bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versus-host disease and graft-versus-leukemia effect
Authors: Schmaltz Cornelius , Alpdogan Onder , Horndasch Kirsten J. , Muriglan Stephanie J. , Kappel Barry J. , Teshima Takanori , Ferrara James L. M. , Burakoff Steven J. , van den Brink Marcel R. M.
Published: July 2002

In allogeneic bone marrow transplantation (BMT) donor T cells are primarily responsible for antihost activity, resulting in graft-versus-host disease (GVHD), and for antileukemia activity, resulting in the graft-versus-leukemia (GVL) effect. The relative contributions of the Fas ligand (FasL) and perforin cytotoxic pathways in GVHD and GVL activity were studied by using FasL-defective or perforin-deficient donor T cells in murine parent → F1 models for allogeneic bone marrow transplantation. It was found that FasL-defective B6.gld donor T cells display diminished GVHD activity but have intact GVL activity. In contrast, perforin-deficient B6.pfp−/− donor T cells have intact GVHD activity but display diminished GVL activity. Splenic T cells from recipients of B6.gld or B6.pfp−/− T cells had identical proliferative and cytokine responses to host antigens; however, splenic T cells from recipients of B6.pfp−/− T cells had no cytolytic activity against leukemia cells in a cytotoxicity assay. In experiments with selected CD4+ or CD8+ donor T cells, the FasL pathway was important for GVHD activity by both CD4+ and CD8+ T cells, whereas the perforin pathway was required for CD8-mediated GVL activity. These data demonstrate in a murine model for allogeneic bone marrow transplantation that donor T cells mediate GVHD activity primarily through the FasL effector pathway and GVL activity through the perforin pathway. This suggests that donor T cells make differential use of cytolytic pathways and that the specific blockade of one cytotoxic pathway may be used to prevent GVHD without interfering with GVL activity.
Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003)
Authors: Dhodapkar Madhav V. , Jacobson Joth L. , Gertz Morie A. , Rivkin Saul E. , Roodman G. David , Tuscano Joseph M. , Shurafa Muhammad , Kyle Robert A. , Crowley John J. , Barlogie Bart
Published: July 2002

Current information on Waldenström macroglobulinemia (WM) is based on retrospective or single-institution studies of patients requiring therapy. Between 1992 and 1998, 231 patients with WM were enrolled in a prospective observational multicenter clinical trial. Of these, 182 patients with symptomatic or progressive disease were treated with 4 to 8 cycles of therapy with a purine nucleoside analogue, fludarabine (FAMP; 30 mg/m2 of body-surface area daily for 5 days every 28 days). A serum β2-microglobulin (β2M) level below 3 mg/L and a hemoglobin level of at least 120 g/L (12 g/dL) at presentation predicted a lower likelihood of requiring therapy. The overall rate of response to FAMP therapy was 36% (95% confidence interval, 29%-44%), with 2% complete remissions. Patients who were 70 years old or older had a substantially lower likelihood of response (odds ratio, 0.34; P = .004) than younger patients. On multivariate analysis, a serum β2M level of 3 mg/L or higher, hemoglobin level below 120 g/L, and serum IgM level below 40 g/L [4 g/dL] were significant adverse prognostic factors for survival. We developed a simple staging system for WM by using these variables and identified 4 distinct subsets of patients with estimated 5-year overall survival rates of 87%, 64%, 53%, and 22%, and 5-year progression-free survival rates of 83%, 55%, 33%, and 12%. Prognosis in WM is highly variable and serum β2M was the dominant predictor of a need for therapy and of survival. FAMP has activity against WM. Our staging system may provide guidance for a risk-based approach to the treatment of WM.
Engraftment of DLA-haploidentical marrow with ex vivo expanded, retrovirally transduced cytotoxic T lymphocytes
Authors: Georges George E. , Storb Rainer , Bruno Benedetto , Brodie Scott J. , Thompson Jennifer D. , Taranova Anna G. , Zaucha J. Maciej , Little Marie-Térèse , Zellmer Eustacia , Moore Peter F. , Gooley Theodore , Sale George , Kiem Hans-Peter , Sandmaier Brenda M. , Lyons Russette M. , Nash Richard A.
Published: July 2002

Genetically modified donor T cells with an inducible “suicide” gene have the potential to improve the safety and availability of allogeneic hematopoietic stem cell transplantation by enhancing engraftment and permitting control of graft-versus-host disease (GVHD). However, several clinical studies of gene-modified T cells have shown limited to no in vivo function of the ex vivo expanded T cells. Using the well-established dog model of allogeneic marrow transplantation, the question was asked if retrovirally transduced, donor derived, ex vivo expanded cytotoxic T lymphocytes (CTLs) that are recipient specific could enhance engraftment of dog leukocyte antigen (DLA)–haploidentical marrow following a single dose of 9.2 Gy total body irradiation and no postgrafting immunosuppression. In this setting, only 4 of 11 control recipients of DLA-haploidentical marrow without added CTLs engrafted. CTLs did not enhance engraftment of CD34+ selected peripheral blood stem cells. However, recipient-specific CTLs enhanced engraftment of DLA-haploidentical marrow in 9 of 11 evaluable recipients (P = .049). All dogs that engrafted developed multiorgan GVHD. To facilitate in vivo tracking, 8 dogs received CTLs transduced with a retroviral vector encoding green fluorescent protein (GFP) and neomycin phosphotransferase (neo). Recipients that engrafted had sharp increases in the numbers of circulating GFP+ CTLs on days +5 to +6 after transplantation. GFP+ CTLs isolated from blood were capable of recipient-specific lysis. At necropsy, up to 7.1% of CD3+ cells in tissues were GFP+ and polymerase chain reaction in situ hybridization for neoshowed infiltration of transduced CTLs in GVHD-affected organs. These results show that ex vivo expanded, transduced T cells maintained in vivo function and enhanced marrow engraftment.
Increased thrombogenesis and embolus formation in mice lacking glycoprotein V
Authors: Ni Heyu , Ramakrishnan Vanitha , Ruggeri Zaverio M. , Papalia Jessie M. , Phillips David R. , Wagner Denisa D.
Published: July 2002

The glycoprotein (GP) Ib-V-IX complex plays a critical role in initiating platelet adhesion to von Willebrand factor (vWF) at the site of vascular injury. The complex also forms a high-affinity binding site for thrombin. Using an intravital microscopy mouse model, it was previously established that vWF plays a critical role in mediating platelet adhesion and thrombus formation following mesenteric arteriolar injury induced by ferric chloride. Further characterization of this model showed that these thrombotic events were also thrombin dependent. Using this vWF- and thrombin-dependent model, this study shows that GP V gene deficiency significantly accelerates both platelet adhesion and thrombus formation in mice following arteriolar injury. The time required for vessel occlusion in GP V–deficient (GP V−/−) mice was significantly shorter than that in wild-type mice. Interestingly, large emboli were also produced in GP V−/− mice, but not in wild-type mice, causing frequent downstream occlusion. However, when the 2 genotypes were compared in the in vitro perfusion chamber where thrombin was inhibited by heparin, no significant differences were found in either initial single-platelet adhesion or thrombus volume. These results demonstrate that GP V−/− mice have accelerated thrombus growth in response to vascular injury and suggest that this is caused by enhanced thrombin-induced platelet activation rather than enhanced binding of GPIb-V-IX to vWF. Absence of GP V also compromises thrombus stability.
Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation
Authors: Moog Sylvie , Mangin Pierre , Lenain Nadège , Strassel Catherine , Ravanat Catherine , Schuhler Simone , Freund Monique , Santer Martine , Kahn Mark , Nieswandt Bernhard , Gachet Christian , Cazenave Jean-Pierre , Lanza François
Published: July 2002

Glycoprotein V (GPV) is a subunit of the platelet GPIb-V-IX receptor for von Willebrand factor and thrombin. GPV is cleaved from the platelet surface during activation by thrombin, but its role in hemostasis is still unknown. It is reported that GPV knockout mice had a decreased tendency to form arterial occluding thrombi in an intravital thrombosis model and abnormal platelet interaction with the subendothelium. In vitro, GPV-deficient platelets exhibited defective adhesion to a collagen type I–coated surface under flow or static conditions. Aggregation studies demonstrated a decreased response of the GPV-deficient platelets to collagen, reflected by an increased lag phase and reduced amplitude of aggregation. Responses to adenosine diphosphate, arachidonic acid, and the thromboxane analog U46619 were normal but were enhanced to low thrombin concentrations. The defect of GPV null platelets made them more sensitive to inhibition by the anti-GPVI monoclonal antibody (mAb) JAQ1, and this was also the case in aspirin- or apyrase-treated platelets. Moreover, an mAb (V.3) against the extracellular domain of human GPV selectively inhibited collagen-induced aggregation in human or rat platelets. V.3 injected in rats as a bolus decreased the ex vivo collagen aggregation response without affecting the platelet count. Finally, surface plasmon resonance studies demonstrated binding of recombinant soluble GPV on a collagen-coupled matrix. In conclusion, GPV binds to collagen and appears to be required for normal platelet responses to this agonist.
Th2 polarization by Der p 1–pulsed monocyte-derived dendritic cells is due to the allergic status of the donors
Authors: Hammad Hamida , Charbonnier Anne-Sophie , Duez Catherine , Jacquet Alain , Stewart Geoffrey A. , Tonnel André-Bernard , Pestel Joël
Published: July 2002

The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC–T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive toDermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite–sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor–α and interleukin (IL)-1β, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite–sensitive patients stimulated by autologous Der p 1–pulsed DCs preferentially produced IL-4 rather than interferon-γ. These effects were abolished in the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite–sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure.
Loss of heterozygosity in childhood de novo acute myelogenous leukemia
Authors: Sweetser David A. , Chen Chien-Shing , Blomberg Adam A. , Flowers David A. , Galipeau Patricia C. , Barrett Michael T. , Heerema Nyla A. , Buckley Jonathan , Woods William G. , Bernstein Irwin D. , Reid Brian J.
Published: July 2002

A genome-wide screening for loss of heterozygosity (LOH), a marker for possible involvement of tumor suppressor genes, was conducted in 53 children with de novo acute myelogenous leukemia (AML). A total of 177 highly polymorphic microsatellite repeat markers were used in locus-specific polymerase chain reactions. This comprehensive allelotyping employed flow-sorted cells from diagnostic samples and whole-genome amplification of DNA from small, highly purified samples. Nineteen regions of allelic loss in 17 patients (32%) were detected on chromosome arms 1q, 3q, 5q, 7q (n = 2), 9q (n = 4), 11p (n = 2), 12p (n = 3), 13q (n = 2), 16q, 19q, and Y. The study revealed a degree of allelic loss underestimated by routine cytogenetic analysis, which failed to detect 9 of these LOH events. There was no evidence of LOH by intragenic markers for p53, Nf1, orCBFA2/AML1. Most lymphocytes lacked the deletions, which were detected only in the leukemic myeloid blast population. Analysis of patients' clinical and biologic characteristics indicated that the presence of LOH was associated with a white blood cell count of 20 × 109/L or higher but was not correlated with a shorter overall survival. The relatively low rate of LOH observed in this study compared with findings in solid tumors and in pediatric acute lymphoblastic leukemia and adult AML suggests that tumor suppressor genes are either infrequently involved in the development of pediatric de novo AML or are inactivated by such means as methylation and point mutations. Additional study is needed to determine whether these regions of LOH harbor tumor suppressor genes and whether specific regions of LOH correlate with clinical characteristics.
The mononucleotide-dependent, nonantisense mechanism of action of phosphodiester and phosphorothioate oligonucleotides depends upon the activity of an ecto-5′-nucleotidase
Authors: Koziolkiewicz Maria , Gendaszewska Edyta , Maszewska Maria , Stein C. A. , Stec Wojciech J.
Published: July 2002

Many reports indicate different nonantisense yet sequence-specific effects of antisense phosphorothioate oligonucleotides. Products of enzymatic degradation of the oligonucleotides can also influence cell proliferation. The cytotoxic effects of deoxyribonucleoside-5′-phosphates (dNMPs) and their 5′-phosphorothioate analogs, deoxyribonucleoside-5′-monophosphorothioates (dNMPSs) on 4 human cell types (HeLa, HL-60, K-562, and endothelial cells) were examined, and the effects were correlated with the catabolism of these compounds. The results indicate that differences in cytotoxicity of dNMPs or dNMPSs in these cells depend upon different activity of an ecto-5′-nucleotidase. It has also been found that dNMPSs stimulate proliferation of human umbilical vein endothelial cells and HL-60 cells in a concentration-dependent manner. This stimulation might be caused by the binding of deoxynucleoside-5′-phosphorothioates to as-yet unidentified nucleotide receptor(s) at the cell surface.
Reduction in drug-induced DNA double-strand breaks associated with β1 integrin–mediated adhesion correlates with drug resistance in U937 cells
Authors: Hazlehurst Lori A. , Valkov Nikola , Wisner Lee , Storey Jonathan A. , Boulware David , Sullivan Daniel M. , Dalton William S.
Published: July 2002

We previously showed that adhesion of myeloma cells to fibronectin (FN) by means of β1 integrins causes resistance to certain cytotoxic drugs. The study described here found that adhesion of U937 human histiocytic lymphoma cells to FN provides a survival advantage with respect to damage induced by the topoisomerase (topo) II inhibitors mitoxantrone, doxorubicin, and etoposide. Apoptosis induced by a topo II inhibitor is thought to be initiated by DNA damage. The neutral comet assay was used to determine whether initial drug-induced DNA damage correlated with cellular-adhesion–mediated drug resistance. Cellular adhesion by means of β1 integrins resulted in a 40% to 60% reduction in mitoxantrone- and etoposide-induced DNA double-strand breaks. When the mechanisms regulating the initial drug-induced DNA damage were examined, a β1 integrin–mediated reduction in drug-induced DNA double-strand breaks was found to correlate with reduced topo II activity and decreased salt-extractable nuclear topo IIβ protein levels. Confocal studies showed changes in the nuclear localization of topo IIβ; however, alterations in the nuclear-to-cytoplasmic ratio of topo IIβ in FN-adhered cells were not significantly different. Furthermore, after a high level of salt extraction of nuclear proteins, higher levels of topo IIβ–associated DNA binding were observed in FN-adhered cells than in cells in suspension. Together, these data suggest that topo IIβ is more tightly bound to the nucleus of FN-adhered cells. Thus, FN adhesion by means of β1 integrins appears to protect U937 cells from initial drug-induced DNA damage by reducing topo II activity secondarily to alterations in the nuclear distribution of topo IIβ.
Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients
Authors: Onida Francesco , Kantarjian Hagop M. , Smith Terry L. , Ball Greg , Keating Michael J. , Estey Elihu H. , Glassman Armand B. , Albitar Maher , Kwari Monica I. , Beran Miloslav
Published: July 2002

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by wide heterogeneity of clinical presentation and course. CMML shares myelodysplastic characteristics with features of myeloproliferative disorders. No treatment has proven effective in modifying the natural course of the disease. To improve the prognostic assessment of clinical outcome, the associations of patient and disease characteristics with survival times of 213 patients with CMML was investigated retrospectively. Median survival was 12 months. Univariate analysis identified low hemoglobin level; low platelet count; high white blood cell, monocyte, and lymphocyte counts; presence of circulating immature myeloid cells, high percentage of marrow blasts, low percentage of marrow erythroid cells, abnormal cytogenetics, and high levels of serum lactate dehydrogenase and β2-microglobulin as characteristics associated with shorter survival. Hemoglobin level below 120 g/L (12 g/dL), presence of circulating immature myeloid cells, absolute lymphocyte count above 2.5 × 109/L, and marrow blasts 10% or more were independently associated with shorter survival by multivariate analysis and were used to generate a prognostic score. The model identified 4 subgroups of patients with median survival of 24, 15, 8, and 5 months for low, intermediate-1, intermediate-2, and high risk, respectively. Researchers could not confer objective evidence suggesting that arbitrary divisions of CMML by white blood cell counts into “dysplastic” and “proliferative” categories reflect clinical entities differing in the risk of acute leukemia development, although a trend of shorter survival in patients with leukocytosis was observed. The prognostic model was compared with 6 previously published scoring systems for myelodysplastic syndrome/CMML. The reported results should provide an improved assessment of prognosis in CMML.
Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: Results From an International Analysis
Authors: Bokemeyer Carsten , Nichols Craig R. , Droz Jean-P. , Schmoll Hans-J. , Horwich Alan , Gerl Arthur , Fossa Sophie D. , Beyer Jörg , Pont Jörg , Kanz Lothar , Einhorn Lawrence , Hartmann Jörg T.
Published: July 2002

PURPOSE: To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies.

PATIENTS AND METHODS: Of an unselected population of 635 consecutive patients treated from 1975 through 1996 at 11 cancer centers, 341 patients (54%) had primary mediastinal EGCT, and 283 patients (45%) had retroperitoneal EGCT. Five hundred twenty-four patients (83%) had a nonseminomatous germ cell tumor (GCT), and 104 patients (16%) had a seminomatous histology.

RESULTS: After platinum-based induction chemotherapy with or without secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow-up, 19 months; range, 1 to 178 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow-up, 29 months; range, 1 to 203 months) are alive (P = .0006). In contrast, the overall survival rate for patients with a seminomatous EGCT is 88%, with no difference between patients with mediastinal or retroperitoneal tumor location (median follow-up, 49 months; range, 4 to 193 months; respective 70 months; range, 1 to 211 months). A significantly lower progression-free survival rate was found in seminoma patients treated with initial radiotherapy alone compared with chemotherapy. Nonseminomatous histology, presence of nonpulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-human chorionic gonadotropin were independent prognostic factors for shorter survival. Hematologic malignancies (n = 17) occurred without exception in patients with primary mediastinal nonseminoma. Sixteen patients developed a metachronous testicular cancer despite the use of platinum-based chemotherapy.

CONCLUSION: Whereas patients with pure seminomatous EGCT histology have a long-term chance of cure of almost 90% irrespective of the primary tumor site, 45% of patients with mediastinal nonseminomas are alive at 5 years. This outcome is clearly inferior compared with patients with nonseminomatous retroperitoneal primary tumors.
Axial Spondyloarthritis
Authors: Bittar Mohamad , Deodhar Atul
Published: December 2024

Importance

Axial spondyloarthritis is an immune-mediated inflammatory condition involving the sacroiliac joints, spine, and peripheral joints. It affects approximately 1% of adults in the US and is associated with impaired physical function and reduced quality of life.

Observations

Inflammatory chronic back pain characterized by gradual onset starting before age 45 years, prolonged morning stiffness, improvement with exercise, and lack of improvement with rest is the most common symptom of axial spondyloarthritis and affects more than 80% of patients. Patients with axial spondyloarthritis may also have inflammatory arthritis in large peripheral joints (most commonly knees) in an oligoarticular, asymmetric fashion; inflammation at tendon insertions (enthesitis); inflammatory eye disease (uveitis); psoriasis; and inflammatory bowel disease. The pathogenesis of axial spondyloarthritis may involve genetic predisposition, gut microbial dysbiosis, and entheseal trauma, with immune cell infiltration of the sacroiliac joints and entheseal insertion areas in the spine. There are currently no diagnostic criteria for axial spondyloarthritis. The diagnosis, often delayed 6 to 8 years after symptom onset, is based on history (ie, inflammatory back pain [sensitivity, 74%-81%; specificity, 25%-44%]), laboratory findings (human leukocyte antigen B27–positive [sensitivity, 50%; specificity, 90%] and elevated C-reactive protein level [sensitivity, 35%; specificity, 91%]), and imaging findings consisting of sacroiliitis on plain radiography (sensitivity, 66%; specificity, 68%) or magnetic resonance imaging (sensitivity, 78%; specificity, 88%). First-line treatments are physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). However, less than 25% of patients achieve complete symptom control with NSAIDs. Approximately 75% of patients require biologic drugs (tumor necrosis factor inhibitors [anti-TNF agents], interleukin 17 inhibitors [anti–IL-17 agents]) or targeted synthetic disease-modifying antirheumatic agents (Janus kinase [JAK] inhibitors) to reduce symptoms, prevent structural damage, and improve quality of life. Clinical trials reported that anti-TNF agents significantly improved ASAS20 (measure of pain, function, and inflammation) in 58% to 64% of patients compared with 19% to 38% for placebo. Similar outcomes were attained with anti–IL-17 agents (48%-61%, vs 18%-29% with placebo) and JAK inhibitors (52%-56%, vs 26%-29% with placebo). Anti-TNF agents, anti–IL-17 agents, and JAK inhibitors have been associated with reduced radiographic progression of axial spondyloarthritis.

Conclusions

Axial spondyloarthritis predominantly affects the sacroiliac joints and spine but is also associated with extraskeletal manifestations such as uveitis, psoriasis, and inflammatory bowel disease. Physical therapy and NSAIDs are first-line treatments, but most patients require therapy with biologics (anti-TNF or anti–IL-17 agents) or JAK inhibitors to achieve improvement in signs and symptoms, inflammation control, and reduced progression of structural damage.
Palmar Fasciitis and Polyarthritis Syndrome
Authors: Ma Xiao , Ma Dong-Lai
Published: December 2024

This case report describes a man in his 50s with palmar fasciitis and polyarthritis syndrome.
LGBTQ+-Inclusive Language in Patient-Reported Outcome Measures for Acne Vulgaris
Authors: Sia Twan , Abou-Taleb Farah , Yeung Howa , Chang Anne Lynn S.
Published: December 2024

This qualitative study examines whether patient-reported outcomes measures for acne incorporate LGBTQ+-inclusive language.
Covalent labeling of the Arabidopsis plasma membrane H+‐ATPase reveals 3D conformational changes involving the C‐terminal regulatory domain
Authors: Blackburn Matthew R. , Nguyen Thao T. , Patton Sophia E. , Bartosiak Jordan M. , Sussman Michael R.
Published: December 2024

The plasma membrane proton pump is the primary energy transducing, electrogenic ion pump of the plasma membrane in plants and fungi. Compared to its fungal counterpart, the plant plasma membrane proton pump's regulatory C‐terminal domain (CTD) contains an additional regulatory segment that links multiple sensory pathways regulating plant cell length through phosphorylation and recruitment of regulatory 14‐3‐3 proteins. However, a complete structural model of a plant proton pump is lacking. Here, we performed covalent labeling with mass spectrometric analysis (CL‐MS) on the Arabidopsis pump AHA2 to identify potential interactions between the CTD and the catalytic domains. Our results suggest that autoinhibition in the plant enzyme is much more structurally complex than in the fungal enzyme.
Robust Optimal Consensus Control for Nonlinear Multi‐agent Systems: Two Hybrid Dynamic Event‐Triggered‐Based Approach
Authors: Zou Haoming , Zhang Guoshan
Published: December 2024

In this paper, the dynamic event‐triggered robust optimal consensus control problem is investigated for nonlinear multi‐agent systems (MASs) with matched and mismatched disturbances via integral sliding mode (ISM) control and the adaptive dynamic programming (ADP) algorithm. First, a dynamic event‐triggered fixed‐time ISM controller is designed to guarantee that the system state converges to the predefined ISM manifold, thereby eliminating the matched disturbances. Next, the consensus control problem is transformed into an optimal control problem by constructing neighborhood error dynamics and a new modified cost function; thus, an event‐triggered‐based coupled Hamilton‐Jacobi‐Bellman equation (HJBE) is established. Then, an ADP‐based single‐critic neural network (NN) is constructed to solve coupled HJBE to obtain the event‐triggered optimal controller, in which the NN weight is updated only at the triggering instants. Through the implementation of these two dynamic event‐triggered mechanisms, resources and controller execution time can be saved. It is proved that the whole closed‐loop system signals are uniformly ultimately bounded by the Lyapunov technique. Finally, two illustrative examples verify the effectiveness and superiority of the proposed control scheme.
Synergistic Strategy toward Enhancing Photosynthesizing Reactive Oxygen Species of Covalent Organic Frameworks
Authors: Zhan Xiaoning , Jin Yucheng , Qu Chen , Liu Heyuan , Jiang Rong , Zhi Qianjun , Qi Dongdong , Wang Kang , Han Bin , Pan Houhe , Jiang Jianzhuang
Published: December 2024

Photocatalytic reactive oxygen species (ROSs) plays an important role in photodynamic therapy and photochemical reactions. However, most reported photocatalysts suffer from insufficient utilization of visible light and low conversion of O2, which requires the development of higher performance catalysts toward practical applications. Herein, a series of porphyrin‐based COFs have been prepared. Comparative experimental and theoretical studies have revealed that the synergistic interaction between the two building blocks can significantly enhance the yields of ROSs by independently accomplishing photon harvesting and oxygen capture with smooth energy transfer between them. Particularly, the 1O2 yield of 3P‐Por‐COF is increased to 1.3 and 3.4 times that of the classical PCN‐224 and porphyrin molecular aggregates. Furthermore, the TOF of 3P‐Por‐COF is as high as 271 h−1 with ≈100% selectivity under red light irradiation in catalyzing thioanisole to methyl phenyl sulfoxide. The conversion and stability of degradation of toluene gas under natural light are also superior to the conventional Fenton catalytic system. The present results should contribute to the design of high‐performance frameworks‐based photocatalysts for ROSs production.
Capillarity‐Assisted 3D Patterning of Liquid Metal
Authors: Gao Ming , Liu Xiaojiang , Fan Jingbo , Gao Jingwen , Zhou Yuning , Zhou Kun
Published: December 2024

Flexible electronics with sophisticated 3D architectures enable multidimensional functionalities and multi‐component integration, thus surpassing their 2D counterparts in soft robotics and wearable sensors. Because of its unique metallic and fluidic characteristics, liquid metal (LM) has proven to be an excellent material for fabricating flexible electronics. However, its low viscosity and high surface tension have primarily restricted LM to the creation of 2D‐patterned films on flat surfaces, significantly limiting the complexity and functionality of the resulting flexible devices. In this work, inspired by the capillary‐driven liquid flow in a hierarchical lattice matrix, a 3D patterning method is proposed for LM and extended to the fabrication of porous materials with flexible conductivity. The feasibility and versatility of the proposed method are showcased by fabricating tunable electromagnetic interference shielding materials, programmable 3D circuits, and customizable wearable sensors, highlighting its potential for promoting the development of integrated circuits and wearable electronics.
Molecular Engineering of Ultrabright Biomimetic NanoGhost for Site‐Selective Tumor Imaging and Biodistribution
Authors: Prasad Rajendra , Prerna Kumari , Temgire Mayur , Banerjee Pinaki , Kumari Rohini , Kundu Gopal C , Hattila Deeksha , Mangannavar Chandrashekhar Venkaraddi , Meena Avtar Singh , Gorain Mahadeo , Bellare Jayesh , Chandra Pranjal , Dubey Vikash Kumar
Published: December 2024

Optically active ultrabright imaging agents are shown to delineate tumor location with deep tissue visualization in pre noclinical tumor models. NanoGhosts (NGs) particles are reconstructed from the cell membrane and integrated with organic fluorophores to attain ultra‐brightness for solid tumor imaging. Moreover, the integration of amphiphilic and lipophilic molecules reveals structural characteristics of NGs (≈70 nm), which also alter their brightness. Upon intravenous administration (10 mg kg−1 single dose), these ultrabright NGs (778 MESF) enable the high‐resolution of tumor site and real‐time tracking of vital organs with high‐contrast fluorescence signals. Engineered biomimetic NGs demonstrates better resolution and tissue penetration as compared to the clinically approved indocyanine green (ICG). High precision in tumor detection (0.5 h) and strong tumor retention (24 h which is further up to 30th day) without affecting healthy tissues ensure the future scope of NGs in early‐stage cancer imaging. These findings suggest that these NGs mimic the biological characteristics of native cells, enabling them to evade immune clearance and target the solid tumor naturally.
Locally Injectable, ROS‐Scavenging, and ROS‐/pH‐Responsive Polymeric‐Micelles‐Embedded Hydrogels for Precise Minimally Invasive and Long‐Lasting Rheumatoid Therapy
Authors: Liu Xinhua , Chen Xing , Fei Yifan , Zhang Jiamin , Yue Ouyang , Wang Xuechuan , Jiang Huie
Published: December 2024

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis, bone‐erosion, and joint‐destruction. Here, we developed a locally injectable, ROS‐scavenging, and ROS‐/pH‐responsive drug‐delivery platform (HC@PTM) by bio‐compositing of aldolizing hyaluronic acid (HA) crosslinked with chitosan (CS), and ROS‐triggered/eliminated micelles (PTM) coupled with the drug methotrexate(MTX). The PTM efficiently eradicate excessive ROS in RA‐joints, precisely triggering drug‐release within inflamed arthritic‐sites and further confer exceptional antioxidant origins to HC@PTM. HC@PTM with outstanding shape‐adaptability and self‐repairing properties effectively conformed to irregular articular cartilage while resisting joint‐induced deformations. Further, the platform's pH‐responsive nature enables on‐demand drug‐release within acidic inflamed synovium, serving as a drug‐reservoir for precise and sustained therapeutic effects. Extensive in vitro and in vivo investigations confirm HC@PTM's ability to induce M2 macrophage polarization, downregulate inflammatory factor expression, and ameliorate the RA‐microenvironment, ultimately achieving synergistic therapeutic outcomes. This study represents significant advancements in precise and long‐term RA‐treatment through a minimally invasive approach, offering potential strategies for novel precision medicine.
Delivery of Encapsulated Intelligent Engineered Probiotic for Inflammatory Bowel Disease Therapy
Authors: Zou Zhen‐Ping , Cai Zhihao , Zhang Xiao‐Peng , Zhang Donghui , Xu Chu‐Ying , Zhou Ying , Liu Runhui , Ye Bang‐Ce
Published: December 2024

Engineered bacterial therapy holds enormous potential for treating intestinal diseases, employing synthetic biology techniques to achieve localized drug delivery within intestines. However, effective delivery of engineered bacteria to lesion sites and ensuring sustained colonization remain challenging. Here, a mucus encapsulated microsphere gel (MM) delivery system is developed to encapsulate genetically engineered bacteria capable of detecting and treating enteritis. The MM delivery system features an external mucosal coating composed of hyaluronic acid and epigallocatechin gallate, along with internal microspheres of highly biocompatible polyserine modified alginates encapsulating with the engineered probiotics. The MM delivery system effectively protects engineered bacteria harsh environment in stomach and significantly improves intestinal adhesion of the probiotics, extending colonization up to 24 h, and does not affect the entry of biomarker or release of Avcystatin. It exhibits notable diagnostic and therapeutic efficacy in inflammatory bowel disease models, thus facilitating the advancement of live biotherapeutic products toward clinical application.
Metal Doping Enabling Defective CoMo‐Layered Double Hydroxide Nanosheets as Highly Efficient Photosensitizers for NIR‐II Photodynamic Cancer Therapy
Authors: Yang Yu , Hu Tingting , Zhao Kexin , Wang Yi‐Chi , Zhu Yanfang , Wang Shibo , Zhou Zhan , Gu Lin , Tan Chaoliang , Liang Ruizheng
Published: December 2024

Photodynamic therapy (PDT) is attracting widespread attention as a promising strategy for tumor treatment. However, the efficacy of PDT is severely limited by the insufficient tissue penetration depth of the light source and low reactive oxygen species (ROS) generation efficiency. Herein, the metal doping strategy is reported to construct a series of defect‐rich M‐doped amorphous CoMo‐layered double hydroxide (a‐M‐CoMo‐LDH, M = Mn, Cu, Al, Ni, Mg, Zn) photosensitizers (PSs) for NIR‐II PDT. Especially, M‐doped CoMo‐LDH nanosheets are synthesized through a simple hydrothermal method and then etched by acid treatment to prepare defect‐rich a‐M‐CoMo‐LDH nanosheets. Under NIR‐II 1270 nm laser irradiation, the defect‐rich a‐Zn‐CoMo‐LDH nanosheets exhibit the optimal PDT performance compared with other a‐M‐CoMo‐LDH nanosheets, and also possess much higher ROS production activity (3.9 times) than that of the pristine a‐CoMo‐LDH, with a singlet oxygen quantum yield up to 1.86, which is the highest among all the reported PSs. After polyethylene glycol (PEG) modification, the a‐Zn‐CoMo‐LDH‐PEG nanosheets can function as an effective inorganic PS for PDT, effectively inducing cell apoptosis in vitro and eradicating tumors in vivo. Notably, transcriptome sequencing analysis and further molecular validation highlight the critical role of the apoptotic/p53/AMPK/oxidative phosphorylation signaling pathways in a‐Zn‐CoMo‐LDH‐PEG‐induced cancer cell apoptosis.
The First Kr‐Selective Carbon Molecular Sieve for Inverse Adsorption of Krypton Over Xenon at Ambient Temperature
Authors: Chen Fuqiang , Zheng Fang , Huang Xinlei , Chu Zhe , Sun Haoran , Yang Liu , Yang Qiwei , Zhang Zhiguo , Ren Qilong , Bao Zongbi
Published: December 2024

The efficient adsorption‐based separation of krypton (Kr) and xenon (Xe) is of paramount importance but is challenged by their similar physicochemical properties. While carbon adsorbents are theoretically promising for Kr/Xe sieving, practical success has remained elusive. Here, a series of ultramicroporous carbon molecular sieves synthesized from sucrose‐derived hydrochar is reported. The study employs careful characterization and controlled thermal pyrolysis to tailor ultramicropore formation and elucidate the evolution of the carbon framework. The leading material, C‐Suc‐750, has an ideal pore size of ≈4.0 Å. In particular, C‐Suc‐750 has achieved a remarkable Kr/Xe uptake ratio of 39.3 at ambient conditions, setting a new benchmark for selective Kr adsorption and molecular sieving of Kr/Xe. Breakthrough experiments further confirm the superior molecular sieving performance of C‐Suc‐750, highlighting its potential for Kr recovery in nuclear waste treatment. Moreover, molecular dynamics (MD) simulations demonstrate the critical role of narrow slit‐pore of the carbon molecular sieve in molecular sieving separation of Kr/Xe, providing insights into the mechanism driving this selectivity.
Tailoring Non‐Covalent Interaction Via Single Atom to Boost Interfacial Charge Transfer Toward Photoelectrochemical Water Oxidation
Authors: Zhang Chuanqi , Wang Yueyue , Sun Wenming , Hua Zhaorui , Zhang Zicong , Gong Shuyan , Wang Dingsheng , Tian Yang
Published: December 2024

Photoelectrochemical (PEC) water splitting for hydrogen generation holds immense potential for addressing environmental and energy crises. Tailoring non‐covalent interaction via a single atom is anticipated to realize prominent hole extracting facilitating PEC performance, but it has never been reported. In this study, single atom Co‐N4 is coordinated with 5‐fluoroanthranilic acid (FAA) molecules, then used as a non‐covalent hole‐extracting layer on a BiVO4 substrate. Experiments including X‐ray absorption fine spectra, Kelvin probe force microscopy, transient absorption, and theoretical calculation demonstrate the FAA coordination alters the local configuration of the central Co atom, adjusting the interfacial non‐covalent interaction, thereby reducing the barrier of charge transfer between BiVO4 and the hole‐extracting layer. Consequently, photogenerated carriers are more effectively separated, and the PEC water oxidation performance is significantly enhanced with the photocurrent density of 5.47 mA cm−2 at 1.23 V versus RHE, much higher than those of previously reported BiVO4 photoanodes composited with porphyrin‐based compounds. Experiments and theoretical simulation confirm that the boosted PEC performance originates from exceptional interfacial charge transfer rather than surface catalysis dynamic. This study provides an efficient strategy for tailoring non‐covalent interaction by regulating single‐atom coordination and promoting hole extract to boost PEC water oxidation activity.
GFRα1 Promotes Axon Regeneration after Peripheral Nerve Injury by Functioning as a Ligand
Authors: Suzuki Tomoaki , Kadoya Ken , Endo Takeshi , Yamasaki Miwako , Watanabe Masahiko , Iwasaki Norimasa
Published: December 2024

The neurotrophic factor, Glial cell line derived neurotrophi factor (GDNF), exerts a variety of biological effects through binding to its receptors, GDNF family receptor alpha‐1 (GFRα1), and RET. However, the existence of cells expressing GFRα1 but not RET raises the possibility that GFRα1 can function independently from RET. Here, it is shown that GFRα1 released from repair Schwann cells (RSCs) functions as a ligand in a GDNF‐RET‐independent manner to promote axon regeneration after peripheral nerve injury (PNI). Local administration of GFRα1 into injured nerve promoted axon regeneration, even more when combined with GDNF blockade. GFRα1 bound to a receptor complex consisting of NCAM and integrin α7β1 of dorsal root ganglion neurons in a GDNF‐RET independent manner. This is further confirmed by the Ret Y1062F knock‐in mice, which cannot transmit most of GDNF‐RET signaling. Finally, local administration of GFRα1 into injured sciatic nerve promoted functional recovery. These findings reveal a novel role of GFRα1 as a ligand, the molecular mechanism supporting axon regeneration by RSCs, and a novel therapy for peripheral nerve repair.
Co‐Translational Deposition of N6‐Acetyl‐L‐Lysine in Nascent Proteins Contributes to the Acetylome in Mammalian Cells
Authors: Guo Dingyuan , Li Nan , Zhang Xiaoyan , Zhou Runxin , He Jie , Ding Xiao‐Ping , Yu Weixing , Tong Fuqiang , Yin Sibi , Wang Yu , Xu Xin , Wang Long , Fan Mingzhu , Feng Shan , Liu Ke , Tang Ke , Ouyang Zhuqing , Guo Yusong R , Wang Yugang
Published: December 2024

N6‐acetyl‐L‐lysine residue is abundant in dietary protein but little is known about its potential influences on the diet‐consumers. Herein, it is reported that Lysyl‐tRNA synthetase (KARS) mediates co‐translational deposition of diet‐derived N6‐acetyl‐L‐lysine (AcK) in nascent proteins to contribute to the acetylome in cells. Acetylated dietary protein is a direct source of AcK that can widely and substantially regulate the acetylome in multiple organs of mice. By analyzing the mechanisms underlying AcK contributing to the acetylome in mammalian cells, it is found that KARS can utilize AcK as an alternative substrate to produce N6‐acetyl‐l‐lysyl‐tRNA. The crystal structure of KARS in complex with AcK at 2.26 Å resolution shows that AcK shares the same substrate‐binding pocket as L‐lysine, allowed by a sidechain flip of Tyr499. The generated N6‐acetyl‐L‐lysyl‐tRNA introduces AcK into growing nascent polypeptide and results in protein acetylation, including the regions buried inside folded proteins that are post‐translational modification (PTM)‐inaccessible and functionally important. This undocumented protein modification mechanism is inherently different from PTM and termed as co‐translational modification (coTM). It is expected to extend the repertoire of acetylome and improve the understanding of protein modification mechanisms in cells.
Tailoring Borate Mediator Species Enables Industrial CO Production with Improved Overall Energy Efficiency by Sustainable Molten Salt CO2 Electrolysis
Authors: Li Xinyu , Deng Bowen , Du Kaifa , Li Wenmiao , Chen Di , Qu Xin , Pang Fangzhao , Zhang Xiaodan , Zha Hao , Yin Huayi , Wang Dihua
Published: December 2024

The electrochemical conversion of CO2 into CO represents a promising strategy for mitigating excessive global greenhouse gas emissions. Nevertheless, achieving industrial‐scale electrochemical CO2‐to‐CO conversion with enhanced selectivity and reduced energy consumption presents significant challenges. In this study, a borate‐enhanced molten salt process for CO2 capture and electrochemical transformation is employed, achieving over 98% selectivity for CO and over 55% energy efficiency without the necessity for complex and costly electrocatalysts. Cathodic CO2 electro‐reduction (CO2ER) with the anodic oxygen evolution reaction (OER) at an overall current density of 500 mA cm−2 using non‐nanostructured transition‐metal plate electrodes at 650 °C is coupled. By regulating the electrolyte's oxo‐basicity with earth‐abundant borax (Na2B4O7), a borate‐enhanced electrolyte is established that accelerates the overall electrochemical reaction efficiently. This system involved a series of well‐designed target borate species (BO33−, BO2−, and B4O72−) that acted as mediators shuttling between the cathode and anode, favoring CO as the primary cathodic product. Manipulating the atmosphere above the anode facilitated a spontaneous transformation of borates, further enhancing OER performance with long‐term operational stability over a cumulative period of 50 h, while also reducing overall energy consumption. This work presents a cost‐effective strategy for the industrial‐scale production of CO derived from CO2, contributing to a lower carbon footprint by establishing a sustainable borate‐mediated closed loop.
Automatic Quantitative Analysis of Internal Quantum Efficiency Measurements of GaAs Solar Cells Using Deep Learning
Authors: Abdullah‐Vetter Zubair , Wright Brendan , Wu Tien‐Chun , Shakiba Ali , Hameiri Ziv
Published: December 2024

A solar cell's internal quantum efficiency (IQE) measurement reveals critical information about the device's performance. This information can be obtained using a qualitative analysis of the shape of the curve, identifying and attributing current losses such as at the front and rear interfaces, and extracting key electrical and optical performance parameters. However, conventional methods to extract the performance parameters from IQE measurements are often time‐consuming and require manual fitting approaches. While several methodologies exist to extract those parameters from silicon solar cells, there is a lack of accessible approaches for non‐silicon cell technologies, like gallium arsenide cells, typically limiting the analysis to only the qualitative level. Therefore, this study proposes using a deep learning method to automatically predict multiple key parameters from IQE measurements of gallium arsenide cells. The proposed method is demonstrated to achieve a very high level of prediction accuracy across the entire range of parameter values and exhibits a high resilience for noisy measurements. By enhancing the quantitative analysis of IQE measurements, the method will unlock the full potential of quantum efficiency measurements as a powerful characterization tool for diverse solar cell technologies.