bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon resistance of cutaneous T-cell lymphoma–derived clonal T-helper 2 cells allows selective viral replication
Authors: Dummer Reinhard , Döbbeling Udo , Geertsen Ralf , Willers Jörg , Burg Günter , Pavlovic Jovan
Published: July 2002

Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of lymphoproliferative disorders that are characterized by an accumulation of T-lymphocytes in the skin and occasionally in blood known as Sézary syndrome (SS). In most cases the dominant clone displays T-helper 2 cytokines. Because IFN-γ is a natural inhibitor of T-helper 2 cells and IFN-α is frequently used in CTCL, the impact of IFNs on SS-derived purified clonal T-helper 2 cells was studied using anti-Vβ antibodies. Moreover, IFNs are known to mediate virus resistance in normal cells. The isolated clonal CD4+ cells, but not the nonclonal CD4+ cells, appeared resistant to IFN-γ and IFN-α stimulation in terms of human leukocyte antigen up-regulation and MxA induction caused in part by alterations in Stat-1 molecule mRNA and IFNγR1 mRNA transcription. The IFN resistance of the patient-derived clonal cells was then targeted by vesicular stomatitis virus infection after IFN-α priming, resulting in selective viral replication in clonal cells. In contrast, nonclonal cells of the same patient showed IFN-dependent MxA expression, which is a major mediator protein of viral protection. The IFN resistance of the dominant T-helper 2 cells might be important for lymphomagenesis. Interferon signaling deficiencies can be targeted for purging patients' cells in vitro. Furthermore, this approach may allow specific molecular interventions, resulting in the efficient treatment of CTCL and other IFN-resistant neoplasms such as lung cancer.
The effect of multidrug-resistance 1 gene versus neotransduction on ex vivo and in vivo expansion of rhesus macaque hematopoietic repopulating cells
Authors: Sellers Stephanie E. , Tisdale John F. , Agricola Brian A. , Metzger Mark E. , Donahue Robert E. , Dunbar Cynthia E. , Sorrentino Brian P.
Published: July 2002

Transduction of murine stem cells with a multidrug-resistance 1 gene (MDR1) retrovirus results in dramatic ex vivo and in vivo expansion of repopulating cells accompanied by a myeloproliferative disorder. Given the use ofMDR1-containing vectors in human trials, investigations have been extended to nonhuman primates. Peripheral blood stem cells from 2 rhesus monkeys were collected, CD34-enriched, split into 2 portions, and transduced with eitherMDR1 vectors or neo vectors and continued in culture for a total of 10 days before reinfusion. At engraftment, the copy number in granulocytes was extremely high from bothMDR vectors and neo vectors, but the copy number fell to 0.01 to 0.05 for both. There were no perturbations of the leukocyte count or differential noted. After 3 cycles of stem cell factor/granulocyte colony-stimulating factor, there were no changes in the levels of MDR1 vector– or neovector–containing cells. There was no evidence for expansion ofMDR1 vector–transduced cells. Long-term engraftment with MDR1 vector– and neo vector–transduced cells occurred despite prolonged culture.
Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function
Authors: Müller-Tidow Carsten , Wang Wenbing , Idos Gregory E. , Diederichs Sven , Yang Rong , Readhead Carol , Berdel Wolfgang E. , Serve Hubert , Saville Mark , Watson Roger , Koeffler H. Phillip
Published: July 2002

Cyclin A1 is tissue-specifically expressed during spermatogenesis, but it is also highly expressed in acute myeloid leukemia (AML). Its pathogenetic role in AML and in the cell cycle of leukemic blasts is unknown. B-myb is essential for G1/S transition and has been shown to be phosphorylated by the cyclin A2/cdk2 complex. Here it is demonstrated that cyclin A1 interacts with the C-terminal portion of B-myb as shown by glutathione S-transferase (GST) precipitation. This interaction is confined to cyclin A1 because binding could not be detected between cyclin A2 and B-myb. Also, cdk2 was not pulled down by GST–B-myb from U937 lysates. In addition, co-immunoprecipitation of cyclin A1 and B-myb in leukemic cells evidenced protein interaction in vivo. Baculovirus-expressed cyclin A1/cdk2 complexes were able to phosphorylate human as well as murine B-myb in vitro. Tryptic phosphopeptide mapping revealed that cyclin A1/cdk2 complexes phosphorylated the C-terminal part of B-myb at several sites including threonine 447, 490, and 497 and serine 581. These phosphorylation sites have been demonstrated to be important for the enhancement of B-myb transcriptional activity. Further studies showed that cyclin A1 cooperated with B-myb to transactivate myb binding site containing promoters including the promoter of the human cyclin A1 gene. Taken together, the data suggest that cyclin A1 is a tissue-specific regulator of B-myb function and activates B-myb in leukemic blasts.
Repression of ferritin expression increases the labile iron pool, oxidative stress, and short-term growth of human erythroleukemia cells
Authors: Kakhlon Or , Gruenbaum Yosef , Cabantchik Zvi Ioav
Published: July 2002

The role of ferritin expression on the labile iron pool of cells and its implications for the control of cell proliferation were assessed. Antisense oligodeoxynucleotides were used as tools for modulating the expression of heavy and light ferritin subunits of K562 cells. mRNA and protein levels of each subunit were markedly reduced by 2-day treatment with antisense probes against the respective subunit. Although the combined action of antisense probes against both subunits reduced their protein expression, antisense repression of one subunit led to an increased protein expression of the other. Antisense treatment led to a rise in the steady-state labile iron pool, a rise in the production of reactive oxygen species after pro-oxidative challenges and in protein oxidation, and the down-regulation of transferrin receptors. When compared to the repression of individual subunits, co-repression of each subunit evoked a more than additive increase in the labile iron pool and the extent of protein oxidation. These treatments had no detectable effects on the long-term growth of cells. However, repression of ferritin synthesis facilitated the renewal of growth and the proliferation of cells pre-arrested at the G1/S phase. Renewed cell growth was significantly less dependent on external iron supply when ferritin synthesis was repressed and its degradation inhibited by lysosomal antiproteases. This study provides experimental evidence that links the effect of ferritin repression on growth stimulation to the expansion of the labile iron pool.
Ineffective erythropoiesis in Stat5a−/−5b−/− mice due to decreased survival of early erythroblasts
Authors: Socolovsky Merav , Nam Hyung-song , Fleming Mark D. , Haase Volker H. , Brugnara Carlo , Lodish Harvey F.
Published: July 2002

Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.
ALCAM (CD166): its role in hematopoietic and endothelial development
Authors: Ohneda Osamu , Ohneda Kinuko , Arai Fumio , Lee James , Miyamoto Takeshi , Fukushima Yoshimi , Dowbenko Donald , Lasky Laurence A. , Suda Toshio
Published: July 2002

A critical role for the endothelium of yolk sac and dorsal aorta has been shown in embryonic hematopoiesis. A stromal cell line derived from yolk sac, YSCL-72, has been chosen to search for a novel molecule associated with embryonic hematopoiesis. Analysis between YSCL-72 and an adult aorta-derived endothelial cell line, EOMA, demonstrated that activated leukocyte cell adhesion molecule (ALCAM, or CD166) was specifically expressed in YSCL-72 but not in EOMA. Immunohistochemical study showed that ALCAM was expressed in the endothelium of yolk sac and dorsal aorta but not in adult aorta. ALCAM-transfected EOMA cells supported development of hematopoietic progenitor cells compared with vector-transfected EOMA cells, suggesting that ALCAM appeared to be crucial for hematopoiesis. In addition, ALCAM was found to be involved in capillary tube formation and hemangioblast differentiation. Taken together with these findings, ALCAM is highly associated not only with embryonic hematopoiesis but also vasculoangiogenesis.
Identification of the human erythropoietin receptor region required for Stat1 and Stat3 activation
Authors: Kirito Keita , Nakajima Koichi , Watanabe Tomoko , Uchida Mie , Tanaka Masaru , Ozawa Keiya , Komatsu Norio
Published: July 2002

Signal transducers and activators of transcription (Stat) proteins play important roles in the regulation of hematopoiesis as downstream molecules of cytokine signal transduction. It was previously demonstrated that erythropoietin (EPO), a major regulator of erythropoiesis, activates 3 different Stat members, Stat1, Stat3, and Stat5, in a human EPO-dependent cell line, UT-7/EPO. To clarify the mechanism by which EPO activates Stat1 and Stat3 via the EPO receptor (EPOR), a series of chimeric receptors was constructed bearing the extracellular domain of the granulocyte colony-stimulating factor receptor linked to the transmembrane domain of EPOR and the full length or several mutants of the cytoplasmic domain of EPOR, and these chimeric receptor complementary DNAs were introduced into UT-7/EPO cells. Tyr432 on human EPOR was important for activation of Stat1 and Stat3 and c-myc gene induction. In addition, Jak2 and Fes tyrosine kinases were involved in EPO-induced activation of Stat1 and Stat3. These results indicate that Stat1 and Stat3 are activated by EPO via distinct mechanisms from Stat5.
Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria
Authors: Horikawa Kentaro , Kawaguchi Tatsuya , Ishihara Sonoko , Nagakura Shoichi , Hidaka Michihiro , Kagimoto Tadashi , Mitsuya Hiroaki , Nakakuma Hideki
Published: July 2002

Acquired mutations of the PIG-A gene result in the hemolysis characteristic of paroxysmal nocturnal hemoglobinuria (PNH). Although the etiology of the mutation(s) is unclear, mutable conditions have been suggested by the coexistence of multiple clones with different mutations of PIG-A and by the appearance of leukemic clones in patients with PNH. This study sought to test this hypothesis by examining the frequency of hypoxanthine-guanine phosphoribosyl transferase (HPRT)gene mutations, identified by both resistance to 6-thioguanine (6-TG) and gene analysis. T-cell colonies resistant to 6-TG formed in methylcellulose culture were found in 8 (67%) of 12 PNH patients and 3 (18%) of 17 age-matched healthy volunteers (P < .02, Fisher exact probability test). The incidence of resistant colonies ranged from 40 to 367 (mean 149, × 10−7) in the 8 patients and from 1 to 16 (mean 7, × 10−7) in the 3 healthy donors. Thus, theHRPT gene mutated more frequently in patients with PNH than in healthy controls (P < .02, Mann-Whitney test). Analysis of bone marrow cells supported these findings. Like the PIG-A mutations in PNH, the HPRT mutations were widely distributed in the coding regions and consisted primarily of base deletions. Unlike PNH cells, 6-TG–resistant cells expressed CD59, indicating that the HPRT mutations did not occur in PNH clones. No correlation was noted between HPRT mutation frequency and content of therapy received by the patients. It is concluded that in PNH patients, conditions exist that favor the occurrence of diverse somatic mutations in blood cells.
Use of blood outgrowth endothelial cells for gene therapy for hemophilia A
Authors: Lin Yi , Chang Liming , Solovey Anna , Healey John F. , Lollar Pete , Hebbel Robert P.
Published: July 2002

A culture of human blood outgrowth endothelial cells (BOECs) was established from a sample of peripheral blood and was transfected using a nonviral plasmid carrying complementary DNA for modified human coagulation factor VIII (B domain deleted and replaced with green fluorescence protein). BOECs were then chemically selected, expanded, cryopreserved, and re-expanded in culture. Stably transfected BOECs were administered intravenously daily for 3 days to NOD/SCID mice at 4 cell dose levels (from 5 × 104 to 40 × 104 cells per injection). In 156 days of observation, mice showed levels of human FVIII that increased with cell dose and time. Mice in all cell dose groups achieved therapeutic levels (more than 10 ng/mL) of human FVIII, and mice in the 3 highest dose groups acquired levels that were normal (100-200 ng/mL) or even above the normal range (highest observed value, 1174 ng/mL). These levels indicate that the BOECs expanded in vivo after administration. When the mice were killed, it was found that BOEC accumulated only in bone marrow and spleen and that these cells retained endothelial phenotype and transgene expression. Cell doses used here would make scale-up to humans feasible. Thus, the use of engineered autologous BOECs, which here resulted in sustained and therapeutic levels of FVIII, may comprise an effective therapeutic strategy for use in gene therapy for hemophilia A.
Identification of the earliest prethymic bipotent T/NK progenitor in murine fetal liver
Authors: Douagi Iyadh , Colucci Francesco , Di Santo James P. , Cumano Ana
Published: July 2002

This article describes the isolation of a novel cell population (B220loc-kit+CD19−) in the fetal liver that represents 70% of T-cell precursors in this organ. Interestingly, these precursors showed a bipotent T-cell and natural killer cell (NK)– restricted reconstitution potential but completely lacked B and erythromyeloid differentiation capacity both in vivo and in vitro. Moreover, not only mature T-cell receptor (TCR)αβ+ peripheral T cells but also TCRγδ+ and TCRαβ+CD8αα+ intestinal epithelial cells of extrathymic origin were generated in reconstituted mice. The presence of this population in the fetal liver of athymic embryos indicates its prethymic origin. The comparison of the phenotype and differentiation potential of B220loc-kit+CD19−fetal liver cells with those of thymic T/NK progenitors indicates that this is the most immature common T/NK cell progenitor so far identified. These fetal liver progenitors may represent the immediate developmental step before thymic immigration.
Cultivation of aorta-gonad-mesonephros–derived hematopoietic stem cells in the fetal liver microenvironment amplifies long-term repopulating activity and enhances engraftment to the bone marrow
Authors: Takeuchi Masaki , Sekiguchi Takashi , Hara Takahiko , Kinoshita Taisei , Miyajima Atsushi
Published: July 2002

During mammalian development, definitive hematopoietic stem cells (HSCs) arise in the aorta-gonad-mesonephros (AGM) region and colonize the fetal liver (FL) before hematopoiesis occurs in the bone marrow. The FL is a unique hematopoietic organ where both HSCs and mature blood cells are actively generated along with functional maturation of hepatic cells as a metabolic organ. To characterize HSCs and FL microenvironments during development, this study establishes a coculture system composed of AGM-originated HSCs and FL nonhematopoietic cells. The results demonstrate that FL cells support significant expansion of lineage-committed hematopoietic cells as well as immature progenitors. More important, long-term repopulating activity was amplified from AGM-originated HSCs in this coculture system. Engraftment of HSCs to the bone marrow was strongly enhanced by coculture. In addition, AGM HSCs produced significantly more hematopoietic cells than E14.5 and E18.5 FL HSCs in vitro. These results suggest that the FL microenvironment not only stimulates expansion of the hematopoietic system, but also possibly modifies the characteristics of AGM HSCs. Thus, this coculture system recapitulates the developmental process of HSCs and the FL microenvironment and provides a novel means to study the development of hematopoiesis.
Handbook of Pediatric Emergencies, Third Edition
Authors: Clem Kathleen
Published: July 2002

By Gregory A. Baldwin. Baltimore, MD: Lippincott Williams & Wilkins, 2000, 736 pp, $39.95 (softcover).
Mission‐based Budgeting Hours Model: An Accurate Way to Understand Physician Costs
Authors: Decker M. Chris , DeBehnke Daniel J.
Published: July 2002

Financial resources to manage academic emergency departments are becoming more scarce. The Association of American Medical Colleges (AAMC) has embraced mission‐based management (MBM) as one viable option to allocate financial and personnel resources based on medical school goals. The key features of this style are integrating financial statements, measuring faculty activity, holding service line leaders accountable, and building a trust through information sharing. The authors describe how they integrated their service line cost through an hours model. From this they describe a formula for calculating the cost of protected time. The authors use mission‐based budgeting to more accurately understand their physician costs and use the formula to effectively negotiate internal and external contracts.
Prognostic Significance of the Number of Axillary Lymph Nodes Removed in Patients With Node-Negative Breast Cancer
Authors: Weir L. , Speers C. , D’yachkova Y. , Olivotto I. A.
Published: July 2002

PURPOSE: The objective of the study was to evaluate the association between the number of lymph nodes removed at axillary dissection and recurrence and survival for patients with node-negative invasive breast cancer.

PATIENTS AND METHODS: Subjects were 2,278 women with pathologically node-negative invasive breast cancer, diagnosed from 1989 to 1993 in British Columbia, Canada. Women aged ≥ 90 years, with pure in-situ, bilateral invasive breast cancer or T4, N1, N2, or M1 stage, or who had axillary radiation were excluded. Two groups were defined for analysis: node-negative with no systemic therapy (n = 1,468) and node-negative with systemic therapy (n = 810). Median follow-up was 7.5 years. Prognostic variables assessed were age at diagnosis, tumor size, tumor grade, invasion of lymphatics, veins, or nerves, estrogen receptor status, and number of nodes removed.

RESULTS: For patients not receiving systemic therapy, regional relapse was significantly increased with smaller numbers of nodes removed (P = .03). There was a trend toward shorter overall survival with fewer nodes removed (P = .06). Node-negative patients who received systemic therapy did not have a higher regional relapse rate or shorter overall survival when fewer nodes were recovered.

CONCLUSION: Recovery of a small number of negative lymph nodes at axillary dissection likely understages patients and leads to undertreatment, resulting in an increased regional relapse rate and poorer survival. The use of systemic therapy may overcome this effect. The number of nodes removed, in conjunction with other prognostic factors, may be useful in selecting node-negative patients for systemic therapy.
Longitudinal Changes in Emergency Medical Services Advanced Airway Management
Authors: Wang Henry E. , Yu Mengda Ivy , Crowe Remle P. , Nassal Michelle M. J. , Gage Christopher , Hyer J. Madison , Powell Jonathan , Ulintz Alexander , Sharkey-Toppen Travis , Wei Lai , Moeller Kim , Panchal Ashish R.
Published: August 2024

Importance

Identifying longitudinal changes in advanced airway management by emergency medical services (EMS) is crucial for understanding practice patterns and optimizing care.

Objective

To examine the longitudinal trends in endotracheal intubation (ETI) and supraglottic airway (SGA) utilization in a national EMS cohort.

Design, Setting, and Participants

This retrospective cross-sectional study analyzed 2011 to 2022 data from the ESO Data Collaborative, a national database of US prehospital electronic health records. The study included all 911 EMS events in which advanced airway management was attempted. Data were analyzed from November 2022 to January 2024.

Exposures

Advanced airway management attempts, including ETI, SGA, and surgical airways.

Main Outcomes and Measures

The annual percentage of ETI and SGA attempts, stratified by underlying condition (cardiac arrest, nonarrest medical, nonarrest trauma, pediatrics).

Results

Among 47.5 million EMS activations, 444 041 (mean [SD] age, 60.6 [19.8] years; 273 296 [61.5%] men) involved advanced airway management, including 305 584 (68.8%) that used ETI and 200 437 (45.1%) that used SGA. The overall incidence was 9.3 per 1000 EMS events. In the cardiac arrest cohort from 2011 to 2022, EMS events with ETI attempts decreased from 2470 of 2831 (87.3%) to 40 083 of 72 793 (55.1%) and those with SGA attempts increased from 711 of 2831 (25.1%) to 44 386 of 72 793 (61.0%). In the pediatric subset, there were similarly large decreases in ETI attempts, from 117 of 182 EMS events (97.3%) to 1573 of 2307 EMS events (68.2%), and increases in SGA attempts, from 11 of 182 EMS events (6.6%) to 1058 of 2307 EMS events (45.9%). In the nonarrest medical and nonarrest trauma cohorts, ETI attempts decreased and SGA attempts increased but to a much lower extent.

Conclusions and Relevance

In this national cross-sectional study of EMS care episodes, there were marked shifts in advanced airway management practices, with the increased use of SGA and decreased use of ETI. These observations highlight current trends in EMS airway management practices.
Enhancing Root Canal Therapy with NIR‐II Semiconducting Polymer AIEgen and Low‐Concentration Sodium Hypochlorite Synergy
Authors: Zhou Yuanzhu , Li Dan , Yue Xin , Shi Yang , Li Cong , Wang Yuhan , Chen Yao , Liu Qian , Ding Dan , Wang Dong , Shen Jing
Published: August 2024

Despite significant efforts to eliminate bacterial biofilm within root canals, achieving effective disinfection remains challenging due to the complex anatomy and limitations of disinfectants. In this study, a second near‐infrared (NIR‐II) semiconducting polymer with aggregation‐induced emission (AIE) properties, named PIDT‐TBT, is deliberately designed and synthesized. This proposes an AIE luminogen‐based sterilization strategy in synergy with a low concentration of sodium hypochlorite (NaClO). Water‐dispersible PIDT‐TBT nanoparticles (NPs) are prepared, demonstrating good biocompatibility, as well as photothermal and photodynamic properties. Subsequent antibacterial tests show that PIDT‐TBT NPs exhibit excellent bactericidal effects against three bacterial strains: Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis, upon 808 nm laser irradiation. In synergy with a low concentration of NaClO (0.5%) solution, PIDT‐TBT NPs significantly improves the outcome of root canal treatment under 808 nm laser irradiation in a human extracted tooth root canal infection model. Additionally, it is found that PIDT‐TBT NPs combine with a low concentration of NaClO solution could safely dissolve dentin debris and further increase the efficiency of root canal preparation by altering the elemental composition of the inner root canal wall.
Systemic Multifunctional Nanovaccines for Potent Personalized Immunotherapy of Acute Myeloid Leukemia
Authors: Zhang Peng , Wang Tanzhen , Cui Guanhong , Ye Ruonan , Wan Wenjun , Liu Tianhui , Zheng Yiran , Zhong Zhiyuan
Published: August 2024

Hematological malignancies (HM) like acute myeloid leukemia (AML) are often intractable. Cancer vaccines possibly inducing robust and broad anti‐tumor immune responses may be a promising treatment option for HM. Few effective vaccines against blood cancers are, however, developed to date partly owing to insufficient stimulation of dendritic cells (DCs) in the body and lacking appropriate tumor antigens (Ags). Here it is found that systemic multifunctional nanovaccines consisting of nucleotide‐binding oligomerization domain‐containing protein 2 (NOD2) and Toll‐like receptor 9 (TLR9) agonists – muramyl dipeptide (MDP) and CpG, and tumor cell lysate (TCL) as Ags (MCA‐NV) induce potent and broad immunity against AML. MCA‐NV show complementary stimulation of DCs and prime homing to lymphoid organs following systemic administration. Of note, in orthotopic AML mouse models, intravenous infusion of different vaccine formulations elicits substantially higher anti‐AML efficacies than subcutaneous administration. Systemic MCA‐NV cure 78% of AML mice and elicit long‐term immune memory with 100% protection from rechallenging AML cells. Systemic MCA‐NV can also serve as prophylactic vaccines against the same AML. These systemic nanovaccines utilizing patient TCL as Ags and dual adjuvants to elicit strong, durable, and broad immune responses can provide a personalized immunotherapeutic strategy against AML and other HM.
Highly Luminescent Manganese‐Doped 2D Hybrid Perovskite Nanoplatelets with Dual Emissions Controlled Through Layer Thickness Modulation
Authors: Yadav Amar Nath , Jang Sung Woo , Samanta Tuhin , Seo Jeong Min , Han Joo Hyeong , Viswanath Noolu Srinivasa Manikanta , Park Yong Min , Im Won Bin
Published: August 2024

Doping semiconductor nanomaterials with manganese ion (Mn2+) introduce a well‐defined photoactive d‐d level within the band structure, paving the way for diverse applications. Although Mn doping in single‐layer 2D hybrid perovskites (n = 1) has been extensively studied, limited research has been conducted on doping with modulation of the layer thickness. Herein, Mn2+ doping in hybrid 2D perovskite nanoplatelets (NPLs), L2An‐1[Pb1‐xMnx]nBr3n+1 (where L = butylammonium, A = methylammonium), with variations in Mn concentration (x = 0–0.60) and layer thickness (n = 1–3) is reported. Substitutional doping of Mn significantly increases the photoluminescence quantum yield as well as the rate of energy transfer efficiency, which strongly depends on the layer thickness of NPLs. The Mn concentration in 2D NPLs determines the rate of forward and backward energy transfer. Low‐temperature emission spectra allow to determine thickness‐dependent exciton binding energy for Mn‐doped 2D NPLs (x = 0.5) with values of 410 ± 11 meV (n = 1), 188 ± 9 meV (n = 2), and 151 ± 17 meV (n = 3). The faster dissociation of band‐edge excitons into free carriers at Mn2+ sites results in high brightness with an excellent CRI of 89.2 for the white light‐emitting diode.
Optical Temperature Sensing and Bioimaging of Aquatic Invertebrates With Nd3+‐ Sensitized Core@Shell Nanoparticles
Authors: Przybylska Dominika , Jurga Natalia , Ekner‐Grzyb Anna , Stopikowska Natalia , Grześkowiak Bartosz F. , Runowski Marcin , Grzyb Tomasz
Published: August 2024

In biomedical and optical applications, multifunctional upconverting nanoparticles (UCNPs) play an essential role where non‐invasive temperature sensing and imaging are necessary. UCNPs smaller than 20 nm, which can be excited under 808 nm wavelength, are particularly promising in this area and can be implemented in humans or other mammals. However, new versatile nanoprobes are still needed for biology, especially for challenging studies of small aquatic invertebrates. Such tools allow better monitoring and understanding of their physiology, biochemistry, and ecological responses, which is crucial due to the growing pollution of water reservoirs and climate change. Herein, multifunctional NaYF4:Yb3+, Er3+@NaNdF4:Yb3+ core@shell NPs (15 nm), forming stable aqueous colloids, exhibiting intense emissions under excitation in the first biological window (808 nm), and presenting high thermal sensitivity and resolution related to the thermally coupled energy levels of Er3+ ions, are designed and synthesized. Such properties of UCNPs are further utilized for optical imaging of aquatic invertebrates (Daphnia magna) and temperature detection inside their bodies under 808 nm excitation. This pioneering application of NaYF4:Yb3+, Er3+@NaNdF4:Yb3+ demonstrates the high potential of developed UCNPs for multifunctional applications, especially for bioimaging and temperature sensing within whole organisms.
Synthesis and HHDH‐Catalyzed Kinetic Resolution of Propargylic Epoxides
Authors: Kolman Robert J. , Švaco Petra , Majerić Elenkov Maja , Dokli Irena
Published: August 2024

The versatile reactivity of propargylic epoxides and alcohols, due to the presence of a triple bond, is used in the synthesis of various organic compounds and building blocks. However, there are not many known methods for the preparation of optically pure propargylic epoxides and alcohols, and the existing ones often require specific reagents. Halohydrin dehalogenases (HHDHs) can be used to obtain enantiomerically pure compounds from racemic epoxides. These important biocatalysts facilitate epoxide ring‐opening reactions with unnatural nucleophiles such as azides. Here we report the biocatalytic transformation of propargylic epoxides using HHDHs. Six propargylic epoxides with different substituents were synthesized. Kinetic resolution reactions catalyzed by HHDHs in the presence of azide were performed. Two enzymes with opposite stereoselectivities, HheC and HheA2‐N178A were used and yielded azido alcohols (98–>99% ee, E‐value >200) and epoxides (29–88% ee). The best performing p‐tolyl propargylic epoxide derivative was used in a sequence of two enzymatic reactions to obtain both enantiomers of the β‐azido alcohol and the (R)‐enantiomer of the α‐azido alcohol, each in >99% ee, through complete conversion of the starting epoxide. The obtained azido alcohols were used in further transformations. The click reactions with terminal acetylenes gave triazolyl propargylic alcohols (>99% ee, 90–98% yield). In the case of the α‐azido alcohol, the click reaction was followed by intramolecular cyclization to form the dihydrofuranyl triazole motif that is found in biologically active compounds.
The EU target for organic farming: Potential economic and environmental impacts of two alternative pathways
Authors: Kremmydas Dimitrios , Beber Caetano , Baldoni Edoardo , Ciaian Pavel , Fellmann Thomas , Gocht Alexander , Hristov Jordan , Pignotti Davide , Vicario Dolores Rey , Stepanyan Davit , Tillie Pascal
Published: August 2024

The EU aims to reach 25% of the total agricultural area under organic farming by 2030. Interlinking a farm‐level and agro‐economic market model, we assess impacts of achieving the target either at Member State or aggregated EU level. Results show that flexible budget allocation across Member States would be more cost‐efficient and less detrimental to EU production. Conversely, targeting at Member State level proves more effective in generating greater aggregated and more evenly distributed environmental benefits across EU regions. The results indicate the importance of leveraging tailored approaches to optimize organic farming outcomes across the EU.
A Compact, High‐Performance, and Deformation‐Resilient Trielectrode Electrostatic Soft Pump for Soft Robotics
Authors: Lin Yangqiao , Yang Xiaoli , Jin Tao , Wang Jieyu , Yi Sicheng , Wang Yue , Zhong Songyi , Yue Tao , Zhang Quan , Tian Yingzhong , Li Long
Published: August 2024

Fluid‐driven soft robotic systems, typically powered by bulky and rigid pumps, face significant limitations in agility and adaptability. Addressing this, various soft pumps have been developed, aiming to achieve better compatibility with soft robotics while ensuring sufficient performance. However, finding an optimal balance between flow rate, pumping pressure, efficiency, and the ability to seamlessly integrate with soft robotic structures remains challenging. Herein, a trielectrode electrostatically driven soft pump is presented, featuring a central diaphragm for active bidirectional pumping of gases and dielectric liquids. This design surpasses previous dual‐electrode soft pumps in electrostatic driving frequency, offering an improved flow rate of up to 330 mL min−1 and pressure of 15.96 kPa, within a compact form measuring 5.42 cm3 in volume and weighing only 11.2 g. In addition, constructed entirely from compliant materials, this pump is fully functional under bending, compression, and torsion, enhancing its integration with soft robotics. To demonstrate its practical utility, the pump is integrated into a soft gripper, enabling the manipulation of various objects. The introduced trielectrode design enables high‐frequency electrostatic actuation, resulting in a compact, high‐performance, and deformation‐resilient soft pump, advancing highly integrated and practical soft robotics.
Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria
Authors: Kulasekararaj Austin , Lanza Francesco , Arvanitakis Alexandros , Langemeijer Saskia , Chonat Satheesh , Tombak Anil , Hanes Vladimir , Cao Jia , Miller Mieke Jill , Colbert Alexander , Shander Benjamin , Mytych Daniel T. , Chow Vincent , Henary Haby
Published: August 2024

ABP 959 is a biosimilar to the eculizumab reference product (RP), which is approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). This multicenter, randomized, double‐blind, active‐controlled, two‐period crossover study randomized eculizumab RP‐treated patients with PNH to one of two treatment sequences (ABP 959/eculizumab RP or eculizumab RP/ABP 959) to evaluate the clinical similarity of ABP 959 when compared with eculizumab RP. This study evaluated the efficacy of ABP 959 when compared with eculizumab RP based on control of intravascular hemolysis as measured by lactate dehydrogenase (LDH) and by the time‐adjusted area under the effect curve of LDH. Secondary outcomes included safety, pharmacokinetics, and immunogenicity. Forty‐two patients were randomized (20 in the ABP 959/eculizumab RP group and 22 in the eculizumab RP/ABP 959 group) across 25 centers. Similarity of efficacy was established by a ratio of geometric least squares means of LDH (ABP 959/eculizumab RP) of 1.0628, with a one‐sided 97.5% upper CI of 1.1576 at week 27, and a geometric means ratio of time‐adjusted area under the effect curve (ABP 959 vs. eculizumab RP) of LDH of 0.981, with a 90% CI of 0.9403–1.0239 from week 13 to 27, week 39 to 53, and week 65 to 79. All secondary efficacy endpoints were comparable between treatment groups. No new safety concerns were identified. The results of this study in patients with PNH, along with previously demonstrated similarity of analytical, nonclinical, and clinical pharmacokinetics and pharmacodynamics in healthy volunteers support a demonstration of no clinically meaningful differences between ABP 959 and eculizumab RP.

Clinical Trial Registration: NCT03818607.
A Review of Multi‐Order Diffraction Beams: From Phase Gradient Metasurface to Metagratings
Authors: Wang Yuxiang , Yuan Yueyi , Zhang Kuang
Published: August 2024

Metasurfaces have attracted progressive attention as 2D metamaterials in recent years. Due to the ability to manipulate the phase, amplitude, and polarization of electromagnetic waves, metasurfaces have become a feasible way to control the wavefront. Here, two main platforms for exciting multi‐order diffraction beams in the far field based on metasurfaces, i.e., phase gradient metasurfaces (PGMs) and metagratings (MGs) are reviewed. First, the concept of generalized Snell's law (GSL) as well as the related works are presented. Then the connection between GSL and diffraction law is elaborated. The multi‐order diffraction methods based on the combination of the two principles are introduced. Following the discussion on several kinds of PGMs platforms for achieving multiple beams, the physical mechanisms of MGs are reviewed and recent progress is summarized. Finally, the typical challenges are outlined and the future development directions are prospected.
Performance Analysis of Microwave Photonic Spectral Filters based on Optical Microcombs
Authors: Li Yang , Sun Yang , Wu Jiayang , Ren Guanghui , Xu Xingyuan , Corcoran Bill , Chu Sai Tak , Little Brent E. , Morandotti Roberto , Mitchell Arnan , Moss David J.
Published: August 2024

Microwave transversal filters, which are implemented based on the transversal filter structure in digital signal processing, offer a high reconfigurability for achieving a variety of signal processing functions without changing hardware. When implemented using microwave photonic (MWP) technologies, also known as MWP transversal filters, they provide competitive advantages over their electrical counterparts, such as large operation bandwidth, strong immunity to electromagnetic interference, and low loss when processing signals at high frequencies. Recent advances in high‐performance optical microcombs provide compact and powerful multi‐wavelength sources for MWP transversal filters that require a larger number of wavelength channels to achieve high performance, allowing for the demonstration of a diverse range of filter functions with improved performance and new features. Here, a comprehensive performance analysis for microcomb‐based MWP spectral filters based on the transversal filter approach is presented. First, the theoretical limitations are investigated in the filter spectral response induced by finite tap numbers. Next, the distortions are analyzed in the filter spectral response resulting from experimental error sources. Finally, the influence of input signal's bandwidth on the filtering errors is assessed. These results provide a valuable guide for the design and optimization of microcomb‐based MWP transversal filters for a variety of applications.
Stability assessment of PTB7‐Th and a quinoxaline‐based polymer in both organic thin film transistors and in organic photovoltaic devices
Authors: Laventure Audrey , Brixi Samantha , Welch Gregory C. , Lessard Benoît H.
Published: August 2024

Herein, we perform a stability assessment of two conjugated polymers that are conventionally used as electron donor polymers in the active layer of organic photovoltaic (OPV). More specifically, the impact of thermal annealing, a post‐treatment commonly applied in the OPV community, is evaluated in terms of device performance and stability. The two polymers are PTB7‐Th and QX1, and they are respectively blended with a non‐fullerene electron acceptor, herein a derivative of N‐annulated perylene diimide, that is, tPDI2N‐EH. These blends are targeted for their relatively high power conversion efficiency in outdoor conditions, but also for their potential as efficient active layer in low‐intensity (indoor) conditions—while these blends have been reported, no study on the impact of thermal annealing on their stability has been performed yet. The performance stability of these devices, tracked via the open circuit voltage, the short‐circuit current, the fill factor, and the power conversion efficiency metrics, were evaluated each day for 2 weeks and correlated to an evaluation of the microstructure of the active layer, evaluated using atomic force microscopy and UV–visible absorbance spectroscopy. Finally, transistors were prepared using only the two electron donor polymers, PTB7‐Th and QX1, to assess if some correlations could be made between the behaviour of the OPV devices and that of the electronic charge mobilities. Results contribute to identify which molecular structures and which post‐treatments are ideal to promote the stability of the active layers in the context of OPV devices.
Drought response of zoysiagrass with varying leaf texture under progressive deficit irrigation
Authors: Meeks Meghyn , Chandra Ambika
Published: August 2024

Improving drought resistance in Zoysiagrass (Zoysia spp.) is a target for both private and public breeding programs. The performance of 26 elite experimental zoysiagrasses was compared under progressive drought stress with Palisades, Diamond, and Zeon. Environmental conditions were warmer and drier in 2020 (66 days) than 2021 (45 days). Irrigation was applied once weekly using potential evapotranspiration (ETo) rates and crop coefficients (Kc) of 0.6 (non‐stress), or 0.40, 0.30, and 0.25 deficit treatments. Turfgrass quality, leaf wilt, normalized difference vegetative index, normalized difference red edge, and volumetric water content were recorded weekly. Genotypes with the highest means (statistical “a” group) contributed to a turfgrass performance index (TPI). Elite zoysiagrass with TPI ≥ Palisades (19) were Zoysia japonica Steud. ecotypes DALZ 1311 (22), 1601 (19), and 1603 (21), and finer textured interspecific hybrids, DALZ 1701 (18), 1713 (26), 1714 (18), and 1801 (24). Relative to an irrigation schedule using a 0.6 Kc, these genotypes survived extreme deficit irrigation, which conserved 40.1% (45,859.6 L) and 66.4% (44, 592.2 L) of water in 2020 and 2021, respectively. Overall, this study demonstrated that significant water consumption could be reduced with proper cultivar selection and deficit‐based irrigation management while maintaining an acceptable turfgrass quality under drought conditions.
Wing technique as a comprehensive method for stator and rotor inter‐turn fault diagnosis in wound rotor induction motors
Authors: Dongare Ujwala V. , Umre Bhimrao S. , Ballal Makarand S. , Dongare Vikas P.
Published: August 2024

Condition monitoring plays a pivotal role in safeguarding three‐phase induction motors (IMs) commonly utilized in industrial and commercial settings. This study focuses on wound rotor induction motors (WRIMs), specifically addressing the adverse impact of the stator and rotor winding inter‐turn short circuits. Unlike prevalent literature concentrating on squirrel cage induction motors (SCIMs) and emphasizing stator inter‐turn and broken rotor bar faults, this paper introduces a comprehensive technique applicable to detecting inter‐turn faults (ITFs) in WRIMs. The proposed method ensures stable motor operation and averts catastrophic failures.

Experimental validation is conducted on a three‐phase, 7.5 hp, 415 V WRIM, affirming the technique's effectiveness under conditions of unbalanced source voltages and asymmetries in stator and rotor windings. The approach employs motor currents‐based experimental emulation, utilizing loci of instantaneous symmetrical components of three‐phase stator currents, £ (is1 – is2) and rotor currents £ (ir1 – ir2) for stator and rotor ITFs detection, respectively. Termed the ‘Wing Technique’ (WT), this method derives its name from the distinctive ‘Wing Shape’ formed by these loci.
Cyclic‐di‐GMP induces inflammation and acute lung injury through direct binding to MD2
Authors: Qian Chenchen , Zhu Weiwei , Wang Jiong , Wang Zhe , Tang Weiyang , Liu Xin , Jin Bo , Xu Yong , Zhang Yuyang , Liang Guang , Wang Yi
Published: August 2024

Background

Severe bacterial infections can trigger acute lung injury (ALI) and acute respiratory distress syndrome, with bacterial pathogen‐associated molecular patterns (PAMPs) exacerbating the inflammatory response, particularly in COVID‐19 patients. Cyclic‐di‐GMP (CDG), one of the PAMPs, is synthesized by various Gram‐positve and Gram‐negative bacteria. Previous studies mainly focused on the inflammatory responses triggered by intracellular bacteria‐released CDG. However, how extracellular CDG, which is released by bacterial autolysis or rupture, activates the inflammatory response remains unclear.

Methods

The interaction between extracellular CDG and myeloid differentiation protein 2 (MD2) was investigated using in vivo and in vitro models. MD2 blockade was achieved using specific inhibitor and genetic knockout mice. Site‐directed mutagenesis, co‐immunoprecipitation, SPR and Bis‐ANS displacement assays were used to identify the potential binding sites of MD2 on CDG.

Results

Our data show that extracellular CDG directly interacts with MD2, leading to activation of the TLR4 signalling pathway and lung injury. Specific inhibitors or genetic knockout of MD2 in mice significantly alleviated CDG‐induced lung injury. Moreover, isoleucine residues at positions 80 and 94, along with phenylalanine at position 121, are essential for the binding of MD2 to CDG.

Conclusion

These results reveal that extracellular CDG induces lung injury through direct interaction with MD2 and activation of the TLR4 signalling pathway, providing valuable insights into bacteria‐induced ALI mechanisms and new therapeutic approaches for the treatment of bacterial co‐infection in COVID‐19 patients.
Single‐nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands
Authors: Altieri Barbara , Secener A. Kerim , Sai Somesh , Fischer Cornelius , Sbiera Silviu , Arampatzi Panagiota , Kircher Stefan , Herterich Sabine , Landwehr Laura‐Sophie , Vitcetz Sarah N. , Braeuning Caroline , Fassnacht Martin , Ronchi Cristina L. , Sauer Sascha
Published: August 2024

The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours.

Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single‐nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular‐endothelial cells and cortical‐neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/β‐catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single‐nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma‐specific clusters, each with varying distributions based on steroid profiles and tumour mutational status.

Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal‐related pathologies.