bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a lipoxygenase inhibitor in A431 cells as a phospholipid hydroperoxide glutathione peroxidase
Authors: Huang Hei-Sheng , Chen Ching-Jiunn , Lu Hsieng S , Chang Wen-Chang
Published: July 2002

An endogenous lipoxygenase inhibitor, purified from the cytosol of human epidermoid carcinoma A431 cells, was analyzed by N‐terminal microsequencing and mass spectrometric analysis. The inhibitor was purified by SDS‐PAGE, then subjected to in‐gel CNBr cleavage and trypsin digestion. The N‐terminal sequence data obtained from a 6–8 kDa band of in‐gel CNBr cleavage and the three isolated peptides of in‐gel trypsin digestion, and the C‐terminal peptide sequence from matrix‐assisted laser desorption ionization mass spectrometry matched the sequence of human phospholipid hydroperoxide glutathione peroxidase. The purified inhibitor exhibited peroxidase activity using phosphatidylcholine hydroperoxides as the substrate. We therefore concluded that the lipoxygenase inhibitor present in A431 cells was a phospholipid hydroperoxide glutathione peroxidase.
Stability and functionality of cysteine‐less FOF1 ATP synthase from Escherichia coli
Authors: Kuo Phillip H , Ketchum Christian J , Nakamoto Robert K
Published: July 2002

All 21 native cysteines in the Escherichia coli FOF1 ATP synthase were replaced by alanines. In isolated E. coli membranes, ATP‐dependent proton pumping, turnover of ATP hydrolysis and steady‐state transition state thermodynamic parameters of the cysteine‐less enzyme were similar to wild‐type. The cysteine‐less enzyme was solubilized in n‐octyl β‐d‐glucopyranoside, purified by affinity chromatography, and reconstituted into pre‐formed liposomes made from E. coli lipids. The properties of the reconstituted, purified enzyme were not significantly different from the membranous enzyme. These data demonstrate that cysteine‐less FOF1 is biochemically stable and has functionality similar to wild‐type.
Critical amino acid residues of AIP, a highly specific inhibitory peptide of calmodulin‐dependent protein kinase II
Authors: Ishida Atsuhiko , Shigeri Yasushi , Tatsu Yoshiro , Uegaki Koichi , Kameshita Isamu , Okuno Sachiko , Kitani Takako , Yumoto Noboru , Fujisawa Hitoshi
Published: July 2002

The importance of the individual amino acid residues of AIP (KKALRRQEAVDAL), a highly specific inhibitor of calmodulin‐dependent protein kinase II (CaMKII), was studied. Replacement of Arg6, Gln7, or Ala9 by other amino acid residues produced a marked increase in the IC50 value. Leu4 and Val10 were also sensitive to replacement, but some hydrophobic amino acids could substitute for these residues. Although replacement of Ala3, Glu8, Ala12, and Leu13 by other residues produced no significant increase in the IC50, the substitution of Lys for Ala3 decreased the IC50. An AIP analog (KKLRRQEADAY), in which Ala3 and Val10 were replaced with Lys and Phe, respectively, showed an IC50 value as low as 4 nM, suggesting that it is a useful tool for studying the physiological roles of CaMKII.
Use of the phage display technique for detection of epitopes recognized by polyclonal rabbit gliadin antibodies
Authors: Osman Awad A , Uhlig Holm , Thamm Barbara , Schneider-Mergener Jens , Mothes Thomas
Published: July 2002

A random phage heptapeptide library was screened with rabbit antibodies against wheat flour proteins comprising gliadins and a small amount of low molecular weight glutenins (gli/glu). Gli/glu antibodies isolated from the sera selected different consensus sequences (CS). All CS contained tri‐ to pentapeptide stretches homologous to gli/glu sequences (proposed epitopes). In α‐ and γ‐type gliadins, these sequences are clustered in the N‐terminal region recently suspected to be toxic for humans with celiac disease. Peptides with CS were synthesized and checked for reactivity. Only immune and no control rabbit sera reacted with synthetic peptides. One of eight human sera containing gliadin antibodies was reactive as well (4/8 peptides) but control sera were negative. Thus the phage display technique is useful for epitope screening of polyclonal antibodies even in the case of a group of homologous but diverse antigens.
The vascular endothelial growth factor mRNA contains an internal ribosome entry site
Authors: Miller Diane L , Dibbens Justin A , Damert Annette , Risau Werner , Vadas Mathew A , Goodall Gregory J
Published: July 2002

Vascular endothelial growth factor (VEGF), an essential regulator of angiogenesis during early development as well as during the growth of solid tumours, bears an unusually large 5′ untranslated region (5′‐UTR) in the mRNA of over 1000 nucleotides. We found that the VEGF 5′‐UTR, despite being GC‐rich and containing an upstream short open reading frame, promotes efficient translation of a luciferase reporter. The VEGF 5′‐UTR also allowed translation of luciferase from a dicistronic mRNA when placed between the two cistrons, demonstrating that it contains an internal ribosome entry site. Deletion analysis indicated that the IRES resides towards the 3′ end of the 5′‐UTR.
Membrane targeting and binding of the 74‐kDa form of mouse l‐histidine decarboxylase via its carboxyl‐terminal sequence
Authors: Suzuki Sawako , Tanaka Satoshi , Nemoto Ken-ichi , Ichikawa Atsushi
Published: July 2002

The role of the C‐terminal region of the 74‐kDa form of l‐histidine decarboxylase (HDC) in the targeting to the endoplasmic reticulum (ER) was investigated in COS‐7 cells. The deletion of a 10‐kDa segment (residues 578–662) of the C‐terminal end of HDC, especially a 20 amino acid sequence (residues 588–607), abrogated the targeting to the ER. The C‐terminal 10‐kDa portion is sufficient to target the green fluorescent protein (GFP) to the ER. The 74‐kDa form of HDC synthesized in an in vitro translation system post‐translationally associated with the heterogeneous canine microsomal membranes. These results suggest that the C‐terminal 10‐kDa portion of HDC contains a signal necessary for HDC to be targeted to the ER membrane.
Isolated endosomes from quiescent rat liver contain the signal transduction machinery
Authors: Pol Albert , Calvo Maria , Enrich Carlos
Published: July 2002

In this study we identify the molecules involved in the MAPK signal transduction pathway (Ras, Raf‐1, Mek, Mek‐P and MAPK) in highly purified endosomal fractions isolated from rat liver. Biochemical analysis shows that only the early‐sorting endocytic compartment contains activated Raf‐1 and Mek. Finally, the exogenous administration of EGF led to redistribution of Raf‐1 from the caveolin‐enriched plasma membrane into the endosomes.
The pro‐phenoloxidase of coleopteran insect, Tenebrio molitor, larvae was activated during cell clump/cell adhesion of insect cellular defense reactions1
Authors: Lee Hyun Seong , Cho Mi Young , Lee Kwang Moon , Kwon Tae Hyuk , Homma Ko-ichi , Natori Shunji , Lee Bok Luel
Published: July 2002

To characterize the proteins involved in cell clump/cell adhesion of insect cellular defense reactions, we induced the cell clump/cell adhesion reaction in vitro with the hemolymph of larvae of the coleopteran insect, Tenebrio molitor. The 72 kDa protein was specifically enriched in the residues of cell clump/cell adhesion and was purified to homogeneity. A cDNA clone for the 72 kDa protein was isolated. We found that the 72 kDa protein was an activated phenoloxidase from Tenebrio pro‐phenoloxidase. We suggest that activated phenoloxidase is involved in the cell clump/cell adhesion reaction as well as in the synthesis of melanin.
Effects of frontotemporal dementia FTDP‐17 mutations on heparin‐induced assembly of tau filaments
Authors: Goedert Michel , Jakes Ross , Crowther R.Anthony
Published: July 2002

Missense mutations and intronic mutations in the gene for microtubule‐associated protein tau cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP‐17). Most missense mutations have as likely primary effect a reduced ability of tau to interact with microtubules. We report here an additional effect of several missense mutations, namely the stimulation of heparin‐induced filament assembly of recombinant tau, despite the absence of any change in structure indicated by circular dichroism. These findings indicate that missense mutations in tau lead to frontotemporal dementia through potentially multiple mechanisms.
Morphological and biochemical analysis of the secretory pathway in melanoma cells with distinct metastatic potential
Authors: Ayala Inmaculada , Babià Teresa , Baldassarre Massimiliano , Pompeo Arsenio , Fabra Angels , Willem Kok Jan , Luini Alberto , Buccione Roberto , Egea Gustavo
Published: July 2002

In this report, we have investigated whether alterations of the morphological and functional aspects of the biosecretory membrane system are associated with the metastatic potential of tumor cells. To this end, we have analyzed the morphology of the Golgi complex, the cytoskeleton organization and membrane trafficking steps of the secretory pathway in two human melanoma A375 cell line variants with low (A375‐P) and high metastatic (A375‐MM) potential. Immunofluorescence analysis showed that in A375‐P cells, the Golgi complex showed a collapsed morphology. Conversely, in A375‐MM cells, the Golgi complex presented a reticular and extended morphology. At the ultrastructural level, the Golgi complex of A375‐P cells was fragmented and cisternae were swollen. When the cytoskeleton was analyzed, the microtubular network appeared normal in both cell variants, whereas actin stress fibers were largely absent in A375‐P, but not in A375‐MM cells. In addition, the F‐actin content in A375‐P cells was significantly lower than in A375‐MM cells. These morphological differences in A375‐P cells were accompanied by acceleration and an increase in the endoplasmic reticulum to Golgi and the trans‐Golgi network to cell surface membrane transport, respectively. Our results indicate that in human A375 melanoma cells, metastatic potential correlates with a well‐structured morphofunctional organization of the Golgi complex and actin cytoskeleton.
Activation of matrix metalloproteinase‐2 in human breast cancer cells overexpressing cyclooxygenase‐1 or ‐2
Authors: Takahashi Yoshitaka , Kawahara Futoshi , Noguchi Masakuni , Miwa Koichi , Sato Hiroshi , Seiki Motoharu , Inoue Hiroyasu , Tanabe Tadashi , Yoshimoto Tanihiro
Published: July 2002

Human breast cancer cell line Hs578T was stably transfected with cDNA for cyclooxygenase‐1 or ‐2. When the cells overexpressing cyclooxygenase‐1 or ‐2 were stimulated with concanavalin A, the processing of matrix metalloproteinase‐2 was observed with the aid of gelatin zymography. This processing was not seen in mock‐transfected and original cells which did not express detectable cyclooxygenase activity. Furthermore, Northern blotting showed 8–13 fold induction of membrane‐type 1 matrix metalloproteinase which processed matrix metalloproteinase‐2 in the cells expressing cyclooxygenases. These findings suggest that both isoforms of cyclooxygenase mediate the processing of matrix metalloproteinase‐2 through induction of membrane‐type 1 metalloproteinase in breast cancer cells.
Substrate specificity determinants of the checkpoint protein kinase Chk1
Authors: Hutchins James R.A. , Hughes Mike , Clarke Paul R.
Published: July 2002

The Chk1 protein kinase plays a critical role in a DNA damage checkpoint pathway conserved between fission yeast and animals. We have developed a quantitative assay for Chk1 activity, using a peptide derived from a region of Xenopus Cdc25C containing Ser‐287, a known target of Chk1. Variants of this peptide were used to determine the residues involved in substrate recognition by Chk1, revealing the phosphorylation motif Φ‐X‐β‐X‐X‐(S/T)*, where * indicates the phosphorylated residue, Φ is a hydrophobic residue (M>I>L>V), β is a basic residue (R>K) and X is any amino acid. This motif suggests that Chk1 is a member of a group of stress‐response protein kinases which phosphorylate target proteins with related specificities.
Quality management re‐visited: a reflective review and agenda for future research
Authors: Sousa Rui , Voss Christopher A
Published: July 2002

Quality management (QM) has become an all‐pervasive management philosophy, finding its way into most sectors of today’s business society. After the initial hype and enthusiasm, it is time to take stock of the knowledge accumulated in what is now a mature field of study and look for directions to take the field further forward. This article reflects on the mass of literature in the field, synthesizing, organizing and structuring knowledge and offering suggestions for future research. It reviews QM research organized along five main themes: the definition of QM, the definition of product quality, the impact of QM on firm performance, QM in the context of management theory and the implementation of QM. The article draws on these themes to reflect on three questions which are fundamental to re‐visit and re‐appraise QM: (i) What is QM? (ii) Is the set of practices associated with QM valid as a whole? (iii) How to implement QM in a real business setting?
Neuronal changes in the basolateral complex during development of the amygdala of the rat
Authors: Berdel Bożena , Moryś Janusz , Maciejewska Beata
Published: July 2002

Neuronal changes in the amygdala basolateral complex were studied during development and maturation in fetal and postnatal rat brains using morphometrical methods. Forty brains of animals of various ages were fixed in formalin, frozen and cut into 25 μm thick sections and stained with cresyl violet or haematoxylin and eosin (H&E). In cresyl violet preparations, the complex appeared for the first time on embryonic day (E)17 and was composed of two homogeneous nuclei—lateral and basolateral. On about the seventh postnatal day, each of these nuclei was divided into two parts—the first one into the dorsolateral and ventromedial and the second one into the anterior and posterior. Morphometric investigations showed a different increase of the neuronal and nuclear size in various parts of the basolateral complex up to postnatal day (P)14; after that time these parameters did not change significantly. The neuronal density and the total number of neurons stabilized at P7 in all parts of this complex, except for the dorsolateral part of the lateral nucleus in which a 30% decrease of the total number of cells was observed. From P14, in all nuclei under study, the total number of neurons did not change significantly.
Perceptions of the real and the ideal ward atmosphere among trainees and staff before and after the introduction of a new work rehabilitation model
Authors: Eklund M. , Hansson L.
Published: July 2002

Changes in the ward atmosphere of a psychiatric work rehabilitation unit were investigated. Both trainees and staff filled in the Community-Oriented Programs Environment Scale (COPES) before and after a new rehabilitation model was implemented. It was hypothesised that the levels of autonomy and practical orientation would increase from both the trainees’ and staff’s perspective concerning the real ward atmosphere and that the staff’s perceptions of an ideal ward atmosphere would change in the same way. The staff perceived an increased level of autonomy with respect to both the real ward atmosphere and to what constitutes an ideal ward atmosphere, which partly confirmed the hypotheses, but the level of practical orientation was stable. Concerning the staff’s estimate of an ideal ward atmosphere, further changes were an increased level of involvement and a decrease in spontaneity, which was not hypothesised, but was not in conflict with the philosophy behind the new model. From the trainee’s perspective there was no change of either autonomy or practical orientation. Instead, there was a decrease in personal problem orientation. Compared to an optimal profile, the ward atmosphere was beneficial, before as well as after implementation of the new programme. Differences were found between the staff and the trainees, but they were not large enough to separate the groups according to what is considered an optimal profile. The few changes found support earlier conclusions that the ward atmosphere is a stable phenomenon over time.
Personality traits in treated Wilson’s disease determined by means of the Karolinska Scales of Personality (KSP)
Authors: Portala K. , Westermark K. , Ekselius L. , von Knorring L.
Published: July 2002

Objective

The aim was to elucidate the personality traits of patients with treated Wilsonˈs disease (WD) in comparison to healthy volunteers.

Method

Twenty-five WD patients, ten females and 15 males, with a mean age of 35.2 ± 8.3 years completed the Karolinska Scales of Personality (KSP), a self-report inventory comprising 15 separate scales. The results were compared to a control series comprising 200 men and 200 women drawn from the general population.

Results

The patients with treated WD scored significantly lower than the healthy controls on aggressivity-hostility-related scales and the scale measuring Psychic Anxiety. Patients with predominantly hepatic symptoms had the lowest aggressivity-related scores and patients with predominantly neurological symptoms had the lowest Irritability, Guilt and Detachment scores and the highest Impulsiveness and Muscular Tension scores. Both groups scored low on the Somatic Anxiety scale.

Conclusion

The present results illustrate that patients with treated WD have significant deviations in personality traits, especially in aggressivity-hostility-related scales and Psychic Anxiety, compared to healthy controls when investigated by means of a self-report inventory, the KSP. The deviations were not related to age, age at onset or duration of the disease.
Does the January effect exist in high‐yield bond market?
Authors: Al‐Khazali Osamah M
Published: July 2002

Previous studies show that January returns in high‐yield bond (HYB) markets are usually large. While these results are ubiquitous, their validity depends on the robustness of statistical procedures used. Virtually every study of seasonal variation in HYB markets has used mean/variance analysis despite it being well documented that returns in HYB markets are nonnormally distributed. This study uses stochastic dominance comparisons to audit previous parametric tests of the January effect in HYB markets in the U.S. from 1926 to 1993. Results indicate that the January effect in HYB markets is robust and that previous findings are not an artifact deriving from violations of distributional assumptions.
Circulating exosomalmiR‐363‐5pinhibits lymph node metastasis by downregulatingPDGFBand serves as a potential noninvasive biomarker for breast cancer
Authors: Wang Xin , Qian Tianyi , Bao Siqi , Zhao Hengqiang , Chen Hongyan , Xing Zeyu , Li Yalun , Zhang Menglu , Meng Xiangzhi , Wang Changchang , Wang Jie , Gao Hongxia , Liu Jiaqi , Zhou Meng , Wang Xiang
Published: May 2021

Sentinel lymph node (LN) biopsy is currently the standard procedure for clinical LN‐negative breast cancer (BC) patients but it is prone to false‐negative results and complications. Thus, an accurate noninvasive approach for LN staging is urgently needed in clinical practice. Here, circulating exosomal microRNA (miRNA) expression profiles in peripheral blood from BC patients and age‐matched healthy women were obtained and analyzed. We identified an exosomal miRNA,miR‐363‐5p, that was significantly downregulated in exosomes from plasma of BC patients with LN metastasis which exhibited a consistent decreasing trend in tissue samples from multiple independent datasets. Plasma exosomalmiR‐363‐5pachieved high diagnostic performance in distinguishing LN‐positive patients from LN‐negative patients. The highmiR‐363‐5p expressionlevel was significantly correlated with improved overall survival. Functional assays demonstrated that exosomalmiR‐363‐5pmodulates platelet‐derived growth factor (PDGF) signaling activity by targeting PDGFB to inhibit cell proliferation and migration. Our study revealed, for the first time, plasma exosomalmiR‐363‐5pplays a tumor suppressor role in BC and has the potential for noninvasive LN staging and prognosis prediction of BC.
Crosstalk between hnRNP K and SET in ATRA‐induced differentiation in acute promyelocytic leukemia
Authors: Padovani Karina Stringhetta , Goto Renata Nishida , Fugio Lais Brigliadori , Garcia Cristiana Bernadelli , Alves Vani Maria , Brassesco Maria Sol , Greene Lewis Joel , Rego Eduardo Magalhães , Leopoldino Andréia Machado
Published: May 2021

HnRNP K protein is a heterogeneous nuclear ribonucleoprotein which has been proposed to be involved in the leukemogenesis of acute promyelocytic leukemia (APL), as well as in differentiation induced by all‐trans retinoic acid (ATRA). We previously demonstrated a connection between SET and hnRNP K function in head and neck squamous cell carcinoma (HNSCC) cells related to splicing processing. The objective of this study was to characterize the participation of hnRNP K and SET proteins in ATRA‐induced differentiation in APL. We observed higher (5‐ to 40‐fold) levels of hnRNP K and SET mRNA in APL patients at the diagnosis phase compared with induction and maintenance phases. hnRNP K knockdown using short‐hairpin RNA led to cell death in ATRA‐sensitive NB4 and resistant NB4‐R2 cells by apoptosis with SET cleavage. In addition, hnRNP K knockdown increased granulocytic differentiation in APL cells, mainly in NB4‐R2 with ATRA. hnRNP K knockdown had an effect similar to that of treatment with U0126 (an meiosis‐specific serine/threonine protein kinase/ERK inhibitor), mainly in NB4‐R2 cells. SET knockdown in APL cells revealed that apoptosis induction in cells with hnRNP K knockdown occurred by SET cleavage rather than by reduction in SET protein. Transplantation of NB4‐R2 cells into nude mice confirmed that arsenic trioxide (ATO) combined with U0126 has higher potential against tumor progression when compared to ATO. Therefore, hnRNP K/SET and ERK are potential therapeutic targets for both antineoplastic leukemia therapy and relapsed APL patients with ATRA resistance.
Representation of Skin Colors in Images of Patients With Lupus
Authors: Rana Amaad , Witt Abbey , Jones Heather , Mwanthi Muithi , Murray Jacob , Zickuhr Lisa
Published: May 2021

Objective

Lupus presents earlier and more severely among patients with skin of color (SOC), and this population experiences worse outcomes. Providers rely on medical education materials when developing skills to care for patients, yet these resources historically underrepresent patients with SOC and marginalize vulnerable populations. In this study, we investigated if this publication bias extends to images depicting patients with lupus.

Methods

We reviewed published images of patients with lupus from rheumatology, dermatology, and internal medicine textbooks and medical journals, SOC atlases, online image libraries, UpToDate, and Google Images. We selected materials published from 2014 to 2019 that were available through our university's online medical library. We used the search terms “lupus” and “lupus rash” to identify images. We rated the skin color in each image using the New Immigrant Survey Skin Color Scale and categorized them as light, medium, or dark. We compared the frequencies of published skin tones with chi‐square and odds ratio analyses.

Results

We assessed the skin tone of 1,417 images. The significant majority (56.4%) of the images represented light skin (χ2 = 490.14, P < 0.001). After SOC atlases, journals were the most inclusive of images depicting dark skin tones. The specialty of dermatology was most inclusive of medium and darker skin tones.

Conclusion

Published images of lupus underrepresent patients with SOC, which may limit providers' ability to deliver care to the patients who are at greatest risk for complications.
In the Dark About Physical Activity – Exploring Patient Perceptions of Physical Activity After Elective Total Knee Joint Replacement: A Qualitative Study
Authors: Hawke Lyndon J. , Taylor Nicholas F. , Dowsey Michelle M. , Choong Peter F. M. , Shields Nora
Published: May 2021

Objective

The study aimed to explore patient perceptions of and motivations for physical activity after total knee joint replacement.

Methods

Participants were purposively sampled after completing a public outpatient rehabilitation exercise group. Semistructured interviews were completed with 22 participants (mean age 70 years, 45% women) 6 to 12 months after total knee joint replacement. Interviews were audiotaped and transcribed verbatim. Themes were identified by an inductive and iterative process of data analysis.

Results

The main theme to emerge was participants were in the dark about physical activity. Participants were typically not familiar with physical activity guidelines and had difficulty distinguishing between low‐ and moderate‐intensity physical activity. Three subthemes were identified: 1) people prioritize participation in meaningful life situations after total knee joint replacement, 2) rehabilitation was perceived to not explicitly address moderate‐intensity physical activity levels, and 3) other health and social reasons replaced knee osteoarthritis as barriers to physical activity.

Conclusion

Limited understanding of physical activity recommendations, prioritization of participation in meaningful life situations, rehabilitation that was impairment focused, and other health and social reasons appeared to contribute to low levels of moderate‐intensity physical activity in adults after knee joint replacement. Addressing being in the dark about physical activity may be an important first step to increase the effectiveness of behavioral interventions designed to promote physical activity after total knee joint replacement.
Use of a Novel Electronic Auto‐Notification Process to Manage Transitions of Care in Patients With Rheumatic Disease Receiving Disease‐Modifying Antirheumatic Drug Therapy
Authors: Bielawski Megan , Newman Eric , Schroeder Lisa L.
Published: May 2021

Objective

To integrate an auto‐notification system into clinical workflow, so timely communication of sentinel events (elective surgery, hospital admission, or emergency room [ER] visit) in immunosuppressed patients with rheumatic disease happened by design.

Methods

We developed an algorithm that triggered auto‐notification within the electronic medical record to rheumatology when a patient experienced a sentinel event. A telephone encounter was created that included event type, baseline therapy, and event date. This was forwarded to the rheumatologist, who recorded guideline‐driven recommendations and returned it to nursing. Instructions were included to communicate recommendations to the patient, inpatient rheumatology team, or other clinician. This was studied over 4 months at a multispecialty medical practice in Central Pennsylvania. Primary outcomes were percentage of total notifications, notifications by sentinel event type where a change in care plan was recommended, as well as percentage of time where rheumatologists were notified of sentinel events compared to prior to the intervention. The secondary outcome was staff work effort.

Results

Two hundred forty notifications were received (57% for elective surgeries, 39% for ER visits, and 4% for admissions). The need for change in care plan was only 17% for ER visits but was 25% for hospital admissions and 44% for elective surgeries. The percentage of time that rheumatologists were notified of events increased from 57.6% to 100%. The average number of messages received per week was 2.2, requiring a weekly average of 13 minutes of work per physician.

Conclusion

We developed an easy, well‐received process that hardwires rheumatologist notification sentinel events to facilitate timely care.
Revealing the Various Electrochemical Behaviors of Sn4P3 Binary Alloy Anodes in Alkali Metal Ion Batteries
Authors: Zhou Junhua , Lian Xueyu , You Yizhou , Shi Qitao , Liu Yu , Yang Xiaoqin , Liu Lijun , Wang Dan , Choi Jin‐Ho , Sun Jingyu , Yang Ruizhi , Rummeli Mark H.
Published: May 2021

Sn4P3 binary alloy anode has attracted much attention, not only because of the synergistic effect of P and Sn, but also its universal popularity in alkali metal ion batteries (AIBs), including lithium‐ion batteries (LIBs), sodium‐ion batteries (SIBs), and potassium‐ion batteries (PIBs). However, the alkali metal ion (A+) storage and capacity attenuation mechanism of Sn4P3 anodes in AIBs are not well understood. Herein, a combination of ex situ X‐ray diffraction, transmission electron microscopy, and density functional theory calculations reveals that the Sn4P3 anode undergoes segregation of Sn and P, followed by the intercalation of A+ in P and then in Sn. In addition, differential electrochemical curves and ex situ XPS results demonstrate that the deep insertion of A+ in P and Sn, especially in P, contributes to the reduction in capacity of AIBs. Serious sodium metal dendrite growth causes further reduction in the capacity of SIBs, while in PIBs it is the unstable solid electrolyte interphase and sluggish dynamics that lead to capacity decay. Not only the failure mechanism, including structural deterioration, unstable SEI, dendrite growth, and sluggish kinetics, but also the modification strategy and systematic analysis method provide theoretical guidance for the development of other alloy‐based anode materials.
Sonosensitizer‐Functionalized Graphene Nanoribbons for Adhesion Blocking and Sonodynamic Ablation of Ovarian Cancer Spheroids
Authors: Lee Hak Rae , Kim Dae Woo , Jones Victoria O. , Choi Yunkyu , Ferry Vivian E. , Geller Melissa A. , Azarin Samira M.
Published: May 2021

Advanced stage ovarian cancer is challenging to treat due to widespread seeding of tumor spheroids throughout the mesothelial lining of the peritoneal cavity. In this work, a therapeutic strategy using graphene nanoribbons (GNR) functionalized with 4‐arm polyethylene glycol (PEG) and chlorin e6 (Ce6), a sonosensitizer, to target metastatic ovarian cancer spheroids is reported. GNR‐PEG‐Ce6 adsorbs onto the spheroids and disrupts their adhesion to extracellular matrix proteins or LP‐9 mesothelial cells. Furthermore, for spheroids that do adhere, GNR‐PEG‐Ce6 delays spheroid disaggregation and spreading as well as mesothelial clearance, key metastatic processes following adhesion. Owing to the sonodynamic effects of Ce6 and its localized delivery via the biomaterial, GNR‐PEG‐Ce6 can kill ovarian cancer spheroids adhered to LP‐9 cell monolayers when combined with mild ultrasound irradiation. The interaction with GNR‐PEG‐Ce6 also loosens cell–cell adhesions within the spheroids, rendering them more susceptible to treatment with the chemotherapeutic agents cisplatin and paclitaxel, which typically have difficulty in penetrating ovarian cancer spheroids. Thus, this material can facilitate effective chemotherapeutic and sonodynamic combination therapies. Finally, the adhesion inhibiting and sonodynamic effects of GNR‐PEG‐Ce6 are also validated with tumor spheroids derived from the ascites fluid of ovarian cancer patients, providing evidence of the translational potential of this biomaterial approach.
Modulation of Gastrointestinal Mucus Properties with Ionic Liquids for Drug Delivery
Authors: Peng Kevin , Gao Yongsheng , Angsantikul Pavimol , LaBarbiera Anthony , Goetz Morgan , Curreri Alexander M. , Rodrigues Danika , Tanner Eden E. L. , Mitragotri Samir
Published: May 2021

The mucus barrier lining the gastrointestinal tract poses a significant barrier to the oral delivery of macromolecular drugs. Successful approaches to overcoming this barrier have primarily focused on reducing drug and carrier interactions with mucus or disrupting the mucus layer directly. Choline‐based ionic liquids (ILs) such as choline geranate and choline glycolate (CGLY) have recently been shown to be effective in enhancing the intestinal absorption of macromolecules such as insulin and immunoglobulin (IgG), respectively. Herein, the use of choline‐based ILs as mucus‐modulating agents for safely improving drug penetration through mucus is described. Choline‐based ILs significantly increase the diffusion rates of cationic dextrans through mucin solution. Choline‐maleic acid (CMLC 2:1) enhances the diffusion of 4 kDa cationic dextran in mucin solution by more than fourfold when compared to phosphate‐buffered saline control. Choline‐based ILs also reduce mucus viscosity without significantly impacting the native mucus gel structure. In vitro studies in a mucus‐secreting coculture model with Caco‐2 and HT29MTX‐E12 cells further demonstrate the effectiveness of ILs in improving transport of cationic molecules in the presence of secreted mucus. This work demonstrates the potential for choline‐based ionic liquids to be used as nondestructive mucus‐modulating agents for enabling enhanced oral delivery of macromolecular drugs.
Enhanced Antitumor Efficacy through an “AND gate” Reactive Oxygen‐Species‐Dependent pH‐Responsive Nanomedicine Approach
Authors: Jäger Eliézer , Humajová Jana , Dölen Yusuf , Kučka Jan , Jäger Alessandro , Konefał Rafał , Pankrác Jan , Pavlova Ewa , Heizer Tomáš , Šefc Luděk , Hrubý Martin , Figdor Carl G. , Verdoes Martijn
Published: May 2021

Anticancer drug delivery strategies are designed to take advantage of the differential chemical environment in solid tumors independently, or to high levels of reactive oxygen species (ROS) or to low pH, compared to healthy tissue. Here, the design and thorough characterization of two functionalizable “AND gate” multiresponsive (MR) block amphiphilic copolymers are reported, aimed to take full advantage of the coexistence of two chemical cues—ROS and low pH—present in the tumor microenvironment. The hydrophobic blocks contain masked pH‐responsive side chains, which are exposed exclusively in response to ROS. Hence, the hydrophobic polymer side chains will undergo a charge shift in a very relevant pH window present in the extracellular milieu in most solid tumors (pH 5.6–7.2) after demasking by ROS. Doxorubicin (DOX)‐loaded nanosized “AND gate” MR polymersomes (MRPs) are fabricated via microfluidic self‐assembly. Chemical characterization reveals ROS‐dependent pH sensitivity and accelerated DOX release under influence of both ROS and low pH. Treatment of tumor‐bearing mice with DOX‐loaded nonresponsive and “AND gate” MRPs dramatically decreases cardiac toxicity. The most optimal “AND gate” MRPs outperform free DOX in terms of tumor growth inhibition and survival, shedding light on chemical requirements for successful cancer nanomedicine.
Active Control of Nanodielectric‐Induced THz Quasi‐BIC in Flexible Metasurfaces: A Platform for Modulation and Sensing
Authors: Tan Thomas CaiWei , Srivastava Yogesh Kumar , Ako Rajour Tanyi , Wang Wenhao , Bhaskaran Madhu , Sriram Sharath , Al‐Naib Ibraheem , Plum Eric , Singh Ranjan
Published: May 2021

A bound state in the continuum (BIC) is a nonradiating state of light embedded in the continuum of propagating modes providing drastic enhancement of the electromagnetic field and its localization at micro–nanoscale. However, access to such modes in the far‐field requires symmetry breaking. Here, it is demonstrated that a nanometric dielectric or semiconductor layer, 1000 times thinner than the resonant wavelength (λ/1000), induces a dynamically controllable quasi‐bound state in the continuum (QBIC) with ultrahigh quality factor in a symmetric metallic metasurface at terahertz frequencies. Photoexcitation of nanostrips of germanium activates ultrafast switching of a QBIC resonance with 200% transmission intensity modulation and complete recovery within 7 ps on a low‐loss flexible substrate. The nanostrips also form microchannels that provide an opportunity for BIC‐based refractive index sensing. An optimization model is presented for (switchable) QBIC resonances of metamaterial arrays of planar symmetric resonators modified with any (active) dielectric for inverse metamaterial design that can serve as an enabling platform for active micro–nanophotonic devices.
Boosting CO2 Electroreduction via the Synergistic Effect of Tuning Cationic Clusters and Visible‐Light Irradiation
Authors: Zhou Yue , Zheng Lirong , Yang Deren , Yang Haozhou , Wang Xun
Published: May 2021

Introducing an external light field can increase the intrinsic activity and energy efficiency for electrochemical CO2 reduction. Herein, a synergistic strategy that introduces photosensitive components and visible light into a stable system is reported to improve the performance for CO2 reduction. The catalytic kinetics studies indicate that the synergistic effect of implantation of cationic Ti and additional light driving is the primary responsibility for accelerating the first electron transfer to form a *COO− intermediate. This leads to a satisfactory CO2‐to‐CO conversion for Zr/Ti‐NB‐Co in terms of high selectivity (Faradaic efficiency of 93.6% at −0.7 V), remarkable catalytic activity (production rate up to 546 mmol g−1 h−1 at −1.1 V), excellent long‐term stability (without performance decay over 11 h), and large turnover frequency of 1028 h−1 at −1.1 V under visible light. These results imply that the photodriven Ti‐based porphyrin catalyst not only can deliver more electrons, but also can act as a photoswitch to adjust the electron transfer pathway.
Formation of Multiple‐Helical Core‐Shell Structure from Polyphenyl and Boron Nitride Nanotube
Authors: Yang Houbo , Zhang Danhui , Liang Ruquan , Liu Zhongkui , Song Yuanmei , Yang Liu , Liu Anmin
Published: May 2021

In this manuscript, a multiple‐helical core‐shell structure is studied from polyphenyl and boron nitride nanotube (BNNT) through the molecular dynamics simulation. The results exhibited that polyphenyl is constrained in the inside of BNNT and self‐coiled to a helical configuration. In these systems, both the van der Waals potential well and the π–π stacking interaction between the polyphenyl and BNNT play a key role in the formation of helical nanostructures. The final configuration of composites can be influenced by many factors such as the diameter of BNNT, the chain number of polymer, the length of polymer, and the simulation temperature which are investigated in detail. This theory research about polyphenyl and BNNT may supply more theoretical foundation in chemical functionalization and helical polymer synthesis, which can be helpful for fabricating nanoscale devices.
OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis
Authors: Gong Zhicheng , Li Aicun , Ding Jiancheng , Li Qing , Zhang Lei , Li Yuanpei , Meng Zhe , Chen Fei , Huang Jialiang , Zhou Dawang , Hu Ronggui , Ye Jing , Liu Wen , You Han
Published: May 2021

Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis is poorly understood. Lysine‐specific demethylase 1 (LSD1) is known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms by which cells maintain LSD1/CoREST complex integrity are unknown. Here, it is reported that LSD1 protein undergoes K63‐linked polyubiquitination. OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63‐linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62‐mediated proteolysis. Consequently, OTUD7B deficiency impairs genome‐wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis. Moreover, physiological fluctuation of OTUD7B modulates cell cycle‐dependent LSD1 oscillation, ensuring the G1/S transition. Both OTUD7B and LSD1 proteins are overpresented in high‐grade or metastatic human breast cancer, while dysregulation of either protein is associated with poor survival and metastasis. Thus, OTUD7B plays a unique partner‐switching role in maintaining the integrity of LSD1/CoREST corepressor complex, LSD1 turnover, and breast cancer metastasis.
Boosting Formate Production from CO2 at High Current Densities Over a Wide Electrochemical Potential Window on a SnS Catalyst
Authors: Zou Jinshuo , Lee Chong‐Yong , Wallace Gordon G.
Published: May 2021

The flow‐cell design offers prospect for transition to commercial‐relevant high current density CO2 electrolysis. However, it remains to understand the fundamental interplay between the catalyst, and the electrolyte in such configuration toward CO2 reduction performance. Herein, the dramatic influence of electrolyte alkalinity in widening potential window for CO2 electroreduction in a flow‐cell system based on SnS nanosheets is reported. The optimized SnS catalyst operated in 1 m KOH achieves a maximum formate Faradaic efficiency of 88 ± 2% at −1.3 V vs reversible hydrogen electrode (RHE) with the current density of ≈120 mA cm−2. Alkaline electrolyte is found suppressing the hydrogen evolution across all potentials which is particularly dominant at the less negative potentials, as well as CO evolution at more negative potentials. This in turn widens the potential window for formate conversion (>70% across −0.5 to −1.5 V vs RHE). A comparative study to SnOx counterpart indicates sulfur also acts to suppress hydrogen evolution, although electrolyte alkalinity resulting in a greater suppression. The boosting of the electrochemical potential window, along with high current densities in SnS derived catalytic system offers a highly attractive and promising route toward industrial‐relevant electrocatalytic production of formate from CO2.
Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination
Authors: Peng Haoyang , Zhang Simin , Peng Yihan , Zhu Shuangyi , Zhao Xin , Zhao Xiaocong , Yang Shuangshuang , Liu Guangxue , Dong Yang , Gan Xiaoli , Li Qing , Zhang Xinghua , Pei Huadong , Chen Xuefeng
Published: May 2021

Histone acetylation is a key histone post‐translational modification that shapes chromatin structure, dynamics, and function. Bromodomain (BRD) proteins, the readers of acetyl‐lysines, are located in the center of the histone acetylation‐signaling network. How they regulate DNA repair and genome stability remains poorly understood. Here, a conserved function of the yeast Bromodomain Factor 1 (Bdf1) and its human counterpart TAF1 is reported in promoting DNA double‐stranded break repair by homologous recombination (HR). Depletion of either yeast BDF1 or human TAF1, or disruption of their BRDs impairs DNA end resection, Replication Protein A (RPA) and Rad51 loading, and HR repair, causing genome instability and hypersensitivity to DNA damage. Mechanistically, it is shown that Bdf1 preferentially binds the DNA damage‐induced histone H4 acetylation (H4Ac) via the BRD motifs, leading to its chromatin recruitment. Meanwhile, Bdf1 physically interacts with RPA, and this interaction facilitates RPA loading in the chromatin context and the subsequent HR repair. Similarly, TAF1 also interacts with H4Ac or RPA. Thus, Bdf1 and TAF1 appear to share a conserved mechanism in linking the HR repair to chromatin acetylation in preserving genome integrity.
Ternary 2D Layered Material FePSe3 and Near‐Infrared Photodetector
Authors: Xu Tengfei , Luo Man , Shen Niming , Yu Yiye , Wang Zhen , Cui Zhuangzhuang , Qin Jiayi , Liang Fang , Chen Yunfeng , Zhou Yong , Zhong Fang , Peng Meng , Zubair Muhammad , Li Ning , Miao Jinshui , Lu Wei , Yu Chenhui , Hu Weida
Published: May 2021

The preparation of ternary 2D layered material (2DLM) FePSe3 and field‐effect transistor (FET) type photodetector are investigated. By advancing an optimized chemical vapor transport method, bulk crystal FePSe3 is synthesized within several growth hours instead of routinely required weeks, from which 2DLM FePSe3 flakes with a thickness of ≈22.0 nm and high crystalline quality are obtained through mechanical exfoliation. Ohmic contacts for FET structure with good linear conductivity and thermal stability are implemented through the combination of electron‐beam lithography and thermal evaporation techniques. Transfer characteristics prove the p‐type conductivity of the 2DLM FePSe3 channel. The transistor devices exhibit good performance at 637 nm with a detectivity of 1.17 × 107 Jones. More importantly, a wide photocurrent spectrum from visible (450 nm) to near‐infrared (940 nm) of ternary 2DLMs is observed, which is attributed to the improvement of crystal quality of 2DLM, relatively low surface defect states, and high‐performance Ohmic electrodes. This work promotes the development of ternary 2DLM and photodetector that are still in their infancy towards continuous broad‐spectrum technology.
Smartphone‐based estimation of green cover depends on the camera used
Authors: Heinonen Reija , Mattila Tuomas J.
Published: May 2021

Smartphone‐based visual assessment of vegetation cover is a promising, fast, and repeatable approach that allows land managers to compare measurements on their farm with other farms. This study determined the influence of the smartphone device on green cover measurements on several crops. The hypothesis was that different smartphones would provide similar green cover (reflectance) for management purposes (i.e., <10% difference). Forty fields in Finland were sampled between 10 and 28 July 2020 with Motorola Moto G7 and Samsung Galaxy A6 smartphones. The results were compared also with Sentinel‐2 remote sensing of normalized difference vegetation index (NDVI) and biomass quadrants. The two smartphones had different green reflectance values that were correlated to each other. Both green reflectance measurements correlated with the NDVI that was measured with the Sentinel 2 satellite sensor and biomass. These findings suggest that smartphone‐based monitoring can be used at least to classify vegetation to low, medium, and high density but that results from different cameras should not be compared.
Adverse events reported to the U.S. Food and Drug Administration Adverse Event Reporting System for tisagenlecleucel
Authors: Dores Graça M. , Jason Christopher , Niu Manette T. , Perez‐Vilar Silvia
Published: May 2021

The U.S. Food and Drug Administration (FDA) approved the first chimeric antigen receptor T‐cell therapy, tisagenlecleucel, in August 2017. We sought to describe adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS) for tisagenlecleucel in the post‐marketing period. We searched FAERS reports to identify U.S. patients treated with tisagenlecleucel between August 30, 2017‐August 31, 2019. We reviewed individual reports, calculated AE frequencies and reporting rates (RRs), and used Empirical Bayesian Geometric Mean methods to identify disproportionate reporting. We identified 646 de‐duplicated reports with a median age at AE of 18 (interquartile range: 11–56) years. The overall RR was 81.0%, and more than 95% of reports described a serious outcome. Cytokine release syndrome (CRS) was the most frequently reported AE (51.1%) with a RR of 41.4%; neurotoxicity was reported less frequently (21.2%), with a RR of 17.2%. Most disproportionately reported AEs were listed on the package insert or confounded by indication. We identified 13 subsequent neoplasms (SPN), the majority occurring within 6 months of tisagenlecleucel administration, and none reporting evidence of insertional mutagenesis. A total of 165 reports (26%) described a death outcome; most deaths occurred >30 days after treatment. The majority of deaths (64%) were due to progression of the underlying lymphoid neoplasm, and few (<5%) were attributed to CRS or neurotoxicity. We did not identify new safety concerns reported for tisagenlecleucel in the post‐marketing period. Reporting rates for CRS and neurotoxicity were lower than identified in the prelicensure clinical trials.