bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cofilactin filaments regulate filopodial structure and dynamics in neuronal growth cones
Authors: Hylton Ryan K. , Heebner Jessica E. , Grillo Michael A. , Swulius Matthew T. 
Published: May 2022

AbstractCofilin is best known for its ability to sever actin filaments and facilitate cytoskeletal recycling inside of cells, but at higher concentrations in vitro, cofilin stabilizes a more flexible, hyper-twisted state of actin known as “cofilactin”. While this filament state is well studied, a structural role for cofilactin in dynamic cellular processes has not been observed. With a combination of cryo-electron tomography and fluorescence imaging in neuronal growth cones, we observe that filopodial actin filaments switch between a fascin-linked and a cofilin-decorated state, and that cofilactin is associated with a variety of dynamic events within filopodia. The switch to cofilactin filaments occurs in a graded fashion and correlates with a decline in fascin cross-linking within the filopodia, which is associated with curvature in the bundle. Our tomographic data reveal that the hyper-twisting of actin from cofilin binding leads to a rearrangement of filament packing, which largely excludes fascin from the base of filopodia. Our results provide mechanistic insight into the fundamentals of cytoskeletal remodeling inside of confined cellular spaces, and how the interplay between fascin and cofilin regulates the dynamics of searching filopodia.
Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis
Authors: Zhang Yun , Li Shuaijun , Jin Peisheng , Shang Ting , Sun Ruizhu , Lu Laiya , Guo Kaijin , Liu Jiping , Tong Yongjuan , Wang Junbang , Liu Sanhong , Wang Chen , Kang Yubin , Zhu Wenmin , Wang Qian , Zhang Xiaoren , Yin Feng , Sun Yi Eve , Cui Lei 
Published: May 2022

AbstractDamaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) “difficult-to-treat”. Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.
Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
Authors: Ibrahim Malek Y. S. , Abolhasani Milad 
Published: May 2022

AbstractSynthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increase the reactivity by 70 fold when compared to Rh/Xantphos in batch reactors. The cooperation between Rh and the co-catalyst facilitates the cleavage of the H–H bond and drives the equilibrium-limited condensation step forward. Online reaction optimization expands the scope to include alkyl, aryl, and primary amines. In-flow solvent tuning enables selectivity switching from amine to enamine without the need for changing the ligand. Furthermore, leveraging the ionic nature of the catalyst, we present a robust Rh recovery strategy up to 4 recycles without loss of activity.
Decarboxylative tandem C-N coupling with nitroarenes via SH2 mechanism
Authors: Wang Shuaishuai , Li Tingrui , Gu Chengyihan , Han Jie , Zhao Chuan-Gang , Zhu Chengjian , Tan Hairen , Xie Jin 
Published: May 2022

AbstractAromatic tertiary amines are one of the most important classes of organic compounds in organic chemistry and drug discovery. It is difficult to efficiently construct tertiary amines from primary amines via classical nucleophilic substitution due to consecutive overalkylation. In this paper, we have developed a radical tandem C-N coupling strategy to efficiently construct aromatic tertiary amines from commercially available carboxylic acids and nitroarenes. A variety of aromatic tertiary amines can be furnished in good yields (up to 98%) with excellent functional group compatibility under mild reaction conditions. The use of two different carboxylic acids also allows for the concise synthesis of nonsymmetric aromatic tertiary amines in satisfactory yields. Mechanistic studies suggest the intermediacy of the arylamine–(TPP)Fe(III) species and might provide a possible evidence for an SH2 (bimolecular homolytic substitution) pathway in the critical C-N bond formation step.
Antipsychotic prescription, assumption and conversion to psychosis: resolving missing clinical links to optimize prevention through precision
Authors: Zhang TianHong , Raballo Andrea , Zeng JiaHui , Gan RanPiao , Wu GuiSen , Wei YanYan , Xu LiHua , Tang XiaoChen , Hu YeGang , Tang YingYing , Liu HaiChun , Chen Tao , Li ChunBo , Wang JiJun 
Published: May 2022

AbstractThe current concept of clinical high-risk(CHR) of psychosis relies heavily on “below-threshold” (i.e. attenuated or limited and intermittent) psychotic positive phenomena as predictors of the risk for future progression to “above-threshold” positive symptoms (aka “transition” or “conversion”). Positive symptoms, even at attenuated levels are often treated with antipsychotics (AP) to achieve clinical stabilization and mitigate the psychopathological severity. The goal of this study is to contextually examine clinicians’ decision to prescribe AP, CHR individuals’ decision to take AP and psychosis conversion risk in relation to prodromal symptoms profiles. CHR individuals (n = 600) were recruited and followed up for 2 years between 2016 and 2021. CHR individuals were referred to the participating the naturalistic follow-up study, which research procedure was independent of the routine clinical treatment. Clinical factors from the Structured Interview for Prodromal Syndromes (SIPS) and global assessment of function (GAF) were profiled via exploratory factor analysis (EFA), then the extracted factor structure was used to investigate the relationship of prodromal psychopathology with clinicians’ decisions to AP-prescription, CHR individuals’ decisions to AP-taking and conversion to psychosis. A total of 427(71.2%) CHR individuals were prescribed AP at baseline, 532(88.7%) completed the 2-year follow-up, 377(377/532, 70.9%) were taken AP at least for 2 weeks during the follow-up. EFA identified six factors (Factor-1-Negative symptoms, Factor-2-Global functions, Factor-3-Disorganized communication & behavior, Factor-4-General symptoms, Factor-5-Odd thoughts, and Factor-6-Distorted cognition & perception). Positive symptoms (Factor-5 and 6) and global functions (Factor-2) factors were significant predictors for clinicians’ decisions to AP-prescription and CHR individuals’ decisions to assume AP, whereas negative symptoms (Factor-1) and global functions (Factor-2) factors predicted conversion. While decisions to AP-prescription, decisions to AP-taking were associated to the same factors (positive symptoms and global functions), only one of those was predictive of conversion, i.e. global functions. The other predictor of conversion, i.e. negative symptoms, did not seem to be contemplated both on the clinician and patients’ sides. Overall, the findings indicated that a realignment in the understanding of AP usage is warranted.
Organocatalytic stereoselective cyanosilylation of small ketones
Authors: Zhou Hui , Zhou Yu , Bae Han Yong , Leutzsch Markus , Li Yihang , De Chandra Kanta , Cheng Gui-Juan , List Benjamin 
Published: May 2022

AbstractEnzymatic stereoselectivity has typically been unrivalled by most chemical catalysts, especially in the conversion of small substrates. According to the ‘lock-and-key theory’1,2, enzymes have confined active sites to accommodate their specific reacting substrates, a feature that is typically absent from chemical catalysts. An interesting case in this context is the formation of cyanohydrins from ketones and HCN, as this reaction can be catalysed by various classes of catalysts, including biological, inorganic and organic ones3–7. We now report the development of broadly applicable confined organocatalysts for the highly enantioselective cyanosilylation of aromatic and aliphatic ketones, including the challenging 2-butanone. The selectivity (98:2 enantiomeric ratio (e.r.)) obtained towards its pharmaceutically relevant product is unmatched by any other catalyst class, including engineered biocatalysts. Our results indicate that confined chemical catalysts can be designed that are as selective as enzymes in converting small, unbiased substrates, while still providing a broad scope.
Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs
Authors: Eschweiler Simon , Ramírez-Suástegui Ciro , Li Yingcong , King Emma , Chudley Lindsey , Thomas Jaya , Wood Oliver , von Witzleben Adrian , Jeffrey Danielle , McCann Katy , Simon Hayley , Mondal Monalisa , Wang Alice , Dicker Martina , Lopez-Guadamillas Elena , Chou Ting-Fang , Dobbs Nicola A. , Essame Louisa , Acton Gary , Kelly Fiona , Halbert Gavin , Sacco Joseph J. , Schache Andrew Graeme , Shaw Richard , McCaul James Anthony , Paterson Claire , Davies Joseph H. , Brennan Peter A. , Singh Rabindra P. , Loadman Paul M. , Wilson William , Hackshaw Allan , Seumois Gregory , Okkenhaug Klaus , Thomas Gareth J. , Jones Terry M. , Ay Ferhat , Friberg Greg , Kronenberg Mitchell , Vanhaesebroeck Bart , Vijayanand Pandurangan , Ottensmeier Christian H. 
Published: May 2022

AbstractPhosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1–3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.
Experimental investigation of four-point bending of thin walled open section steel beam loaded and set in the shear center
Authors: Obst Maciej , Wasilewicz Piotr , Adamiec Jarosław 
Published: May 2022

AbstractThin walled cold formed structures were, and still are, very popular structural elements used in mechanical engineering. Modern technology and the progress in materials engineering allow to fabricate various shapes of thin walled cold formed components. Therefore, combinations between technology possibilities, material properties, loads and engineering requirements are wide and unlimited for thin walled components. The aim of this paper is to perform an experimental study of cold formed C-channel steel beams under four-points bending loads based on the global and the local buckling phenomena. A test rig was developed with a specially designed support system to subject thin-walled steel beams to a four-point bending load, where the support and loads were applied to the shear center of the open section steel beam. It is shown that it is not possible to completely eliminate the torque load on a thin-walled beam with an open section where load and support are applied in the shear center because investigated beams weren’t ideal made. Thin walled open section beams are very sensitive for boundary conditions and geometrical accuracy. The force of gravity is also working. The presented research methodology can be improved and do test with other open section thin walled beams.
Pulsed electromagnetic fields inhibit mandibular bone deterioration depending on the Wnt3a/β-catenin signaling activation in type 2 diabetic db/db mice
Authors: Li Jianjun , Cai Jing , Liu Liheng , Wu Yuwei , Chen Yan 
Published: May 2022

AbstractType 2 diabetes mellitus (T2DM) patients have compromised mandibular bone architecture/quality, which markedly increase the risks of tooth loosening, tooth loss, and failure of dental implantation. However, it remains lacks effective and safe countermeasures against T2DM-related mandibular bone deterioration. Herein, we studied the effects of pulsed electromagnetic fields (PEMF) on mandibular bone microstructure/quality and relevant regulatory mechanisms in T2DM db/db mice. PEMF exposure (20 Gs, 15 Hz) for 12 weeks preserved trabecular bone architecture, increased cortical bone thickness, improved material properties and stimulated bone anabolism in mandibles of db/db mice. PEMF also upregulated the expression of canonical Wnt3a ligand (but not Wnt1 or Wnt5a) and its downstream β-catenin. PEMF improved the viability and differentiation of primary osteoblasts isolated from the db/db mouse mandible, and stimulated the specific activation of Wnt3a/β-catenin signaling. These positive effects of PEMF on mandibular osteoblasts of db/db mice were almost totally abolished after Wnt3a silencing in vitro, which were equivalent to the effects following blockade of canonical Wnt signaling using the broad-spectrum antagonist DKK1. Injection with Wnt3a siRNA abrogated the therapeutic effects of PEMF on mandibular bone quantity/quality and bone anabolism in db/db mice. Our study indicates that PEMF might become a non-invasive and safe treatment alternative resisting mandibular bone deterioration in T2DM patients, which is helpful for protecting teeth from loosening/loss and securing the dental implant stability.
Antioxidative and osmoprotecting mechanisms in carrot plants tolerant to soil salinity
Authors: Kamińska Iwona , Lukasiewicz Aneta , Klimek-Chodacka Magdalena , Długosz-Grochowska Olga , Rutkowska Julia , Szymonik Kamil , Baranski Rafal 
Published: May 2022

AbstractSoil salinization is a growing problem for agriculture worldwide and carrot is one the most salt-sensitive vegetable species. However, some varieties are capable of withstanding high salt concentrations due to unknown genetic and physiological mechanisms. The aim of this work was to reveal protecting mechanisms against osmotic and ionic stresses that contribute to salt tolerance in carrot. For this purpose, changes in biochemical traits due to soil salinity occurring in the salt-tolerant and salt-sensitive plants were determined. The obtained results showed that the tolerance of the salt-tolerant variety was partially determined constitutively, however, the exposition to saline soil triggered a physiological response that was more evident in the root than in the leaves. The most noticeable changes were the high increase in the content of osmoprotective proline and other low molecular antioxidants such as glutathione and ascorbic acid, and the decrease in the ratio of reduced to oxidized glutathione forms. These changes imply an efficient operation of the ascorbate–glutathione cycle that together with a high activity of antioxidative enzymes such as peroxidases, indicate on the induction of mechanisms associated mainly with protection against excessive reactive oxygen species.
Highly efficient hole injection from Au electrode to fullerene-doped triphenylamine derivative layer
Authors: Matsuda Shofu , Itagaki Chikara , Tatsuguchi Kyoya , Ito Masamichi , Sasaki Hiroto , Umeda Minoru 
Published: May 2022

AbstractTriphenylamine derivatives are superior hole-transport materials. For their application to high-functional organic semiconductor devices, efficient hole injection at the electrode/triphenylamine derivative interface is required. Herein, we report the design and evaluation of a Au/fullerene-doped α-phenyl-4′-[(4-methoxyphenyl)phenylamino]stilbene (TPA) buffer layer/TPA/Au layered device. It exhibits rectification conductivity, indicating that hole injection occurs more easily at the Au/fullerene-doped TPA interface than at the Au/TPA interface. The Richardson-Schottky analysis of the device reveals that the hole injection barrier (ΦB) at the Au/fullerene-doped TPA interface decreases to 0.021 eV upon using C70 as a dopant, and ΦB of Au/TPA is as large as 0.37 eV. The reduced ΦB of 0.021 eV satisfies the condition for ohmic contact at room temperature (ΦB$$\le $$
≤
0.025 eV). Notably, C70 doping has a higher barrier-reduction effect than C60 doping. Furthermore, a noteworthy hole-injection mechanism, in which the ion–dipole interaction between TPA and fullerenes plays an important role in reducing the barrier height, is considered based on cyclic voltammetry. These results should facilitate the design of an electrode/organic semiconductor interface for realizing low-voltage driven organic devices.
Associations between serum levels of brain-derived neurotrophic factor, corticotropin releasing hormone and mental distress in vitiligo patients
Authors: Kussainova Assiya , Kassym Laura , Akhmetova Almira , Dvoryankova Eugenia , Glushkova Natalya , Khismetova Zaituna , Adilgozhina Saltanat , Tuleutayeva Raikhan , Kaskabayeva Alida , Massabayeva Meruyert , Pak Laura , Semenova Yuliya 
Published: May 2022

AbstractVitiligo is clinically characterized by the appearance of non-symptomatic depigmented macules, but the disorder is highly correlated with a wide range of psychiatric disorders and psychological problems. The aim of our study was to investigate serum brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) levels in vitiligo patients and healthy controls in relation to the observed symptoms of depression and anxiety disorders. This study comprised 96 vitiligo patients and 96 healthy controls who filled out the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Serum levels of BDNF and CRH were measured using enzyme-linked immunosorbent assay (ELISA) technique. There was a significant increase of depression and anxiety scores in vitiligo patients as compared with healthy controls (P < 0.05). The serum levels of BDNF were significantly lower in vitiligo patients than in healthy individuals (Z = 4.002; P < 0.001), while the serum levels of CRH were markedly higher in cases than those in controls (Z = 3.764; P < 0.001). The significant positive correlations between serum CRH levels and GAD-7, PHQ-9 scores were observed. However, the aforementioned psychometric scales did not correlate significantly with serum BDNF level. Vitiligo is associated with the depression and is closely linked with lower BDNF levels.
Different effects of hydrogen-rich water intake and hydrogen gas inhalation on gut microbiome and plasma metabolites of rats in health status
Authors: Xie Fei , Jiang Xue , Yi Yang , Liu Zi-Jia , Ma Chen , He Jin , Xun Zhi-ming , Wang Meng , Liu Meng-yu , Mawulikplimi Adzavon Yao , Zhao Peng-xiang , Ma Xue-mei 
Published: May 2022

AbstractThe potential for preventive and therapeutic applications of H2 have now been confirmed in various disease. However, the effects of H2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The metabolic function was determined by metabolic cage analysis and showed that HI decreased the voluntary intake and excretions of rats, while HRW intake did not. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.
The influence of land use in the catchment area of small waterbodies on the quality of water and plant species composition
Authors: Szpakowska Barbara , Świerk Dariusz , Dudzińska Anna , Pajchrowska Maria , Gołdyn Ryszard 
Published: May 2022

AbstractLand use significantly affects the function of waterbodies in landscape. Although there have been numerous studies on the influence of the catchment area on the trophic and ecological status of waterbodies, still is not reached an agreement on the width of the buffer zone that is necessary for effective protection of waterbodies. The aim of the study was to show whether small waterbodies are predominantly influenced by land use in the entire catchment area or only in the zone extending 100 or 200 m away from the shoreline. For two years the waters in six small waterbodies located in the Wielkopolska region (Poland) were analysed. The canonical correspondence analysis (CCA) showed that the influence of land use, especially agricultural land, was much greater within the zone extending 100 m from the shore line of the waterbodies than in the total catchment area. Therefore, it would be advisable to move the border of intensive farming areas beyond the entire 100-m-wide buffer zone, or at least to reduce the intensity of agriculture and to introduce diversified and perennial vegetation creating effective biogeochemical barriers.