bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardioprotective effects of Cu(II)ATSM in human vascular smooth muscle cells and cardiomyocytes mediated by Nrf2 and DJ-1
Authors: Srivastava Salil , Blower Philip J. , Aubdool Aisah A. , Hider Robert C. , Mann Giovanni E. , Siow Richard C.
Published: November 2016

Cu(II)ATSM was developed as a hypoxia sensitive positron emission tomography agent. Recent reports have highlighted the neuroprotective properties of Cu(II)ATSM, yet there are no reports that it confers cardioprotection. We demonstrate that Cu(II)ATSM activates the redox-sensitive transcription factor Nrf2 in human coronary artery smooth muscle cells (HCASMC) and cardiac myocytes (HCM), leading to upregulation of antioxidant defense enzymes. Oral delivery of Cu(II)ATSM in mice induced expression of the Nrf2-regulated enzymes in the heart and aorta. In HCASMC, Cu(II)ATSM increased expression of the Nrf2 stabilizer DJ-1, and knockdown of Nrf2 or DJ-1 attenuated Cu(II)ATSM-mediated heme oxygenase-1 and NADPH quinone oxidoreductase-1 induction. Pre-treatment of HCASMC with Cu(II)ATSM protected against the pro-oxidant effects of angiotensin II (Ang II) by attenuating superoxide generation, apoptosis, proliferation and increases in intracellular calcium. Notably, Cu(II)ATSM-mediated protection against Ang II-induced HCASMC apoptosis was diminished by Nrf2 knockdown. Acute treatment with Cu(II)ATSM enhanced the association of DJ-1 with superoxide dismutase-1 (SOD1), paralleled by significant increases in intracellular Cu(II) levels and SOD1 activity. We describe a novel mechanism by which Cu(II)ATSM induces Nrf2-regulated antioxidant enzymes and protects against Ang II-mediated HCASMC dysfunction via activation of the Nrf2/DJ-1 axis. Cu(II)ATSM may provide a therapeutic strategy for cardioprotection via upregulation of antioxidant defenses.
Erratum: Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis
Authors: Shen Jian , Song Ning , Williams Christopher J. , Brown Celeste J. , Yan Zheng , Xu Chen , Forney Larry J.
Published: November 2016

Scientific Reports 6: Article number: 24380; published online: 22 April 2016; updated: 29 November 2016 The original version of this Article contained errors in Affiliations 3, 4 and 5 which were incorrectly given as ‘Departments of Statistical Science, University of Idaho, Moscow, ID, 83844, Russia’, ‘Biological Sciences, University of Idaho, Moscow, ID, 83844, Russia’ and ‘Institute for Bioinformatics and Evolutionary Studies (IBEST), University of Idaho, Moscow, ID, 83844, Russia’ respectively.
TMED3 promotes hepatocellular carcinoma progression via IL-11/STAT3 signaling
Authors: Zheng Hao , Yang Yuan , Han Jun , Jiang Wei-hua , Chen Cheng , Wang Meng-chao , Gao Rong , Li Shuai , Tian Tao , Wang Jian , Ma Li-jun , Ren Hao , Zhou Wei-ping
Published: November 2016

Transmembrane p24 trafficking protein 3(TMED3) is a metastatic suppressor in colon cancer, but its function in the progression of hepatocellular carcinoma (HCC) is unknown. Here, we report that TMED3 was up-regulated in HCC and portal vein tumor thrombus. TMED3 up-regulation in HCC was significantly correlated with aggressive characteristics and predicted poor prognosis in HCC patients. TMED3 overexpression in HCC cell lines promoted cell migration and invasion. In contrast, TMED3 knockdown suppressed HCC metastasis both in vitro and in vivo. Gene microarray analysis revealed decreased IL-11 expression in TMED3-knockdown cells. We propose that TMED3 promotes HCC metastasis through IL-11/STAT3 signaling. Taken together, these findings demonstrate that TMED3 promotes HCC metastasis and is a potential prognostic biomarker in HCC.
Design and development of novel antibacterial Ti-Ni-Cu shape memory alloys for biomedical application
Authors: Li H. F. , Qiu K. J. , Zhou F. Y. , Li L. , Zheng Y. F.
Published: November 2016

In the case of medical implants, foreign materials are preferential sites for bacterial adhesion and microbial contamination, which can lead to the development of prosthetic infections. Commercially biomedical TiNi shape memory alloys are the most commonly used materials for permanent implants in contact with bone and dental, and the prevention of infections of TiNi biomedical shape memory alloys in clinical cases is therefore a crucial challenge for orthopaedic and dental surgeons. In the present study, copper has been chosen as the alloying element for design and development novel ternary biomedical Ti‒Ni‒Cu shape memory alloys with antibacterial properties. The effects of copper alloying element on the microstructure, mechanical properties, corrosion behaviors, cytocompatibility and antibacterial properties of biomedical Ti‒Ni‒Cu shape memory alloys have been systematically investigated. The results demonstrated that Ti‒Ni‒Cu alloys have good mechanical properties, and remain the excellent shape memory effects after adding copper alloying element. The corrosion behaviors of Ti‒Ni‒Cu alloys are better than the commercial biomedical Ti‒50.8Ni alloys. The Ti‒Ni‒Cu alloys exhibit excellent antibacterial properties while maintaining the good cytocompatibility, which would further guarantee the potential application of Ti‒Ni‒Cu alloys as future biomedical implants and devices without inducing bacterial infections.
Quantitative Evaluation of the Mechanical Risks Caused by Focal Cartilage Defects in the Knee
Authors: Venäläinen Mikko S. , Mononen Mika E. , Salo Jari , Räsänen Lasse P. , Jurvelin Jukka S. , Töyräs Juha , Virén Tuomas , Korhonen Rami K.
Published: November 2016

Focal cartilage lesions can proceed to severe osteoarthritis or remain unaltered even for years. A method to identify high risk defects would be of utmost importance to guide clinical decision making and to identify the patients that are at the highest risk for the onset and progression of osteoarthritis. Based on cone beam computed tomography arthrography, we present a novel computational model for evaluating changes in local mechanical responses around cartilage defects. Our model, based on data obtained from a human knee in vivo, demonstrated that the most substantial alterations around the defect, as compared to the intact tissue, were observed in minimum principal (compressive) strains and shear strains. Both strain values experienced up to 3-fold increase, exceeding levels previously associated with chondrocyte apoptosis and failure of collagen crosslinks. Furthermore, defects at the central regions of medial tibial cartilage with direct cartilage-cartilage contact were the most vulnerable to loading. Also locations under the meniscus experienced substantially increased minimum principal strains. We suggest that during knee joint loading particularly minimum principal and shear strains are increased above tissue failure limits around cartilage defects which might lead to osteoarthritis. However, this increase in strains is highly location-specific on the joint surface.
Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation
Authors: Shen Chong , Jiang Lifang , Shao Huawei , You Chuangang , Zhang Guoliang , Ding Sitong , Bian Tingwei , Han Chunmao , Meng Qin
Published: November 2016

Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by Pseudomonas aeruginosa, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including α-SMA expression and collagen secretion/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and α-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring.
Research of CO2 and N2 Adsorption Behavior in K-Illite Slit Pores by GCMC Method
Authors: Chen Guohui , Lu Shuangfang , Zhang Junfang , Xue Qingzhong , Han Tongcheng , Xue Haitao , Tian Shansi , Li Jinbu , Xu Chenxi , Pervukhina Marina , Clennell Ben
Published: November 2016

Understanding the adsorption mechanisms of CO2 and N2 in illite, one of the main components of clay in shale, is important to improve the precision of the shale gas exploration and development. We investigated the adsorption mechanisms of CO2 and N2 in K-illite with varying pore sizes at the temperature of 333, 363 and 393 K over a broad range of pressures up to 30 MPa using the grand canonical Monte Carlo (GCMC) simulation method. The simulation system is proved to be reasonable and suitable through the discussion of the impact of cation dynamics and pore wall thickness. The simulation results of the excess adsorption amount, expressed per unit surface area of illite, is in general consistency with published experimental results. It is found that the sorption potential overlaps in micropores, leading to a decreasing excess adsorption amount with the increase of pore size at low pressure, and a reverse trend at high pressure. The excess adsorption amount increases with increasing pressure to a maximum and then decreases with further increase in the pressure, and the decreasing amount is found to increase with the increasing pore size. For pores with size greater larger than 2 nm, the overlap effect disappears.
Dietary Protein Intake and Type 2 Diabetes Among Women and Men in Northeast China
Authors: Li Jie , Sun Changhao , Liu Simin , Li Ying
Published: November 2016

We conducted a comprehensive and in-depth assessment of different dietary protein sources related to type 2 diabetes (T2D) and determined whether the association is mediated by insulin resistance (IR) and β-cell dysfunction in a population-based cross sectional study of 4,427 women and 2,394 men aged 20–74 years in northeast China. We observed that the intake of total protein, animal protein, and red meat protein was positively associated with T2D prevalence in women. Comparing the women in the highest quintile of protein intake with those in the lowest quintile, the multivariable-adjusted odds ratios of T2D were 2.13 [95% confidence interval (CI): 1.18–3.81] for total protein, 2.27 (95% CI: 1.18–4.35) for animal protein, and 1.75 (95% CI: 1.14–2.68) for red meat protein. Mediation analyses indicated that these associations were mediated mainly by the IR as measured by the homeostasis model (HOMA-IR). The proportions via the mediation of HOMA-IR were 29.0% (95% CI: 10.3%–55.5%), 35.0% (95% CI: 12.9%–83.3%), and 17.2% (95% CI: 5.2%–44.8%) for total protein-, animal protein-, and red meat protein–T2D associations, respectively. These findings support the notion that modifying the sources of dietary protein may be potentially applied to prevent T2D.
Functional brain mapping using specific sensory-circuit stimulation and a theoretical graph network analysis in mice with neuropathic allodynia
Authors: Komaki Yuji , Hikishima Keigo , Shibata Shinsuke , Konomi Tsunehiko , Seki Fumiko , Yamada Masayuki , Miyasaka Naoyuki , Fujiyoshi Kanehiro , Okano Hirotaka J. , Nakamura Masaya , Okano Hideyuki
Published: November 2016

Allodynia, a form of neuropathic pain, is defined as pain in response to a non-nociceptive stimulus. The brain regions responsible for pain, which are not normally activated, can be activated in allodynic mice by providing a suitable stimulus to Aβ-fibers, which transmit signals from tactile sensory fibers. Functional MRI (fMRI) can be used to objectively observe abnormal brain activation. In the present study, fMRI was conducted to investigate allodynia in mice; allodynia was generated by surgical injury at the L4 spinal nerve root, thus selectively stimulating sensory nerve fibers. In intact mice, only the primary somatosensory cortex (S1) was activated by stimulation of Aβ-fibers. Meanwhile, allodynic mice showed significantly higher BOLD signals in the anterior cingulate area (ACA) and thalamus. Using resting state fMRI, both degree and eigenvector centrality were significantly decreased in the contralateral S1, clustering coefficient and local efficiency were significantly increased in the ACA, and betweenness centrality was significantly higher in the ventral posterolateral nucleus of the thalamus. These results suggest that the observed abnormal BOLD activation is associated with defects in Aβ-fibers when Aβ-fibers in allodynic mice are selectively stimulated. The objective approach enabled by fMRI can improve our understanding of pathophysiological mechanisms and therapeutic efficacy.
Sparsity-based multi-height phase recovery in holographic microscopy
Authors: Rivenson Yair , Wu Yichen , Wang Hongda , Zhang Yibo , Feizi Alborz , Ozcan Aydogan
Published: November 2016

High-resolution imaging of densely connected samples such as pathology slides using digital in-line holographic microscopy requires the acquisition of several holograms, e.g., at >6–8 different sample-to-sensor distances, to achieve robust phase recovery and coherent imaging of specimen. Reducing the number of these holographic measurements would normally result in reconstruction artifacts and loss of image quality, which would be detrimental especially for biomedical and diagnostics-related applications. Inspired by the fact that most natural images are sparse in some domain, here we introduce a sparsity-based phase reconstruction technique implemented in wavelet domain to achieve at least 2-fold reduction in the number of holographic measurements for coherent imaging of densely connected samples with minimal impact on the reconstructed image quality, quantified using a structural similarity index. We demonstrated the success of this approach by imaging Papanicolaou smears and breast cancer tissue slides over a large field-of-view of ~20 mm2 using 2 in-line holograms that are acquired at different sample-to-sensor distances and processed using sparsity-based multi-height phase recovery. This new phase recovery approach that makes use of sparsity can also be extended to other coherent imaging schemes, involving e.g., multiple illumination angles or wavelengths to increase the throughput and speed of coherent imaging.
Enhanced Absorption and Diffusion Properties of Lithium on B,N,VC-decorated Graphene
Authors: Jin Mengting , Yu L. C. , Shi W. M. , Deng J. G. , Zhang Y. N.
Published: November 2016

Systematic first-principles calculations were performed to investigate the adsorption and diffusion of Li on different graphene layers with B/N-doping and/or C-vacancy, so as to understand why doping heteroatoms in graphene anode could significantly improve the performance of lithium-ion batteries. We found that the formation of single or double carbon vacancies in graphene are critical for the adsorption of Li atoms. While the N-doping facilitates the formation of vacancies, it introduces over binding issue and hinders the Li diffusion. The presence of B takes the excessive electrons from Li and N and reduces the energy barrier of Li diffusion on substrates. We perceive that these clear insights are crucial for the further development of graphene based anode materials for lithium-ion batteries.
Diagnostic performance of Contrast-enhanced CT in Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstructive Syndrome
Authors: Kan Xuefeng , Ye Jin , Rong Xinxin , Lu Zhiwen , Li Xin , Wang Yong , Yang Ling , Xu Keshu , Song Yuhu , Hou Xiaohua
Published: November 2016

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS.
Association between dioxin and cancer incidence and mortality: a meta-analysis
Authors: Xu Jinming , Ye Yao , Huang Fang , Chen Hanwen , Wu Han , Huang Jian , Hu Jian , Xia Dajing , Wu Yihua
Published: November 2016

The objective of the present study was to systematically assess the association between dioxin/2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer incidence and mortality. Systematic literature searches were conducted until July 2015 in Pubmed, Embase and Cochrane library to identify relevant studies. A random-effects model was applied to estimate the pooled odds ratio (OR), risk ratio (RR), standard incidence ratio (SIR) or standard mortality ratio (SMR) for cancer incidence or mortality. In addition, dose-response, meta-regression, subgroup, and publication bias analyses were conducted. Thirty-one studies involving 29,605 cancer cases and 3,478,748 participants were included. Higher external exposure level of TCDD was significantly associated with all cancer mortality (pooled SMR = 1.09, 95% CI: 1.01–1.19, p = 0.04), but not all cancer incidence (pooled RR = 1.01, 95% CI: 0.97–1.06, p = 0.49). Higher blood level of TCDD was both significantly associated with all cancer incidence (pooled RR = 1.57, 95% CI: 1.21–2.04, p = 0.001) and all cancer mortality (pooled SMR = 1.45, 95% CI: 1.25–1.69, p < 0.001). Subgroup analysis suggested that higher external exposure and blood level of TCDD were both significantly associated with the mortality caused by non-Hodgkin’s lymphoma. In conclusion, external exposure and blood level of TCDD were both significantly associated with all cancer mortality, especially for non-Hodgkin’s lymphoma.
A chitin deacetylase from the endophytic fungus Pestalotiopsis sp. efficiently inactivates the elicitor activity of chitin oligomers in rice cells
Authors: Cord-Landwehr Stefan , Melcher Rebecca L. J. , Kolkenbrock Stephan , Moerschbacher Bruno M.
Published: November 2016

To successfully survive in plants, endophytes need strategies to avoid being detected by the plant immune system, as the cell walls of endophytes contain easily detectible chitin. It is possible that endophytes “hide” this chitin from the plant immune system by modifying it, or oligomers derived from it, using chitin deacetylases (CDA). To explore this hypothesis, we identified and expressed a CDA from Pestalotiopsis sp. (PesCDA), an endophytic fungus, in E. coli and characterized this enzyme and its chitosan oligomer products. We found that when PesCDA modifies chitin oligomers, the products are partially deacetylated chitosan oligomers with a specific acetylation pattern: GlcNAc-GlcNAc-(GlcN)n-GlcNAc (n ≥ 1). Then, in a bioactivity assay where suspension-cultured rice cells were incubated with the PesCDA products (processed chitin hexamers), we found that, unlike the substrate hexamers, chitosan oligomer products no longer elicited the plant immune system. Thus, this endophytic enzyme can prevent the endophyte from being recognized by the plant immune system; this might represent a more general hypothesis for how certain fungi are able to live in or on their hosts.
Analgesic effect and safety of single-dose intra-articular magnesium after arthroscopic surgery: a systematic review and meta-analysis
Authors: Zeng Chao , Li Yu-sheng , Wei Jie , Xie Dong-xing , Xie Xi , Li Liang-jun , Gao Shu-guang , Luo Wei , Xiong Yi-lin , Xiao Wen-feng , Lei Guang-hua
Published: November 2016

To examine the analgesic effect and safety of single-dose intra-articular (IA) magnesium (Mg) after arthroscopic surgery. Pubmed, Embase and Cochrane library were searched through in January 2016. Eight RCTs and eight experimental studies were included. The IA Mg exhibited a significantly lower pain score when compared with placebo (MD, −0.41, 95% CI, −0.78 to −0.05, p = 0.03). There was no significant difference between Mg and bupivacaine in terms of pain relief and the time to first analgesic request. Furthermore, statistically significant differences both in pain score (MD, −0.62, 95% CI, −0.81 to −0.42, p < 0.00001) and time to first analgesic request (MD, 6.25, 95% CI, 5.22 to 7.29, p < 0.00001) were observed between Mg plus bupivacaine and bupivacaine alone. There was no statistically significant difference among the various groups with respect to adverse reactions. Most of the included in vitro studies reported the chondrocyte protective effect of Mg supplementation. There were also two in vivo studies showing the cartilage protective effect of IA Mg. The single-dose IA Mg following arthroscopic surgery was effective in pain relief without increasing adverse reactions, and it could also enhance the analgesic effect of bupivacaine. In addition, Mg seemed to possess the cartilage or chondrocyte protective effect based on experimental studies.
Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models
Authors: Rangarajan Janaki Raman , Vande Velde Greetje , van Gent Friso , De Vloo Philippe , Dresselaers Tom , Depypere Maarten , van Kuyck Kris , Nuttin Bart , Himmelreich Uwe , Maes Frederik
Published: November 2016

Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study.
Tumor-specific delivery of biologics by a novel T-cell line HOZOT
Authors: Onishi Teppei , Tazawa Hiroshi , Hashimoto Yuuri , Takeuchi Makoto , Otani Takeshi , Nakamura Shuji , Sakurai Fuminori , Mizuguchi Hiroyuki , Kishimoto Hiroyuki , Umeda Yuzo , Shirakawa Yasuhiro , Urata Yasuo , Kagawa Shunsuke , Fujiwara Toshiyoshi
Published: November 2016

“Cell-in-cell” denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion. HOZOT cells were successfully loaded via human CD46 antigen with an attenuated adenovirus containing the fiber protein of adenovirus serotype 35 (OBP-401/F35), in which the telomerase promoter regulates viral replication. OBP-401/F35–loaded HOZOT cells were efficiently internalized into human cancer cells and exhibited tumor-specific killing by release of viruses, even in the presence of anti-viral neutralizing antibodies. Moreover, intraperitoneal administration of HOZOT cells loaded with OBP-401/F35 significantly suppressed peritoneally disseminated tumor growth in mice. This unique cell-in-cell property provides a platform for selective delivery of biologics into human cancer cells, which has important implications for the treatment of human cancers.
FSH protects mouse granulosa cells from oxidative damage by repressing mitophagy
Authors: Shen Ming , Jiang Yi , Guan Zhiqiang , Cao Yan , Sun Shao-chen , Liu Honglin
Published: November 2016

Oxidative stress has been implicated in triggering granulosa cell (GC) death during follicular atresia. Recent studies suggested that follicle-stimulating hormone (FSH) has a pivotal role in protecting GCs from oxidative injury, although the exact mechanism remains largely unknown. Here, we report that FSH promotes GC survival by inhibiting oxidative stress-induced mitophagy. The loss of GC viability caused by oxidative stress was significantly reduced after FSH treatment, which was correlated with impaired activation of mitophagy upon oxidative stress. Compared with FSH treatment, blocking mitophagy displayed approximate preventive effect on oxidative stress-induced GC death, but FSH did not further restore viability of cells pretreated with mitophagy inhibitor. Importantly, FSH suppressed the induction of serine/threonine kinase PINK1 during oxidative stress. This inhibited the mitochondrial translocation of the E3 ligase Parkin, which is required for the subsequent clearance of mitochondria, and ultimately cell death via mitophagy. In addition, knocking down PINK1 using RNAi confirmed the role of the FSH-PINK1-Parkin-mitophagy pathway in regulating GC survival under oxidative conditions. These findings introduce a novel physiological function of FSH in protecting GCs against oxidative damage by targeting PINK1-Parkin-mediated mitophagy.
Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells
Authors: Lin Ze-Min , Yang Xiao-Qian , Zhu Feng-Hua , He Shi-Jun , Tang Wei , Zuo Jian-Ping
Published: November 2016

SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4+ T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4+ T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.
Coupling template nanocasting and self-activation for fabrication of nanoporous carbon
Authors: Kong Lingjun , Liu Mingxiang , Diao Zenghui , Chen Diyun , Chang Xiangyang , Xiong Ya
Published: November 2016

Hierarchical nanoporous carbon (NPC) with great surface area and developed pore size distribution has been intently concerned. Herein, we report a facile method coupling template nanocasting and self-activation to fabricate nanoporous carbon with continuous micro, meso and macro pores, in which CaCO3 acted as template and activation reagent while the flour was the carbon precursor. Effects of mass ratio of CaCO3 to flour and carbonized temperature on the pore structures of NPC were investigated by nitrogen adsorption-desorption isotherms and SEM analysis. Another kind of carbon was prepared by directly mixed powder CaCO3 with flour carbonized at 800 °C (NPC-p) to comparatively investigate the pore fabricating mechanism. Results shown that carbonized at 800 °C was favorable to fabricate the continuous macro, meso and micro pores. The resulted NPC in a mass ratio of 1 to 2 had the considerable SBET and VT of 575.4 m2/g and 0.704 cm3/g, respectively. Only surface activation was observed for NPC-p. Nanocasting of the powder CaCO3 contributed to fabricate macropores and the CO2 activation contributed to meso- and micropores. Coupling activation and nanocasting effect due to the decomposition of CaCO3 template into CO2 and CaO was ascribed to synthesize the nanoporous carbon.
Polymorphism of fibrillar structures depending on the size of assembled Aβ17-42 peptides
Authors: Cheon Mookyung , Kang Mooseok , Chang Iksoo
Published: November 2016

The size of assembled Aβ17-42peptides can determine polymorphism during oligomerization and fibrillization, but the mechanism of this effect is unknown. Starting from separate random monomers, various fibrillar oligomers with distinct structural characteristics were identified using discontinuous molecular dynamics simulations based on a coarse-grained protein model. From the structures observed in the simulations, two characteristic oligomer sizes emerged, trimer and paranuclei, which generated distinct structural patterns during fibrillization. A majority of the simulations for trimers and tetramers formed non-fibrillar oligomers, which primarily progress to off-pathway oligomers. Pentamers and hexamers were significantly converted into U-shape fibrillar structures, meaning that these oligomers, called paranuclei, might be potent on-pathway intermediates in fibril formation. Fibrillar oligomers larger than hexamers generated substantial polymorphism in which hybrid structures were readily formed and homogeneous fibrillar structures appeared infrequently.
Low-level light treatment ameliorates immune thrombocytopenia
Authors: Yang Jingke , Zhang Qi , Li Peiyu , Dong Tingting , Wu Mei X.
Published: November 2016

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.
Rab14 specifies the apical membrane through Arf6-mediated regulation of lipid domains and Cdc42
Authors: Lu Ruifeng , Wilson Jean M.
Published: November 2016

The generation of cell polarity is essential for the development of multi-cellular organisms as well as for the function of epithelial organs in the mature animal. Small GTPases regulate the establishment and maintenance of polarity through effects on cytoskeleton, membrane trafficking, and signaling. Using short-term 3-dimensional culture of MDCK cells, we find that the small GTPase Rab14 is required for apical membrane specification. Rab14 knockdown results in disruption of polarized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical membrane. These effects are mediated through tight control of lipid localization, as overexpression of the phosphatidylinositol 4-phosphate 5-kinase α [PtdIns(4)P5K] activator Arf6 or PtdIns(4)P5K alone, or treatment with the phosphatidylinositol 3-kinase (PtdInsI3K) inhibitor wortmannin, rescued the multiple-apical domain phenotype observed after Rab14 knockdown. Rab14 also co-immunoprecipitates and colocalizes with the small GTPase Cdc42, and Rab14 knockdown results in increased Cdc42 activity. Furthermore, Rab14 regulates trafficking of vesicles to the apical domain, mitotic spindle orientation, and midbody position, consistent with Rab14’s reported localization to the midbody as well as its effects upon Cdc42. These results position Rab14 at the top of a molecular cascade that regulates the establishment of cell polarity.
Hill number as a bacterial diversity measure framework with high-throughput sequence data
Authors: Kang Sanghoon , Rodrigues Jorge L. M. , Ng Justin P. , Gentry Terry J.
Published: November 2016

Bacterial diversity is an important parameter for measuring bacterial contributions to the global ecosystem. However, even the task of describing bacterial diversity is challenging due to biological and technological difficulties. One of the challenges in bacterial diversity estimation is the appropriate measure of rare taxa, but the uncertainty of the size of rare biosphere is yet to be experimentally determined. One approach is using the generalized diversity, Hill number (Na), to control the variability associated with rare taxa by differentially weighing them. Here, we investigated Hill number as a framework for microbial diversity measure using a taxa-accmulation curve (TAC) with soil bacterial community data from two distinct studies by 454 pyrosequencing. The reliable biodiversity estimation was obtained when an increase in Hill number arose as the coverage became stable in TACs for a ≥ 1. In silico analysis also indicated that a certain level of sampling depth was desirable for reliable biodiversity estimation. Thus, in order to attain bacterial diversity from second generation sequencing, Hill number can be a good diversity framework with given sequencing depth, that is, until technology is further advanced and able to overcome the under- and random-sampling issues of the current sequencing approaches.
Maternal high-fat diet prevents developmental programming by early-life stress
Authors: Rincel M , Lépinay A L , Delage P , Fioramonti J , Théodorou V S , Layé S , Darnaudéry M
Published: November 2016

Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such asBdnf(brain derived neurotrophic factor),5HT-r1a(serotonin receptor 1a) andRest4(neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposureper se,on brain vulnerability during development.
Introduction to the Structural Biology of Membrane Proteins
Authors: Luckey Mary
Published: November 2016

The tremendous progress in the structural biology of membrane proteins, built on a vast accumulation of experimental data and fueled by an exponential increase in the number of high resolution structures, provides a base for advances using cutting-edge biophysical and computational tools. Membrane proteins must be considered in the context of their lipid environment, which provides fluidity, lateral heterogeneity (allowing specialized microdomains), as well as variations normal to the bilayer. The low dielectric of the membrane interior drives the need for hydrogen-bonded secondary structures in transmembrane segments, resulting in two structural classes of integral membrane proteins: bundles of α-helices and β-barrels. Membrane proteins function as channels, transporters, enzymes, and receptors, and salient features of each are presented.
Experimental and Computational Approaches to Study Membranes and Lipid–Protein Interactions
Authors: Sengupta Durba , Kumar G. Aditya , Prasanna Xavier , Chattopadhyay Amitabha
Published: November 2016

Biological membranes are complex two-dimensional, non-covalent assemblies of a diverse variety of lipids and proteins. A hallmark of membrane organization is varying degrees of spatiotemporal heterogeneity spanning a wide range. Membrane proteins are implicated in a wide variety of cellular functions, and comprise ∼30% of the human proteome and ∼50% of the current drug targets. Their interactions with membrane lipids are recognized as crucial elements in their function. In this article, we provide an overview of experimental and theoretical approaches to analyze membrane organization, dynamics, and lipid–protein interactions. In this context, we highlight the wide range of time scales that membrane events span, and approaches that are suitable for a given time scale. We discuss representative fluorescence-based approaches (FRET and FRAP) that help to address questions on lipid–protein and protein–cytoskeleton interactions in membranes. In a complimentary fashion, we discuss computational methods, atomistic and coarse-grain, that are required to address a given membrane problem at an appropriate scale. We believe that the synthesis of knowledge gained from experimental and computational approaches will enable us to probe membrane organization, dynamics, and interactions at increasing spatiotemporal resolution, thereby providing a robust model for the membrane in health and disease.
Computational Characterization of Molecular Mechanisms of Membrane Transporter Function
Authors: Trebesch Noah , Vermaas Josh V. , Tajkhorshid Emad
Published: November 2016

Transport of materials across the cellular membrane is a fundamental process in biology. Active membrane transporters constitute one of the major classes of proteins that mediate this process, and they do so in a highly regulated and selective manner. In order to transport substrates uphill, these molecular machines rely on a diverse spectrum of conformational changes spanning multiple time and size scales, and they couple these motions to various sources of energy, including transmembrane electrochemical gradients and ATP hydrolysis. Computational techniques such as molecular dynamics simulations and free energy calculations provide us with a powerful repertoire of biophysical tools offering unparalleled spatial and temporal resolutions that complement experimental methodologies and help us understand the molecular basis of function in membrane transporters. In this chapter, we present an overview of a number of examples of recent studies performed in our own lab in which computational methods and simulation techniques have been successfully employed to investigate and to characterize the microscopic molecular events that underlie membrane transporter function. While highlighting a number of recent approaches developed specifically to tackle challenging problems in membrane transporters, e.g., characterizing the nature of large-scale conformational changes, the presented studies also provide examples of a variety of mechanistically interesting and biologically important transporter systems.
[18F]-Fluoride capture and release: azeotropic drying free nucleophilic aromatic radiofluorination assisted by a phosphonium borane
Authors: Perrio Cécile , Schmitt Sébastien , Pla Daniel , Gabbaï François P. , Chansaenpak Kantapat , Mestre-Voegtle Béatrice , Gras Emmanuel
Published: November 2016

[18F]-Fluoride ready for SNAr was prepared according to a simple process including trapping of aqueous [18F]-fluoride on a cartridge pre-loaded with the phosphonium borane [(Ph2MeP)C6H4(BMes2)]+, then releasing by elution of TBACN in dry acetonitrile.
Chiral expression of adsorbed (MP) 5-amino[6]helicenes: from random structures to dense racemic crystals by surface alloying
Authors: Fuhr Javier D. , van der Meijden Maarten W. , Cristina Lucila J. , Rodríguez Luis M. , Kellogg Richard M. , Gayone J. Esteban , Ascolani Hugo , Lingenfelder Magalí
Published: November 2016

The chiral expression of a molecule on a surface is driven from a random solid solution on Cu(100) to a racemic crystal on a Sn/Cu(100) alloy.
Planar pentacoordinate carbon atoms embedded in a metallocene framework
Authors: Cui Zhong-hua , Vassilev-Galindo Valentin , Luis Cabellos José , Osorio Edison , Orozco Mesías , Pan Sudip , Ding Yi-hong , Merino Gabriel
Published: November 2016

Planar pentacoordinate carbon embedded in a metallocene framework is reported for the first time.
Sulfoxidation of alkenes and alkynes with NFSI as a radical initiator and selective oxidant
Authors: Zhang Yuexia , Wong Zeng Rong , Wu Xingxing , Lauw Sherman J. L. , Huang Xuan , Webster Richard D. , Chi Yonggui Robin
Published: November 2016

A one-pot metal-free facile synthesis of sulfoxides from alkenes and alkynes is disclosed. NFSI is used to enable radical generation for thiol–ene/yne reaction and subsequent selective oxidation of sulfides to sulfoxides.
On the accuracy of the general, state-specific polarizable-continuum model for the description of correlated ground- and excited states in solution
Authors: Mewes Jan-Michael , Herbert John M. , Dreuw Andreas
Published: November 2016

Equilibrium and non-equilibrium formulations of the state-specific PCM are evaluated in combination with correlated ground- and excited-state densities provided by ADC/ISR approach of up to third order of perturbation theory.
The effect of gme topology on multicomponent adsorption in zeolitic imidazolate frameworks
Authors: Gotzias Anastasios
Published: November 2016

A direct comparison of density profiles inside the pores of 8 gme ZIF crystals, as resulted from multicomponent adsorption simulations.
BN-schwarzite: novel boron nitride spongy crystals
Authors: Gao Pengfei , Chen Xi , Guo Lei , Wu Zhifeng , Zhang Erhu , Gong Baihua , Zhang Yang , Zhang Shengli
Published: November 2016

Novel 3-D BN crystals with a negative curvature, intrinsic porosity and a large specific surface area are proposed for the first time by first-principles study, suggesting that the BN crystals hold great promise in the fields of energy storage, molecular sieving, and environmental remediation.
Ternary solvent for CH3NH3PbI3 perovskite films with uniform domain size
Authors: Xie Lin , Hwang Heewon , Kim Minjung , Kim Kyungkon
Published: November 2016

A ternary solvent system consisting of dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL) and N-methyl-2-pyrrolidone (NMP) has been developed to improve the uniformity of CH3NH3PbI3 (MAPbI3) perovskite domains.
Identification of photofragmentation patterns in trihalide anions by global analysis of vibrational wavepacket dynamics in broadband transient absorption data
Authors: Schott Sebastian , Ress Lea , Hrušák Jan , Nuernberger Patrick , Brixner Tobias
Published: November 2016

Photodissociation pathways of a trihalide series are systematically investigated by globally fitting vibrational wavepacket signals in broadband transient absorption spectra.
Interfacial assembly structures and nanotribological properties of saccharic acids
Authors: Shi Hongyu , Liu Yuhong , Zeng Qingdao , Yang Yanlian , Wang Chen , Lu Xinchun
Published: November 2016

The larger friction of the successfully constructed assembly of saccharic acid indicates the higher potential energy barrier at the interface.
Improving thermoelectric performance of TiNiSn by mixing MnNiSb in the half-Heusler structure
Authors: Berry T. , Ouardi S. , Fecher G. H. , Balke B. , Kreiner G. , Auffermann G. , Schnelle W. , Felser C.
Published: November 2016

We synthesized a Ti1−xMnxNiSn1−xSbx system which is a promising thermoelectric material over the substitution range of x = 0.01–0.05.
Size-dependent hardness of five-fold twin structured Ag nanowires
Authors: Jung Joo Young , Qaiser Nadeem , Feng Gang , Hwang Byung-il , Kim Taegeon , Kim Jae Hyun , Han Seung Min
Published: November 2016

In this study, the size dependent hardness of silver nanowires with a five-fold twin structure was examined using nanoindentation.
A platform with connections in many directions – further remarkable facets to the multifaceted methylbiquinoxen dication
Authors: Leblanc Nicolas , Genovese Damiano , De Cola Luisa , Powell Annie K.
Published: November 2016

New directions for the methylbiquinoxen platform.
Chiral organocatalysts based on lipopeptide micelles for aldol reactions in water
Authors: Soares B. M. , Aguilar A. M. , Silva E. R. , Coutinho-Neto M. D. , Hamley I. W. , Reza M. , Ruokolainen J. , Alves W. A.
Published: November 2016

Self-assembly of a proline-capped lipopeptide in water provides unprecedented enhancement of catalytic activity in aldol reactions.
Structural and dynamic studies of substrate binding in porous metal–organic frameworks
Authors: Easun Timothy L. , Moreau Florian , Yan Yong , Yang Sihai , Schröder Martin
Published: November 2016

Porous metal–organic frameworks (MOFs) are the subject of considerable research interest because of their high porosity and capability of specific binding to small molecules, thus underpinning a wide range of materials functions such as gas adsorption, separation, drug delivery, catalysis, and sensing.
Correction: Mesoporous carbon nitrides: synthesis, functionalization, and applications
Authors: Lakhi Kripal S. , Park Dae-Hwan , Al-Bahily Khalid , Cha Wangsoo , Viswanathan Balasubramanian , Choy Jin-Ho , Vinu Ajayan
Published: November 2016

Correction for ‘Mesoporous carbon nitrides: synthesis, functionalization, and applications’ by Kripal S. Lakhi et al., Chem. Soc. Rev., 2017, DOI: 10.1039/c6cs00532b.
Phosphinines versus mesoionic carbenes: a comparison of structurally related ligands in Au(i)-catalysis
Authors: Rigo Massimo , Hettmanczyk Lara , Heutz Frank J. L. , Hohloch Stephan , Lutz Martin , Sarkar Biprajit , Müller Christian
Published: November 2016

Gold(i) complexes based on a 2,4,6-triarylphosphinine and a mesoionic carbene derivative have been prepared and applied in catalytic reactions.