bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Polymer‐Based Nerve Guide Conduits to Promote Peripheral Nerve Regeneration
Authors: Zhang Xi , Qu Wenrui , Li Di , Shi Kai , Li Rui , Han Yanqiu , Jin E , Ding Jianxun , Chen Xuesi
Published: May 2020

Bridging critical‐sized defects in peripheral nerves to achieve functional recovery is a challenge for orthopedic and hand surgeons. Inadequate regeneration of peripheral nerve axons often results in long‐term partial or total sensory and/or motor impairment. Currently, the best treatment available for long‐gap peripheral nerve regeneration is autologous nerve transplantation, while the successful implementation of this approach requires for secondary surgery and donor nerves. The nerve guide conduit (NGC) serves as an alternative to autograft of nerve, as it connects the proximal and distal ends of nerve defects and provides physical and biochemical guidances for axon regeneration. Functionalized NGCs enhance nerve regeneration by providing neuroprotection, antioxidation, vascular regeneration enhancement, and immune regulatory effects. In this review, the authors summarize the latest advances in functional polymer‐based NGCs for peripheral nerve regeneration and present the perspectives on the development of peripheral NGCs for potential clinical applications.
Trajectory and Functional Analysis of PD‐1high CD4+CD8+ T Cells in Hepatocellular Carcinoma by Single‐Cell Cytometry and Transcriptome Sequencing
Authors: Zheng Bo , Wang Dongfang , Qiu Xinyao , Luo Guijuan , Wu Tong , Yang Shuai , Li Zhixuan , Zhu Yanjing , Wang Shan , Wu Rui , Sui Chengjun , Gu Ziqi , Shen Siyun , Jeong Seogsong , Wu Xuan , Gu Jin , Wang Hongyang , Chen Lei
Published: May 2020

The spatial heterogeneity of immune microenvironment in hepatocellular carcinoma (HCC) remains elusive. Here, a single‐cell study involving 17 432 600 immune cells of 39 matched HCC (T), nontumor (N), and leading‐edge (L) specimens by mass cytometry is conducted. The tumor‐associated CD4/CD8 double‐positive T (DPT) cells are found enriched in L regions with synergetic expression of PD‐1/HLA‐DR/ICOS/CD45RO and exhibit a higher level of IFN‐γ, TNF‐α, and PD‐1 upon stimulation. The enrichment of DPT and PD‐1+DPT in L regions indicates favorable prognosis. These tumor‐associated DPT cells with similar phenotype are also verified in other tumors and HCC animal models. Single‐cell RNA‐seq further characterizes the molecular features of DPT cells and uncovers 11 clusters with different cytotoxicity, exhaustion, and activation scores. TCR‐based trajectory analysis reveals that tumor‐associated DPT clusters share separated ancestries with local CD4+ or CD8+SPT cells rather than CD3+PBMC cells. TCR clones with frequency above 10 are mainly found coexisting in DPT and CD8+SPT cells. Specifically, PD‐1highDPT cluster (TDPT_10) shares the same ancestry with exhausted CD8+SPT cluster (TCD8T_2) and shows higher expression similarity and closer pathological location to PD‐1+CD8+ than PD‐1+CD4+T cells. Together, this study systematically characterizes the unique distribution of PD‐1+DPTs in HCC and puts forward new insights for the function and origin of tumor‐associated DPT cells.
Tall fescue germplasm response to freezing temperatures
Authors: Interrante Sindy M. , Stein Jimmy D. , Trammell Michael A. , Webb Stephen L. , Butler Twain J.
Published: May 2020

Tall fescue [Schedonorus arundinaceus (Schreb.) Dumort., nom. cons.] is a perennial cool‐season grass in which improved freeze tolerance could result in greater winterhardiness and persistence. Our objective was to evaluate survival and freeze‐tolerance thresholds of ‘Flecha’ summer‐dormant (SD) and ‘Texoma Max QII’ summer‐active (SA) tall fescue at seedling (1–2 leaves) and tillered (5–6 leaves) growth stages using controlled environment freezing chambers. Target temperatures ranged from 0 to −9 °C (seedlings) and 0 to −12 °C (tillered plants). Predicted lethal temperature at which 50% mortality occurs (LT50) was −5.7 and −5.5 °C for SA and SD seedlings, respectively, and −6.0 and −5.7 °C for SA and SD tillered plants, respectively. Based on these results, a controlled temperature chamber appears to be a useful tool for plant breeders when evaluating survival and freeze tolerance of SA and SD tall fescue germplasm at seedling and tillered growth stages.
In Situ Dynamic Manipulation of Graphene Strain Sensor with Drastically Sensing Performance Enhancement
Authors: Luo Zewei , Li Xinming , Li Quanling , Tian Xiyue , Fan Tianyi , Wang Chaolun , Wu Xing , Shen Guozhen
Published: May 2020

It is extremely challenging to directly observe how the relative position of the nanosheet changes the charge transport in the channel. Previous work on graphene stacking strain sensors relies on nanosheet slip to detect small mechanical signals. However, the direct experimental verification evidence is still inadequate. In this work, the sliding conductive transmission of graphene nanosheets slip is directly measured through an improved in situ transmission electron microscopy observation technique. By accurately manipulating the atomic scale of graphene nanosheets to achieve nanoscale sliding, the resistance change between nanosheets in the in situ observation system can be directly measured. Besides, a mechanical sensor based on graphene layer structure is designed, which demonstrates a high gauge factor (4303 at maximum strain of 93.3%), negligible hysteresis (5–10%), and excellent stability over 3000 stretch–release cycles. Besides, the precise control of characteristics offers a practical approach of retaining high stability from device to device. This strain sensor is applied in various cases, especially the health monitor of the human cervical vertebra.
Prognostic impact of Philadelphia chromosome in mixed phenotype acute leukemia (MPAL): A cancer registry analysis on real‐world outcome
Authors: Qasrawi Ayman , Ramlal Reshma , Munker Reinhold , Hildebrandt Gerhard C.
Published: May 2020

Mixed phenotype acute leukemia (MPAL) is thought to have poor outcome, and presence of the Philadelphia chromosome (Ph+) has been considered to be an adverse prognostic marker. However, most of these reports were in the pre‐tyrosine kinase inhibitors (TKIs) era. Recent limited reports indicate improved outcomes for MPAL with the addition of TKIs. We examined the outcomes of 241 cases of MPAL according to the 2008 WHO classification from the Surveillance, Epidemiology, and End Results registry. The MLL+ patients had a median age of 6 years while other subtypes occurred mostly in adults and had comparable age. On multivariate analyses and after adjustment for age, year of diagnosis and chemotherapy status, Ph+ MPAL patients had reduced risk of death in comparison to Ph(–) MPAL patients (hazard ratio [HR] = 0.28, P = .002). So, MLL+ MPAL had the worst outcome with a 10‐fold increased risk of death in comparison to Ph+ MPAL patients (HR = 10.2, P < .001). Importantly, the outcome of Ph+ MPAL was comparable to Ph+ acute lymphoblastic leukemia in a 1:1 matched case‐control analysis. In conclusion, this is the largest registry study which examines the outcomes of MPAL subtypes. We confirm that MPAL is a heterogenous disease. Note, Ph+ MPAL nowadays has a better OS in comparison to other subtypes and is comparable to Ph+ ALL patients. This is most likely secondary to changes in practice and more utilization of TKIs. On the other hand, MLL rearrangement is associated with infantile MPAL and has a dismal prognosis.
Unveiling 79‐Year‐Old Ixene and Its BN‐Doped Derivative
Authors: Pati Palas Baran , Jin Eunji , Kim Yohan , Kim Yongchul , Mun Jinhong , Kim So Jung , Kang Seok Ju , Choe Wonyoung , Lee Geunsik , Shin Hyung‐Joon , Park Young S.
Published: May 2020

Polycyclic aromatic hydrocarbons (PAHs) are key components of organic electronics. The electronic properties of these carbon‐rich materials can be controlled through doping with heteroatoms such as B and N, however, few convenient syntheses of BN‐doped PAHs have been reported. Described herein is the rationally designed, two‐step syntheses of previously unknown ixene and BN‐doped ixene (B2N2‐ixene), and their characterizations. Compared to ixene, B2N2‐ixene absorbs longer‐wavelength light and has a smaller electrochemical energy gap. In addition to its single‐crystal structure, scanning tunneling microscopy revealed that B2N2‐ixene adopts a nonplanar geometry on a Au(111) surface. The experimentally obtained electronic structure of B2N2‐ixene and the effect of BN‐doping were confirmed by DFT calculations. This synthesis enables the efficient and convenient construction of BN‐doped systems with extended π‐conjugation that can be used in versatile organic electronics applications.
Catalytic Dehydrogenative Cyclization of o‐Teraryls under pH‐Neutral and Oxidant‐Free Conditions
Authors: Tsukamoto Tatsuhiro , Dong Guangbin
Published: May 2020

A cobaloxime‐catalyzed acceptorless dehydrogenative cyclization of o‐teraryls was developed. In stark contrast to the established methods such as the Scholl or Mallory reactions, this method does not require any strong acids or oxidants, and shows high atom economy and a broad substrate scope. It operates at near room temperature with light as the source of energy. Acid‐ or oxidant‐sensitive functional groups, such as 4‐methoxyphenyl, unprotected benzyl alcohol, silyl ether, and thiophene groups are tolerated. Remarkably, aryls with electron‐withdrawing groups, and electron‐poor heteroarenes, such as pyridine and pyrimidine, can also react. Preliminary mechanistic study reveals that hydrogen gas is released during the reaction, and both light and the cobalt catalyst are important for the dehydrogenation step.
PROTACs and Other Chemical Protein Degradation Technologies for the Treatment of Neurodegenerative Disorders
Authors: Tomoshige Shusuke , Ishikawa Minoru
Published: May 2020

Neurodegenerative disorders (NDs) are a group of diseases that cause neural cell damage, leading to motility and/or cognitive dysfunctions. One of the causative agents is misfolded protein aggregates, which are considered as undruggable in terms of conventional tools, such as inhibitors and agonists/antagonists. Indeed, there is currently no FDA‐approved drug for the causal treatment of NDs. However, emerging technologies for chemical protein degradation are opening up the possibility of selective elimination of target proteins through physiological protein degradation machineries, which do not depend on the functions of the target proteins. Here, we review recent efforts towards the treatment of NDs using chemical protein degradation technologies, and we briefly discuss the challenges and prospects.
Synergistic Dual‐Additive Electrolyte Enables Practical Lithium‐Metal Batteries
Authors: Li Siyuan , Zhang Weidong , Wu Qiang , Fan Lei , Wang Xinyang , Wang Xiao , Shen Zeyu , He Yi , Lu Yingying
Published: May 2020

A rechargeable Li metal anode coupled with a high‐voltage cathode is a promising approach to high‐energy‐density batteries exceeding 300  Wh kg−1. Reported here is an advanced dual‐additive electrolyte containing a unique solvation structure and it comprises a tris(pentafluorophenyl)borane additive and LiNO3 in a carbonate‐based electrolyte. This system generates a robust outer Li2O solid electrolyte interface and F‐ and B‐containing conformal cathode electrolyte interphase. The resulting stable ion transport kinetics enables excellent cycling of Li/LiNi0.8Mn0.1Co0.1O2 for 140 cycles with 80 % capacity retention under highly challenging conditions (≈295.1 Wh kg−1 at cell‐level). The electrolyte also exhibits high cycling stability for a 4.6 V LiCoO2 (160 cycles with 89.8 % capacity retention) cathode and 4.95 V LiNi0.5Mn1.5O4 cathode.
Airway obstruction during general anaesthesia in a patient with a vagal nerve stimulator
Authors: Gibbins M. , Quader K. , Watson G. , Pichierri A.
Published: May 2020

For patients with epilepsy refractory to medical management, vagal nerve stimulator implantation may reduce the number of seizures and/or reduce their severity. A 34‐year‐old woman with epilepsy underwent a change in vagal nerve stimulator battery under general anaesthesia with a supraglottic airway device and total intravenous anaesthesia. During the procedure, she developed clinically significant airway obstruction, which resolved only when the device was disabled. We recommend that anaesthetists and others providing peri‐operative care for patients with a vagal nerve stimulator remain vigilant to the possibility of device‐related airway obstruction, which may occur even in asymptomatic patients. All patients with a vagal nerve stimulator are provided with a magnet that will disable the device, should complications arise. There is a need to establish a standard approach to the peri‐operative care of these patients, including the identification and management of device‐related airway obstruction.
Two d10 metal–organic frameworks based on a novel semi‐rigid aromatic biscarboxylate ligand: Syntheses, structures and luminescent properties
Authors: Wang Yong‐Tao , Tang Gui‐Mei , Wang Cui‐Cui
Published: May 2020

Two new d10 metal–organic frameworks based on a novel semi‐rigid aromatic biscarboxylate ligand, namely, [Zn (RGAA)(BPY)1/2] (1) and [Cd5(μ3‐OH)2(RGAA)4] (2) [H2RGAA = 4‐(carboxymethyl)‐2‐ethoxybenzoic acid, BPY = 4,4′‐bipyridine], have been synthesized by the hydrothermal reaction, and characterized by Fourier transform‐infrared, elemental analyses, X‐ray single‐crystal diffraction, powder X‐ray diffraction and thermogravimetric analyses. Complex 1 displays a three‐dimensional (3D) network with a (2,3,4)‐connected (6ˆ3.8ˆ2.10)2(6ˆ3)2(8) topology, while complex 2 exhibits a 3D framework with a (3,10)‐connected (3.4.5)2(3ˆ4.4ˆ6.5ˆ18.6ˆ14.7ˆ2.8) topology. The luminescent properties of compounds 1 and 2 have been investigated in detail, where the emission maxima are 464 and 349 nm, respectively.
Synthesis, characterization, density functional theory calculations, and in vitro antibacterial activity of novel transition metal complexes containing an O3‐tridentate amoxicillin‐based Schiff base: A silver(II) complex as alternative against Pseudomonas aeruginosa resistant to amoxicillin
Authors: Anacona J.R. , Loroño Marcos , Marpa Daniela , Ramos Cesar , Celis Freddy
Published: May 2020

Transition metal complexes containing an amoxicillin‐based Schiff base (H2L, 3) obtained from the condensation of amoxicillin 1 with salicylaldehyde 2 were prepared. Spectroscopic and physicochemical techniques, namely, UV–visible, Fourier‐transform infrared spectroscopy, 1H NMR, electron paramagnetic resonance, transmission electron microscopy, mass spectrometry, magnetic susceptibility, molar conductance, density functional theory (DFT) calculations, together with elemental and thermal analyses were used to characterize the synthesized complexes. Based on these studies, the general formulae [ML(H2O)3], where M = Mn 4, Ni 5, Zn 6, and [ML(H2O)], where M = Cu 7, Ag 8, were proposed for the complexes. The amoxicillin‐based Schiff base ligand behaved as a dianionic O3‐tridentate chelating agent. DFT studies and magnetic and spectral data revealed octahedral geometries for Mn, Ni, and Zn atoms and distorted tetrahedral geometries for Cu(II) and Ag(II) complexes. Synthesized compounds were tested for antibacterial activity by both agar disk diffusion method and the minimum inhibitory concentration. in vitro bacterial viability revealed that complex 5 had similar antibacterial activity as 1 against Staphylococcus aureus and Staphylococcus epidermidis, whereas Pseudomonas aeruginosa, resistant to amoxicillin, was sensitive to complex 8. The antibacterial activity of complex 8 could be attributed to its greater catalytic activity as shown by DFT calculations. Toxicity bioassay of the tested compounds showed LC50 values > 1000 ppm, indicating their nontoxicity against brine shrimp nauplii (Artemia salina).
Cutaneous Manifestations of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Micheletti Robert G. , Chiesa Fuxench Zelma , Craven Anthea , Watts Richard A. , Luqmani Raashid A. , Merkel Peter A. ,   the DCVAS Investigators
Published: May 2020

Objective

Cutaneous manifestations of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), are poorly characterized. This report describes the dermatologic features of AAV and their association with systemic manifestations of vasculitis.

Methods

A cross‐sectional study identifying and comparing the cutaneous manifestations of AAV was performed using data from a large, international, collaborative effort in order to collect comprehensive clinical data on patients with vasculitis.

Results

Data from 1,184 patients with AAV from 130 centers worldwide were available. Cutaneous manifestations were common in all AAV subtypes: GPA (223 of 656, or 34%), MPA (85 of 302, or 28%), and EGPA (106 of 226, or 47%). The most frequent cutaneous manifestation in AAV (all types) was petechiae/purpura, which was observed in 181 patients (15%). Allergic and nonspecific manifestations, such as pruritus, urticaria, and maculopapular rash, were more common in EGPA than in other disease subtypes (all P < 0.01). Skin biopsy, while underutilized (performed in 22–44% of patients), was frequently found to be an effective test suitable for diagnosis of AAV (diagnostic in 68–94% of patients). Compared to patients without cutaneous manifestations, those with skin lesions more frequently had severe systemic manifestations of vasculitis (such as alveolar hemorrhage and glomerulonephritis), specifically patients with GPA or EGPA and cytoplasmic/anti–proteinase 3 (anti‐PR3) ANCA–positive or ANCA‐negative patients (hazard ratio >1.9 for all), but not those with MPA or perinuclear/antimyeloperoxidase ANCAs.

Conclusion

Cutaneous manifestations are common and varied in AAV and are associated with disease severity in patients with GPA, EGPA, cytoplasmic/anti‐PR3 ANCA, or ANCA‐negative disease. These findings underscore the potential diagnostic and prognostic importance of the cutaneous examination in the evaluation and management of AAV.
Large‐scale Two‐dimensional MoSx Catalyst Prepared under Mild Conditions for Enhancing Electrocatalytic Hydrogen Evolution Reaction
Authors: Yu Xiaoxia , Li Lihong , Chen Binda , Qian Cuncun , Li Zheng , Su Meng , Song Yanlin , Xing Xianran
Published: May 2020

As an electrocatalyst with abundant resources and great potential, molybdenum disulfide is regarded as one of the most likely alternatives to expensive noble‐metals catalysts. However, it is still a challenge to achieve large scale production of few‐layer MoS2 with enhancing activity of electrocatalytic hydrogen reaction at ambient conditions. Herein, we developed a simple environmentally friendly two‐step method, which included intercalation reaction and a subsequent electrochemical reduction reaction for mass preparation of defect‐rich desulfurized MoSx (D−MoSx) nanosheets with plentiful sulfur vacancies. The ratio of sulfur‐molybdenum atoms can be adjusted from 2 : 1 to 1.4 : 1 by regulating the desulfurization voltage. It was found that the HER catalytic activity of the D−MoSx was enhanced compared with that of pristine MoS2 (P−MoS2), the current density of D−MoSx (desulfurization at −1.0 V) at −0.3 V versus RHE was about 169% of the P−MoS2, and the Tafel slope decreased to 136 mV dec−1. This method can be widely applied to large‐scale preparation of other two‐dimensional materials.
Screening and molecular characterization of new thermo‐ and ethanol‐tolerant Acetobacter malorum strains isolated from two biomes Moroccan cactus fruits
Authors: Es‐sbata Ikram , Lakhlifi Tarik , Yatim Meriem , El‐Abid Hassan , Belhaj Abdelhaq , Hafidi Majida , Zouhair Rachid
Published: May 2020

Industrially, the sensitivity of acetic acid bacteria (AAB) to the high temperatures and the high ethanol concentrations is the major concerns for manufacturers. This study was conceived and designed to isolate and identify new thermo‐ and ethanol‐tolerant AAB from Opuntia ficus‐indica L. fruits.

As a result, among 140 isolated bacterial strains, five selected strains (CR1, CR5, CR23, CZ2, and CZ15) exhibited important acetic acid production until 40 °C. The use of 16S rDNA gene analysis was insufficient to identify selected bacteria. Indeed, except CR5 that presented 100% similarity to A. cerevisiae, the other strains presented similar homology rates simultaneously to the 16S rDNA sequences of A. cerevisiae and A. malorum. The reidentification by 16S‐23S rDNA gene sequencing showed that CR1, CR23, and CZ15 were A. malorum, which were shown tolerance to the highest concentration of ethanol (12%) and produced elevated amount (40 g/L) of acetic acid at 37 °C.

In summary, we showed the thermotolerance and ethanol tolerant character of new A. malorum strains, which can be used as a starter for vinegar production. Furthermore, during the molecular characterization of the isolated strains, we concluded that 16S‐23S rDNA internal transcribed spacer sequence is of great importance for discriminating between AAB species as a complement to the identification by 16S rDNA sequencing.
Molecular Targets for the Testing of COVID‐19
Authors: Yong Suh Kuan , Su Ping‐Chia , Yang Yuh‐Shyong
Published: May 2020

The pandemic outbreaks of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), spread all over the world in a short period of time. Efficient identification of the infection by SARS‐CoV‐2 has been one of the most important tasks to facilitate all the following counter measurements in dealing with the infectious disease. In Taiwan, a COVID‐19 Open Science Platform adheres to the spirit of open science: sharing sources, data, and methods to promote progress in academic research while corroborating findings from various disciplines has established in mid‐February 2020, for collaborative research in support of the development of detection methods, therapeutics, and a vaccine for COVID‐19. Research priorities include infection control, epidemiology, clinical characterization and management, detection methods (including viral RNA detection, viral antigen detection, and serum antibody detection), therapeutics (neutralizing antibody and small molecule drugs), vaccines, and SARS‐CoV‐2 pathogenesis. In addition, research on social ethics and the law are included to take full account of the impact of the COVID‐19 virus.
Synthesis, Antimicrobial Activity and Molecular Docking Study of Novel α‐(Diphenylphosphoryl)‐ and α‐(Diphenylphosphorothioyl)cycloalkanone Oximes
Authors: Jebli Nejib , Hamimed Selma , Van Hecke Kristof , Cavalier Jean‐François , Touil Soufiane
Published: May 2020

A series of novel α‐(diphenylphosphoryl)‐ and α‐(diphenylphosphorothioyl)cycloalkanone oximes have been synthesized in search for novel bioactive molecules. Their structures were characterized by various spectroscopic methods including IR, NMR (1H, 31P, 13C), mass spectrometry and single crystal X‐ray diffraction. The newly synthesized phosphorus‐containing oximes were screened for their in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium) and fungal strains (Candida albicans and Candida glabrata). The biological assays showed that all the studied compounds exhibited high antibacterial and antifungal activities at only 0.1–2.1 μg/mL. In silico molecular docking studies in FabH enzyme active site were performed in order to predict the possible interaction modes and binding energies of the drug candidates at the molecular level.
Panta rhei, also drug eluting stent technology
Authors: Chiarito Mauro , Mehran Roxana
Published: May 2020

Key Points

The Resolute zotarolimus eluting stent (ZES) is a next‐generation durable polymer, thin‐struts drug eluting stent. Although several randomized and observational studies have proven its safety and efficacy, long‐term follow‐up data are still limited.

This prospective, multicenter, single arm study, showed favorable 5‐year outcomes in patients undergoing Resolute ZES implantation, with considerably low rate of repeated revascularization and stent thrombosis.

Data on long‐term performance of next‐generation drug eluting stents are of paramount importance to adequately inform decision‐making in contemporary clinical practice.
Stenting in unprotected left main coronary stenosis—“What no progress”?
Authors: Tommaso Carl L.
Published: May 2020

Key Points

There does not appear to be a difference in patient outcomes of percutaneous coronary intervention for unprotected left main coronary artery stenosis whether using first‐ or second‐generation drug elutting stent.

This is despite increase in patients having more adjunctive procedures such as intravascular imaging and newer generation antiplatelet agents.

This single‐center study provokes questions as to why there has not been improvement in outcomes.
Biomimetic Gemcitabine–Lipid Prodrug Nanoparticles for Pancreatic Cancer
Authors: Bulanadi Jerikho C. , Xue Aiqun , Gong Xiaojuan , Bean Penelope A. , Julovi Sohel M. , de Campo Liliana , Smith Ross C. , Moghaddam Minoo J.
Published: May 2020

Gemcitabine (Gem) is a key drug for pancreatic cancer, yet limited by high systemic toxicity, low bioavailability and poor pharmacokinetic profiles. To overcome these limitations, Gem prodrug amphiphiles were synthesised with oleyl, linoleyl and phytanyl chains. Self‐assembly and lyotropic mesophase behaviour of these amphiphiles were examined using polarised optical microscopy and Synchrotron SAXS (SSAXS). Gem‐phytanyl was found to form liquid crystalline inverse cubic mesophase. This prodrug was combined with phospholipids and cholesterol to create biomimetic Gem‐lipid prodrug nanoparticles (Gem‐LPNP), verified by SSAXS and cryo‐TEM to form liposomes. In vitro testing of the Gem‐LPNP in several pancreatic cancer cell lines showed lower toxicity than Gem. However, in a cell line‐derived pancreatic cancer mouse model Gem‐LPNP displayed greater tumour growth inhibition than Gem using a fraction (<6 %) of the clinical dose and without any systemic toxicity. The easy production, improved efficacy and low toxicity of Gem‐LPNP represents a promising new nanomedicine for pancreatic cancer.
High dispersal capacity and biogeographic breaks shape the genetic diversity of a globally distributed reef‐dwelling calcifier
Authors: Prazeres Martina , Morard Raphaël , Roberts T. Edward , Doo Steve S. , Jompa Jamaluddin , Schmidt Christiane , Stuhr Marleen , Renema Willem , Kucera Michal
Published: May 2020

Understanding the role of dispersal and adaptation in the evolutionary history of marine species is essential for predicting their response to changing conditions. We analyzed patterns of genetic differentiation in the key tropical calcifying species of large benthic foraminifera Amphistegina lobifera to reveal the evolutionary processes responsible for its biogeographic distribution. We collected specimens from 16 sites encompassing the entire range of the species and analyzed hypervariable fragments of the 18S SSU rDNA marker. We identified six hierarchically organized genotypes with mutually exclusive distribution organized along a longitudinal gradient. The distribution is consistent with diversification occurring in the Indo‐West Pacific (IWP) followed by dispersal toward the periphery. This pattern can be explained by: (a) high dispersal capacity of the species, (b) habitat heterogeneity driving more recent differentiation in the IWP, and (c) ecological‐scale processes such as niche incumbency reinforcing patterns of genotype mutual exclusion. The dispersal potential of this species drives the ongoing range expansion into the Mediterranean Sea, indicating that A. lobifera is able to expand its distribution by tracking increases in temperature. The genetic structure reveals recent diversification and high rate of extinction in the evolutionary history of the clade suggesting a high turnover rate of the diversity at the cryptic level. This diversification dynamic combined with high dispersal potential, allowed the species to maintain a widespread distribution over periods of geological and climatic upheaval. These characteristics are likely to allow the species to modify its geographic range in response to ongoing global warming without requiring genetic differentiation.
Trigger‐dependent differences determine therapeutic outcome in murine primary hemophagocytic lymphohistiocytosis
Authors: Gather Ruth , Aichele Peter , Goos Nadja , Rohr Jan , Pircher Hanspeter , Kögl Tamara , Zeiser Robert , Hengel Hartmut , Schmitt‐Gräff Annette , Weaver Casey , Ehl Stephan
Published: May 2020

Familial hemophagocytic lymphohistiocytosis (FHL) is a hyperinflammatory syndrome affecting patients with genetic cytotoxicity defects. Perforin‐deficient (PKO) mice recapitulate the full clinical picture of FHL after infection with lymphocytic choriomeningitis virus (LCMV). Hyperactivated CD8+ T cells and IFN‐γ have been identified as the key drivers of FHL and represent targets for therapeutic interventions. However, the response of patients is variable. This could be due to trigger‐dependent differences in pathogenesis, which is difficult to address in FHL patients, since the trigger frequently escapes detection. We established an alternative FHL model using intravenous infection of PKO mice with murine CMV (MCMV)Smith. PKO mice developed acute FHL after both infections and fulfilled HLH diagnostic criteria accompanied by excessive IFN‐γ production by disease‐inducing T cells, that enrich in the BM. However, direct comparison of the two infection models disclosed trigger‐dependence of FHL progression and revealed a higher contribution of CD4 T cells and NK cells to IFN‐γ production after MCMV infection. Importantly, therapeutic intervention by IFN‐γ neutralization or CD8+ T‐cell depletion had less benefit in MCMV‐triggered FHL compared to LCMV‐triggered FHL, likely due to MCMV‐induced cytopathology. Thus, the context of the specific triggering viral infection can impact the success of targeted immunotherapeutic HLH control.
Titanium‐Based Tetrakis‐2,3‐[5,6‐di(Substituted)pyrazino]porphyrazine: Synthesis and Characterization
Authors: Renzi Polyssena , Mazzapioda Lucia , Nardelli Francesca , Martini Francesca , Geppi Marco , Mancone Carmine , Assunta Navarra Maria , D'Acunzo Francesca , Gentili Patrizia
Published: May 2020

Tetrapyrazinoporphyrazine (TPysPz) ligands and metal complexes find, generally, application as electronic materials and catalysts. Considering the limited application of Titanium (Ti), we prepared and characterized a family of ligands and Ti‐based complexes of tetrakis‐2,3‐[5,6‐di‐R8‐pyrazino]porphyrazine (R = H, 2‐Py, Ph). UV/Vis measurements in different solvents confirm molecular aggregation, which results more pronounced in the presence of 2‐pyridil and phenyl substituents on the macrocycle edge. Because of low solubility, solid state NMR was applied for structure characterization. Additional IR and MALDI‐TOF were carried out to complete the characterization. Cyclic voltammetry in DMSO/Bu4NBF4 0.1 m unveiled that our Ti complexes can take part in up to five redox events. The first two quasi‐reversible reductions involve Ti(IV), whereas the further to or three occur at the expense of the TPysPz macrocycle. To test the applicability of our compounds as catalytic materials, we performed a preliminary cyclic voltammetry investigation in the solid‐state, which showed typical peaks of hydrogen redox reactions.
Lipids Analysis and Rapid Identification of Cod Products
Authors: Feng Heng , Huang Xue , Tai Jingjing , Liang Xinle , Zhang Fuming , Zhang Hong
Published: May 2020

In this study, fatty acid analysis and lipid nutrition assessment of five common cod products from fishery markets are performed by gas chromatography (GC). Meanwhile, a lipid‐based rapid identification method for cod products using thin‐layer chromatography (TLC) is established. GC analysis showed that 13, 11, 13, 13, and 6 types of fatty acids are identified in Atlantic cod, Pacific cod, sablefish, silver cod, and oilfish, respectively. The nutrition assessment shows that Atlantic cod, Pacific cod, sablefish, and silver cod have healthier atherogenicity index (AI) and thrombogenic index (TI), suggesting these four types of fish have higher nutritive value. In terms of the fatty acid, the five species of fish can be classified by systematic clustering and heat map analysis. The TLC‐rapid lipid identification method shows that sablefish and silver cod contain characteristic triglyceride, and oilfish contains characteristic wax ester, which are obviously different from the Atlantic cod and the Pacific cod. The oilfish could be distinguished from the high nutritive value of sablefish, silver cod, Atlantic cod, and Pacific cod by the rapid identification method in a few minutes. This study provides important nutritional information and a method for rapid identification of cod products.
An Efficient Cyclic Di‐AMP Based Artificial Metalloribozyme for Enantioselective Diels–Alder Reactions
Authors: Qi Qianqian , Lv Shuting , Hao Min , Dong Xingchen , Gu Youkun , Wu Peizhe , Zhang Wenyue , Chen Yashao , Wang Changhao
Published: May 2020

The diverse structures of nucleic acids as scaffolds have brought the significant advancement for DNA‐based enantioselective catalysis, yet RNA‐based enantioselective catalysis is lacking investigation. Herein, we report a small, natural RNA of cyclic di‐AMP (c‐di‐AMP) and Cu2+ ions assemble into an artificial metalloribozyme (c‐di‐AMP·Cu2+), that could effectively catalyze the enantioselective Diels–Alder reactions with up to 80 % ee. The enantioselective catalytic performance of c‐di‐AMP·Cu2+ has been studied by thorough investigations of different metal cofactors, c‐di‐AMP/Cu2+ molar ratios, additives, buffers and c‐di‐AMP analogues. In addition, the assembly of c‐di‐AMP·Cu2+ gives rise to 300‐fold and 5‐fold rate acceleration compared to the uncatalyzed reaction and Cu2+ ions, respectively. This work provides a simple and efficient strategy to construct the RNA‐based catalysts that would expand the current nucleic acids‐based catalysis and might hint the possible catalytic RNA in primordial chemistry.
Selective Recognition of Chloride by a 24‐Membered Macrocyclic Host with a Hydrophobic Methylenepyrene Substituent
Authors: Dąbrowa Kajetan , Lindner Marcin , Wasiłek Sylwia , Jurczak Janusz
Published: May 2020

A structure‐guided design, synthesis, and characterization of neutral unclosed cryptand functionalized with a bulky and hydrophobic 1‐methylene‐pyrene substituent is described. The host selectively binds spherical chloride (Cl–) over bigger and more basic carboxylates (MeCO2–, PhCO2–) and dihydrogenphosphate (H2PO4–) in a competitive [D6]DMSO + 0.5 % H2O solvent mixture. The capture of chloride is accompanied by formation of sandwich‐type complex stabilized by π–π and CH–π interactions. Step‐wise addition of MeOH triggers release of the cargo in a controllable manner.
High‐repetition‐rate source delivering optical pulse trains with a controllable level of amplitude and temporal jitters
Authors: Andral Ugo , Finot Christophe
Published: May 2020

We theoretically propose and numerically validate an all‐optical scheme to generate optical pulse trains with varying peak‐powers and durations. A shaping of the spectral phase thanks to discrete π/2 phase shifts enables an efficient phase‐to‐intensity conversion of a temporal phase modulation based on a two‐tone sinusoidal beating. Experiments carried out at telecommunication wavelengths and at a repetition rate of 10 GHz confirm the ability of our approach to efficiently generate a train made of pulses with properties that vary from pulse‐to‐pulse. The levels of jitters can be accurately controlled.
Optimisation of extraction conditions for terpenoids in Schizandra chinensis Baillon using the response surface method
Authors: Yang So‐Jeong , Lee Kwang‐Geun
Published: May 2020

Terpenoids, which are the major volatile compounds of Schizandra chinensis Baillon (Omija), are the main component of phytoncide. The purpose of the present study was to provide more ways to utilise Omija by optimising terpenoid extraction. The response surface method (RSM) was used to maximise the levels of monoterpene, which has substantial physiological activity and sesquiterpene, which has strong impacts on flavour. Central composite design was used to optimise the extraction pressure (X1: 0.01‐0.1 Mpa), ethanol concentration (X2: 0%‐50%), and sample concentration (X3: 0.01‐0.2 g/mL). Analysis of variance showed that X1, X2 and X3 affected total terpenoid levels (Y1) and monoterpene levels (Y2), whereas only X1 and X3 significantly affected sesquiterpene content (Y3) (P < .05). The optimal conditions based on the individual responses were as follows: Y1 and Y2, X1 = 0.07 Mpa, X2 = 36% and X3 = 0.17 g/mL; Y3, X1 = 0.10 Mpa, X2 = 50% and X3 = 0.20 g/mL.
Effect of Toluene on PEMFC Performance
Authors: Viitakangas J. , Auvinen S. , Costantino M. , Viik S. , Ihonen J.
Published: May 2020

Liquid organic hydrogen carriers (LOHCs) are promising means for hydrogen transportation. They are compatible with existing liquid fuel transport infrastructure and enable for efficient and safe hydrogen storage and transfer over long distances. Toluene and dibenzyltoluene are considered the two most promising LOHCs. Toluene is probably a contaminant found in hydrogen released from these LOHC liquids.

The impact of hydrocarbon contaminants on automotive type fuel cells has been analyzed to a limited extent, and a few species only have specific limits (CO, CO2, HCOOH, HCHO, CH4). Currently, hydrocarbons are limited to a total of 2 ppm (methane basis) in the automotive hydrogen fuel standard, ISO 14687:2019. This may lead to strict impurity levels for species from LOHC, and therefore higher costs of hydrogen purification and quality assurance.

This work presents contamination studies with toluene. The measurements were conducted using a PEMFC short stack with anode recirculation and with high fuel utilization (98%). The results show no effect or only a small contamination effect with up to 20 ppm toluene, and clear contamination with 50 ppm toluene. This supports the need for more studies so that a separate limit can be defined for toluene in future versions of the ISO 14687.
Development of an Aging Estimation Tool for a PEM Fuel Cell Submitted to a Mission Profile
Authors: Pessot A. , Turpin C. , Jaafar A. , Soyez E. , Rallières O. , d'Arbigny J. , Chadourne N.
Published: May 2020

The purpose of the presented work is to propose an inventive approach to estimate the aging of a fuel cell submitted to a mission profile. A mission profile can be decomposed in quasi‐static and dynamic sub‐missions. The proposed approach is based on the superposition principle considering that the cell voltage degradation, due to the application of the mission profile, can be determined using the cell voltage degradations experimentally evaluated for all the sub‐missions. In our case, four aging campaigns have been performed: an aging campaign for an aeronautical mission profile and three campaigns for quasi‐static sub‐missions. Each aging campaign consists in around 900 h of profile regularly interrupted to perform characterization phases. The cell voltage degradation attributed to a given solicitation can be estimated using polarization curves carried out during the regular characterization phases, and/or using instantaneous “voltage versus time” curves obtained during the ageing phases. In this paper, results of these campaigns are used to investigate concretely the proposed approach and several examples of application are presented. In all these examples, the results show a good agreement between the experimental cell voltage degradation and the estimated one using superposition principle, attesting of the potential of the proposed approach.
Predicting rehospitalisation in older inpatients with a psychotic disorder
Authors: Kist Nicolien , van den Berg Julia F. , Kok Rob M.
Published: May 2020

Objective

The objective of this study was to predict rehospitalisation in a psychiatric clinic in older inpatients with a psychotic disorder.

Methods/Design

In this prospective, observational study, all eligible inpatients aged 55 years and over with a primary psychotic disorder, admitted to a specialised ward for older psychotic patients in a large psychiatric inpatient clinic in the Netherlands, were asked to participate. Whether or not patients were rehospitalised and time to rehospitalisation were assessed 1 year after discharge from the ward. We recorded age, gender, living arrangement, psychiatric diagnosis, severity of psychotic symptoms, duration of index episode, age of onset of psychotic disorder, number of previous admissions, involuntary admission and use of depot medication at discharge. All patients underwent a neuropsychological assessment.

Results

Of the 90 patients that were included, 32 (35.6%) had been readmitted within 1 year after discharge. None of the demographic or clinical variables predicted rehospitalisation or the time to rehospitalisation.

Conclusion

Factors that predict rehospitalisationin younger adult patients with schizophrenia may not predict rehospitalisationin older patients with a psychotic disorder, of which the majority suffered from schizophrenia. We expect that other factors than those investigated may be of greater importance to predict rehospitalisation, as for example social support and coping mechanisms.
Clozapine‐induced agranulocytosis in Japan: Changes in leukocyte/neutrophil counts before and after discontinuation of clozapine
Authors: Matsui Kentaro , Ishibashi Mikiko , Kawano Masahiko , Oshibuchi Hidehiro , Ishigooka Jun , Nishimura Katsuji , Inada Ken
Published: May 2020

Objective

To determine the prevalence, background factors, and progression of and recovery from clozapine‐induced agranulocytosis in Japan.

Methods

Data on treatment‐resistant schizophrenia patients registered with the Clozaril Patient Monitoring Service (CPMS) between July 29, 2009 and January 20, 2016 were extracted. Patients with a neutrophil count <500/mm3 were defined as having agranulocytosis, and those with a leukocyte count <3,000/mm3 or a neutrophil count <1,500/mm3 but not meeting the criteria for agranulocytosis were defined as having leukopenia/neutropenia.

Results

Of 3,746 patients, agranulocytosis and leukopenia/neutropenia were observed in 38 (1.0%) and 182 (4.9%) patients, respectively. Age was significantly higher in the agranulocytosis group (p < .001). Decreased leukocyte counts 1 week prior to discontinuation were observed only in the agranulocytosis group. The median number of days to recovery from agranulocytosis and leukopenia/neutropenia was 10 and 4, respectively, with more variation in the latter.

Conclusions

Although some patients with leukopenia/neutropenia might carry less pathologic significance, the results of this study reconfirmed the importance of regular blood monitoring for preventing agranulocytosis.
Adolescents' family obligation and activities in rural and urban Vietnam: Implications for social change
Authors: Park Heejung , Weiss Bahr , Trung Lam T. , Ngo Victoria K. , Lau Anna S.
Published: May 2020

This study examined how urbanisation may modify adolescents' values and activities concerning family obligation by surveying 572 adolescents (Mage = 15.75, SD = .73) in rural and urban Vietnam. Compared with their rural peers, urban adolescents reported a stronger sense of family obligation but spent less time actually engaging in family assistance, findings that were partly explained by urban households' less financial hardship and higher parental education levels. As expected, stronger family obligation values were associated with greater family assistance activities across rural and urban Vietnam. However, stronger family obligation values were associated with more study hours only in urban Vietnam, indicating that urbanisation may broaden the meaning of family obligation to encompass the academic domain. Additionally, weaker family obligation values were associated with more employment hours only in rural Vietnam, suggesting that rural adolescents with little attachment to the traditional value of family obligation may pursue autonomy through employment outside the home. In traditionally familistic societies undergoing urbanisation, family obligation may take on different meaning depending on adolescents' ecological settings that construct cultural values and behavioural norms.
Dual‐color STED super‐resolution microscope using a single laser source
Authors: Wang Jialin , Zhang Jia , Wang Luwei , Gao Xinwei , Shao Yonghong , Liu Liwei , Yang Zhigang , Yan Wei , Qu Junle
Published: May 2020

STED (stimulated emission depletion) microscopy is one of the most promising super‐resolution fluorescence microscopies，due to its fast imaging and ultra‐high resolution. In this paper, we present a dual‐color STED microscope with a single laser source. Polarization beam splitters are used to separate the output from a supercontinuum laser source into four laser beams, including two excitation beams (488, 635 nm) and two depletion beams (592, 775 nm). These four laser beams are then used to build a low cost dual‐color STED system to achieve a spatial resolution of 75 nm in cell samples.
Self‐assembling hydrogel loaded with 5‐FU PLGA microspheres as a novel vitreous substitute for proliferative vitreoretinopathy
Authors: Yu Zhen , Ma Shisi , Wu Mengfan , Cui Huan , Wu Rong , Chen Sizhe , Xu Chenlin , Lu Xiaohe , Feng Songfu
Published: May 2020

The vitreous substitute for proliferative vitreoretinopathy (PVR) surgery remains an unmet clinical need in ophthalmology. In our study, we developed an in situ formed hydrogel by crosslinking polyvinyl alcohol (PVA) and chitosan as a potential vitreous substitute. 5‐fluorouracil (5‐FU) Poly (lactic‐co‐glycolic acid) (PLGA) microspheres were developed and loaded onto the PVA/chitosan hydrogels to treat PVR. In vitro, PVA/chitosan hydrogels at four concentrations were subjected to morphological, physical, rheological analyses, and cytotoxicity was evaluated together with the characterization of 5‐FU PLGA microspheres. In vivo, pharmacologically induce PVR rabbits were performed a vitrectomy. In the PVA group, 3% PVA/chitosan hydrogel was injected into the vitreous cavity. In the PVA/MS group, 3% PVA/chitosan hydrogel and 5‐FU PLGA microspheres were injected. In the Control group, phosphate‐buffered saline was injected. Therapeutic efficacy was evaluated with postoperative examinations and histological analyses. This study demonstrated that the 3% PVA/chitosan hydrogel showed properties similar to those of the human vitreous and could be a novel in situ crosslinked vitreous substitute for PVR. Loading 5‐FU PLGA microspheres onto this hydrogel may represent an effective strategy to improve the prognosis of PVR.