuclease H-like domain. SG2 is a positive regulator downstream of GLYCOGEN SYNTHASE KINASE2 (GSK2) in response to BR signaling, and its mutation causes insensitivity to exogenous BR treatment. Genetical and biochemical analysis showed that GSK2 interacts with and phosphorylates SG2. We further found that BRs enhance the accumulation of SG2 in the nucleus, and subcellular distribution of SG2 is regulated by GSK2 kinase activity. In addition, Oryza sativa OVATE family protein 19 (OsOFP19), a negative regulator of grain shape, interacts with SG2 and plays an antagonistic role with SG2 in controlling gene expression and grain size. Our results indicated that SG2 is a new component of GSK2-related BR signaling response and regulates grain size by interacting with OsOFP19., (© 2022 Institute of Botany, Chinese Academy of Sciences.)

Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. While SRC1 inhibits the differentiation of regulatory T cells (T regs ) critical for establishing immune tolerance, we show here that SRC2 stimulates T reg differentiation. SRC2 is dispensable for the development of thymic T regs , whereas naive CD4 + T cells from mice deficient of SRC2 specific in T regs ( SRC2 fl/fl /Foxp3 YFP-Cre ) display defective T reg differentiation. Furthermore, the aged SRC2 fl/fl /Foxp3 YFP-Cre mice spontaneously develop autoimmune phenotypes including enlarged spleen and lung inflammation infiltrated with IFNγ-producing CD4 + T cells. SRC2 fl/fl /Foxp3 YFP-Cre mice also develop severer experimental autoimmune encephalomyelitis (EAE) due to reduced T regs . Mechanically, SRC2 recruited by NFAT1 binds to the promoter and activates the expression of Nr4a2 , which then stimulates Foxp3 expression to promote T reg differentiation. Members of SRC family coactivators thus play distinct roles in T reg differentiation and are potential drug targets for controlling immune tolerance.

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., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

With the development of electronic equipment, heat problem and electromagnetic pollution severely affect both their functions and human health, which leads to great interests in developing materials synchronously with outstanding thermal conductivity and electromagnetic interference (EMI) shielding performance. Here, ultrathin Ti 3 C 2 T x /h-BN two-dimensional (2D) heterostructure films were prepared via coulombic assembly between Ti 3 C 2 T x MXene and h-BN nanosheet through ultrasonic blending. After the addition of h-BN nanosheet as thermal conductive nanofillers, the hybrid films achieved a higher value of thermal conductivity, compared to Ti 3 C 2 T x composite film without h-BN. The higher thermal conductivity offered by h-BN enables the Ti 3 C 2 T x /h-BN films have good potential for EMI shielding applications on wearable and portable electronic devices. When the mass ratio of Ti 3 C 2 T x /h-BN is 7:3, the hybrid film with the thickness of 47.60 µm exhibited electrical conductivity of 57.67 S/cm and the maximum EMI shielding effectiveness of 37.29 dB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

p16 INK4a (p16) inhibits the vital G 1 to S phase transition during cell cycle progression through the p16/cyclin D1/CDK4/retinoblastoma(Rb)/E2F1 pathway. Hyperoxia can suppress the G 1 /S checkpoint and induce more lung fibroblasts (LFs) to transition from the G 1 phase to the S phase and undergo cell proliferation. The present study investigated the rate of p16 gene promoter methylation and the protein expression levels of p16, cyclin D1, CDK4, Rb and E2F1 in LFs from the lungs of rats exposed to hyperoxia and normoxia on postnatal days 3, 7 and 14. In the hyperoxia-exposed group, the methylation rate was 50 and 80% on days 7 and 14, respectively. Cyclin D1 and CDK4 overexpression was associated with p16 loss and Rb inactivation by phosphorylation. Rb phosphorylation induced E2F1 release in the G 1 phase, which promoted cell proliferation. No methylation was observed in the normoxia-exposed group. These observations suggested that p16 loss may stimulate aberrant LF proliferation via the p16/cyclin D1/CDK4/Rb/E2F1 pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

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.

Ti 3 C 2 T x MXenes with excellent metallic conductivity have proved promising in its application of electromagnetic interference (EMI) shielding. A hierarchical hybrid film with ultrathin thickness composed of Ti 3 C 2 T x MXene layers embedded with yarn-ball-shaped microspheres of cellulose nanofibrils (CNF) and multiwalled carbon nanotube (MWCNT) was designed to improve the absorption of electromagnetic waves (EMWs). The addition of yarn-ball-shaped microspheres is to shield more EMWs via multiple reflections in the inner space and reduce the undesirable emissions into the air. After thermal annealing treatment, the ultrathin film with intercalation of the carbonized yarn-ball-shaped CNF/MWCNT microspheres exhibited enhanced EMWs absorption as an important part of shielding effectiveness (45.1±0.9 dB) as well as excellent mechanical stability (≈0.9 million bending times). Thus, the well-designed structure of multilayered hybrid films with intercalated conductive microspheres can be a good candidate for higher absorption in EMI shielding effectiveness and outstanding mechanical properties., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

High-efficient electromagnetic interference (EMI) shielding films were successfully fabricated by electroless deposition of silver nanoparticles (AgNPs) on polydopamine (PDA) functionalized cellulose nanofibrils (CNFs) as building blocks according to a pressured-extrusion film-forming process. PDA was first functionalized on CNFs by oxidative self-polymerization of dopamine (DA) to synthesize CNFs@PDA, on which AgNPs were electrolessly deposited. The obtained CNFs@PDA@AgNPs composite films served as tightly-connected conductive network, so as to significantly improve the whole electrical conductivity of the EMI shielding films. Utilizing CNFs as green and soft matrix, the fabricated CNFs@PDA@AgNPs EMI films show an outstanding mechanical enduring performance. The CNFs@PDA@AgNPs films with weight ratios of CNFs:AgNO 3 = 1:24 exhibited superb electrical conductivity of 1,000,000 S m -1 and remarkable EMI shielding effectiveness of 93.8 dB at 8.2 GHz in X band. This work provides a simple methodology to achieve surface metallization of insulating fibers to supersede traditional metals for highly efficient EMI shielding applications., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to retrospectively analyze the therapeutic outcomes of using glucocorticoid combined with a vasodilator, breviscapine, versus glucocorticoid alone in patients with sudden sensorineural hearing loss (SSNHL) and to explore the impact on different audiometric curves., Methods: Data from 154 patients were collected between January 2017 and December 2018. Patients received treatments of either glucocorticoid combined with breviscapine (GC + Bre) or glucocorticoid alone (GC). These two groups were stratified into low frequencies SSNHL (LF-SSNHL), high frequencies SSNHL (HF-SSNHL), all frequencies SSNHL (AF-SSNHL), and total deafness SSNHL (TD-SSNHL) subgroups according to their corresponding audiograms. The hearing level was evaluated by pure tone audiometry, and hearing recovery was calculated by comparing the pure tone average (PTA) at pretreatment and 4 weeks after therapy., Results: Hearing recovery was significantly greater for GC + Bre than GC-only treatment in the AF-SSNHL and TD-SSNHL subgroups (P < 0.05) and to a lesser extent in the LF-SSNHL and HF-SSNHL subgroups (P > 0.05). Logistic regression analysis also showed a favorable outcome for SSNHL in the GC + Bre group (odds ratio 2.848, P < 0.05)., Conclusion: Treating SSNHL using glucocorticoid combined with breviscapine could be more beneficial than using glucocorticoid alone, especially for patients with AF-SSNHL and TD-SSNHL., Trial Registration Number: ChiCTR18000170072.

Study Objectives: Obstructive sleep apnea (OSA) is thought to be associated with dyslipidemia. However, differences concerning dyslipidemia during rapid eye movement (REM) and non-REM (NREM) sleep have yet to be determined. This study was designed to explore the association between lipid profiles and OSA during REM or NREM sleep., Methods: This is a clinical cohort. A total of 2,619 participants with at least 30 minutes of REM sleep were included. Sleep variables and fasting lipid profiles [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo)A-I, apoB, apoE, and lipoprotein(a) (Lp(a))] were obtained from each participant. Apnea-hypopnea indices in REM and NREM sleep (AHI REM and AHI NREM , respectively) were recorded. Linear regression analysis was used to assess the associations of AHI REM and AHI NREM with lipid profiles., Results: When stratified by the AHI REM severity of OSA, all demographics, clinical variables, and sleep parameters differed between the groups except for apoA-I. In fully-adjusted multivariate linear regression models, AHI REM was independently associated with increasing levels of TG, HDL-C, and apoE (P = .04, P = .01 and P = .01, respectively). AHI NREM was independently associated with increasing levels of TC, TG, LDL, and apoB, and lower level of HDL-C (all P < .05). In sensitivity analyses by only exploring associations in patients who had an AHI NREM or AHI REM < 5 events/h in separate regression models, AHI REM was not associated with all-lipid profile in almost all adjusted models (all P > .05), whereas AHI NREM was associated with elevated TC, LDL-C, and apoB (P = .03, P = .01 and P = .01, respectively)., Conclusions: AHI NREM was independently associated with the greatest alterations in serum lipids, including TC, LDL-C, and apoB., (© 2020 American Academy of Sleep Medicine.)

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&#95;006941.3: c.937&#95;947del; p.Tyr313Argfs*85), with a concurrent hotspot mutation in the GJB2 gene (NM&#95;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., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hyperoxia may cause pulmonary fibrosis in neonates and is characterized by the epithelial‑to‑mesenchymal transition (EMT) of alveolar epithelial cells. The placental growth factor (PLGF) gene is a member of the vascular endothelial growth factor family and is highly expressed in lung tissues that have been exposed to hyperoxia. The aim of the present study was to assess the role of PLGF in the EMT of lung tissue. Lung tissue exhibiting low PLGF expression was obtained by injecting rats exposed to hyperoxia with a PLGF‑silencing lentiviral plasmid. Western blot analysis and immunohistochemistry revealed that expression levels of the EMT‑related protein epithelial‑cadherin were increased, whereas its inhibitor protein zinc‑finger E‑box binding homeobox 2 was decreased in these rats. These data demonstrated that PLGF silencing may significantly mitigate hyperoxia‑induced EMT in rat lung tissue. Additionally, an increase in phosphorylated‑p38 MAPK protein expression indicated that PLGF may be able to regulate hyperoxia‑induced lung injury in rats via the p38 MAPK pathway.

Background: 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 < 0.01). The cell growth rate at each tested time point was lower in the 5-aza-CdR-treated group compared with that in the control group after 72 hours (p < 0.01). Flow cytometry revealed that the cells in the 1.0 μmol/L and 5.0 μmol/L 5-aza-CdR-treated groups were apparently arrested in the G0/G1 phase and that the number of cells in the S phase was significantly lower than the control group (p < 0.01)., Conclusion: 5-aza-CdR inhibits the growth of the LFs in hyperoxia-induced neonatal BPD rats in vitro by demethylating the P16 gene., (Copyright © 2016. Published by Elsevier B.V.)

Epithelial-to-mesenchymal transition (EMT) occurs frequently in lung epithelium in response to damage stimuli, such as inflammation and oxidative stress. Our group has already found an excessive release of placental growth factor (PLGF) in hyperoxic lung injury in newborn rodents. Nonetheless, whether this increased PLGF plays a role in mediating EMT process of alveolar epithelial cells (AECs) is unclear and requires further investigation. In this study, primary type II AECs were first isolated for neonatal Sprague Dawley (SD) rats and treated with different doses (25 or 100 ng/ml) of recombinant PLGF for 48 hr. As compared to the untreated AECs, exogenous PLGF induced a reduction in E-cadherin (a critical epithelial maker) and increases in vimentin and fibronectin (mesenchymal markers) in a dose-dependent manner. The higher dose was more potent in promoting the EMT-like changes in AECs. We also found that PLGF promoted the degradation of nuclear factor κB (NFκB) inhibitor (IκBα), induced phosphorylation of NFκB p65 at Ser 536 and enhanced p65 nuclear translocation in primary AECs. In addition, the NFκB inhibitor BAY 11-7082 partly counteracted PLGF-induced alterations in EMT-related proteins in rat AECs. In summary, our study demonstrates that exogenous PLGF can induce EMT-like changes in type II AECs at least partly by activating NFκB signalling transduction in vitro. PLGF may play a role in driving fibrotic lesions and thus can be a promising target for lung diseases., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

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 (AHI MSM ) and compared with that determined by PSG (AHI PSG ), 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 AHI PSG cut-off of ≥5, ≥15 and ≥30 events/h, the sensitivity (specificity) of detecting an AHI MSM 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 AHI PSG 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.

Life-saving mechanical ventilation can also cause lung injury through the overproduction of reactive oxygen species (ROS), leading to bronchopulmonary dysplasia (BPD)-like symptoms in preterm infants. It is reported that the autophagic protein microtubule-associated protein-1 light chain (LC)-3B can confer protection against hyperoxia-induced DNA damage in lung alveolar epithelium. However, its role in the transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I cells (AECIs) is unclear and requires further investigation. In this study, newborn Sprague-Dawley rats were exposed to 90% oxygen for up to 14 days to mimic BPD in human infants, with neonatal pups exposed to room air (21% oxygen) as controls. Primary rat AECIIs were cultured under hyperoxic conditions for up to 24 hours to further investigate the underlying mechanisms. This study found that hyperoxia promoted a significant and time-dependent increase of AECII marker surfactant protein (SP)-C in the lung. The increase of AECI marker T1α was repressed by hyperoxia during lung development. These results indicated an impaired AECII transdifferentiation. Pulmonary ROS concentration and expression of autophagic protein LC-3B were increased gradually in response to hyperoxia exposure. Furthermore, AECIIs produced more ROS when cultured under hyperoxic conditions in vitro. Both the LC3B expression and the conversion from LC3BI to LC3BII were enhanced in hyperoxic AECs. Interestingly, inhibition of LC3B either by ROS inhibitor N-acetyl-l-cysteine (NAC) or adenovirus-mediated LC3B shRNA could partly restore AECII transdifferentiation under hyperoxia condition. In summary, the current study reveals a novel role of activated LC3B induced by hyperoxia in AECII transdifferentiation., (© 2016 John Wiley & Sons Australia, Ltd.)

Although supplemental high-level oxygen treatment can promote the survival of premature infants, hyperoxia may adversely induce acute lung injury (ALI) in newborns. Our prior work illustrated that hyperoxic exposure could enhance the release of placental growth factor (PLGF) in the lungs of neonatal rats. We therefore postulated that PLGF contributed to hyperoxic ALI in newborns and evaluated the anti-PLGF treatment mediated by systematic delivery of lentivirus in hyperoxic ALI in this study. Lentivirus particles containing PLGF specific shRNA were injected into neonatal rats prior to hyperoxic exposure (90% oxygen for 72h) to inhibit PLGF expression. Hyperoxia induced oxidative damages in lung tissues as evidenced by the increased malondialdehyde and myeloperoxidase, and the decreased antioxidant superoxide dismutase. Also, hyperoxia caused excessive infiltration of inflammatory cells and overproduction of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β and interleukin-6) in rat lung tissue. These pathological alterations were partly reversed by PLGF shRNA delivery. The expression levels and activities of metalloproteinase (MMP)-2 and MMP9 were up-regulated in response to hyperoxia, whereas down-regulated when PLGF was inhibited. Moreover, PLGF shRNA inhibited nuclear factor kappa B (NFκB) signaling delivery in hyperoxic rat lungs. Additionally, exogenous PLGF-induced activation of MMPs in rat RLE-6TN alveolar epithelial cells was suppressed by NFκB inhibitor pyrrolidine dithiocarbamate. These results suggest that therapy targeting PLGF may be beneficial for infants with hyperoxic ALI., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aims: To investigate the role of placenta growth factor (PLGF) in hyperoxia-induced lung injury in preterm born rats., Main Methods: Primary alveolar epithelial cells type II (AECIIs) were exposed to 90% oxygen for 24h. Preterm born rats were delivered by caesarean section, injected with PLGF-shRNA, and exposed to 90% oxygen for 14days. MTT was used to examine the viability of cells. ELISA was used to measure the secretion of PLGF in primary AECIIs and bronchoalveolar lavage fluid. Flow cytometry and TUNEL staining were used to measure cell apoptosis in the lung. Expression of PLGF mRNA was detected using real-time PCR, and protein expression of PLGF and apoptotic proteins was detected using Western blotting analysis. Immunofluorescence staining was used to measure the expression of E-cadherin and α-smooth muscle actin (α-SMA)., Key Findings: Exogenous PLGF inhibited viability of AECIIs. In addition, treatment of PLGF increased the percentage of apoptotic cells, regulated the expression of E-cadherin and α-SMA in the primary AECIIs. Moreover, PLGF exacerbated these pathological changes in hyperoxia-exposed AECIIs. In the in vivo study, shRNA mediated PLGF inhibition attenuated lung injury induced by hyperoxia exposure. In addition, PLGF inhibition reduced the percentage of apoptotic cells, increased the expression of Bcl-2 and decreased expression of Bax and cleaved-caspase 3. PLGF inhibition also reduced collagen deposition and inhibited epithelial-to-mesenchymal transition (EMT) in the lung of hyperoxia-exposed rat pups., Significance: Our findings suggested that PLGF contributed to hyperoxia-induced lung injury through promoting apoptosis and EMT. PLGF may become a therapeutic target of hyperoxia-induced lung injury., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: We aimed to evaluate gaps in noise (GIN) detection and visual analog scale (VAS) for measuring perceived tinnitus loudness and annoyance caused thereby. We quantified the outcomes and effectiveness of repetitive transcranial magnetic stimulation (rTMS) on chronic tinnitus., Methods: Fourteen tinnitus patients with normal hearing underwent a 10 day course of active 1-Hz rTMS to the left region of the temporoparietal cortex. GIN (in which the matched pitch and loudness of tinnitus was used to determine the frequency and intensity of background noise) and VAS was used to assess tinnitus loudness and the extent of annoyance caused thereby. Both ten patients with tinnitus who underwent left temporoparietal sham stimulation and fifteen volunteers with normal hearing without tinnitus participated with GIN detection as a control. Correlations between VAS scores and GIN detection were determined via Spearman's correlation analysis., Results: The mean GIN thresholds of tinnitus-affected (5.87 ms) ears and the ears of control subjects (4.85 ms) differed significantly. In the tinnitus group, 42.8% (6/14) patients experienced significant reductions in tinnitus annoyance, as assessed by VAS. 71.4% (10/14) patients experienced significant reductions in tinnitus loudness, as evidenced by GIN evaluation. Three tinnitus subjects (21.4%) achieved 30% decrease of the threshold of GIN detection. There was no significant change in GIN detection and VAS scores after sham stimulation. A significant positive correlation was evident between GIN data and VAS scores (r=0.84, p<0.001)., Conclusions: Gaps in noise detection, combined with VAS scores, affords a promising sensitive method by which to evaluate tinnitus loudness and annoyance. Low frequency rTMS significantly decreased tinnitus after the active, but not the sham, treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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<0.001). The increased values of the BODE index, HADS-D and Fagerström score also correlated positively (P<0.001). The co-presence of depressive symptoms and smoking significantly increased the BODE index by 11.99-fold with significant biological interactions, relative excess risk of interaction (RERI) was 12.12, the biological interactions were increased with increasing nicotine addiction., Conclusions: Patients with depressive symptoms who also smoke have an increased risk of severity from COPD interaction effects. The risk for severity of COPD and depressive symptoms increased with increasing the severity of nicotine addiction.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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.

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 follow-up. 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., (Copyright © 2015 by Daedalus Enterprises.)

Background: Depressive and anxiety symptoms increase the risk of death in patients with Chronic Obstructive Pulmonary Disease (COPD), but the combined effects of the two factors are unknown., Purpose: To assess the possible interactive effects of depressive and anxiety symptoms on the death of patients with COPD., Methods: Prospective data for 7787 Chinese patients with COPD was analyzed and the deaths were recorded. Depressive and anxiety symptoms were evaluated using the Hospital Anxiety and Depression Scale. A product of depressive and anxiety symptoms was added to the logistic regression model to evaluate the multiplicative interaction, and relative excess risk of interaction (RERI), attributable proportion (AP) of interaction, and synergy index (S) were applied to evaluate the additive interaction of the two factors. Bootstrap was used to calculate 95% confidence intervals (CIs) of RERI, AP and S. RERI > 0, AP > 0, or S > 1 indicated biological interaction., Results: After 4 years' follow-up, the cumulative mortality was 20.0%, and the percentages of deaths in patients with depressive and anxiety symptoms were 28.5% and 30.9%, respectively. When adjusting for variables such as age, sex, disease duration, marital status, income, education level, co-morbidity, smoke status, biomass smoke, 6MWD, MRC, BMI and FEV1. the RERI, AP, and S (with 95% CIs) resulted in depression and anxiety scores of 6.54 (1.23-13.79), 0.54 (0.18-0.83), and 2.64 (1.33-4.75) respectively., Conclusion: Interaction effects were found between depressive and anxiety symptoms on the death of patients with COPD. Patients with both depressive and anxiety symptoms have an increased risk of death from COPD.

Sirtuins maintain energy balance. Particularly, sirtuin 1 (SIRT1) activation mimics calorie restriction and nutrient utilization. However, no medications are available for the up-regulation of SIRT1. Methylene blue (MB) had been in clinical trials for the treatment of neurological diseases. This study investigated the effect of MB on sirtuin expression in association with the treatment of steatosis and steatohepatitis, and explored the underlying basis. The effects of MB on mitochondrial function, molecular markers, pharmacokinetics, and histopathology were assessed using hepatocyte and/or mouse models. Immunoblotting, PCR and reporter assays were done for molecular experiments. After oral administration, MB was well distributed in the liver. MB treatment increased NAD(+)/NADH ratio in hepatocytes. Of the major forms, MB treatment up-regulated SIRT1, and thereby decreased PGC-1α acetylation. Consistently, hepatic mitochondrial DNA contents and oxygen consumption rates were enhanced. MB treatment also notably activated AMPK, CPT-1 and PPARα: the AMPK activation relied on SIRT1. Activation of LXRα and the induction of SREBP-1c and its target genes by T0901317 were diminished by MB. In addition, MB treatment antagonized the ability of palmitate to acetylate PGC-1α, and increase SERBP-1c, FAS, and ACC levels. In mice fed on a high-fat diet for 8 weeks, MB treatment inhibited excessive hepatic fat accumulation and steatohepatitis. The ability of MB to activate SIRT1 promotes mitochondrial biogenesis and oxygen consumption and activates AMPK, contributing to anti-lipogenesis in the liver. Our results provide new information on the potential use of MB for the treatment of steatosis and steatohepatitis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Carbon-modified titanium dioxide (TiO2) was prepared by a sol-gel method using tetrabutyl titanate as precursor, with calcination at various temperatures, and tested for the photocatalytic oxidation (PCO) of gaseous NH3 under visible and UV light. The test results showed that no samples had visible light activity, while the TiO2 calcined at 400°C had the best UV light activity among the series of catalysts, and was even much better than the commercial catalyst P25. The catalysts were then characterized by X-ray diffractometry, Brunauer-Emmett-Teller adsorption analysis, Raman spectroscopy, thermogravimetry/differential scanning calorimetry coupled with mass spectrometry, ultraviolet-visible diffuse reflectance spectra, photoluminescence spectroscopy and in situ diffuse reflectance infrared Fourier transform spectroscopy. It was shown that the carbon species residuals on the catalyst surfaces induced the visible light adsorption of the samples calcined in the low temperature range (< 300°C). However, the surface acid sites played a determining role in the PCO of NH3 under visible and UV light over the series of catalysts. Although the samples calcined at low temperatures had very high SSA, good crystallinity, strong visible light absorption and also low PL emission intensity, they showed very low PCO activity due to their very low number of acid sites for NH3 adsorption and activation. The TiO2 sample calcined at 400°C contained the highest number of acid sites among the series of catalysts, therefore showing the highest performance for the PCO of NH3 under UV light., (Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

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. Chinese Clinical Trials Registration ChiCTR-TRC-12001958.

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.

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., Trial Registration: Chinese Clinical Trials Registration (ChiCTR-TRC-12001958).

Objective: To discuss the role of forehead flap in large external nasal defect reconstruction., Method: We retrospectively reviewed the clinical and follow-up data of 11 patients with large or full-thickness external nasal defects, which were reconstructed with single-or two-stage interpolated or island forehead flaps from January 2007 to June 2011. All patients were male,defects of 9 cases were resulted from resection of skin malignant tumor and traumatic defect in 2 cases. The average diameter of defects was 3.3 cm (2.5-5.0 cm). Four cases had alar full thickness defect. The supratrochlear and angular artery of the elders (>70 yrs) and patients with suspicious peripheral blood vessel lesions were scanned before the surgery by Doppler ultrasonic. The defects were reconstructed by two-stage interpolated flap in 7 cases; five cases were reconstructed by single-stage island flap technique. A nasolabial flap based on piriform aperture was turned into the nasal cavity to reconstruct the lining., Result: All defects were repaired successfully. All tissue flap survived and the scar was not conspicuous. One patient had nostril stenosis with mild nasal congestion complain at the 6th postoperative month., Conclusion: The forehead flap, interpolated or island, can be used safely and effectively to repair the large external nasal defect in experienced hands.

Objective: To determine the dynamic expression of E2F1 in lung of premature rats with hyperoxia-induced chronic lung disease and the relation between E2F1 and pulmonary fibrosis., Methods: Premature Wistar rats at 21 days gestation were randomly and equally divided into a hyperoxia group and a room air group. The hyperoxia group was continuously exposed to hyperoxia (90%) while the air group in room air. Lung tissues in the 2 groups were obtained at 3, 7 and 14 days after exposing to either room air or hyperoxia. The changes of pulmonary histopathology at different time points were observed by hematoxylin and eosin staining; the severity of pulmonary fibrosis was evaluated; and the expression of E2F1 in lung tissue was detected by immunohistochemistry and Western blot., Results: After 3 days of hyperoxia, no significant interstitial fibrosis was observed; while after 7 days in the hyperoxia group, interstitial fibrosis was observed. These changes became more obvious after 14 days of prolonged hyperoxia exposure. No significant difference in the expressions of E2F1 protein was found between the hyperoxia group and the room air group 3 days postnatally (P>0.05). The expression of E2F1 in the hyperoxia group significantly increased 7 days and 14 days postnatally (P<0.05, P<0.01)., Conclusion: Abnormality of E2F1 expression is involved in the pathological process of the proliferation of lung fibroblasts in hyperoxia-induced chronic lung disease neonatal rats, and it plays an important role in lung fibrosis.

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., Trial Registration: Chinese Clinical Trials Registration(ChiCTR-TRC-12001958).

Objectives: To investigate the association between self-reported sleep duration, sleep quality and the prevalence of diabetes in a contemporary sample of Chinese adults., Design: Cross-sectional survey., Setting: Community-based investigation in Xuzhou, China., Participants: 16 893 Chinese men and women aged 18-75 who fulfilled the inclusion and exclusion criteria were enrolled., Primary and Secondary Outcome Measures: Self-reported quality and duration of sleep were obtained by questionnaire, and type 2 diabetes was assessed by fasting blood glucose. Sleep quality was categorised as good, common or poor. Sleep duration was measured by average hours of sleep per night, with categories of ≤6 h, 6-8 h and ≥8 h. A logistic regression model was used to evaluate the association between sleep duration or sleep quality and diabetes., Results: Both poor quality of sleep and short sleep duration (≤6 h) were associated with increased prevalence of diabetes, with higher rates in relatively healthy Chinese people. Compared with the group with good quality of sleep and 6-8 h sleep duration, diabetes was the most prevalent in individuals with poor sleep quality and ≤6 h sleep duration (OR 1.41, 95% CI 1.07 to 1.85) and in those with poor sleep quality who slept ≥8 h (OR 1.39, 95% CI 0.85 to 2.26), even after adjustment for a large number of further possible factors., Conclusions: The results suggest that sleep of poor quality and short duration is associated with diabetes.

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.

Background: Little information is available regarding the vulnerability of patients with chronic obstructive pulmonary disease (COPD) in China. We aimed to assess this according to patient gender., Methods: A cross-sectional study was conducted in the rural area of Xuzhou in China. We interviewed and administered questionnaires to 2825 male and 2825 female patients with COPD and subjected the data generated to statistical analysis. We compared differences between proportions of male and female patients using the χ(2) test., Results: The rate of current smoking in men was 30.1%, whereas that in women was 10.9%, and 31.5% of men had a history of using biomass fuel compared with 75.3% of women. Further, 26.0% of the male patients and 16.4% of the female patients did not take theophylline regularly when their disease was stable. During acute exacerbations, 65.8% of the male patients and 39.7% of the female patients took theophylline or similar drugs. The average potential shortening of life expectancy was 1.76 years for men and 1.18 years for women. The average indirect economic burden was 11158.4 yuan for men and 7481.2 yuan for women. The quality of life was worse in female patients than in male patients., Conclusion: We found that patients with COPD were vulnerable and that factors determining vulnerability were different for men than for women. Therefore, we recommend adopting different measures for men and women when attempting to prevent, control, and treat COPD, rehabilitate these patients, and improve their quality of life.

The process of new drug development consists of several stages; after identifying potential candidate compounds, preclinical studies using animal models link the laboratory and human clinical trials. Among many steps in preclinical studies, toxicology and safety assessments contribute to identify potential adverse events and provide rationale for setting the initial doses in clinical trials. Gene modulation is one of the important tools of modern biology, and is commonly employed to examine the function of genes of interest. Advances in new drug development have been achieved by exploding information on target selection and validation using genetically modified animal models as well as those of cells. In this review, a recent trend of genetically modified methods is discussed with reference to safety assessments, and the exemplary applications of gene-modulating tools to the tests in new drug development were summarized.

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.

Objective: To explore a comprehensive surgical approach of genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty on the treatment of severe obstructive sleep apnea hypopnea syndrome., Method: Eighteen patients with severe OSAHS (RDI > 40)diagnosed by polysomnography. The obstruction in both the oropharynx and the hypopharynx were determined by preoperative physical examination, fiberoptic pharyngolaryngoscopy, cephalometry, and computed tomography of the upper airway. All the cases were given continuous airway pressure via nose,five to seven days before operation and then were performed genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty. The follow up was at least 6 months postoperatively. The Wilcoxon Signed Rank test was used to compare the preoperative and postoperative results by SPSS11.0 for windows., Result: Postoperative 6-24 months, there were statistically significance in all but BMI between preoperative and postoperative measurement. Mean RDI was reduced from preoperative (63.83 +/- 16.34) to postoperative (21.43 +/- 20. 34), lowest mean oxygen saturation increased from (72.44 +/- 7.07)% to (81.33 +/- 13.32)%. According to criterion at home, the 6-month rate of responder is 83.33%. The severe complications such as fracture of the mandible and injure of apex of inferior anterior teeth did not occurred., Conclusion: GAHM plus UPPP is effective surgical approach for patients with severe OSAHS who suffer from oropharyngeal and hypopharyngeal obstruction.

Objective: To discuss the changes of the auditory brain stem response in patients with Ramsay Hunt syndrome., Method: Thirty-six patients of Ramsay Hunt syndrome,who have only unilateral involvement with contralateral good ear, were studied with pure tone test and auditory brain stem response. The latencies of peaks I, III and V and interpeak latencies of I-III, I-V and III-V in bilateral ears were analyzed by SPSS 10.0 for windows., Result: Compared to the controlateral, the affected ears were significantly increased in latencies of II, V and interpeak latencies of I-III, I-V ( P < 0.05)., Conclusion: The audiological data suggested that cochlear or retrocochlear involvement or involvement at more than one site along the auditory pathway existed in Ramsay Hunt syndrome, but pure cochlear hearing loss is not common.