bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges for the Periodic Systems of Elements: Chemical, Historical and Mathematical Perspectives
Authors: Restrepo Guillermo
Published: October 2019

We celebrate 150 years of periodic systems that reached their maturity in the 1860s. They began as pedagogical efforts to project corpuses of substances on the similarity and order relationships of the chemical elements. However, these elements are not the canned substances wrongly displayed in many periodic tables, but rather the abstract preserved entities in compound transformations. We celebrate the systems, rather than their tables or ultimate table. The periodic law, we argue, is not an all‐encompassing achievement, as it does not apply to every property of all elements and compounds. Periodic systems have been generalised as ordered hypergraphs, which solves the long‐lasting question on the mathematical structure of the systems. In this essay, it is shown that these hypergraphs may solve current issues such as order reversals in super‐heavy elements and lack of system predictive power. We discuss research in extending the limits of the systems in the super‐heavy‐atom region and draw attention to other limits: the antimatter region and the limit arising from compounds under extreme conditions. As systems depend on the known chemical substances (chemical space) and such a space grows exponentially, we wonder whether systems still aim at projecting knowledge of compounds on the relationships among the elements. We claim that systems are not based on compounds anymore, rather on 20th century projections of the 1860s systems of elements on systems of atoms. These projections bring about oversimplifications based on entities far from being related to compounds. A linked oversimplification is the myth of vertical group similarity, which raises questions on the approaches to locate new elements in the system. Finally, we propose bringing back chemistry to the systems by exploring similarity and order relationships of elements using the current information of the chemical space. We ponder whether 19th century periodic systems are still there or whether they have faded away, leaving us with an empty 150thcelebration.
Photoracemization‐Based Viedma Ripening of a BINOL Derivative
Authors: Belletti Giuseppe , Tortora Carola , Mellema Indradevi D. , Tinnemans Paul , Meekes Hugo , Rutjes Floris P. J. T. , Tsogoeva Svetlana B. , Vlieg Elias
Published: October 2019

Viedma ripening is a deracemization process that has been used to deracemize a range of chiral molecules. The method has two major requirements: the compound needs to crystallize as a conglomerate and it needs to be racemizable under the crystallization conditions. Although conglomerate formation can be induced in different ways, the number of racemization methods is still rather limited. To extend the scope of Viedma ripening, in the present research we applied UV‐light‐induced racemization in a Viedma ripening process, and report the successful deracemization of a BINOL derivative crystallizing as a conglomerate. Irradiation by UV light activates the target compound in combination with an organic base, required to promote the excited‐state proton transfer (ESPT), leading thereafter to racemization. This offers a new tool towards the development of Viedma ripening processes, by using a cheap and “green” catalytic source like UV light to racemize suitable chiral compounds.
Biomimetic Mineralization of Protein Nanogels for Enzyme Protection
Authors: Yu Qianyu , Ma Xiaoteng , Liu Yingze , Zhao Hanying
Published: October 2019

Protein nanogels have found a wide variety of applications, ranging from biocatalysis to drug/protein delivery. However, in practical applications, proteins in nanogels may suffer from enzymic hydrolysis and denaturation. Inspired by the structure and functionalities of the fowl eggshells, biomimetic mineralization of protein nanogels was studied in this research. Protein nanogels with embedded porcine pancreas lipase (PPL) in the cross‐linked nanostructures were synthesized through the thiol–disulfide reaction between thiol‐functionalized PPL and poly(N‐isopropylacrylamide) with pendant pyridyl disulfide groups. The nanogels were further reacted with reduced bovine serum albumin (BSA) and BSA molecules were coated on the nanogels. Mineralization of BSA leads to the synthesis of biomineralized shells on the nanogels. With the growth of CaCO3 on the shells, the nanogels aggregate into suprastructures. Thermogravimetric analysis, XRD, dynamic light scattering, and TEM were employed to study the mechanism of the biomineralization process and analyze the structures of the mineralized nanogels. The biomineralized shells can effectively protect the PPL molecules from hydrolysis by trypsin; meanwhile, the nanosized channels on the mineralized shells allow the transport of small‐molecule substrates across the shells. Bioactivity measurements indicate that PPL in the nanogels maintains more than 80 % bioactivity after biomineralization.
Toward Transition‐Metal‐Templated Construction of Arylated B4 Chains by Dihydroborane Dehydrocoupling
Authors: Lenczyk Carsten , Roy Dipak Kumar , Oberdorf Kai , Nitsch Jörn , Dewhurst Rian D. , Radacki Krzysztof , Halet Jean‐François , Marder Todd B. , Bickelhaupt Matthias , Braunschweig Holger
Published: October 2019

The reactivity of a diruthenium tetrahydride complex towards three selected dihydroboranes was investigated. The use of [DurBH2] (Dur=2,3,5,6‐Me4C6H) and [(Me3Si)2NBH2] led to the formation of bridging borylene complexes of the form [(Cp*RuH)2BR] (Cp*=C5Me5; 1 a: R=Dur; 1 b: R=N(SiMe3)2) through oxidative addition of the B−H bonds with concomitant hydrogen liberation. Employing the more electron‐deficient dihydroborane [3,5‐(CF3)2‐C6H3BH2] led to the formation of an anionic complex bearing a tetraarylated chain of four boron atoms, namely Li(THF)4[(Cp*Ru)2B4H5(3,5‐(CF3)2C6H3)4] (4), through an unusual, incomplete threefold dehydrocoupling process. A comparative theoretical investigation of the bonding in a simplified model of 4 and the analogous complex nido‐[1,2(Cp*Ru)2(μ‐H)B4H9] (I) indicates that there appear to be no classical σ‐bonds between the boron atoms in complex I, whereas in the case of 4 the B4 chain better resembles a network of three B−B σ bonds, the central bond being significantly weaker than the other two.
Role of Gold in Inflammation and Tristetraprolin Activity
Authors: Ok Kiwon , Li Wenjing , Neu Heather M. , Batelu Sharon , Stemmler Timothy L. , Kane Maureen A. , Michel Sarah L. J.
Published: October 2019

The zinc finger protein tristetraprolin (TTP) regulates inflammation by downregulating cytokine mRNAs. Misregulation results in arthritis, sepsis and cancer, and there is an interest in modulating TTP activity with exogenous agents. Gold has anti‐inflammatory properties and has recently been shown to modulate the signaling pathway that produces TTP, suggesting that TTP may be a target of gold. The reactivity of [AuIII(terpy)Cl]Cl2 with TTP was investigated by UV/Vis spectroscopy, spin‐filter inductively coupled plasma mass spectrometry, X‐ray absorption spectroscopy and native electrospray ionization mass spectrometry. AuIII was found to replace zinc in the protein active site in the reduced AuI form, with the AuI ion coordinated to two cysteine residues in a linear geometry. The replacement of ZnII with AuI results in loss of both secondary structure and RNA binding function. In contrast, when ZnIITTP is bound to its RNA target, no replacement of ZnII with AuI is observed, even in the presence of excess AuIIIterpy. This discovery of differential reactivity of gold with TTP versus TTP/RNA offers a potential strategy for selective targeting with gold complexes to control inflammation.
Mono‐Heteroatom Substitution for Harnessing Excited‐State Structural Planarization of Dihydrodibenzo[a,c]phenazines
Authors: Chen Yi , Chen Deng‐Gao , Chen Yi‐An , Wu Cheng‐Ham , Chang Kai‐Hsin , Meng Fan‐Yi , Chen Meng‐Chi , Lin Jia‐An , Huang Chun‐Ying , Su Jianhua , Tian He , Chou Pi‐Tai
Published: October 2019

With the aim of generalizing the structure–properties relationship of bending heterocyclic molecules that undergo prominent photoinduced structural planarization (PISP), a series of new dihydrodibenzo[ac]phenazine derivatives in which one nitrogen atom is replaced by oxygen (PNO), sulfur (PNS), selenium (PNSe), or dimethylmethanediyl (PNC) was strategically designed and synthesized. Compounds PNO, PNS, and PNSe have significantly nonplanar geometries in the ground state, which undergo PISP to give a planarlike conformer and hence a large emission Stokes shift. A combination of femtosecond early relaxation dynamics and computational approaches established an R*→I* (intermediate)→P* sequential kinetic pattern for PNS and PNSe, whereas PNO undergoes R*→P* one‐step kinetics. The polarization ability of the substituted heteroatoms, which is in the order O<S<Se, correlates with their increase in π conjugation, and hence the Stokes shift of the emission is in the order PNO<PNS<PNSe. Compound PNSe with the largest PISP barrier was shown to be a highly sensitive viscosity probe. Further evidence for heteroatom‐harnessing PISP is given by PNC, in which the dimethylmethanediyl substituent lacks lone pair electrons for π extension, showing the normal emission of the bent structure. The results led to the conclusion that PISP is ubiquitous in dihydrodibenzo[ac]phenazines, for which the driving force is elongation of the π delocalization to gain stabilization in the excited state.
Competition and succession among coral endosymbionts
Authors: McIlroy Shelby E. , Cunning Ross , Baker Andrew C. , Coffroth Mary Alice
Published: October 2019

Host species often support a genetically diverse guild of symbionts, the identity and performance of which can determine holobiont fitness under particular environmental conditions. These symbiont communities are structured by a complex set of potential interactions, both positive and negative, between the host and symbionts and among symbionts. In reef‐building corals, stable associations with specific symbiont species are common, and we hypothesize that this is partly due to ecological mechanisms, such as succession and competition, which drive patterns of symbiont winnowing in the initial colonization of new generations of coral recruits. We tested this hypothesis using the experimental framework of the de Wit replacement series and found that competitive interactions occurred among symbionts which were characterized by unique ecological strategies. Aposymbiotic octocoral recruits within high‐ and low‐light environments were inoculated with one of three Symbiodiniaceae species as monocultures or with cross‐paired mixtures, and we tracked symbiont uptake using quantitative genetic assays. Priority effects, in which early colonizers excluded competitive dominants, were evidenced under low light, but these early opportunistic species were later succeeded by competitive dominants. Under high light, a more consistent competitive hierarchy was established in which competitive dominants outgrew and limited the abundance of others. These findings provide insight into mechanisms of microbial community organization and symbiosis breakdown and recovery. Furthermore, transitions in competitive outcomes across spatial and temporal environmental variation may improve lifetime host fitness.
Structural, Theoretical and Spectroscopic Characterisation of a Series of Novel Gold(I)‐Norbornene Complexes Supported by Phenanthrolines: Effects of the Supporting Ligand
Authors: Cinellu Maria A. , Arca Massimiliano , Ortu Fabrizio , Stoccoro Sergio , Zucca Antonio , Pintus Anna , Maiore Laura
Published: October 2019

A series of novel gold(I) alkene complexes of general formula [Au(N^N)(η2‐nb)][PF6] [N^N = PHEN (1,10‐phenanthroline), NCP (2,9‐dimethyl‐1,10‐phenanthroline), 4,7‐DMP (4,7‐dimethyl‐1,10‐phenanthroline), TMP (3,4,7,8‐tetramethyl‐1,10‐phenanthroline), BTP (4,7‐diphenyl‐1,10‐phenanthroline) and BTC (2,9‐dimethyl‐4,7‐diphenyl‐1,10‐phenanthroline); nb = norbornene] were synthesized by a novel synthetic pathway. The novel cationic gold(I)‐norbornene complexes were fully characterized by 1H and 13C NMR spectroscopy and the crystal structure of three complexes was solved by single‐crystal X‐ray diffraction. The correlations between the nature and position of the substituents on the ancillary ligand and the spectroscopic and structural data highlight variations on the nature of the bonding. The combination of experimental and DFT data allowed to evaluate the extent of σ‐donation and π back‐donation in the bond with the olefin, suggesting that a fine interplay between electronic and steric effects on the ancillary ligand can affect the bond properties and structural features of the complexes.
Highly Diastereoselective Synthesis of Cyclic α‐Aminophosphonic and α‐Aminophosphinic Acids from Glycyl‐l‐Proline 2,5‐Diketopiperazine
Authors: Ordóñez Mario , Torres‐Hernández Fernando , Viveros‐Ceballos José Luis
Published: October 2019

This paper describes the first diastereoselective synthesis of cyclic α‐aminophosphonic and α‐amino phosphonic acids from glycyl‐l‐proline 2,5‐diketopiperazine (S)‐6 prepared according to the usual peptide coupling procedures. The highlights of this contribution is the chemoselective reduction of the carbamate‐imide activated carbonyl group in the N‐Boc 2,5‐diketopiperazine (S)‐11 to generate the unstable hemiaminals (1R,8aS)‐12 and (1S,8aS)‐13, followed by the highly diastereoselective nucleophilic addition of trimethyl phosphite or dimethyl phenylphosphonite to the chiral carbenium ion (S)‐5. Acid hydrolysis of the phosphonate and phosphinate functionalities with simultaneous cleavage of the tert‐butyl carbamate protecting group led to the target compounds. The high diastereoselectivity in the nucleophilic addition of trivalent phosphorus to the chiral carbenium ion (S)‐5 is in agreement with our precedent reports.
Fabrication of the Enzyme‐less Voltammetric Bilirubin Sensor Based on Sol‐gel Imprinted Polymer
Authors: Akhoundian Maedeh , Alizadeh Taher , Pan Guoqing
Published: October 2019

Measuring the serum bilirubin (BR) level is part of the common test for newborns, since high concentrations of bilirubin in the blood can cause brain damage and even death for them. Therefore, achieving a fast, accurate and cost effective method for bilirubin assay in medical diagnosis and Medical management of patients with jaundice, especially neonates, is very important. In this study, an electrochemical sensor was developed to detect low amounts of bilirubin in serum samples. The basis of the work is the BR imprinted polymer synthesis and the use of this polymer as a recognition element in the production of the bilirubin voltammetric sensor. For this purpose, bilirubin imprinted polymer was synthesized using the simple sol gel method and the prepared polymer is characterized by SEM and FT‐IR. In the next step, this polymer was applied to modify the carbon paste electrode and provide a sensitive and selective sensor for the BR molecule. The proposed sensor was able to measure the bilirubin in the concentration range of 1 to 100 μM after optimizing the operating conditions. The limit of detection (LOD) and limit of quantification (LOQ) was calculated 0.75 μM and 2.5 μM respectively. It is also applicable to bilirubin assay in serum samples.
Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis
Authors: Kalinin Sergey , Meares Gordon P. , Lin Shao Xia , Pietruczyk Elizabeth A. , Saher Gesine , Spieth Lena , Nave Klaus‐Armin , Boullerne Anne I. , Lutz Sarah E. , Benveniste Etty N. , Feinstein Douglas L.
Published: October 2019

Liver kinase B1 (LKB1) is a ubiquitously expressed kinase involved in the regulation of cell metabolism, growth, and inflammatory activation. We previously reported that a single nucleotide polymorphism in the gene encoding LKB1 is a risk factor for multiple sclerosis (MS). Since astrocyte activation and metabolic function have important roles in regulating neuroinflammation and neuropathology, we examined the serine/threonine kinase LKB1 in astrocytes in a chronic experimental autoimmune encephalomyelitis mouse model of MS. To reduce LKB1, a heterozygous astrocyte‐selective conditional knockout (het‐cKO) model was used. While disease incidence was similar, disease severity was worsened in het‐cKO mice. RNAseq analysis identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched in het‐cKO mice relating to mitochondrial function, confirmed by alterations in mitochondrial complex proteins and reductions in mRNAs related to astrocyte metabolism. Enriched pathways included major histocompatibility class II genes, confirmed by increases in MHCII protein in spinal cord and cerebellum of het‐cKO mice. We observed increased numbers of CD4+ Th17 cells and increased neuronal damage in spinal cords of het‐cKO mice, associated with reduced expression of choline acetyltransferase, accumulation of immunoglobulin‐γ, and reduced expression of factors involved in motor neuron survival. In vitro, LKB1‐deficient astrocytes showed reduced metabolic function and increased inflammatory activation. These data suggest that metabolic dysfunction in astrocytes, in this case due to LKB1 deficiency, can exacerbate demyelinating disease by loss of metabolic support and increase in the inflammatory environment.
Role of implants surface modification in osseointegration: A systematic review
Authors: Liu Yu , Rath Björn , Tingart Markus , Eschweiler Jörg
Published: October 2019

Long‐term and stable fixation of implants is one of the most important points for a successful orthopedic surgery in the field of endoprosthesis. Osseointegration (OI), functional connection between bone and implants, is considered as a pivotal process of cementless implant fixation and integration, respectively. OI is affected by various factors of which the property of implants is of high significance. The modification of implants surface for better OI has raised increasing attention in modern orthopedic medicine. Here, the process of OI and the interactions between implants and ambient bone tissues were emblazed. The knowledge regarding the contemporary surface modification strategies was systematically analyzed and reviewed, including materials used for the fabrication of implants, advanced modification techniques, and key factors in the design of porous implants structure. We discussed the superiority of current surface modification programs and concluded that the problems remain to be solved. The primary intention of this systematic review is to provide comprehensive reference information and an extensive overview for better fabrication and design of orthopedic implants.
Mono‐silicon isoelectronic replacement in CAl4: van't hoff/le bel carbon or not?
Authors: Zheng Hai‐Feng , Xu Jing , Ding Yi‐Hong
Published: October 2019

In cluster studies, the isoelectronic replacement strategy has been successfully used to introduce new elements into a known structure while maintaining the desired topology. The well‐known penta‐atomic 18 valence electron (ve) species and its Al−/Si or Al/Si+ isoelectronically replaced clusters CAl3Si−, CAl2Si2, , and , all possess the same anti‐van't Hoff/Le Bel skeletons, that is, nontraditional planar tetracoordinate carbon (ptC) structure. In this article, however, we found that such isoelectronic replacement between Si and Al does not work for the 16ve‐CAl4 with the traditional van't Hoff/Le Bel tetrahedral carbon (thC) and its isoelectronic derivatives CAl3X (X = Ga/In/Tl). At the level of CCSD(T)/def2‐QZVP//B3LYP/def2‐QZVP, none of the global minima of the 16ve mono‐Si‐containing clusters CAl2SiX+ (X = Al/Ga/In/Tl) maintains thC as the parent CAl4 does. Instead, X = Al/Ga globally favors an unusual ptC structure that has one long C─X distance yet with significant bond index value, and X = In/Tl prefers the planar tricoordinate carbon. The frustrated formation of thC in these clusters is ascribed to the CSi bonding that prefers a planar fashion. Inclusion of chloride ion would further stabilize the ptC of CAl2SiAl+ and CAl2SiGa+. The unexpectedly disclosed CAl2SiAl+ and CAl2SiGa+ represent the first type of 16ve‐cationic ptCs with multiple bonds. © 2019 Wiley Periodicals, Inc.
miR‐22‐3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis
Authors: Li Bo , Wang Zhijie , Yu Mei , Wang Xu , Wang Xin , Chen Chuanjie , Zhang Zheng , Zhang Meiling , Sun Chao , Zhao Chenxi , Li Qiang , Wang Wei , Wang Tianyi , Zhang Liang , Ning Guangzhi , Feng Shiqing
Published: October 2019

Spinal cord injury (SCI) is a devastating disease. Strategies that enhance the intrinsic regenerative ability are very important for the recovery of SCI to radically prevent the occurrence of sensory disorders. Epidermal growth factor (EGF) showed a limited effect on the growth of primary sensory neuron neurites due to the degradation of phosphorylated‐epidermal growth factor receptor (p‐EGFR) in a manner dependent on Casitas B‐lineage lymphoma (CBL) (an E3 ubiquitin‐protein ligase). MiR‐22‐3p predicted from four databases could target CBL to inhibit the expression of CBL, increase p‐EGFR levels and neurites length via STAT3/GAP43 pathway rather than Erk1/2 axis. EGF, EGFR, and miR‐22‐3p were downregulated sharply after injury. In vivo miR‐22‐3p Agomir application could regulate CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis, and restore spinal cord sensory conductive function. This study clarified the mechanism of the limited promotion effect of EGF on adult primary sensory neuron neurite and targeting miR‐22‐3p could be a novel strategy to treat sensory dysfunction after SCI.
A prognostic eight‐lncRNA expression signature in predicting recurrence of ER‐positive breast cancer receiving endocrine therapy
Authors: Tang Jianing , Cui Qiuxia , Zhang Dan , Kong Deguang , Liao Xing , Ren Jiangbo , Gong Yan , Wu Gaosong
Published: October 2019

Long noncoding RNAs (lncRNAs) have the main role in the tumorigenesis of breast cancer. In the present study, lncRNA expression profiling was collected to identify a lncRNA expression signature from the Gene Expression Omnibus database. An eight‐lncRNA signature was established to predict the survival of patients with estrogen receptor (ER)‐positive breast cancer receiving endocrine therapy. Patients were separated into a low‐risk group and a high‐risk group based on this signature. Patients in high‐risk group have worse survival compared to those in low‐risk group using Kaplan–Meier curve analysis with log‐rank test. Receiver operating characteristic analysis suggested good diagnostic efficiency of the eight‐lncRNA signature. When adjusting the clinical features, including age, grade, lymph node status, and tumor size, this signature was independently associated with the relapse‐free survival. The prognostic value of the lncRNA prognostic model was then validated in validation sets. When validated in a cohort of patients treated with neoadjuvant chemotherapy and endocrine therapy, this signature demonstrated good performance as well. Besides, we have built a nomogram that integrated the conventional clinicopathological features and the eight‐lncRNA‐based signature. To sum up, our results indicated that the eight‐lncRNA prognostic model was a reliable tool to group patients at high and low risk of disease relapse. This signature may have possible implication in prognostic evaluations of patients with ER‐positive breast cancer receiving endocrine therapy.
Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal–organic frameworks nanoparticles on breast cancer
Authors: Lei Jun , Wang Hongjian , Zhu Daoming , Wan Yibin , Yin Lei
Published: October 2019

CD8+ T cells play a vital role in cancer immunotherapy and can be shaped by metabolism. Avasimibe is an acyl coenzyme A‐cholesterol acyltransferase (ACAT) inhibitor, which has been clinically verified safe in other phase Ⅲ clinical trials. It can potentiate the killing function of CD8+ T cells by modulating cholesterol metabolism. Doxorubicin (DOX) is an anticancer drug widely used in many cancers to induce tumor cell apoptosis. Unfortunately, DOX also can induce toxic and side effects in many organs, compromising its usage and efficacy. Herein, we report the combinational usage of avasimibe and a safe pH sensitive nano‐drug delivery system composing of DOX and metal–organic frameworks nanoparticles (MNPs). Our findings demonstrated that DOX–MNPs treatment inhibited tumor growth with good safety profile and avasimibe treatment combined DOX–MNPs treatment exhibited a better efficacy than monotherapies in 4T1 breast cancer therapy.
Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment
Authors: Wei Shouchao , Peng Wanjuan , Mai Yingren , Li Kanglan , Wei Wei , Hu Li , Zhu Shaoping , Zhou Haihong , Jie Wanxin , Wei Zhuangsheng , Kang Chenyao , Li Ruikai , Liu Zhou , Zhao Bin , Cai Zhiyou
Published: October 2019

Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well‐known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood–brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3β (GSK‐3β) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin‐1β, and tumour necrosis factor‐α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK‐3β pathway and finally leading to cognitive impairment.
MiR‐34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2
Authors: Ge Xin , Gao Jie , Sun Qiu‐Wangyue , Wang Chen‐Xing , Deng Wei , Mao Guang‐Yan , Li Huai‐Qi , Guo Song‐Song , Cheng Jie , Wu Yu‐Nong , Ye Jin‐Hai
Published: October 2019

In various kinds of carcinomas, the special AT‐rich sequence‐binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR‐34a downstream is the intended endeavor of this study. In te OSCCs the miR‐34a expression was determined by quantitative real‐time polymerase chain reaction (q‐PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q‐PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR‐34a on the initiation of OSCC were conducted. As a direct target of the miR‐34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR‐34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR‐34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR‐34a was confirmed by the cotransfection of miR‐34a mimics specifically the decrease in the expression of luciferase of SATB2–3′UTR‐wt reporter. As a whole, our study confirmed the inhibition of miR‐34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.
Focal adhesion kinase promotes BMP2‐induced osteogenic differentiation of human urinary stem cells via AMPK and Wnt signaling pathways
Authors: Sun Xingwei , Zheng Weiwei , Qian Chen , Wu Qin , Hao Yuefeng , Lu Guohai
Published: October 2019

Human urine‐derived stem cells (hUSCs) serve as favorable candidates for bone transplants due to their efficient proliferative and multipotent differentiation abilities, as well as the capacity to secrete a variety of vasoactive agents to facilitate tissue engineering. The present study aimed to explore the role of focal adhesion kinase (FAK) in bone morphogenetic protein 2 (BMP2)‐induced osteogenic differentiation of hUSCs and to investigate the underlying mechanism. The degree of osteogenic differentiation and the correlated signals, following BMP2 overexpression and siRNA‐mediated silencing of FAK, were determined in vitro. Moreover, hUSCs induced bone formation in a rat model with cranial defects, in vivo. Our findings revealed that alkaline phosphatase production, calcium deposits, osteocalcin and osteopontin expression, and bone formation were upregulated in vitro and in vivo following BMP2‐induced osteogenic differentiation, and AMPK and Wnt signaling pathway activation by FAK could effectively regulate BMP2‐enhanced osteogenic differentiation of hUSCs. Taken together, these findings indicated that FAK could mediate BMP2‐enhanced osteogenic differentiation of hUSCs through activating adenosine 5’‐monophosphate‐activated protein kinase and Wnt signaling pathways.
Comparison of pan‐ethnic and ethnic‐based carrier screening panels for individuals of Ashkenazi Jewish descent
Authors: Rosenblum Lynne S. , Zhu Hui , Zhou Zhaoqing , Teicher Jennifer , Heim Ruth A. , Leach Natalia T.
Published: October 2019

The intent of carrier screening is to identify individuals at risk for having a child with a genetic disorder. American College of Medical Genetics and Genomics (ACMG) guidelines currently recommend that individuals of Ashkenazi Jewish (AJ) descent be screened for carrier status for nine disorders. However, a joint statement from five professional organizations acknowledges benefits of expanded carrier screening and this is becoming common practice. To better understand the impact of expanded carrier screening for the AJ population, we performed a retrospective analysis comparing detection rates for AJ individuals screened by two targeted panels: a pan‐ethnic panel comprising 87 disorders and an AJ panel comprising an 18‐disorder subset of the pan‐ethnic panel. We also extrapolated the detection rates for the 18 AJ disorders from the pan‐ethnic panel data and for the nine ACMG‐recommended disorders using data from both panels. We found that with the pan‐ethnic panel 431/1150 (37.5%) individuals were carriers of at least one disorder, compared to 319/1248 (25.6%) individuals with the AJ panel. If the pan‐ethnic panel cohort were tested in the AJ panel or for the nine ACMG‐recommended disorders, the detection rates would have been 280/1150 (24.3%) and 207/1150 (18.0%) respectively. Therefore, the pan‐ethnic expanded carrier screening panel of 87 disorders increased the carrier detection rate in AJ individuals by approximately 50% and 100%, respectively, compared with a panel of 18 disorders considered relevant to the AJ population and the ACMG‐recommended disorders. Twenty disorders accounted for the difference in carrier detection rates between the pan‐ethnic and AJ panels. Of these, three were among the 10 most commonly identified disorders. Our findings reinforce published data that targeted AJ panels are less effective than a pan‐ethnic panel in carrier detection among AJ individuals and provide metrics to address the impact of expanded carrier screening in this population.
Does Gadoterate Meglumine Cause Gadolinium Retention in the Brain of Children? A Case–Control Study
Authors: Topcuoglu Elif Dilara , Topcuoglu Osman Melih , Semiz Oysu Aslihan , Bukte Yasar
Published: October 2019

Background

Accumulation of macrocyclic gadolinium agents in children's brains remain to be determined.

Purpose

To demonstrate whether there is an intracranial macrocyclic gadolinium deposition after multiple contrast‐enhanced MRI with gadoterate meglumine in a pediatric population.

Study Type

Retrospective case–control.

Population

In all, 45 children (age range: 5–17 years; mean, 13.7 ± 3.4 years) for the study group and 45 healthy children (age range: 5–17 years; mean, 13.7 ± 3.4 years) for the control group.

Field Strength/Sequence

T1‐ and T2‐weighted axial images on a 1.5T scanner.

Assessment

Children with at least three enhanced brain MRIs and an age‐ and sex‐matched control group with an unenhanced brain MRIs were compared in terms of T1 signal intensity (SI). All patients in the study group received gadoterate meglumine intravenously (0.1 mmol/kg). SI measurements were made by drawing six regions of interest (ROIs): dentate nuclei (DN), pons, globus pallidi (GP), frontal white matter (FWM), thalamus (T), clivus, and cerebrospinal fluid (CSF) for both groups on unenhanced T1‐weighted images.

Statistical Tests

Student's t‐test was used for comparison of SI. The Pearson correlation was calculated for the correlation between the SI and the number of gadolinium administrations.

Results

A significant difference was detected between two groups for DN/CSF, pons/CSF, GP/CSF, thalamus/CSF, and FWM/CSF (P < 0.001, P < 0.001, P = 0.002, P = 0.002, P = 0.024, respectively). There was no significant difference between the two groups for clivus/CSF (P = 0.15). A good correlation between the number of gadoterate meglumine administrations and the SI for DN/CSF, pons/CSF, GP/CSF, and T/CSF (r = 0.80, r = 0.73, r = 0.91, and r = 0.90, respectively) was found.

Data Conclusion

A significant T1 SI increase reflecting gadolinium retention in the brain was detected for children with at least three gadoterate meglumine administrations in this series. The number of administrations correlated well with the increased SI.

Level of Evidence: 3

Technical Efficacy Stage: 5

J. Magn. Reson. Imaging 2020;51:1471–1477.
Identification ofIDHandTERTpmutation status using1H‐MRS in 112 hemispheric diffuse gliomas
Authors: Ozturk‐Isik Esin , Cengiz Sevim , Ozcan Alpay , Yakicier Cengiz , Ersen Danyeli Ayca , Pamir M. Necmettin , Özduman Koray , Dincer Alp
Published: October 2019

Background

There is a growing interest in noninvasively defining molecular subsets of hemispheric diffuse gliomas based on the isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutation status, which correspond to distinct tumor entities, and differ in demographics, natural history, treatment response, recurrence, and survival patterns.

Purpose

To investigate whether metabolite levels detected with short echo time (TE) proton MR spectroscopy (1H‐MRS) at 3T can be used for noninvasive molecular classification ofIDHandTERTpmutation‐based subsets of gliomas.

Study Type

Retrospective.

Subjects

In all, 112 hemispheric diffuse gliomas (70 males/42 females, mean age: 42.1 ± 13.9 years).

Field Strength/Sequence

Short‐TE1H‐MRS (repetition time (TR) = 2000 msec, TE = 30 msec, number of signal averages = 192) and routine clinical brain tumor MR protocols were acquired at 3T.

Assessment

1H‐MRS data were quantified using LCModel software.TERTpandIDH1orIDH2(IDH1/2) mutations in the tissue were determined by either minisequencing or Sanger sequencing.

Statistical Tests

Metabolic differences betweenIDHmutant andIDHwildtype gliomas were assessed by a Mann–WhitneyU‐test. A Kruskal–Wallis test followed by a Tukey–Kramer test was used to analyze metabolic differences betweenIDHandTERTpmutational molecular subsets of gliomas. A Spearman rank correlation coefficient was used to assess the correlations of metabolite intensities with the Ki‐67 index. Furthermore, machine learning was employed to classify theIDHandTERTpmutational status of gliomas, and the accuracy, sensitivity, and specificity values were estimated.

Results

Short‐TE1H‐MRS classified the presence of anIDHmutation with 88.39% accuracy, 76.92% sensitivity, and 94.52% specificity, and aTERTpmutation within primaryIDHwildtype gliomas with 92.59% accuracy, 83.33% sensitivity, and 95.24% specificity.

Data Conclusion

Short‐TE1H‐MRS could be used to identify molecular subsets of hemispheric diffuse gliomas corresponding toIDHandTERTpmutations.

Level of Evidence:3

Technical Efficacy Stage:2

J. Magn. Reson. Imaging 2020;51:1799–1809.
Meta‐analysis of MRI for the diagnosis of liver metastasis in patients with pancreatic adenocarcinoma
Authors: Hong Seung Baek , Choi Sang Hyun , Kim Kyung won , Kim So Yeon , Kim Jin Hee , Kim Suk , Lee Nam Kyung
Published: October 2019

Background

Determining if a given patient with primary pancreatic adenocarcinoma (PDA) has hepatic metastasis is important for treatment planning. Several previous studies reported on the diagnostic performance of MRI for liver metastasis in patients with PDA. But the reported data are quite variable.

Purpose

To systematically determine the diagnostic performance of MRI for liver metastasis in patients with PDA, including comparing it with computed tomography (CT).

Study Type

Systemic review and meta‐analysis.

Subjects

In all, 457 patients from five eligible articles.

Field Strength/Sequence

Conventional MR sequences with or without contrast enhancement at 1.5T and 3T.

Assessment

Two reviewers independently performed the data extraction. The reviewers identified and reviewed the original articles reporting the diagnostic performance of MRI for liver metastases in patients with PDA, including those articles making comparisons with CT.

Statistical Tests

Meta‐analytic summary sensitivity and specificity were calculated on a per‐patient basis using a bivariate random effects model. We compared the meta‐analytic summary sensitivity and specificity between MRI and CT.

Results

The meta‐analytic summary sensitivity and specificity were 85% (95% confidence interval [CI], 74–92%; I2 = 0%) and 98% (95% CI, 78–100%; I2 = 85%), respectively. In comparison with CT, MRI showed a higher sensitivity (85% vs. 75%) but similar specificity (98% vs. 94%).

Data Conclusion

MRI had good overall diagnostic performance for liver metastasis in patients with PDA, with a higher sensitivity than CT.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2020;51:1737–1744.
Mass spectrometry and planetary exploration: A brief review and future projection
Authors: Arevalo Ricardo , Ni Ziqin , Danell Ryan M.
Published: October 2019

Since the inception of mass spectrometry more than a century ago, the field has matured as analytical capabilities have progressed, instrument configurations multiplied, and applications proliferated. Modern systems are able to characterize volatile and nonvolatile sample materials, quantitatively measure abundances of molecular and elemental species with low limits of detection, and determine isotopic compositions with high degrees of precision and accuracy. Consequently, mass spectrometers have a rich history and promising future in planetary exploration. Here, we provide a short review on the development of mass analyzers and supporting subsystems (eg, ionization sources and detector assemblies) that have significant heritage in spaceflight applications, and we introduce a selection of emerging technologies that may enable new and/or augmented mission concepts in the coming decades.
Sustainable use of the spent mushroom substrate of Pleurotus florida for production of lignocellulolytic enzymes
Authors: Rajavat Asha S. , Rai Sudheer , Pandiyan Kuppusamy , Kushwaha Prity , Choudhary Prassan , Kumar Murugan , Chakdar Hillol , Singh Arjun , Karthikeyan Nanjappan , Bagul Samadhan Y. , Agnihotri Abha , Saxena Anil K.
Published: October 2019

Spent mushroom substrate (SMS), a major byproduct of the mushroom industry, is a lignocellulosic biomass, which contains approximately 57–74.3% of holocellulose fraction. This study was aimed at utilizing SMS of Pleurotus florida for recovery of lignocellulolytic enzymes and sugars and also as a substrate for production of cellulolytic enzymes using different isolates of Trichoderma and Aspergillus under solid‐state fermentation (SSF). SMS of P. florida extracts contained significant amounts of laccase (3,015.8 ± 29.5 U/g SMS) and xylanase (1,187.9 ± 12 U/g SMS) activity. Crystallinity pattern and chemical changes in SMS revealed that SMS had a lower crystallinity index (34.2%) as compared with the raw biomass (37.8%), which, in turn, helps in enhancing the accessibility of cellulolytic enzymes to holocellulose. Among the isolates, Trichoderma longibrachiatum A‐01 showed maximum activity of endoglucanase (220.4 ± 5.9 U/mg), exoglucanase (78.5 ± 3.2 U/mg) and xylanase (1,550.4 ± 11.6 U/mg) while Aspergillus aculeatus C‐08 showed maximum activity of cellobiase (113.9 ± 3.9 U/mg). Extraction with sodium citrate buffer (pH 4.8) showed maximum cellulolytic enzyme activity as compared with other solvents tested. Partial purification of endoglucanase, exoglucanase, xylanase, and cellobiase resulted in 56.3% (1,112.5 U/mg), 48.4% (212.5 U/mg), 44% (4,492.3 U/mg), and 62% (705.0 U/mg) yield with an increase by 5.2‐, 4.5‐, 4.1‐, and 5.0‐fold as compared with crude extract. The results reveal that SMS from P. florida could be a potential and cost‐effective substrate for production of cellulolytic enzymes from T. longibrachiatum A‐01 and A. aculeatus C‐08.
Occupancy Patterns of Breeding American Black Ducks
Authors: Roberts Anthony J. , Royle J. Andrew , Padding Paul I. , Devers Patrick K. , Lepage Christine , Bordage Daniel
Published: October 2019

Occupancy patterns can assist with the determination of habitat limitation during breeding or wintering periods and can help guide population and habitat management efforts. American black ducks (Anas rubripes; black ducks) are thought to be limited by habitat and food availability during the winter, but breeding sites may also limit the size or growth potential of the population. The Canadian Wildlife Service conducts an annual breeding waterfowl survey that we used to explore the hypothesis that black duck carrying capacity is limited by wetlands available for breeding in Québec, Canada. We applied single‐visit, multi‐species occupancy models to the 1990–2015 population survey data to determine if there was evidence the black duck population was limited by breeding habitat. Using a dynamic (multi‐season) occupancy modeling approach, we estimated latent occupancy (occupancy accounting for imperfect detection) of black ducks and then used latent occupancy estimates to derive occupancy, colonization, and extirpation rates. We jointly modeled the occupancy dynamics of black ducks and other duck species in wetlands where both species were present. Throughout the duration of the survey, 44% of wetlands were never observed to be occupied by black ducks. Occupancy models showed wetland size was positively associated with occupancy at the first time step (initial occupancy) and colonization. All 2‐species models indicated initial black duck occupancy, persistence (continued occupancy), and colonization were positively associated with the presence of a second species. Colonization rate over the 26‐year period ranged from 7% to 27% across all models. Extirpation rates were similar and were constant through time within each model. Low occupancy rates, combined with approximately equal colonization and extirpation rates, suggest there are available wetlands for breeding black ducks in their core breeding area. If breeding habitats are not saturated, this suggests migration or wintering areas may be more limiting to black duck population abundance. © 2019 The Wildlife Society.
Lipopolysaccharide and tumor necrosis factor‐alpha alter gene expression of oocytes and cumulus cells during bovine in vitro maturation
Authors: Piersanti Rachel L. , Santos José E. P. , Sheldon I. Martin , Bromfield John J.
Published: October 2019

Communication between the oocyte and cumulus facilitates oocyte growth, cell cycle regulation, and metabolism. This communication is mediated by direct contact between oocytes and cumulus cells, and soluble secreted molecules. Secreted molecules involved in this process are known inflammatory mediators. Lipopolysaccharide (LPS) is detected in follicular fluid and is associated with reduced fertility, whereas accumulation of inflammatory mediators in follicular fluid, including tumor necrosis factor‐α (TNF‐α), is associated with female infertility. Maturation of oocytes in the presence of LPS or TNF‐α reduces meiotic maturation and the capacity to develop to the blastocyst. Here we evaluated the abundance of 92 candidate genes involved immune function, epigenetic modifications, embryo development, oocyte secreted factors, apoptosis, cell cycle, and cell signaling in bovine cumulus cells or zona‐free oocytes after exposure to LPS or TNF‐α during in vitro maturation. We hypothesize that LPS or TNF‐α will alter the abundance of transcripts in oocytes and cumulus cell in a cell type dependent manner. Exposure to LPS altered abundance of 31 transcripts in oocytes (including ACVR1V, BMP15, DNMT3A) and 12 transcripts in cumulus cells (including AREG, FGF4, PIK3IP1). Exposure to TNF‐α altered 1 transcript in oocytes (IGF2) and 4 transcripts in cumulus cells (GJA1, PLD2, PTGER4, STAT1). Cumulus expansion was reduced after exposure to LPS or TNF‐α. Exposing COCs to LPS had a marked effect on expression of targeted transcripts in oocytes. We propose that altered oocyte transcript abundance is associated with reduced meiotic maturation and embryo development observed in oocytes cultured in LPS or TNF‐α.
Is it time to rethink using digital palpation for assessment of muscle stiffness?
Authors: Davidson Melissa J. , Nielsen Poul M.F. , Taberner Andrew J. , Kruger Jennifer A.
Published: October 2019

Aim

Physiotherapists typically use digital palpation to determine residual tension in a muscle, referred to as muscle stiffness or tone. These assessments are subjective, and little is known about their accuracy or repeatability. Despite this, it is standard practice to base clinical treatment on these findings. The aim of this study was to assess physiotherapists’ ability to assign a seven‐point palpation scale to quantitative stiffness values generated by a novel device.

Methods

Prospective observational study involving 125 musculoskeletal and pelvic floor physiotherapists. A novel device was developed that replicates the haptic feedback that clinicians assess as muscle stiffness. Measurements of displacement, force, and stiffness were recorded.

Results

There was wide overlap between each scale category assigned to the stiffness values, from low stiffness at −3 (119 [106, 132] N/m) to moderate stiffness at 0 (462 [435,489] N/m); to high stiffness at +3 (897 [881,913] N/m). Consistency in applying the scale was poor, and the probability of a similar value of stiffness being assigned to the same scale category by different participants was low.

Conclusions

While palpation is used globally by physiotherapists as a readily available and low‐cost method of assessing muscle stiffness, these results indicate that it should be used with caution in diagnosing and defining patient care. Clinical assessment of muscle stiffness requires a validated and reliable palpation scale if this metric is to be used to diagnose pathology and develop treatment protocols. Training in this scale should then be recommended to improve reliability in patient assessment.