bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of gene expression from systemic lupus erythematosus synovium reveals myeloid cell-driven pathogenesis of lupus arthritis
Authors: Hubbard Erika L. , Catalina Michelle D. , Heuer Sarah , Bachali Prathyusha , Robl Robert , Geraci Nicholas S. , Grammer Amrie C. , Lipsky Peter E.
Published: October 2020

Arthritis is a common manifestation of systemic lupus erythematosus (SLE) yet understanding of the underlying pathogenic mechanisms remains incomplete. We, therefore, interrogated gene expression profiles of SLE synovium to gain insight into the nature of lupus arthritis (LA), using osteoarthritis (OA) and rheumatoid arthritis (RA) as comparators. Knee synovia from SLE, OA, and RA patients were analyzed for differentially expressed genes (DEGs) and also by Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules of highly co-expressed genes. Genes upregulated and/or co-expressed in LA revealed numerous immune/inflammatory cells dominated by a myeloid phenotype, in which pathogenic macrophages, myeloid-lineage cells, and their secreted products perpetuate inflammation, whereas OA was characterized by fibroblasts and RA of lymphocytes. Genes governing trafficking of immune cells into the synovium by chemokines were identified, but not in situ generation of germinal centers (GCs). Gene Set Variation Analysis (GSVA) confirmed activation of specific immune cell types in LA. Numerous therapies were predicted to target LA, including TNF, NFκB, MAPK, and CDK inhibitors. Detailed gene expression analysis identified a unique pattern of cellular components and physiologic pathways operative in LA, as well as drugs potentially able to target this common manifestation of SLE.
Detection of REEs with lightweight UAV-based hyperspectral imaging
Authors: Booysen René , Jackisch Robert , Lorenz Sandra , Zimmermann Robert , Kirsch Moritz , Nex Paul A. M. , Gloaguen Richard
Published: October 2020

Rare earth elements (REEs) supply is important to ensure the energy transition, e-mobility and ultimately to achieve the sustainable development goals of the United Nations. Conventional exploration techniques usually rely on substantial geological field work including dense in-situ sampling with long delays until provision of analytical results. However, this approach is limited by land accessibility, financial status, climate and public opposition. Efficient and innovative methods are required to mitigate these limitations. The use of lightweight unmanned aerial vehicles (UAVs) provides a unique opportunity to conduct rapid and non-invasive exploration even in socially sensitive areas and in relatively inaccessible locations. We employ drones with hyperspectral sensors to detect REEs at the earth’s surface and thus contribute to a rapidly evolving field at the cutting edge of exploration technologies. We showcase for the first time the direct mapping of REEs with lightweight hyperspectral UAV platforms. Our solution has the advantage of quick turn-around times (< 1 d), low detection limits (< 200 ppm for Nd) and is ideally suited to support exploration campaigns. This procedure was successfully tested and validated in two areas: Marinkas Quellen, Namibia, and Siilinjärvi, Finland. This strategy should invigorate the use of drones in exploration and for the monitoring of mining activities.
The physical origin of rate promoting vibrations in enzymes revealed by structural rigidity
Authors: Chalopin Yann
Published: October 2020

Enzymes are the most efficient catalysts known to date. However, decades of research have failed to fully explain the catalytic power of enzymes, and most of the current attempts to uncloak the details of atomic motions at active sites remain incomplete. Here, a straightforward manner for understanding the interplay between the complex or irregular enzyme topology and dynamical effects at catalytic sites is introduced, by revealing how fast localized vibrations form spontaneously in the stiffest parts of the scaffold. While shedding light on a physical mechanism that allowed the selection of the picosecond (ps) timescale to increase the catalytic proficiency, this approach exposes the functional importance of localized motions as a by-product of the stability-function tradeoff in enzyme evolution. From this framework of analysis—directly accessible from available diffraction data—experimental strategies for engineering the catalytic rate in enzymatic proteins are proposed.
Uncertainty quantification based cloud parameterization sensitivity analysis in the NCAR community atmosphere model
Authors: Pathak Raju , Sahany Sandeep , Mishra Saroj K.
Published: October 2020

Using uncertainty quantification techniques, we carry out a sensitivity analysis of a large number (17) of parameters used in the NCAR CAM5 cloud parameterization schemes. The LLNL PSUADE software is used to identify the most sensitive parameters by performing sensitivity analysis. Using Morris One-At-a-Time (MOAT) method, we find that the simulations of global annual mean total precipitation, convective, large-scale precipitation, cloud fractions (total, low, mid, and high), shortwave cloud forcing, longwave cloud forcing, sensible heat flux, and latent heat flux are very sensitive to the threshold-relative-humidity-for-stratiform-low-clouds ($$rhminl)$$

r
h
m
i
n
l
)

and the auto-conversion-size-threshold-for-ice-to-snow $$\left( {dcs} \right).$$

dcs

.

The seasonal and regime specific dependence of some parameters in the simulation of precipitation is also found for the global monsoons and storm track regions. Through sensitivity analysis, we find that the Somali jet strength and the tropical easterly jet associated with the south Asian summer monsoon (SASM) show a systematic dependence on $$dcs$$

dcs

and $$rhminl$$

rhminl

. The timing of the withdrawal of SASM over India shows a monotonic increase (delayed withdrawal) with an increase in $$dcs$$

dcs

. Overall, we find that $$rhminl$$

rhminl

, $$dcs$$

dcs

, $$ai,$$

a
i
,

and $$as$$

as

are the most sensitive cloud parameters and thus are of high priority in the model tuning process, in order to reduce uncertainty in the simulation of past, present, and future climate.
Role of the paramagnetic donor-like defects in the high n-type conductivity of the hydrogenated ZnO microparticles
Authors: Savchenko Dariya , Vasin Andrii , Kuz Oleksandr , Verovsky Igor , Prokhorov Andrey , Nazarov Alexey , Lančok Jan , Kalabukhova Ekaterina
Published: October 2020

The magnetic and electronic properties of the hydrogenated highly conductive zinc oxide (ZnO) microparticles were investigated by electron paramagnetic resonance (EPR) and contactless microwave (MW) conductivity techniques in the wide temperature range. The EPR spectra simulation allowed us to resolve four overlapping EPR signals in ZnO microparticles. The Lorentzian EPR line with isotropic g-factor 1.9623(5) was related to the singly ionized oxygen vacancy. Another Lorentzian line with g|| = 1.9581(5), g⊥ = 1.9562(5) was attributed to the zinc interstitial shallow donor center, while EPR signal with g|| = 1.9567(5), g⊥ = 1.9556(5) and Gaussian lineshape was assigned to the hydrogen interstitial shallow effective-mass-like donor. The EPR signal with g|| = 1.9538(5), g⊥ = 1.9556(5) and Lorentzian lineshape was tentatively attributed to the shallow donor center. The charge transport properties in ZnO microparticles have been investigated by the contactless MW conductivity technique at T = 5–296 K. Two conduction mechanisms, including ionization of electrons from the shallow donors to the conduction band and hopping conduction process, have been distinguished. The hopping conduction process follows Mott’s variable-range hopping T−1/4 law at T = 10–100 K. The evaluated values of the average hopping distance (15.86 Å), and hopping energy (1.822 meV at 40 K) enable us to estimate the donor concentration in the investigated ZnO microparticles as ~ 1018 cm−3.
Vertical transmission of hepatitis E virus in pregnant rhesus macaques
Authors: Yu Wenhai , Hao Xianhui , Li Yi , Yang Chenchen , Li Yunlong , He Zhanlong , Huang Fen
Published: October 2020

Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. HEV causes high mortality in pregnant women. Its infection during pregnancy usually leads to fulminant hepatic failure, spontaneous abortions, premature delivery, or stillbirth. Vertical transmission of HEV has been reported, but the pathogenesis during pregnancy remains largely elusive. Pregnant rhesus macaques were infected with HEV to explore the pathogenesis of genotype 4 HEV infection during pregnancy. Active HEV infections were established with shedding viruses in the feces and blood, and elevated liver enzymes. Notably, higher viral titers and longer durations of HEV infection were found in HEV-infected pregnant rhesus macaques than in non-pregnant macaques. Premature delivery and fetal death occurred in one of the HEV-infected pregnant rhesus macaques. HEV RNA was detected in the liver, spleen, kidneys, and intestines of the dead fetus. This result strongly indicated vertical HEV transmission from mother to fetus. Maternal-transferred antibodies were observed in one of the babies with poor protection. The expressions of interferon-stimulated genes (ISGs) related to HEV infection were completely different between pregnant and non-pregnant rhesus macaques. During pregnancy, impaired innate immune responses, reduced progesterone levels, and shifts in immune states may aggravate HEV infection and result in adverse pregnancy outcomes.
Generalized enzymatic mechanism of catalysis by tetrameric l-asparaginases from mesophilic bacteria
Authors: Strzelczyk Pawel , Zhang Di , Dyba Marzena , Wlodawer Alexander , Lubkowski Jacek
Published: October 2020

The mechanism of catalysis by the l-glutaminase-asparaginase from Pseudomonas 7A (PGA) was investigated using structural, mass spectrometry, and kinetic data. We had previously proposed mechanism of hydrolysis of l-Asn by the type II l-asparaginase from E. coli (EcAII), but that work was limited to just one enzyme. Based on results presented in this report, we postulate that all homotetrameric l-asparaginases from mesophilic bacteria utilize a common ping-pong mechanism of catalysis consisting of two subsequent nucleophilic substitutions. Several new structures of non-covalent complexes of PGA with different substrates, as well as structures of covalent acyl-enzyme intermediates of PGA with canonical substrates (l-Asp and l-Glu) and an opportunistic ligand, a citrate anion, were determined. The results of kinetic experiments monitored by high-resolution LC/MS, when combined with new structural data, clearly show that the reaction catalyzed by l-glutaminase-asparaginases proceeds through formation of a covalent intermediate, as observed previously for EcAII. Additionally, by showing that the same mechanism applies to l-Asn and l-Gln, we postulate that it is common for all these structurally related enzymes.
Associations of second-hand smoke exposure with hand eczema and atopic dermatitis among college students in China
Authors: Jing Danrong , Li Juan , Tao Juan , Wang Xiaohui , Shan Shijun , Kang Xiaojing , Wu Bin , Zhang Yichi , Xiao Yi , Chen Xiang , Shen Minxue
Published: October 2020

Smoking has been identified as a risk factor for atopic dermatitis and hand eczema, but less is known about the association of exposure to second-hand smoke (SHS) with hand eczema. The study aimed to investigate the association of SHS exposure with hand eczema and atopic dermatitis in a group of adolescents. We conducted a cross-sectional study among first-year college students. SHS exposure was measured by a self-administered questionnaire. Skin diseases were diagnosed by dermatologists in the field survey. Mixed models were used to estimate the associations. A total of 20,129 participants that underwent skin examination and a questionnaire survey were included in the analyses. The prevalence rates of atopic dermatitis and hand eczema were 3.86% and 3.35%, respectively. Crude and adjusted estimates consistently showed that exposure to SHS was significantly associated with atopic dermatitis and hand eczema in a dose–response manner. Attention deficit/hyperactivity disorder mediated minimal or no effect of SHS on hand eczema and atopic dermatitis. Subgroup analysis by type of hand eczema, and sensitivity analysis by excluding data with center effect showed consistent results. Exposure to SHS is an independent but modifiable risk factor for hand eczema and atopic dermatitis in adolescents.
In vivo bactericidal effect of colistin–linezolid combination in a murine model of MDR and XDR Acinetobacter baumannii pneumonia
Authors: Ma Xiao-Lin , Guo Yong-Zhong , Wu Yan-Min , Gong Wei-Tao , Sun Jie , Huang Zhen
Published: October 2020

Recently, paradoxical combinations of colistin with anti-Gram-positive bacterial agents were introduced as a treatment alternative for multidrug-resistant Acinetobacter baumannii (MDRAB) infection. We assessed the therapeutic efficacy of the colistin–linezolid combination regimen in vitro and in a murine model of Acinetobacter baumannii pneumonia. A multidrug-resistant clinical strain (MDRAB31) and an extensively drug-resistant clinical strain (XDRAB78) were used in this study. The survival rates of mice and bacterial counts in lung tissue were used to assess the effects of colistin–linezolid combination. The survival rates of colistin–linezolid combination groups significantly increased compared with colistin groups for MDRAB31 (72% versus 32%, P = 0.03) and for XDRAB78 (92% versus 68%, P = 0.031). The colistin–linezolid combination groups significantly reduced the bacterial counts in lung tissue compared with colistin groups for MDRAB31 and for XDRAB78 (P < 0.05). The colistin–linezolid combination had a bactericidal and synergistic effect compared with colistin alone in time-kill assay and in murine model of pneumonia. Our data demonstrated the synergistic effect of colistin–linezolid combination regimen as a treatment alternative for the severe pulmonary infection caused by MDRAB and XDRAB.
Structural insights into metal-metalloid glasses from mass spectrometry
Authors: Baksi Ananya , Bag Soumabha , Kruk Robert , Nandam Sree Harsha , Hahn Horst
Published: October 2020

Despite being studied for nearly 50 years, smallest chemically stable moieties in the metallic glass (MG) could not be found experimentally. Herein, we demonstrate a novel experimental approach based on electrochemical etching of amorphous alloys in inert solvent (acetonitrile) in the presence of a high voltage (1 kV) followed by detection of the ions using electrolytic spray ionization mass spectrometry (ESI MS). The experiment shows stable signals corresponding to Pd, PdSi and PdSi2ions, which emerges due to the electrochemical etching of the Pd80Si20metallic glass electrode. These fragments are observed from the controlled dissolution of the Pd80Si20melt-spun ribbon (MSR) electrode. Annealed electrode releases different fragments in the same experimental condition. These specific species are expected to be the smallest and most stable chemical units from the metallic glass which survived the chemical dissolution and complexation (with acetonitrile) process. Theoretically, these units can be produced from the cluster based models for the MG. Similar treatment on Pd40Ni40P20MSR resulted several complex peaks consisting of Pd, Ni and P in various combinations suggesting this can be adopted for any metal-metalloid glass.
Impact of volatile organic compounds on chromium containing atmospheric particulate: insights from molecular dynamics simulations
Authors: Shah Dhawal , Karibayev Mirat , Adotey Enoch Kwasi , Amouei Torkmahalleh Mehdi
Published: October 2020

The effect of volatile organic compounds (VOCs) on chromium-containing atmospheric particles remains obscured because of difficulties in experimental measurements. Moreover, several ambiguities exist in the literature related to accurate measurements of atmospheric chromium concentration to evaluate its toxicity. We investigated the interaction energies and diffusivity for several VOCs in chromium (III)-containing atmospheric particles using classical molecular dynamics simulations. We analyzed xylene, toluene, ascorbic acid, carbon tetrachloride, styrene, methyl ethyl ketone, naphthalene, and anthracene in Cr(III) solutions, with and without air, to compare their effects on solution chemistry. The interaction energy between Cr(III) and water changed from 48 to 180% for different VOCs, with the highest change with anthracene and the lowest change with naphthalene. The results revealed no direct interactions between Cr(III) particles and the analyzed volatile organic compounds, except ascorbic acid. Interactions of Cr(III) and ascorbic acid differ significantly between the solution phase and the particulate phase. The diffusion of Cr(III) and all the VOCs also were observed in a similar order of magnitude (~ 10−5 cm2/s). The results can further assist in exploring the variation in chromium chemistry and reaction rates in the atmospheric particles in the presence of VOCs.
Recombinant thrombomodulin alleviates oxidative stress without compromising host resistance to infection in rats infected with methicillin-resistant Staphylococcus aureus
Authors: Ito Takashi , Shrestha Binita , Kakihana Yasuyuki , Maruyama Ikuro
Published: October 2020

Recombinant thrombomodulin (rTM) has been used for treatment of sepsis-associated disseminated intravascular coagulation. Recent studies have suggested that anticoagulant therapy might dampen the protective role of immunothrombosis. We examined if rTM might worsen infectious diseases. Male Sprague–Dawley rats with jugular-vein catheterization were divided into three groups: no anticoagulation; rTM pretreatment; rTM treatment at 6 h. Live methicillin-resistant Staphylococcus aureus (MRSA) was inoculated into the tail vein of rats. rTM was administered into the jugular-vein catheter before or 6 h after MRSA inoculation, while an equal volume of saline was administered in the no-anticoagulation group. Blood samples were collected from the jugular-vein catheter before, 6 h and 12 h after MRSA inoculation. Tissue samples were collected from anesthetized rats when moribund or 18 h after MRSA inoculation. The survival rate of rats in the no-anticoagulation group, rTM pretreatment group, and rTM treatment at 6-h group was 50%, 25%, and 75%, respectively. Bacterial burden in blood, lung, liver, and spleen was neither increased nor decreased in rats treated with rTM. The ratio of bacteria found in the extravascular space to those in the intravascular space was increased in rats treated with rTM although the statistical power for this was low because of the small sample size. Metabolomics analysis revealed that rTM treatment alleviated oxidative stress, as evidenced by the decrease in levels of oxidized glutathione with reference to reduced glutathione. rTM did not promote bacterial propagation but alleviated oxidative stress in our rat model of bloodstream infection with MRSA. Further large-scale studies are needed to confirm these findings.
Evaluation of the RAS signaling network in response to MEK inhibition using organoids derived from a familial adenomatous polyposis patient
Authors: Osumi Hiroki , Muroi Atsushi , Sakahara Mizuho , Kawachi Hiroshi , Okamoto Takuya , Natsume Yasuko , Yamanaka Hitomi , Takano Hiroshi , Kusama Daisuke , Shinozaki Eiji , Ooki Akira , Yamaguchi Kensei , Ueno Masashi , Takeuchi Kengo , Noda Tetsuo , Nagayama Satoshi , Koshikawa Naohiko , Yao Ryoji
Published: October 2020

RAS signaling is a promising target for colorectal cancer (CRC) therapy, and a variety of selective inhibitors have been developed. However, their use has often failed to demonstrate a significant benefit in CRC patients. Here, we used patient-derived organoids (PDOs) derived from a familial adenomatous polyposis (FAP) patient to analyze the response to chemotherapeutic agents targeting EGFR, BRAF and MEK. We found that PDOs carrying KRAS mutations were resistant to MEK inhibition, while those harboring the BRAF class 3 mutation were hypersensitive. We used a systematic approach to examine the phosphorylation of RAS effectors using reverse-phase protein array (RPPA) and found increased phosphorylation of MEK induced by binimetinib. A high basal level of ERK phosphorylation and its rebound activation after MEK inhibition were detected in KRAS-mutant PDOs. Notably, the phosphorylation of EGFR and AKT was more closely correlated with that of MEK than that of ERK. Transcriptome analysis identified MYC-mediated transcription and IFN signaling as significantly correlated gene sets in MEK inhibition. Our experiments demonstrated that RPPA analysis of PDOs, in combination with the genome and transcriptome, is a useful preclinical research platform to understand RAS signaling and provides clues for the development of chemotherapeutic strategies.
The role of transcriptional repressor activity of LexA in salt-stress responses of the cyanobacterium Synechocystis sp. PCC 6803
Authors: Takashima Kosuke , Nagao Syota , Kizawa Ayumi , Suzuki Takehiro , Dohmae Naoshi , Hihara Yukako
Published: October 2020

Different from typical LexA repressors in heterotrophic bacteria exerting SOS response by auto-cleavage, cyanobacterial LexAs, especially that of Synechocystis sp. PCC 6803 (S.6803), have been suggested be involved in regulation of a number of genes related to various cellular processes, rather than the typical SOS regulon. When and how cyanobacterial LexAs are triggered to regulate its target genes have remained unknown. In this study, we found the profound repressing effect of LexA on salt-stress inducible genes in S.6803. The repressing activity of LexA was likely to persist during salt stress and the salt response of these genes was mainly achieved by other regulators than LexA, suggesting that the physiological role of LexA is fine-tuning of gene expression in response to environmental changes. Although the amount and oligomeric state of LexA were unchanged upon salt stress, two-dimensional electrophoresis and liquid chromatography-tandem mass spectrometry analyses detected a change in posttranslational modification in a small fraction of LexA molecules, possibly dephosphorylation of Ser173, after 30 min upon the upshift in salt concentration. Activity of LexA in S.6803 may be under gradual control by posttranslational modification to fine-tune gene expression, which is contrasted with the digital switching-off regulation by auto-cleavage in heterotrophic bacteria.
Molecular simulations unravel the molecular principles that mediate selective permeability of carboxysome shell protein
Authors: Faulkner Matthew , Szabó István , Weetman Samantha L. , Sicard Francois , Huber Roland G. , Bond Peter J. , Rosta Edina , Liu Lu-Ning
Published: October 2020

Bacterial microcompartments (BMCs) are nanoscale proteinaceous organelles that encapsulate enzymes from the cytoplasm using an icosahedral protein shell that resembles viral capsids. Of particular interest are the carboxysomes (CBs), which sequester the CO2-fixing enzymes ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) to enhance carbon assimilation. The carboxysome shell serves as a semi-permeable barrier for passage of metabolites in and out of the carboxysome to enhance CO2fixation. How the protein shell directs influx and efflux of molecules in an effective manner has remained elusive. Here we use molecular dynamics and umbrella sampling calculations to determine the free-energy profiles of the metabolic substrates, bicarbonate, CO2and ribulose bisphosphate and the product 3-phosphoglycerate associated with their transition through the major carboxysome shell protein CcmK2. We elucidate the electrostatic charge-based permeability and key amino acid residues of CcmK2 functioning in mediating molecular transit through the central pore. Conformational changes of the loops forming the central pore may also be required for transit of specific metabolites. The importance of these in-silico findings is validated experimentally by site-directed mutagenesis of the key CcmK2 residue Serine 39. This study provides insight into the mechanism that mediates molecular transport through the shells of carboxysomes, applicable to other BMCs. It also offers a predictive approach to investigate and manipulate the shell permeability, with the intent of engineering BMC-based metabolic modules for new functions in synthetic biology.
TAP2, a peptide antagonist of Toll-like receptor 4, attenuates pain and cartilage degradation in a monoiodoacetate-induced arthritis rat model
Authors: Park Hyewon , Hong Jinpyo , Yin Yuhua , Joo Yongbum , Kim Youngmo , Shin Juhee , Kwon Hyeok Hee , Shin Nara , Shin Hyo Jung , Beom Jaewon , Kim Dong Woon , Kim Jinhyun
Published: October 2020

Because inflammation in osteoarthritis (OA) is related to the Toll-like receptor 4 (TLR4) signaling cascades, TLR4 is a reasonable target for developing therapeutics for OA. Thus, we investigated whether TAP2, a peptide antagonist of TLR4, reduces the monoiodoacetate (MIA)-induced arthritic pain and cartilage degradation in rats. TLR4 expression of human OA chondrocytes and synoviocytes and the knee joint tissue of MIA-induced arthritis were evaluated. MIA-induced arthritic model using Sprague–Dawley rats (6 week-old-male) were treated with TAP2, a TLR4 antagonist, and evaluated with behavioral test, immunohistochemistry, and quantitative PCR. TLR4 was highly expressed in the knee joints of patients with OA and the MIA-induced rat model. Further, a single intraarticular injection of TAP2 (25 nmol/rat) molecules targeting TLR4 on day 7 after MIA injection dramatically attenuated pain behavior for about 3 weeks and reduced cartilage loss in the knee joints and microglial activation in the spinal dorsal horns. Likewise, the mRNA levels of TNFα and IL-1β, reactive oxygen species, and the expression of MMP13 in the knee joints of TAP2-treated rats was significantly decreased by TAP2 treatment compared with the control. Moreover, interestingly, the duration of OA pain relief by TAP2 was much longer than that of chemical TLR4 antagonists, such as C34 and M62812. In conclusion, TAP2 could effectively attenuate MIA-induced arthritis in rats by blocking TLR4 and its successive inflammatory cytokines and MMP13. Therefore, TAP2 could be a prospective therapeutic to treat patients with OA.
Experimental optimization of the energy for breast-CT with synchrotron radiation
Authors: Oliva Piernicola , Di Trapani Vittorio , Arfelli Fulvia , Brombal Luca , Donato Sandro , Golosio Bruno , Longo Renata , Mettivier Giovanni , Rigon Luigi , Taibi Angelo , Tromba Giuliana , Zanconati Fabrizio , Delogu Pasquale
Published: October 2020

Breast Computed Tomography (bCT) is a three-dimensional imaging technique that is raising interest among radiologists as a viable alternative to mammographic planar imaging. In X-rays imaging it would be desirable to maximize the capability of discriminating different tissues, described by the Contrast to Noise Ratio (CNR), while minimizing the dose (i.e. the radiological risk). Both dose and CNR are functions of the X-ray energy. This work aims at experimentally investigating the optimal energy that, at fixed dose, maximizes the CNR between glandular and adipose tissues. Acquisitions of both tissue-equivalent phantoms and actual breast specimens have been performed with the bCT system implemented within the Syrma-3D collaboration at the Syrmep beamline of the Elettra synchrotron (Trieste). The experimental data have been also compared with analytical simulations and the results are in agreement. The CNR is maximized at energies around 26–28 keV. These results are in line with the outcomes of a previously presented simulation study which determined an optimal energy of 28 keV for a large set of breast phantoms with different diameters and glandular fractions. Finally, a study on photon starvation has been carried out to investigate how far the dose can be reduced still having suitable images for diagnostics.
The extremal pentagon-chain polymers with respect to permanental sum
Authors: Wu Tingzeng , Wang Hongge , Zhang Shanjun , Deng Kai
Published: October 2020

The permanental sum of a graphGcan be defined as the sum of absolute value of coefficients of permanental polynomial ofG. It is closely related to stability of structure of a graph, and its computing complexity is #P-complete. Pentagon-chain polymers is an important type of organic polymers. In this paper, we determine the upper and lower bounds of permanental sum of pentagon-chain polymers, and the corresponding pentagon-chain polymers are also determined.
Effectiveness of hysteroscopic resection of a uterine caesarean niche can be predicted: a prospective cohort study
Authors: Zhu Qian , He Xiaoqing , Jiang Ling , Liang Guiling , Zhu Chenfeng , Pan Hongjie , Zhang Jian , Huirne Judith Anna
Published: October 2020

This study aimed to develop and validate a model for the preoperative prediction of the effectiveness of hysteroscopic resection of a uterine cesarean niche in patients with postmenstrual spotting. The predictive model was developed in a primary prospective cohort consisting of 208 patients with niche treated by hysteroscopic resection. Multivariable logistic regression analysis was performed to develop the predictive model, which incorporated preoperative menstrual characteristics and magnetic resonance imaging (MRI) findings. Surgical efficacy was defined as a decrease in postmenstrual spotting duration of at least 3 days at the 3-month follow-up compared with baseline. The predictive model was presented with a nomogram, and the performance was assessed with respect to its calibration, discrimination, and clinical use. Internal validation was performed using tenfold cross-validation. The predictive factors in the final model were as follows: preoperative menstrual duration, thickness of the residual myometrium (TRM), length, TRM/thickness of the adjacent myometrium ratio, angle γ, area, and presence of a lateral branch of the niche. The model showed good performance in predicting the effectiveness of hysteroscopic niche resection. Incorporating the preoperative duration of the menstrual period and MRI findings of the niche into an easy-to-use nomogram facilitates the individualized prediction of the effectiveness of a hysteroscopic niche resection by 26 Fr resectoscope, but multicenter prospective studies are needed to validate it.
Reliability of pre-operative diffusion tensor imaging parameter measurements of the cervical spine in patients with cervical spondylotic myelopathy
Authors: Lee Eugene , Lee Joon Woo , Bae Yun Jung , Kim Hyo Jin , Kang Yusuhn , Ahn Joong Mo
Published: October 2020

The present study assessed test–retest and inter-observer reliability of diffusion tensor imaging (DTI) in cervical spondylotic myelopathy (CSM), as well as the agreement among measurement methods. A total 34 patients (12 men, 22 women; mean age, 58.7 [range 45–79] years) who underwent surgical decompression for CSM, with pre-operative DTI scans available, were retrospectively enrolled. Four observers independently measured fractional anisotropy (FA) values twice, using three different measurement methods. Test–retest and inter-observer reliability was assessed using intraclass correlation coefficients (ICCs). Overall, inter-observer agreements varied according to spinal cord level and the measurement methods used, and ranged from poor to excellent agreement (ICC = 0.374–0.821), with relatively less agreement for the sagittal region of interest (ROI) method. The radiology resident and neuro-radiologist group showed excellent test–retest reliability at almost every spinal cord level (ICC = 0.887–0.997), but inter-observer agreements varied from fair to good (ICC = 0.404–0.747). Despite excellent test–retest reliability of the ROI measurements, FA measurements in patients with CSM varied widely in terms of inter-observer reliability. Therefore, DTI parameter data should be interpreted carefully when applied clinically.
Relative fat mass at baseline and its early change may be a predictor of incident nonalcoholic fatty liver disease
Authors: Kim Hwi Young , Baik Su Jung , Lee Hye Ah , Lee Byoung Kwon , Lee Hye Sun , Kim Tae Hun , Yoo Kwon
Published: October 2020

The relationship between changes in body components and the risk of nonalcoholic fatty liver disease (NAFLD) is not fully understood. We investigated the effects of body components and subsequent changes on incident NAFLD at follow-up ultrasound scanning in a longitudinal cohort. We included 9967 participants without NAFLD at baseline who underwent serial health examinations. Sex-specific, weight-adjusted skeletal muscle index (SMI_Wt) was used. Mean follow-up duration was 48.5 ± 33.5 months. NAFLD developed in 2395 participants (24.0%). Body composition was measured using bioelectrical impedance analysis. The following baseline body components were significantly associated with incident NAFLD: the lowest and middle SMI_Wt tertiles in the normal-weight group (adjusted hazard ratio [aHR] = 2.20 and 1.54, respectively), and fat percentage in the normal-weight (aHR = 1.12), overweight (aHR = 1.05), and obese groups (aHR = 1.03) (all P < 0.05). Among 5,033 participants who underwent ≥ 3 health examinations, SMI_Wt increase between the first and second examinations was an independent protective factor against incident NAFLD in non-obese groups (P < 0.05). Increased fat percentage was an independent risk factor for incident NAFLD in all weight categories (P < 0.05). High fat mass at baseline may be a better predictor of incident NAFLD than muscle mass. Reciprocal changes in fat and muscle mass during the first year of follow-up predicted incident NAFLD in non-obese groups.
Differential processing of dissolved and particulate organic matter by deep-sea sponges and their microbial symbionts
Authors: Bart Martijn C. , de Kluijver Anna , Hoetjes Sean , Absalah Samira , Mueller Benjamin , Kenchington Ellen , Rapp Hans Tore , de Goeij Jasper M.
Published: October 2020

Deep-sea sponges create hotspots of biodiversity and biological activity in the otherwise barren deep-sea. However, it remains elusive how sponge hosts and their microbial symbionts acquire and process food in these food-limited environments. Therefore, we traced the processing (i.e. assimilation and respiration) of 13C- and 15N-enriched dissolved organic matter (DOM) and bacteria by three dominant North Atlantic deep-sea sponges: the high microbial abundance (HMA) demosponge Geodia barretti, the low microbial abundance (LMA) demosponge Hymedesmia paupertas, and the LMA hexactinellid Vazella pourtalesii. We also assessed the assimilation of both food sources into sponge- and bacteria-specific phospholipid-derived fatty acid (PLFA) biomarkers. All sponges were capable of assimilating DOM as well as bacteria. However, processing of the two food sources differed considerably between the tested species: the DOM assimilation-to-respiration efficiency was highest for the HMA sponge, yet uptake rates were 4–5 times lower compared to LMA sponges. In contrast, bacteria were assimilated most efficiently and at the highest rate by the hexactinellid compared to the demosponges. Our results indicate that phylogeny and functional traits (e.g., abundance of microbial symbionts, morphology) influence food preferences and diet composition of sponges, which further helps to understand their role as key ecosystem engineers of deep-sea habitats.
Identification and characterization of a new isoform of small GTPase RhoE
Authors: Dai Yuan , Luo Weijia , Yue Xiaojing , Ma Wencai , Wang Jing , Chang Jiang
Published: October 2020

The Rho family of GTPases consists of 20 members including RhoE. Here, we discover the existence of a short isoform of RhoE designated as RhoEα, the first Rho GTPase isoform generated from alternative translation. Translation of this new isoform is initiated from an alternative start site downstream of and in-frame with the coding region of the canonical RhoE. RhoEα exhibits a similar subcellular distribution while its protein stability is higher than RhoE. RhoEα contains binding capability to RhoE effectors ROCK1, p190RhoGAP and Syx. The distinct transcriptomes of cells with the expression of RhoE and RhoEα, respectively, are demonstrated. The data propose distinctive and overlapping biological functions of RhoEα compared to RhoE. In conclusion, this study reveals a new Rho GTPase isoform generated from alternative translation. The discovery provides a new scope of understanding the versatile functions of small GTPases and underlines the complexity and diverse roles of small GTPases.
Pacific subsurface ocean temperature as a long-range predictor of South China tropical cyclone landfall
Authors: Sparks Nathan , Toumi Ralf
Published: October 2020

Seasonal forecasts of the tropical cyclones which frequently make landfall along the densely populated South China coast are highly desirable. Here, we analyse observations of landfalling tropical cyclones in South China and of subsurface ocean temperatures in the Pacific warm pool region, and identify the possibility of forecasts of South China tropical cyclone landfall a year ahead. Specifically, we define a subsurface temperature index, subNiño4, and build a predictive model based on subNiño4 anomalies with a robust double cross-validated forecast skill against climatology of 23%, similar in skill to existing forecasts issued much later in the spring. We suggest that subNiño4 ocean temperatures precede the surface El Niño/Southern Oscillation state by about 12 months, and that the zonal shifts in atmospheric heating then change mid-level winds to steer tropical cyclones towards landfall in South China. We note that regional subsurface ocean temperature anomalies may permit atmospheric predictions in other locations at a longer range than is currently thought possible.
Curcuminoids – Isolation, Formulations and Bioavailability Problems
Authors: Löffler Bernd-Michael , Jude Shintu , Amalraj Augustine , Gopi Sreeraj
Published: October 2020

Curcuminoids are one of the most widely studied phytochemical moieties, owing to their potential therapeutic efficiency as well as the limitations observed in their bioavailability. So far, curcumin is the derivative that is at the center of research. Despite the elucidation of the molecular and cellular mechanisms by which curcumin interacts with the signal transduction pathways of mammalian cells, many studies have been conducted, reserved for the improvement in bioavailability of curcumin after oral administration and thereby contributing towards better bio efficacy. As a result, there are a number of formulations/products developed hitherto; some of which are discussed in the chapter, including relevant examples and their effect in bioavailability. So far, there is little information in the literature on the intravenous application of curcumin. This chapter also highlights the concerns of clinical study aspects and bioavailability considerations.
Biosynthesis of Curcumin and Molecular Targets and the Biological Mechanism of Curcumin
Authors: Baspinar Y. , Akbaba H.
Published: October 2020

The biosynthesis of curcumin can be viewed from different perspectives, a natural pathway in Curcuma Longa (turmeric) and artificial pathways in Oryza sativa (rice) and rice bran pitch respectively, using Esterichia coli (E. Coli). The natural pathway for the synthesis of curcumin can be divided into two, an upstream and a downstream section. The transcription factor nuclear factor κB (NF-κB) governs several cellular signaling pathways associated with cancer, and targets various cytokines, proinflammatory molecules, growth factors, cell adhesion molecules, oncogenes and pro/anti-apoptotic proteins during carcinogenesis. Curcumin targets the transcription factors, protein kinases (PKs), angiogenesis, cell cycle regulators, sirtuins, NF-κB signaling pathway, E-cadherin, vascular endothelial growth factor (VEGF), signal transducers and activators of the transcription 3 (STAT-3) signaling pathway, B-cell lymphoma (Bcl-2), p53, DNA, microRNA (miRNA), apoptosis and autophagy. The biological mechanism comprises different activities that are antioxidant, anticancer, antiviral, antifungal, antiproliferative, anti-immunomodulatory and anti-inflammatory. The main focus of this chapter is to provide valuable information on the biological synthesis, biological mechanism and molecular targets of curcumin.
The Effect of Turmeric in Gut Diseases
Authors: Amalraj Augustine , Sukumaran Nimisha Pulikkal , Nair Akhila , Gopi Sreeraj
Published: October 2020

Gastrointestinal disorders are the most common problem in tropical countries and highly associated with chronic inflammatory conditions of the gastrointestinal tract with a diverse array of symptoms including diarrhea, abdominal pain, abdominal distention, gastrointestinal bleeding, intestinal obstruction, malabsorption or malnutrition. So far, there are very few effective therapeutic strategies for disease management with minimal side effects. Therefore, it is extremely important to use the information derived from various systems of traditional medicine to develop new integrative medicines. Turmeric, the golden spice that has been prized for its anti-inflammatory powers, has been used as an alternative medicine for thousands of years to treat many diseases and conditions, including stomach problems and digestive issues. Most importantly, a polyphenol compound in the spice turmeric, curcumin, has been found to have potent antioxidative and anti-inflammatory activities. This chapter seeks to summarize the therapeutic effects of turmeric and explores the possibilities of its active ingredient in treating gut diseases.
Curcumin as Dietary Supplements Against Various Diseases: An Insight into the New Trends and Future Perspectives
Authors: Nair Akhila , Gopi Sreeraj
Published: October 2020

The ever-evolving technological era has witnessed a great revolution in the diet and lifestyle of individuals, which has created many lifestyle-associated diseases such as diabetes, obesity, cardiovascular, brain disorders, gastrointestinal, bacterial and viral infections and so on. Therefore, concerns regarding longevity have motivated people to find effective alternatives in natural dietary supplements. Curcumin is recognized by the U.S Food and Drug Administration as a dietary herb that can improve health conditions. This review acknowledges the benevolent characteristics of curcumin supplements by including an evidenced-based study for treating various diseases. Although curcumin holds promising applications, its solubility and bioavailability attempt to suppress its virtues. Hence, the current review provides an outlook on resolving these limitations by adopting various food-grade carrier agents and novel techniques to form novel encapsulates that improve their functionalities. Curcumin supplements that embrace these advancements promise to enhance the delivery of curcumin in safe, efficient and economical manner.
Structural-based connectivity and omic phenotype evaluations (SCOPE): a cheminformatics toolbox for investigating lipidomic changes in complex systems
Authors: Odenkirk Melanie T. , Zin Phyo Phyo K. , Ash Jeremy R. , Reif David M. , Fourches Denis , Baker Erin S.
Published: October 2020

SCOPE is a toolbox for expanding upon lipid data interpretation capabilities. Herein we utilize SCOPE to explore how lipid structure, biological connections and metadata linkages contribute to the results observed from lipidomic experiments.
A colorimetric immuno-microarray for the quantitation and direct visualization of illicit drugs in body fluids
Authors: Zhang Lingling , Li Xiaochun , Li Yunchao , Yu Hua-Zhong
Published: October 2020

The design and testing of integrated colorimetric microarray immunochips (immuno-microarrays) are reported for the quantitation and direct visual determination of multiple illicit drugs (e.g., morphine, cocaine and amphetamine) in body fluids.
Silk fibroin photo-lyogels containing microchannels as a biomaterial platform for in situ tissue engineering
Authors: Baptista Marissa , Joukhdar Habib , Alcala-Orozco Cesar R. , Lau Kieran , Jiang Shouyuan , Cui Xiaolin , He Steven , Tang Fengying , Heu Celine , Woodfield Tim B. F. , Lim Khoon S. , Rnjak-Kovacina Jelena
Published: October 2020

Silk photo-lyogels fabricated by di-tyrosine photo-crosslinking and ice-templating silk fibroin on 3D printed templates toward in situ tissue engineering applications.
In vivo vocal fold augmentation using an injectable polyethylene glycol hydrogel based on click chemistry
Authors: Kwon Soonmin , Choi Hyunsu , Park Changhee , Choi Sangkee , Kim Eunha , Kim Sung Won , Kim Choung-Soo , Koo Heebeom
Published: October 2020

A click chemistry-based PEG hydrogel was applied for vocal fold augmentation in vivo. In rabbit models, it stably fixed the paralyzed vocal fold and minimized the glottic gap.
Full-spectrum responsive ZrO2-based phototheranostic agent for NIR-II photoacoustic imaging-guided cancer phototherapy
Authors: Zhu Chengyuan , Ding Zhaoyang , Guo Zhengxi , Guo Xiaolu , Yang Aijia , Li Zhilang , Jiang Bang-Ping , Shen Xing-Can
Published: October 2020

A second near-infrared window (NIR-II) responsive, cancer targeting ZrO2-based phototheranostic agent has been fabricated for imaging-guided precise synergetic phototherapy.
Monocarboxylate-driven structural growth in Calix[n]arene-polyoxotitanate hybrid systems: utility in hydrogen production from water
Authors: Yang Xin-Xue , Yu Wei-Dong , Yi Xiao-Yi , Li Lei-Jiao , Liu Chao
Published: October 2020

A carboxylate-driven assembly strategy has been developed for the first time to build calix[n]arene-based polyoxotitanate clusters with tuneable nuclearity and structures.
Nitric oxide-releasing platinum(iv) prodrug efficiently inhibits proliferation and metastasis of cancer cells
Authors: Dai Yi , Zhu Yang , Cheng Junjie , Shen Juan , Huang Hai , Liu Manman , Chen Zhaolin , Liu Yangzhong
Published: October 2020

Pt–furoxan, a nitric oxide-releasing platinum(iv) prodrug, exhibits a dual function by releasing cytotoxic cisplatin to induce cell apoptosis, and signaling molecule NO to inhibit tumor metastasis.
The investigation and bioorthogonal anticancer activity enhancement of a triphenylphosphine-labile prodrug of seleno-combretastatin-4
Authors: Hou Liyuan , Huang Wei , Cheng Jiaqi , Deng Xuanru , Lai Haoqiang , Chen Zhen , Zhan Zepang , Feng Pengju , Li Yiqun , Yang Fang , Chen Tianfeng
Published: October 2020

A triphenylphosphine-labile prodrug of seleno-combretastatin-4 was designed and synthesized, which was safe in circulating blood, could react with TPP to release CA-4 and a selenodiazole derivative, accompanying powerful anticancer properties.
Revealing the electronic structure of organic emitting semiconductors at the single-molecule level
Authors: Huang Mingzhu , Dong Jianqiao , Wang Zhiye , Li Yunchuan , Yu Lei , Liu Yichong , Qian Gongming , Chang Shuai
Published: October 2020

Single-molecule conductance measurements of OLED molecules show that the holes injected from metal electrode can be suppressed by adding electron-withdrawing arms, benefiting the electron–hole balance of OLED devices whose holes are excessive.
A metal-free reaction of sulfur dioxide, cyclopropanols and electron-deficient olefins
Authors: Zhang Chun , Huang Jiapian , Ye Shengqing , Tang Jie , Wu Jie
Published: October 2020

An efficient route to γ-keto sulfones through a metal-free reaction of cyclopropanols, sulfur dioxide and electron-deficient olefins is achieved. This reaction proceeds smoothly under mild conditions without the need of a catalyst, oxidant or additive.
Nickel-catalyzed C-alkylation of thioamide, amides and esters by primary alcohols through a hydrogen autotransfer strategy
Authors: Yang Peng , Wang Xiuhua , Ma Yu , Sun Yaxin , Zhang Li , Yue Jieyu , Fu Kaiyue , Zhou Jianrong Steve , Tang Bo
Published: October 2020

A simple catalyst of Ni(OAc)2/P(t-Bu)3 enables selective C-alkylation of thioacetamides and primary acetamides with alcohols for the first time.
ε-InSe single crystals grown by a horizontal gradient freeze method
Authors: Sun Maojun , Wang Wei , Zhao Qinghua , Gan Xuetao , Sun Yuanhui , Jie Wanqi , Wang Tao
Published: October 2020

Indium selenide (InSe) single crystals have been considered as promising candidates for future optical, electrical, and optoelectronic device applications.