bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutational analysis of Caenorhabditis elegans CED‐4
Authors: Seshagiri Somasekar , Chang Wen-teh , Miller Lois K
Published: July 2002

Much of our knowledge concerning the genetics that regulate cell death has come from the studies of cell death during the development of the nematode Caenorhabditis elegans. Of the 14 genes identified as components of nematode cell death pathways, two genes, ced‐3 and ced‐4, are required to promote cell death and a third, ced‐9, blocks cell death. Recent studies show CED‐4 to be an activator of CED‐3 and CED‐9 to be an inhibitor of CED‐4. Two published sequence alignments suggest that CED‐4 contains a death effector domain (DED), a protein sequence motif present in other death signaling proteins like Fadd and Flice; one study suggests a DED sequence similarity near the N‐terminus while the other found sequence similarity near the C‐terminus of CED‐4. Using mutational analysis we have tested the functional significance of the conserved residues found within the putative DEDs of CED‐4. Mutations in two conserved residues within the putative N‐terminal DED of CED‐4 affected its function, while mutations in the conserved residues within the putative C‐terminal DED had no effect on CED‐4 function. Our results do not support the presence of a DED in the C‐terminus of CED‐4 and suggest a potential role for the N‐terminus in CED‐4 function, possibly as a DED or as a CARD (caspase recruitment domain). We also found that CED‐9 associated with all the CED‐4 mutants and inhibited the activity of all the active‐CED‐4 mutants.
Single mutations strongly alter the K+‐selective pore of the Kin channel KAT1
Authors: Dreyer Ingo , Becker Dirk , Bregante Monica , Gambale Franco , Lehnen Michaela , Palme Klaus , Hedrich Rainer
Published: July 2002

Voltage‐dependent potassium uptake channels represent the major pathway for K+ accumulation underlying guard cell swelling and stomatal opening. The core structure of these Shaker‐like channels is represented by six transmembrane domains and an amphiphilic pore‐forming region between the fifth and sixth domain. To explore the effect of point mutations within the stretch of amino acids lining the K+ conducting pore of KAT1, an Arabidopsis thaliana guard cell Kin channel, we selected residues deep inside and in the periphery of the pore. The mutations on positions 256 and 267 strongly altered the interaction of the permeation pathway with external Ca2+ ions. Point mutations on position 256 in KAT1 affected the affinity towards Ca2+, the voltage dependence as well as kinetics of the Ca2+ blocking reaction. Among these T256S showed a Ca2+ phenotype reminiscent of an inactivation‐like process, a phenomenon unknown for Kin channels so far. Mutating histidine 267 to alanine, a substitution strongly affecting C‐type inactivation in Shaker, this apparent inactivation could be linked to a very slow calcium block. The mutation H267A did not affect gating but hastened the Ca2+ block/unblock kinetics and increased the Ca2+ affinity of KAT1. From the analysis of the presented data we conclude that even moderate point mutations in the pore of KAT1 seem to affect the pore geometry rather than channel gating.
Phosphatidylethanolamine mediates insertion of the catalytic domain of leader peptidase in membranes
Authors: van Klompenburg Wim , Paetzel Mark , de Jong Joris M. , Dalbey Ross E. , Demel Rudy A. , von Heijne Gunnar , de Kruijff Ben
Published: July 2002

Leader peptidase is an integral membrane protein of E. coli and it catalyses the removal of most signal peptides from translocated precursor proteins. In this study it is shown that when the transmembrane anchors are removed in vivo, the remaining catalytic domain can bind to inner and outer membranes of E. coli. Furthermore, the purified catalytic domain binds to inner membrane vesicles and vesicles composed of purified inner membrane lipids with comparable efficiency. It is shown that the interaction is caused by penetration of a part of the catalytic domain between the lipids. Penetration is mediated by phosphatidylethanolamine, the most abundant lipid in E. coli, and does not seem to depend on electrostatic interactions. A hydrophobic segment around the catalytically important residue serine 90 is required for the interaction with membranes.
DNA sequence recognition by bis‐linked netropsin and distamycin derivatives
Authors: Grokhovsky S.L , Surovaya A.N , Burckhardt G , Pismensky V.F , Chernov B.K , Zimmer Ch , Gursky G.V
Published: July 2002

We studied the interaction of cis‐diammine Pt(II)‐bridged bis‐netropsin, cis‐diammine Pt(II)‐bridged bis‐distamycin and oligomethylene‐bridged bis‐netropsin with synthetic DNA fragments containing pseudosymmetrical AT‐rich nucleotide sequences and compared it with the interaction of the parent compounds netropsin and distamycin A. For fragments containing multiple blocks of (A/T)4 and (T/A)4 separated by zero, one, two and three GC‐base pairs, DNase I footprinting and CD spectroscopy studies reveal that 5′‐TTTTAAAA‐3′ is the strongest affinity binding site for cis‐diammine Pt(II)‐bridged bis‐netropsin and bis‐distamycin. They both bind less strongly to a DNA region containing the sequence 5′‐AAAATTTT‐3′. Netropsin, distamycin A and oligomethylene‐bridged bis‐netropsin exhibit far less sequence discrimination.
The role of the cysteine‐rich region of the β2 integrin subunit in the leukocyte function‐associated antigen‐1 (LFA‐1, αLβ2, CD11a/CD18) heterodimer formation and ligand binding
Authors: Douglass Wendy A. , Hyland Robert H. , Buckley Christopher D. , Al-Shamkhani Aymen , Shaw Jacqueline M. , Scarth Sarah L. , Simmons David L. , Law S.K.Alex
Published: July 2002

The cysteine‐rich region (CRR) of the β2 integrin subunit was replaced by that of β1 to give the chimera β2NV1. β2NV1 can combine with αL to form a variant leukocyte‐function‐associated antigen (LFA)‐1 on COS cell surface, suggesting that the specificity of the β2 interaction with αL does not lie in the CRR. Unlike those expressing wild‐type LFA‐1, COS cells expressing αLβ2NV1 are constitutively active in intercellular adhesion molecule (ICAM)‐1 adhesion. These results suggest that activation of LFA‐1 involves the release of an intramolecular constraint, which is maintained, in part, by the authentic β2 CRR.
Phosphatidylinositol 3‐kinase and protein kinase C are required for the inhibition of caspase activity by epidermal growth factor
Authors: Lan Li , Wong Nai-Sum
Published: July 2002

The mechanism by which growth factors exert an anti‐apoptotic function on many cell types is not well understood. This issue is addressed in relation to epidermal growth factor (EGF) which inhibits apoptosis induced by staurosporine or wortmannin in an epithelial tumour cell line (CNE‐2). The presence of EGF substantially reduced the in vitro Ac‐DEVD‐AMC hydrolytic activity and almost completely suppressed the intracellular cleavage of poly(ADP‐ribose) polymerase in staurosporine‐ or wortmannin‐treated cells. Staurosporine but not wortmannin caused the intracellular proteolytic processing of pro‐caspase‐3 and this event was transiently inhibited by EGF. Staurosporine‐induced apoptosis was not inhibited by EGF in the presence of wortmannin or LY294002. Similarly, EGF failed to inhibit wortmannin‐induced apoptosis in the presence of staurosporine, chelerythrine chloride or Gö6850. These results suggest that phosphatidylinositol 3‐kinase and protein kinase C play a role in the survival function of EGF but the reduction of cellular caspase activity cannot be satisfactorily explained by a lack of pro‐caspase‐3 activation.
A novel 45 kDa secretory protein from rat olfactory epithelium: primary structure and localisation
Authors: Merkulova Maria I. , Andreeva Svetlana G. , Shuvaeva Tatyana M. , Novoselov Sergey V. , Peshenko Igor V. , Bystrova Marina F. , Novoselov Vladimir I. , Fesenko Evgeny E. , Lipkin Valery M.
Published: July 2002

cDNA clones encoding the 45 kDa protein were isolated from a rat olfactory epithelium cDNA library and their inserts were sequenced. The reconstructed protein sequence comprises 400 amino acids with a calculated molecular mass of 46 026 Da. A homology was revealed between the amino acid sequence of the 45 kDa protein and the proteins involved in the transfer of hydrophobic ligands. Using in situ hybridisation, the 45 kDa protein mRNA expression was detected in the layer of supportive cells of olfactory epithelium, apical region of trachea, surface layer of the ciliated bronchial epithelium in lung and in skin epidermis.
Arfaptin 1 forms a complex with ADP‐ribosylation factor and inhibits phospholipase D
Authors: Williger B.-T , Provost J.J , Ho W.-T , Milstine J , Exton J.H
Published: July 2002

ADP‐ribosylation factors (ARFs) regulate coatomer assembly on the Golgi as well as recruitment of clathrin adapter proteins and are therefore involved in vesicle budding from the Golgi and vesicular transport. They are also regulators of phospholipase D (PLD) activity. Arfaptin 1 is an ARF binding protein that inhibits PLD activation, vesicular trafficking and secretion. In the present report, we show that arfaptin 1 interacts with ‘high speed’ membranes independently of ARF. However, addition of myristoylated ARF3 (myrARF3) increases the association of arfaptin 1 with the membranes, suggesting that arfaptin 1 and ARF form a complex on the Golgi. Utilizing several deletion mutants of arfaptin 1 it is shown that the association of arfaptin 1 with myrARF3 is mediated via two binding sites on arfaptin 1. These two domains are needed for arfaptin 1 inhibition of PLD activation by myrARF3 in vitro.
Mutagenesis and crystallographic studies of Zymomonas mobilis tRNA‐guanine transglycosylase to elucidate the role of serine 103 for enzymatic activity
Authors: Grädler Ulrich , Ficner Ralf , Garcia George A. , Stubbs Milton T. , Klebe Gerhard , Reuter Klaus
Published: July 2002

The tRNA modifying enzyme tRNA‐guanine transglycosylase (TGT) is involved in the exchange of guanine in the first position of the anticodon with preQ1 as part of the biosynthesis of the hypermodified base queuine (Q). Mutation of Ser90 to an alanine in Escherichia coli TGT leads to a dramatic reduction of enzymatic activity (Reuter, K. et al. (1994) Biochemistry 33, 7041–7046). To further clarify the role of this residue in the catalytic center, we have mutated the corresponding Ser103 of the crystallizable Zymomonas mobilis TGT into alanine. The crystal structure of a TGT(S103A)/preQ1 complex combined with biochemical data presented in this paper suggest that Ser103 is essential for substrate orientation in the TGT reaction.
Intracellular pH in one‐cell mouse embryo differs between subcellular compartments and between interphase and mitosis
Authors: Amirand Claudine , Mentré Pascale , van de Geijn Sjoerd , Waksmundzka Malgorzata , Debey Pascale
Published: July 2002

The pH‐sensitive dual‐emission fluorophore SNARF‐1 coupled with a laser confocal microspectrofluorimeter was used to measure the internal pH (pHi) in different subcellular and subnuclear compartments of early mouse embryos. By this method we analysed the first cell cycle of naturally fertilised embryos in order to detect possible pHi changes correlated to cellular events, particularly the onset of replication or transcription and the first mitosis. Throughout interphase, significant differences of pHi were observed between cytoplasm and pronuclei, and, even more striking, between these compartments and nucleolus precursor bodies, whose pHi was systematically lower. We could detect significant pHi change neither during the replication phase nor at the onset of zygotic transcription, but pHi increased at the end of the one‐cell stage in both cytoplasm and chromatin regions, a process that seemed specifically correlated with mitosis.
The impact of purchasing integration and practices on manufacturing performance
Authors: Narasimhan Ram , Das Ajay
Published: July 2002

Purchasing integration remains an under‐researched concept, despite being described as a key competence in the literature. This study explicates the concept of purchasing integration and examines its relationships with purchasing practices and manufacturing performance. Purchasing integration refers to the integration of strategic purchasing practices and goals with a firm’s objectives. Alternative models linking purchasing integration to purchasing practices and manufacturing performance are hypothesized and tested using empirical data. Purchasing integration was found to moderate the relationship between purchasing practices and manufacturing performance. Increased investments in purchasing integration were observed to lead to higher performance returns from investments in purchasing practices.
The service concept: the missing link in service design research?
Authors: Goldstein Susan Meyer , Johnston Robert , Duffy JoAnn , Rao Jay
Published: July 2002

The service concept plays a key role in service design and development. But while the term is used frequently in the service design and new service development literature, surprisingly little has been written about the service concept itself and its important role in service design and development. The service concept defines the how and the what of service design, and helps mediate between customer needs and an organization’s strategic intent. We define the service concept and describe how it can be used to enhance a variety of service design processes. As illustrations here, we apply the service concept to service design planning and service recovery design processes. Employing the service concept as an important driver of service design decisions raises a number of interesting questions for research which are discussed here.
The impact of market requirements focus and manufacturing characteristics focus on plant performance
Authors: Bozarth Cecil , Edwards Steve
Published: July 2002

This study examines the relationship between market requirements focus, manufacturing characteristics focus, and manufacturing performance. Results from a sample of plants serving the automotive industry support the general argument that market requirements focus and manufacturing characteristics focus have an impact on manufacturing performance, and provide partial support for a mediation model of focus proposed by Bozarth (1993). The results also show that focused work cells or plants‐within‐a‐plant might not be entirely successful at buffering plants from the negative impact of diverse market requirements.
Operations management research: an update for the 1990s
Authors: Pannirselvam Gertrude P , Ferguson Lisa A , Ash Robert C , Siferd Sue P
Published: July 2002

The issue of operations management (OM) research agendas was first advanced in the literature in 1980 with updates and additions in 1981, 1987, and 1989. We believe that the time is ripe for an analysis of the OM research agenda in the decade of the 90's. In this study, we examine operations management research methodologies and output during the period 1992–1997. Amoako‐Gyampah and Meredith [Amoako‐Gyampah, K., Meredith, J.R., 1989. Journal of Operations Management 8, 250‐262] published a study in which they examined operations management research output from 1982 through 1987. Our objectives are to examine the state of operations management research in the 1990s from the standpoint of topics and methodologies to look for trends, and to determine implications for future research. We assessed the state of research in operations management by examining the research topics addressed and the methodologies used in a subset of seven academic journals that are representative of publications in operations management research. We also surveyed pipeline research in the operations management area by analyzing the topics discussed in national conferences attended by operations management academicians and researchers. Our findings show some significant changes in the kind of research being performed in the 1990s vs. the 1980s. Greater interest in strategy and quality are now apparent in the literature. OM research in the 1990s is also more integrative in nature. We were surprised to find no apparent shift away from modeling solution methods nor any significant shift toward empirical methodologies.
The diagnostic stability of ICD-10 psychiatric diagnoses in clinical practice
Authors: Daradkeh TK , El-Rufaie OEF , Younis YO , Ghubash R
Published: July 2002

This study examines the stability of ICD-10 diagnoses of patients admitted to Al Ain (United Arab Emirates) inpatients psychiatric unit during the period from November 1993 to August 1995. Diagnostic stability is a measure of the degree to which diagnoses remained unchanged at a later hospital admission. One hundred and seven patients were admitted more than once during this period, accounting for 168 readmissions. High levels of diagnostic stability were found for ICD-10 Fl-psychiatric disorders (100%), F2-schizophrenia (87%), F3-bipolar disorders (87%) and F3-depressive disorders (73%). A poor level of stability was found for patients with neurotic, stress related and adjustment disorders (F4), ranging from zero for somatoform disorders to 50% for generalized anxiety and panic disorders. Poor levels of stability were also found for other psychoses (excluding schizophrenia and affective psychoses) and personality disorders. We conclude that the introduction of ICD-10 as a formal diagnostic system has greatly improved the temporal stability of the most commonly encountered psychiatric disorders (ICD-10 Fl to F3 disorders), confirming the construct validity of those psychiatric disorders. Further investigations are required to evaluate the diagnostic stability of neurotic and other psychotic disorders.
First‐dose hypotension after angiotensin‐converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril
Authors: Vítovec Jirí , Špinar Jindrich ,   Czech and Slovak Investigator Group
Published: July 2002

Background:

First‐dose hypotension refers to an observed reduction in blood pressure after the administration of the first dose of ACE inhibitors in patients with congestive heart failure.

Aim:

To compare the first‐dose responses of low‐dose enalapril and perindopril in patients with stable symptomatic chronic heart failure.

Methods:

Single blind, randomised, multicenter, parallel, prospective study. Patients (N = 298) with chronic heart failure due to ischemic heart disease or dilated cardiomyopathy, NYHA II–IV, ejection fraction < 40%, age > 18 years, naive to ACE inhibitors or ATI‐receptor blocker, were randomised to receive a single dose of 2.5 mg enalapril or 2.0 mg perindopril. Baseline laboratory and clinical examinations were performed before entry into the study. Ambulatory blood pressure monitoring started 2 h before the study medication was given, and continued for at least 10 h after the medication.

Results:

The maximum drop in blood pressure appeared approximately 4 h after dose administration in both groups, and was more pronounced in the enalapril group. Patients in the enalapril group had a significantly higher incidence of asymptomatic hypotension. No symptomatic hypotension requiring a change in medication or a prolongation of hospitalisation was observed.

Conclusion:

A low dose of perindopril is well‐tolerated at initiation of ACE inhibitor therapy in patients with chronic heart failure and causes less first‐dose hypotension than a low dose of enalapril.
Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges
Authors: Garcia‐Pelaez José , Barbosa‐Matos Rita , Gullo Irene , Carneiro Fátima , Oliveira Carla
Published: March 2021

Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low‐risk factors and hereditary GC is caused by inherited high‐risk mutations, so far identified only for the diffuse histotype. DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC‐specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC‐related histological subtypes [signet‐ring cell carcinoma (SRCC) and poorly cohesive carcinoma not otherwise specified (PCC‐NOS)]. Indeed, DGC and DGC‐related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC‐NOS vs SRCC. In this systematic review, we revised the histological presentations, molecular classifications and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC‐NOS). We aimed at identifying histology‐associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC‐NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC‐specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.
Synthetic Multiscale Graphene Aerogel Polymer Composites with High‐Conductive Performances for Hyperthermia Equipment
Authors: Wang Haopeng , Wu Lixin , Xu Lingyun , Zheng Longhui , Wu Yadong , Wu Kechen , Wang Jianlei , Chen Qinhui
Published: March 2021

3D interconnection structures are preconstructed by the hydrothermal method, which is considered an effective way to prepare conductive polymers. However, the fabrication of conductive composites to meet the application remains a challenge for relatively low conductive filler content. Herein, a 3D interconnection network is designed by combination of 2D functionalized graphene oxide (FGO), 1D acidified carbon nanotube (ACNT), and 0D copper element to establish conductive aerogel, which is used as reinforcement to prepare conductive FGO‐ACNT/epoxy nanocomposites. Both elementary Cu and crisscrossed ACNT act as bridges among graphene nanosheets, which is beneficial to electron or phonon conduction, making the nanocomposites possess high‐efficiency electric heating performance and temperature stability. Its electrical conductivity reaches 3.33 S m−1 with only 1.1% of FGO‐ACNT, and the temperature quickly reaches up to 344 °C at the voltage of 9 V within 73 s. Importantly, the FGO‐ACNT/epoxy nanocomposite shows prompt heat‐responsivity, and it can heat up to 60 °C within 7 s from room temperature. When the FGO‐ACNT/epoxy nanocomposite is used as a hyperthermia equipment, it exhibits excellent electrical conductivity, prompt heat‐responsivity, and good temperature stability. These excellent properties make it possible to be used as a physical therapy device to help human health.
Nanostructured Multilayer Coatings for Spatial Filtering
Authors: Grineviciute Lina , Babayigit Ceren , Gailevičius Darius , Peckus Martynas , Turduev Mirbek , Tolenis Tomas , Vengris Mikas , Kurt Hamza , Staliunas Kestutis
Published: March 2021

Spatial filtering is an important mechanism to improve the spatial quality of laser beams. Typically, a confocal arrangement of lenses with a diaphragm in the focal plane is used for intracavity spatial filtering. Such conventional filtering requires access to the far‐field domain. In microlasers, however, conventional filtering is impossible due to the lack of space in microresonators to access the far‐field. Therefore, a novel concept for more compact and efficient spatial filtering is necessary. In this study, a conceptually novel mechanism of spatial filtering in the near‐field domain is proposed and demonstrated, by a nanostructured multilayer coating—a 2D photonic crystal structure with a periodic index modulation along the longitudinal and transverse directions to the beam propagation. The structure is built on a nanomodulated substrate, to provide the transverse periodicity. The physical vapor deposition is used to provide self‐repeating modulation in the longitudinal direction. A 5 µm thick photonic multilayer structure composed of nanostructured multiple layers of alternating high‐ and low‐index materials providing spatial filtering in the near‐infrared frequencies with 2° low angle passband is experimentally demonstrated. The proposed photonic structure can be considered as an ideal component for intracavity spatial filtering in microlasers.
BODIPY‐Pt‐Porphyrins Polyads for Efficient Near‐Infrared Light‐Emitting Electrochemical Cells
Authors: Fresta Elisa , Charisiadis Asterios , Cavinato Luca M. , Palandjian Nadia , Karikis Kostas , Nikolaou Vasilis , Charalambidis Georgios , Coutsolelos Athanassios G. , Costa Rubén D.
Published: March 2021

The synthesis, characterization, and application in light‐emitting electrochemical cells (LECs) of two near‐infrared (NIR)‐emitting Pt‐porphyrins (Pt‐por) with none or 20 F atoms and their respective Pt‐por polyads containing from 1 to 4 BODIPY (BDP) units (PtBDP) connected via tetra‐fluorophenyl triazole spacer groups are reported. The functionalization of PtBDPs is tuned with respect to the number of BDP units and F atoms optimizing 1) the NIR emission through an efficient energy transfer from the BDP to the Pt‐por core, 2) the electronic structure to decouple charge transport via BDP and exciton formation at the Pt‐por, and 3) the ionic conductivity in thin films. A comprehensive rationale on how the molecular design rules the device performance is provided, achieving LECs with emission at 780 nm. This is realized using PtBDP‐2‐8, in which a host:guest strategy between BDP and Pt‐por in thin films is fully operative accompanied by an optimal ionic conductivity. This is supported by spectroelectrochemical findings and device analysis with both Pt‐por references and the PtBDP series. Overall, this work highlights that Pt‐porphyrins are efficient emitters in developing NIR LECs due to their rich functionalization, enabling to control charge transport, energy transfer, and ionic conductivities.
Phosphorus‐Directed C−H Borylation
Authors: Auth Marin R. , McGarry Kathryn A. , Clark Timothy B.
Published: March 2021

Phosphorus‐containing compounds have a long history of utility in a broad range of fields, including agricultural, pharmaceutical, and metal‐mediated reactions. In recent decades, numerous methods have been developed to streamline the synthesis of organophosphorus reagents based on these numerous applications. This review focuses upon the recent development of phosphorus(III)‐ and phosphorus(V)‐directed C−H borylation reactions. This transformation has evolved significantly in the past two years, resulting in several new methods that provide access to organic substrates containing both phosphorus and boron. Further functionalization of the carbon−boron bond to provide functionalized organophosphorus products is discussed.

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Tumor Exosomes Reprogrammed by Low pH Are Efficient Targeting Vehicles for Smart Drug Delivery and Personalized Therapy against their Homologous Tumor
Authors: Gong Changguo , Zhang Xiao , Shi Min , Li Feng , Wang Shuang , Wang Yan , Wang Yugang , Wei Wei , Ma Guanghui
Published: March 2021

As membrane‐bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes are evaluated, and low‐pH treatment caused increased uptake efficiency and retained cell‐type specificity is found. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self‐aggregation‐based mechanism for the enhanced homologous uptake. Furthermore, these low‐pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near‐infrared irradiance‐triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor.
Smart Cargo Delivery System based on Mesoporous Nanoparticles for Bone Disease Diagnosis and Treatment
Authors: Pan Panpan , Yue Qin , Li Juan , Gao Meiqi , Yang Xuanyu , Ren Yuan , Cheng Xiaowei , Cui Penglei , Deng Yonghui
Published: March 2021

Bone diseases constitute a major issue for modern societies as a consequence of progressive aging. Advantages such as open mesoporous channel, high specific surface area, ease of surface modification, and multifunctional integration are the driving forces for the application of mesoporous nanoparticles (MNs) in bone disease diagnosis and treatment. To achieve better therapeutic effects, it is necessary to understand the properties of MNs and cargo delivery mechanisms, which are the foundation and key in the design of MNs. The main types and characteristics of MNs for bone regeneration, such as mesoporous silica (mSiO2), mesoporous hydroxyapatite (mHAP), mesoporous calcium phosphates (mCaPs) are introduced. Additionally, the relationship between the cargo release mechanisms and bone regeneration of MNs‐based nanocarriers is elucidated in detail. Particularly, MNs‐based smart cargo transport strategies such as sustained cargo release, stimuli‐responsive (e.g., pH, photo, ultrasound, and multi‐stimuli) controllable delivery, and specific bone‐targeted therapy for bone disease diagnosis and treatment are analyzed and discussed in depth. Lastly, the conclusions and outlook about the design and development of MNs‐based cargo delivery systems in diagnosis and treatment for bone tissue engineering are provided to inspire new ideas and attract researchers’ attention from multidisciplinary areas spanning chemistry, materials science, and biomedicine.
Direct Visualization and Effects of Atomic‐Scale Defects on the Optoelectronic Properties of Hexagonal Boron Nitride
Authors: Ares Pablo , Santos Hernán , Lazić Snežana , Gibaja Carlos , Torres Iñigo , Pinilla Sergio , Gómez‐Herrero Julio , van der Meulen Herko P. , García‐González Pablo , Zamora Félix
Published: March 2021

Hexagonal boron nitride (hBN) has attracted a lot of attention in the past years, thanks to its many remarkable properties. These include the presence of single‐photon emitters with superior optical properties, which make it an ideal candidate for a plethora of photonic technologies. However, despite the large number of experimental results and theoretical calculations, the structure of the defects responsible for the observed emission is still under debate. In this work, individual atomic‐scale defects in hBN with atomic force microscopy under ambient conditions are visualized and multiple narrow emission lines from optically stable emitters are observed. This direct observation of the structure of the defects combined with density functional theory calculations of their band structures and electronic properties allows associating the existence of several single‐photon transitions to the observed defects. The work sheds light on the origin of single‐photon emission in hBN that is important for the understanding and tunability of high‐quality emitters in optoelectronics and quantum technologies.
Interseeding annual warm‐season grasses into pastures: Forage nutritive value and yields
Authors: Guretzky John A. , Harmoney Keith R. , Moyer Joseph L. , Volesky Jerry D. , Stephenson Mitchell B.
Published: March 2021

Interseeding annual warm‐season grasses into pastures often increases forage accumulation. Yet, impacts on nutritive value and yields remain unreported. We analyzed forage collected from five Nebraska and Kansas experiments in 2015–2016 (eight environments) for crude protein (CP), neutral detergent fiber (NDF), and in vitro organic matter digestibility (IVOMD) concentrations and yields. Each experiment subjected perennial cool‐season grasses to two harvest frequencies (once at 90 d and twice at 45 and 90 d after interseeding) and four interseeded annual warm‐season grass types–pearl millet [Pennisetum glaucum (L.) R. Br.], sudangrass [Sorghum bicolor (L.) Moench ssp. drummondii (Nees ex Steud) de Wet & Harlan], a sorghum–sudangrass hybrid (S. bicolor × S. bicolor var. sudanense), and an unseeded control. Across environments, 90‐d CP and IVOMD concentrations increased while CP and IVOMD yields decreased in interseeded pastures when harvested twice, indicating presence of nutritive value‐yield tradeoffs. Pastures interseeded with sorghum–sudangrass had greater 90‐d IVOMD concentrations and CP and IVOMD yields when harvested once but only greater 90‐d IVOMD concentrations when harvested twice compared to unseeded pastures. Interseeding sorghum–sudangrass provided an effective strategy to increase CP and IVOMD yields in late summer in humid environments with tall fescue [Schedonorus arundinaceus (Schreb.) Dumort., nom. cons.] and in mid‐ and late summer in humid environments with smooth bromegrass (Bromus inermis Leyss.) and semiarid environments with western wheatgrass [Pascopyrum smithii (Rydb.) Á. Löve]. Interseeding annual warm‐season grasses did not consistently increase CP and IVOMD yields in semiarid environments with smooth bromegrass and crested wheatgrass [Agropyrum cristatum (L.)  Gaertn.].
Combination of CD19 and CD22 CAR‐T cell therapy in relapsed B‐cell acute lymphoblastic leukemia after allogeneic transplantation
Authors: Liu Shuangyou , Deng Biping , Yin Zhichao , Lin Yuehui , An Lihong , Liu Dan , Pan Jing , Yu Xinjian , Chen Bingzhen , Wu Tong , Chang Alex H. , Tong Chunrong
Published: March 2021

The prognosis of relapsed acute lymphoblastic leukemia (ALL) after allogeneic transplantation is dismal when treated with conventional approaches. While single‐target CD19 or CD22 chimeric antigen receptor (CAR) T‐cell therapy has achieved high complete remission (CR) rates in refractory/relapsed B‐ALL, it could not maintain a durable remission in most patients. To prolong relapse‐free survival, we sequentially combined CD19 and CD22 CAR‐T cells to treat post‐transplant relapsed B‐ALL patients with both CD19/CD22 antigen expression on lymphoblasts. Patient‐derived donor cells were collected to produce CAR‐T cells that were transfected by lentiviral vectors encoding second generation CARs composed of CD3ζ and 4–1BB. The second T‐cell infusion was scheduled at least 1 month, and usually within 6 months after the first CAR‐T treatment. Twenty‐seven adult and pediatric patients, including 11 (41%) with extramedullary diseases (EMD), received the first CD19 CAR‐T and 23 (85%) achieved CR. Subsequently, 21 out of 27 patients received the second CD22 CAR‐T and were followed‐up for a median of 19.7 (range, 5.6–27.3) months; 14 cases remained in CR, seven relapsed and two of them died from disease progression; Kaplan–Meier survival analysis showed overall survival and event‐free survival rates of 88.5% and 67.5%, respectively, at both 12 months and 18 months. CAR‐T associated graft‐versus‐host disease (GVHD) occurred in 23% of patients, with 8% new‐onset acute GVHD and 15% persistent or worsened pre‐existing cGVHD before CAR‐T. This combination strategy of sequential CD19 and CD22 CAR‐T therapy significantly improved the long‐term survival in B‐ALL patients who relapsed after transplantation.
National patterns of injury and outcomes of gunshot wounds to the penis: A Trauma Quality Programs retrospective cohort analysis
Authors: Maxwell Bryan G. , Chouhan Jyoti D. , Lundeberg Megan R. , Liu Jen‐Jane
Published: March 2021

Aim

Gunshot wounds (GSW) to the penis represent a rare type of traumatic injury in the civilian United States population. Although small, single‐center studies have reported results of care for these types of injured patients, no national analyses have examined this group.

Methods

A cohort of patients with GSW to the penis was identified using the 2017 American College of Surgeons Trauma Quality Programs database, a comprehensive national database of 753 accredited trauma centers.

Results

Gunshot wounds to the penis occurred in 722 patients, which represents 1.7% of all GSW patients (n = 41,017). Gunshot wounds from altercations with law enforcement or accidental discharge of a firearm were rare; the vast majority (n = 655, 90.7%) occurred as a result of assault, intentional self‐harm, attempted suicide, or attempted homicide. Patients with a major concomitant non‐genitourinary injury comprised 119 (16.5%) patients of the cohort. Most patients (n = 499, 69.1%) underwent a genitourinary procedure during their trauma admission. Penile salvage was successful in most cases, with only 13 (1.8%) patients requiring completion penectomy. Most patients (87.8%) required admission with a median length of stay of 49.8 h. Most patients were treated at the initial trauma center without requiring transfer to another center, and complications during admission were rare.

Conclusions

This analysis, the first national examination of care of patients with GSW to the penis, reveals overall favorable outcomes. Admission and surgical intervention were required in most patients, but penectomy was rare and length of stay was generally short. These results will guide resource utilization and quality improvement efforts in this patient cohort.
Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker
Authors: Aktas Orhan , Smith Michael A. , Rees William A. , Bennett Jeffrey L. , She Dewei , Katz Eliezer , Cree Bruce A. C. ,   the N‐MOmentum scientific group and the N‐MOmentum study investigators
Published: March 2021

Objective

Blood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of inebilizumab treatment.

Methods

N‐MOmentum was a prospective, multicenter, double‐blind, placebo‐controlled, randomized clinical trial in adults with NMOSD. sGFAP levels were measured by single‐molecule arrays (SIMOA) in 1,260 serial and attack‐related samples from 215 N‐MOmentum participants (92% aquaporin 4‐immunoglobulin G‐seropositive) and in control samples (from healthy donors and patients with relapsing–remitting multiple sclerosis).

Results

At baseline, 62 participants (29%) exhibited high sGFAP concentrations (≥170 pg/ml; ≥2 standard deviations above healthy donor mean concentration) and were more likely to experience an adjudicated attack than participants with lower baseline concentrations (hazard ratio [95% confidence interval], 3.09 [1.6–6.1], p = 0.001). Median (interquartile range [IQR]) concentrations increased within 1 week of an attack (baseline: 168.4, IQR = 128.9–449.7 pg/ml; attack: 2,160.1, IQR = 302.7–9,455.0 pg/ml, p = 0.0015) and correlated with attack severity (median fold change from baseline [FC], minor attacks: 1.06, IQR = 0.9–7.4; major attacks: 34.32, IQR = 8.7–107.5, p = 0.023). This attack‐related increase in sGFAP occurred primarily in placebo‐treated participants (FC: 20.2, IQR = 4.4–98.3, p = 0.001) and was not observed in inebilizumab‐treated participants (FC: 1.1, IQR = 0.8–24.6, p > 0.05). Five participants (28%) with elevated baseline sGFAP reported neurological symptoms leading to nonadjudicated attack assessments.

Interpretation

Serum GFAP may serve as a biomarker of NMOSD activity, attack risk, and treatment effects. ANN NEUROL 2021;89:895–910
Tetraphenylethylene‐Based Multicomponent Emissive Metallacages as Solid‐State Fluorescent Materials
Authors: Mu Chaoqun , Zhang Zeyuan , Hou Yali , Liu Haifei , Ma Lingzhi , Li Xiaopeng , Ling Sanliang , He Gang , Zhang Mingming
Published: March 2021

The construction of solid‐state fluorescent materials with high quantum yield and good processability is of vital importance in the preparation of organic light‐emitting devices. Herein, a series of tetraphenylethylene (TPE)‐based multicomponent emissive metallacages are prepared by the coordination‐driven self‐assembly of tetra‐(4‐pyridylphenyl)ethylene, cis‐Pt(PEt3)2(OTf)2 and tetracarboxylic ligands. These metallacages exhibit good emission both in solution and in the solid state because the coordination bonds and aggregation restrict the molecular motions of TPE synergistically, which suppresses the non‐radiative decay of these metallacages. Impressively, one of the metallacages achieves very high fluorescence quantum yield (ΦF=88.46 %) in the solid state, which is further used as the coatings of a blue LED bulb to achieve white‐light emission. The study not only provides a general method to the preparation of TPE‐based metallacages but also explores their applications as solid‐state fluorescent materials, which will promote the future design and applications of metallacages as useful emissive devices.
Zugang zu funktionalisierten Pyrenen, Peropyrenen, Terropyrenen und Quarterropyrenen über reduktive Aromatisierung
Authors: Werner Simon , Vollgraff Tobias , Sundermeyer Jörg
Published: March 2021

Wir berichten über ein vielseitig anwendbares Konzept zur Synthese vierfach funktionalisierter, löslicher Pyrene, Peropyrene, Terropyrene und Quarterropyrene. Diese wurden durch eine modulare Synthesestrategie über Suzuki‐Miyaura‐Kreuzkupplung, oxidative Cyclodehydrierung in Gegenwart von Caesiumhydroxid unter Luft und schließlich zinkvermittelte reduktive Silylierung erhalten. Die silylierten Reaktionsprodukte wurden mittels Einkristallstrukturanalysen charakterisiert. Wir stellen das erste Beispiel eines synthetisierten und kristallisierten Quarterropyrens und dessen Oxidationsreaktion vor. Die funktionalisierten Ropyrene wurden systematisch mittels UV/Vis‐NIR‐ und Photolumineszenz‐Spektroskopie charakterisiert und zeigten eine bathochrome Verschiebung von 80 nm pro Naphthalin‐Einheit und einen nahezu linearen Anstieg der Extinktionskoeffizienten. Cyclovoltammogramme und DFT‐Rechnungen identifizieren sie als elektronenreiche Farbstoffe und zeigen eine Verkleinerung des elektrochemisch bestimmten HOMO‐LUMO‐Abstands und niedrigere Oxidationspotentiale für die höheren Homologen.
Macroscopic Ultralight Aerogel Monoliths of Imine‐based Covalent Organic Frameworks
Authors: Martín‐Illán Jesús Á. , Rodríguez‐San‐Miguel David , Castillo Oscar , Beobide Garikoitz , Perez‐Carvajal Javier , Imaz Inhar , Maspoch Daniel , Zamora Félix
Published: March 2021

The use of covalent organic frameworks (COFs) in practical applications demands shaping them into macroscopic objects, which remains challenging. Herein, we report a simple three‐step method to produce COF aerogels, based on sol‐gel transition, solvent‐exchange, and supercritical CO2 drying, in which 2D imine‐based COF sheets link together to form hierarchical porous structures. The resultant COF aerogel monoliths have extremely low densities (ca. 0.02 g cm−3), high porosity (total porosity values of ca. 99 %), and mechanically behave as elastic materials under a moderate strain (<25–35 %) but become plastic under greater strain. Moreover, these COF aerogels maintain the micro‐ and meso‐porosity of their constituent COFs, and show excellent absorption capacity (e.g. toluene uptake: 32 g g−1), with high removal efficiency (ca. 99 %). The same three‐step method can be used to create functional composites of these COF aerogels with nanomaterials.
Advances in ultra‐high‐pressure and multi‐dimensional liquid chromatography instrumentation and workflows
Authors: De Vos Jelle , Stoll Dwight , Buckenmaier Stephan , Eeltink Sebastiaan , Grinias James P.
Published: March 2021

The present contribution discusses recent advances in ultra‐high‐pressure liquid chromatography (UHPLC) and multi‐dimensional liquid chromatography (MDLC) technology. First, new developments in UHPLC column technology and system design are highlighted. The latter includes a description of a novel injector concept enabling method speed‐up, emerging detectors, and instrument diagnostics approaches. Next, online MDLC workflows are reviewed and advances in modulation technology are highlighted. Finally, key applications published in 2020 are reviewed.
Preparation and characterization of poly(vinyl alcohol)/gum tragacanth/cellulose nanocomposite film
Authors: Moghadam Majid Alizadeh , Mohammadi Reza , Sadeghi Ehsan , Mohammadifar Mohammad Amin , Nejatian Mohammad , Fallah Maryam , Rouhi Milad
Published: March 2021

The effects of gum tragacanth obtained from two species of Astragalus Gossypinus (GT‐G) and A. Parrowianus (GT‐P) at two levels of 10% and 30% combined with cellulose nanofibers (CNF; 5%) on the physico‐mechanical and structural properties of polyvinyl alcohol (PVA) nanocomposite film were investigated in this study. The water solubility and water vapor permeability of the films decreased with increasing the content of both gums, especially in the film containing 30% GT‐P. The highest values of the tensile strength (39.3 MPa) and elongation at break (445%) belonged to the treatment containing 10% GT‐P (90/10P/0). The FTIR and DSC analyses confirmed good interactions between GT and PVA in the 90/10P/0 treatment. SEM images indicated the dense structure of this film as the optimum treatment. Although the presence of CNF in the films containing GT‐G improved some properties, especially the Young modulus, it impaired all the functional properties of nanocomposite GT‐P film.
Investigation of the elastic properties of poly (methyl methacrylate) reinforced with graphene nanoplatelets
Authors: Muhammettursun Mahmut , Bel Tayfun , Kocacinar Elif , Erman Ecem , Gul Fuat Berke , Augousti Andy , Baydogan Nilgun
Published: March 2021

The technique for synthesis of poly (methyl methacrylate) (PMMA) by atom transfer radical polymerization has been strengthened by using graphene nanoplatelets (GNPs) to enhance the elastic properties of the polymer. In order to improve practical, economical and mechanical performance, the requirements for effective implementation of production control as a smart bulk polymer nanocomposite were determined for cost‐effective bulk production. Three‐dimensional inspection (using an ultrasound interrogation method for the whole volume under test) confirmed the synthesis of the nanocomposite to be free of agglomeration and bubbles. As a result of this elimination of defects, an enhancement in compressive strength of 42.7% was achieved and the Rockwell hardness was increased by 19.9% through the addition of GNPs at 2 wt% by mass. The deformation and mechanical failure properties have been characterized in the mechanical enhancement of the polymer nanocomposite. Elastic parameters determined using ultrasound testing identified that changes in the structural features following the addition of these GNPs were uniquely connected to the enhancements in these elastic parameters (such as Young's modulus, Poisson's ratio, shear modulus, and microhardness) of the PMMA/GNPs nanocomposite.
Phenol removal from wastewater using eco‐friendly hybrid hydrogels
Authors: Dutra Mariana Alves Leite , Marques Nívia do Nascimento , Souza Filho Men de Sá Moreira de , Balaban Rosangela de Carvalho
Published: March 2021

The intent of this study was to evaluate the ability of low‐cost polyacrylamide/starch hybrid hydrogels in removing organic pollutants from wastewater, using phenol as a model compound, besides of investigating the adsorption/desorption behavior as a function of hydrogels composition. The results indicated that the hydrogel with the lowest amount of starch and crosslinking agent exhibited the maximum phenol adsorption capacity, 21 mg g−1. The adsorption isotherm data were described by Langmuir and Freundlich adsorption isotherm models. According to linear regression analysis, the Freundlich isotherm model was the best fit among the isotherm models for the adsorption process. Furthermore, desorption study revealed a minimum of about 60% of phenol release, indicating reusability to wastewater treatment.