bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective blockade of CD28 and not CTLA-4 with a single-chain Fv–α1-antitrypsin fusion antibody
Authors: Vanhove Bernard , Laflamme Geneviève , Coulon Flora , Mougin Marie , Vusio Patricia , Haspot Fabienne , Tiollier Jérôme , Soulillou Jean-Paul
Published: March 2003

B7-1 and B7-2 are costimulatory molecules expressed on antigen-presenting cells. The CD28/B7 costimulation pathway is critical for T-cell activation, proliferation, and Th polarization. Blocking both cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and CD28 interactions with a CTLA-4/Ig fusion protein inhibits various immune-mediated processes in vivo, such as allograft rejection and autoimmunity. However, selective blockade of CD28 may represent a better strategy for immunosuppression than B7 blockade, because CTLA-4/B7 interactions have been shown to participate in the extinction of the T-cell receptor–mediated activation signal and to be required for the induction of immunologic tolerance. In addition, selective CD28 inhibition specifically decreases the activation of alloreactive and autoreactive T cells, but not the activation of T cells stimulated by exogenous antigens presented in the context of self major histocompatibility complex (MHC) molecules. CD28 blockade cannot be obtained with anti-CD28 dimeric antibodies, which cluster their target and promote T-cell costimulation, whereas monovalent Fab fragments can block CD28 and reduce alloreactivity. In this study, we report the construction of a monovalent single-chain Fv antibody fragment from a high-affinity antihuman CD28 antibody (CD28.3) that blocked adhesion of T cells to cells expressing the CD28 receptor CD80. Genetic fusion with the long-lived serum protein α1-antitrypsin led to an extended half-life without altering its binding characteristics. The anti-CD28 fusion molecule showed biologic activity as an immuno-suppressant by inhibiting T-cell activation and proliferation in a mixed lymphocyte reaction.
Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome
Authors: Deutsch Samuel , Rideau Alexandra , Bochaton-Piallat Marie-Luce , Merla Giuseppe , Geinoz Antoine , Gabbiani Giulio , Schwede Torsten , Matthes Thomas , Antonarakis Stylianos E. , Beris Photis
Published: March 2003

May-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), Sebastian syndrome (SBS), and Epstein syndrome (EPS) are a group of rare, autosomal dominant disorders characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies, together with variable manifestations of Alport-like symptoms that include high-tone sensorineural deafness, cataracts, and nephritis. These disorders result from mutations in the MYH9 gene, which encodes for the nonmuscle myosin heavy chain A protein (also known as NMMHC-A). To date 20 different mutations have been characterized for this gene, but no clear phenotype-genotype correlation has been established, and very little is known regarding the molecular pathogenesis of this group of diseases. Here, we describe 2 new families with MHA/FTNS phenotypes that have been characterized in terms of their mutations, protein localization in megakaryocytes, protein expression, and mRNA stability. Our findings suggest that, at least for the Asp1424Asn mutation in the MYH9 gene, the phenotypes result from a highly unstable protein. No abnormalities in protein localization or mRNA stability were observed. We hypothesize that haploinsufficiency of the MYH9 results in a failure to properly reorganize the cytoskeleton in megakaryocytes as required for efficient platelet production.
Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis
Authors: Giuliani Nicola , Colla Simona , Lazzaretti Mirca , Sala Roberto , Roti Giovanni , Mancini Cristina , Bonomini Sabrina , Lunghi Paolo , Hojden Magda , Genestreti Giovenzio , Svaldi Mirija , Coser Paolo , Fattori Pier Paolo , Sammarelli Gabriella , Gazzola Gian Carlo , Bataille Regis , Almici Camillo , Caramatti Cecilia , Mangoni Lina , Rizzoli Vittorio
Published: March 2003

Patients with multiple myeloma (MM) have increased bone marrow (BM) angiogenesis; however, the proangiogenic properties of myeloma cells and the mechanisms of MM-induced angiogenesis are not completely clarified. The angiopoietin system has been identified as critical in the regulation of vessel formation. In this study we have demonstrated that myeloma cells express several proangiogenic factors, and, in particular, we found that angiopoietin-1 (Ang-1), but not its antagonist Ang-2, was expressed by several human myeloma cell lines (HMCLs) at the mRNA and the protein levels. In a transwell coculture system, we observed that myeloma cells up-regulated the Ang-1 receptor Tie2 in human BM endothelial cells. Moreover, in an experimental model of angiogenesis, the conditioned medium of HMCLs significantly stimulated vessel formation compared with control or vascular endothelial growth factor (VEGF) treatment. The presence of anti-Tie2 blocking antibody completely blunted the proangiogenic effect of XG-6. Finally, our in vitro results were supported by the in vivo finding of Ang-1, but not Ang-2, mRNA and protein expression in purified MM cells obtained from approximately 47% of patients and by high BM angiogenesis in patients with MM positive for Ang-1, suggesting that the angiopoietin system could be involved, at least in part, in MM-induced angiogenesis.
Therapeutic effect of idiotype-specific CD4+ T cells against B-cell lymphoma in the absence of anti-idiotypic antibodies
Authors: Lundin Katrin U. , Hofgaard Peter O. , Omholt Hilde , Munthe Ludvig A. , Corthay Alexandre , Bogen Bjarne
Published: March 2003

Immunoglobulin (Ig) variable (V) region idiotypes (Id's) are highly tumor-specific antigens produced by B-lymphoma cells and are promising targets for immunotherapy. Id vaccination has proven effective in experimental mouse models and may possibly prevent recurrence of B lymphomas in humans. It has previously been shown that anti-Id antibodies protect against B-cell lymphoma in the absence of T cells. We here demonstrate in a T-cell–receptor transgenic mouse model that the contrary is also true: Id-specific CD4+ T cells can protect against Id+ B-lymphoma cells in the absence of B cells, antibodies, and CD8+ T cells. Moreover, Id-specific CD4+ T cells have a curative potential since they could be transferred as late as 17 days after subcutaneous tumor cell injection of severe combined immunodeficiency (SCID) mice and still abrogate tumor development in about 50% of mice. Such mice undergo an acute inflammatory swelling with infiltration of neutrophils at the site of tumor injection, which subsides over weeks, with some mice cured and delayed emergence of lymphomas in other mice. Adoptively transferred CD4+ T cells accumulated in the tumor and were activated (CD69+). In vitro experiments demonstrated that memory, but not naive, Id-specific CD4+ T cells kill Id+ B-lymphoma cells. The results show that Id-specific CD4+ T cells, in the absence of antibodies home to subcutaneous Id+ B lymphoma, become activated, induce inflammation, and prevent tumor development.
Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation
Authors: Pérez-Simón José A. , Díez-Campelo María , Martino Rodrigo , Sureda Anna , Caballero Dolores , Cañizo Consuelo , Brunet Salut , Altes Albert , Vazquez Lourdes , Sierra Jordi , Miguel Jesús F. San
Published: March 2003

We analyzed the impact of CD34+ cell dose on the outcome of 86 patients undergoing reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation. The RIC was based on fludarabine 150 mg/m2 and melphalan 140 mg/m2 or busulphan 10 mg/kg. A median of 5.68 × 106 CD34+ cells/kg and 2.86 × 108 CD3+ cells/kg were infused. All patients receiving more than percentile 75 (p75) of CD34+ cells reached complete chimerism in T lymphocytes by days 21 to 28, compared with 44% among those receiving p75 or fewer cells (P = .046). Overall, 30.3% patients developed grade 2 to 4 acute graft-versus-host disease (aGVHD). Among 83 evaluable patients, 55.8% developed chronic GVHD (cGVHD). The dose of CD34+ cells infused did influence the development of cGVHD, with a cumulative incidence of extensive cGVHD of 74% vs 47% (P = .02) among patients receiving more than p75 CD34+ cells vs those receiving p75 or fewer. Projected overall survival (OS) and event-free survival (EFS) at 43 months were 60% and 46%, respectively. Neither the dose of CD34+ cells nor the dose of CD3+ cells infused significantly influenced OS and EFS, although among patients categorized as high-risk, 36% of those receiving p75 or fewer CD34+ cells relapsed or progressed, compared with only 9% among those receiving more than p75 CD34+ cells (P = .07). Among patients receiving p75 or fewer CD34+ cells, 36% of high-risk patients relapsed, compared with 10% of low- and intermediate-risk patients (P = .004), while relapse rates were not significantly different between both subgroups when we infused more than p75 CD34+ cells, thus indicating that infusing high doses of CD34+ cells ameliorates the negative effect of advanced disease status at transplantation. cGVHD was associated with better EFS (63% vs 16% at 43 months for patients with and without cGVHD; P < .0001) and better OS (78% vs 28% for patients with and without cGHVD; P < .001). The number of CD34+ cells infused should be tailored to prevent extensive cGVHD among patients categorized as low-risk, while high-risk patients, in whom the graft-versus-leukemia effect may determine disease outcome, should receive high doses of CD34+ cells.
Tolerance induction to a mammalian blood group—like carbohydrate antigen by syngeneic lymphocytes expressing the antigen, II: tolerance induction on memory B cells
Authors: Mohiuddin Muhammad M. , Ogawa Haruko , Yin Deng-Ping , Galili Uri
Published: March 2003

Induction of immune tolerance on memory B cells specific to transplantation carbohydrate antigens was studied in the experimental animal model of α1,3galactosyltransferase knockout (KO) mice, which lack the α-gal epitope (Galα1-3Galβ1-4GlcNAc-R) and can produce the anti-Gal antibody against it. Memory anti-Gal B cells were generated by immunization of KO mice with pig kidney membranes (ie, xenogeneic cell membranes expressing an abundance of α-gal epitopes). Lymphocytes including memory anti-Gal B cells were administered into lethally irradiated KO mice, together with syngeneic wild-type (WT) lymphocytes expressing α-gal epitopes. Memory anti-Gal B cells were completely tolerized after being in vivo for 14 days with WT lymphocytes. This was indicated by the lack of anti-Gal immunoglobulin G (IgG) response following immunization with pig kidney membranes vs the extensive anti-Gal response in mice that did not receive WT lymphocytes. Tolerance induction was prevented if T cells were activated by alloantigens. This tolerance was highly specific to anti-Gal B cells and did not affect memory B cells with closely related specificity, such as B cells with anti–blood group A specificity. Tolerance induction on anti-Gal B cells was found to be time dependent and required more than 10 days of in vivo exposure of these B cells to WT lymphocytes. These observations suggest a novel method for induction of tolerance to transplantation carbohydrate antigens in humans, by in vitro transduction of autologous blood lymphocytes with an adenovirus containing the corresponding glycosyltransferase gene and administration of the transduced cells into the circulation after removal of natural antibodies to the antigen. (Blood. 2003;102:229-236)
Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507
Authors: Zhang Zhuo , Zhang Meili , Ravetch Jeffrey V. , Goldman Carolyn , Waldmann Thomas A.
Published: March 2003

Adult T-cell leukemia (ATL) develops in a small proportion of individuals infected with the retrovirus human T-cell leukemia virus (HTLV-1). We evaluated the efficacy of MEDI-507 (a humanized monoclonal antibody directed against CD2) alone and in combination with humanized anti-Tac (HAT) directed toward CD25, the interleukin-2 receptor α (IL-2Rα) using a human adult T-cell leukemia xenograft model. Weekly treatments (4) with HAT significantly prolonged the survival of the ATL-bearing mice when compared with phosphate-buffered saline (PBS)–treated controls (P < .0001). Mice treated with MEDI-507 (100 μg/wk for 4 weeks) survived longer than those treated with HAT (P < .0025). Furthermore, prolonged treatment (6 months) of ATL with MEDI-507 significantly improved the outcome when compared with a short course (4 weeks) of therapy (P < .0036). Such treatment with weekly MEDI-507 for 6 months led to a prolonged survival of the ATL-bearing mice that was comparable with the survival observed in the control group of mice that did not receive a tumor or therapeutic agent. We also found that the expression of Fcγ receptors (FcRγ) on polymorphonuclear leukocytes and monocytes was required for MEDI-507–mediated tumor killing in vivo. Thus, the tumor-killing mechanism with MEDI-507 in vivo required the expression of the receptor FcRγIII on polymorphonuclear leukocytes and monocytes, suggesting that it is mediated by a form of antibody-dependent cellular cytotoxicity. These results demonstrate that MEDI-507 has therapeutic efficacy on ATL in vivo and provides support for a clinical trial involving this monoclonal antibody in the treatment of patients with CD2-expressing leukemias and lymphomas. (Blood. 2003; 102:284-288)
Platelet-collagen interaction: is GPVI the central receptor?
Authors: Nieswandt Bernhard , Watson Steve P.
Published: March 2003

At sites of vascular injury, platelets come into contact with subendothelial collagen, which triggers their activation and the formation of a hemostatic plug. Besides glycoprotein Ib (GPIb) and αIIbβ3 integrin, which indirectly interact with collagen via von Willebrand factor (VWF), several collagen receptors have been identified on platelets, most notably α2β1 integrin and the immunoglobulin (Ig) superfamily member GPVI. Within the last few years, major advances have been made in understanding platelet-collagen interactions including the molecular cloning of GPVI, the generation of mouse strains lacking individual collagen receptors, and the development of collagen receptor–specific antibodies and synthetic peptides. It is now recognized that platelet adhesion to collagen requires prior activation of integrins through “inside-out” signals generated by GPVI and reinforced by released second-wave mediators adenosine diphosphate (ADP) and thromboxane A2. These developments have led to revision of the original “2-site, 2-step” model, which now places GPVI in a central position in the complex processes of platelet tethering, activation, adhesion, aggregation, degranulation, and procoagulant activity on collagen. This review discusses these recent developments and proposes possible mechanisms for how GPVI acts in concert with other receptors and signaling pathways to initiate hemostasis and arterial thrombosis.
IVIg-mediated amelioration of murine ITP via FcγRIIB is independent of SHIP1, SHP-1, and Btk activity
Authors: Crow Andrew R. , Song Seng , Freedman John , Helgason Cheryl D. , Humphries R. Keith , Siminovitch Katherine A. , Lazarus Alan H.
Published: March 2003

It has been established that amelioration of murine immune thrombocytopenia purpura (ITP) by IVIg is dependent on the inhibitory receptor FcγRIIB. Co-cross-linking of the FcγRIIB with the B-cell receptor complex or with FcϵRI in mast cells results in cell inhibition, which is mediated by recruitment of the inositol phosphatase SHIP1 to the cytoplasmic tail of the FcγR. The FcγRIIB can also associate with protein tyrosine phosphatase SHP-1 as a potential secondary target of the receptor. Alternatively, homoaggregation of FcγRIIB can induce a proapoptotic state in B cells that is dependent on the presence of Bruton tyrosine kinase (Btk), a kinase also expressed in monocytes. We sought to determine if these signaling pathways may direct IVIg-mediated FcγRIIB-dependent regulation of in vivo monocyte function in a murine model of ITP in which IVIg functions in an FcγRIIB-dependent manner. We demonstrate that mice deficient in SHIP1, SHP-1, and Btk respond to the ameliorating effects of IVIg with the same kinetics as control mice. We conclude that IVIgmediated inhibitory pathways operating via monocyte FcγRIIB may involve a transmembrane signaling pathway different from that of B cells.
Water in Supercritical CO2 Microemulsion Formation by Fluorinated Surfactants
Authors: Nagai Takabumi , Fujii Kazuhisa , Otake Katsuto , Abe Masahiko
Published: March 2003

We examined the ability for microemulsion formation of fluorinated surfactants containing perfluoropolyether moieties for the CO2-philic tail group and carboxylic acid ammonium or poly(ethylene glycol) methyl ether for the hydrophilic groups and found that the hydrophilic CO2-philic balance of surfactants plays an important role in the formation of microemulsions.
Citing Harms, Momentum Grows to Remove Race From Clinical Algorithms
Authors: Kuehn Bridget M.
Published: January 2024

This Medical News article discusses efforts to evaluate the inclusion of race as a factor in widely used clinical decision-making algorithms.
Impact of Bempedoic Acid on Total Cardiovascular Events
Authors: Nicholls Stephen J. , Nelson Adam J. , Lincoff A. Michael , Brennan Danielle , Ray Kausik K. , Cho Leslie , Menon Venu , Li Na , Bloedon LeAnne , Nissen Steven E.
Published: January 2024

Importance

The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown.

Objective

To determine the impact of bempedoic acid on the total incidence of MACE.

Design, Setting, and Participants

Included in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022.

Interventions

Patients were randomly assigned to treatment with bempedoic acid or placebo daily.

Main Outcomes and Measures

The primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups.

Results

A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients.

Conclusion and Relevance

Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.
In search of the origins of crime continuity: Aggressive versus nonaggressive delinquency as a key factor in the psychological inertia process
Authors: Walters Glenn D. , Kremser Jon , Runell Lindsey
Published: January 2024

The purpose of this study was to test whether the psychological inertia process believed to give rise to crime continuity is limited to aggressive delinquency or evolves from both aggressive and nonaggressive delinquency. Self‐report data provided by 845 early adolescent youth (406 boys, 439 girls) were analyzed in an effort to test the hypothesis that aggressive rather than nonaggressive delinquency precipitates a rise in delinquency through the intervening influence of cognitive impulsivity but not moral neutralization. The hypothesis stated that of the four models evaluated in this study (aggressive delinquency → moral neutralization → offense variety; aggressive delinquency → cognitive impulsivity → offense variety; nonaggressive delinquency → moral neutralization → offense variety; nonaggressive delinquency → cognitive impulsivity → offense variety), only the aggressive delinquency → cognitive impulsivity → offense variety model would achieve significance. Consistent with this hypothesis, only the aggressive delinquency → cognitive impulsivity → offense variety pathway was, in fact, significant. The current findings suggest that the psychological inertia process may be driven by a pattern of aggressive delinquency followed by cognitive impulsivity and that neither nonaggressive delinquency nor moral neutralization contribute to the process. Theoretical and practical implications of these results are discussed.
Feasibility evaluation of radiotherapy positioning system guided by augmented reality and point cloud registration
Authors: Zhai Shaozhuang , Wei Ziwen , Wu Xiaolong , Xing Ligang , Yu Jinming , Qian Junchao
Published: January 2024

Purpose

To develop a radiotherapy positioning system based on Point Cloud Registration (PCR) and Augmented Reality (AR), and to verify its feasibility.

Methods

The optimal steps of PCR were investigated, and virtual positioning experiments were designed to evaluate its accuracy and speed. AR was implemented by Unity 3D and Vuforia for initial position correction, and PCR for precision registration, to achieve the proposed radiotherapy positioning system. Feasibility of the proposed system was evaluated through phantom positioning tests as well as real human positioning tests. Real human tests involved breath‐holding positioning and free‐breathing positioning tests. Evaluation metrics included 6 Degree of Freedom (DOF) deviations and Distance (D) errors. Additionally, the interaction between CBCT and the proposed system was envisaged through CBCT and optical cross‐source PCR.

Results

Point‐to‐plane iterative Closest Point (ICP), statistical filtering, uniform down‐sampling, and optimal sampling ratio were determined for PCR procedure. In virtual positioning tests, a single registration took only 0.111 s, and the average D error for 15 patients was 0.015 ± 0.029 mm., Errors of phantom tests were at the sub‐millimeter level, with an average D error of 0.6 ± 0.2 mm. In the real human positioning tests, the average accuracy of breath‐holding positioning was still at the sub‐millimeter level, where the errors of X, Y and Z axes were 0.59 ± 0.12 mm, 0.54 ± 0.12 mm, and 0.52 ± 0.09 mm, and the average D error was 0.96 ± 0.22 mm. In the free‐breathing positioning, the average errors in X, Y, and Z axes were still less than 1 mm. Although the mean D error was 1.93 ± 0.36 mm, it still falls within a clinically acceptable error margin.

Conclusion

The AR and PCR‐guided radiotherapy positioning system enables markerless, radiation‐free and high‐accuracy positioning, which is feasible in real‐world scenarios.
Causal diagramming to improve students' monitoring accuracy and text comprehension: Effects of diagram standards and self‐scoring instructions
Authors: Braumann Sophia , van Wermeskerken Margot , van de Pol Janneke , Pijeira‐Díaz Héctor J. , de Bruin Anique B. H. , van Gog Tamara
Published: January 2024

Students' monitoring of their text comprehension must be accurate for self‐regulated learning to be effective. Completing causal diagrams after reading (i.e., diagramming) already improves students' monitoring accuracy to some extent. We investigated whether providing secondary school students with a standard (i.e., correctly completed) diagram and self‐scoring instructions would further improve their monitoring accuracy and text comprehension in a delayed (Experiment 1; n = 98) or immediate (Experiment 2; n = 177) diagramming design. Self‐scoring instructions did not improve monitoring accuracy or text comprehension compared to the control condition(s) in either experiment. Presumably, students self‐scored their diagrams even without instructions to do so. In contrast to findings from prior diagramming research without standards, an explorative analysis suggests that delayed and immediate diagramming did not produce differences in monitoring accuracy. Immediate diagramming, however, led to better text comprehension than delayed diagramming and may therefore be preferable over delayed diagramming under certain conditions.
Injectable and Microporous Microgel Assembly with Sequential Bioactive Factor Release for the Endogenous Repair of Nucleus Pulposus
Authors: Luo Huitong , Wang Zetao , Yu Fanglei , Zhou Zhiyu , Wang Jianmin , Chen Dafu , Feng Qi , Cao Xiaodong
Published: January 2024

Harnessing endogenous stem/progenitor cells to enhance extracellular matrix (ECM) deposition in the nucleus pulposus (NP) is considered as a potential treatment for intervertebral disc degeneration (IVDD), but is limited by the lack of suitable scaffolds for cell infiltration and growth, as well as the tailored release of bioactive factors. Herein, an injectable cell‐free microgel assembly (MA‐TNS) with interconnected microporous structure is developed to recruit stem/progenitor cells and induce the differentiation of the recruited cells by releasing stromal cell‐derived factor‐1α (SDF‐1α) and transforming growth factor‐β1 (TGF‐β1) sequentially. TGF‐β1 is initially loaded by the chondroitin sulfate/gelatin nanoparticles. Together with SDF‐1α, these nanoparticles are co‐encapsulated into the photo‐cross‐linked microgels, which are then assembled into a microporous scaffold via dynamic boronate ester bonds. An initial rapid release of SDF‐1α followed by a sustained release of TGF‐β1 lasting over 28 days is achieved. MA‐TNS significantly promotes the recruitment, infiltration, and chondrocyte‐like differentiation of marrow mesenchymal stem cells in vitro. Furthermore, in vivo experiments on rats and cynomolgus monkeys prove that MA‐TNS can inhibit IVDD and recover ECM deposition markedly, thereby enabling long‐term NP reconstruction. The resulting efficacy in rats and nonhuman primates supports that MA‐TNS is a promising scaffold for intervertebral disc repair and regeneration.
Novel Operation Mechanism and Multifunctional Applications of Bubble Microrobots
Authors: Zhou Yuting , Cheng Wen , Dai Liguo , Guo Songyi , Wu Junfeng , Wang Xiaodong , Wu Anhua , Liu Lianqing , Jiao Niandong
Published: January 2024

Microrobots have emerged as powerful tools for manipulating particles, cells, and assembling biological tissue structures at the microscale. However, achieving precise and flexible operation of arbitrary‐shaped microstructures in 3D space remains a challenge. In this study, three novel operation methods based on bubble microrobots are proposed to enable delicate and multifunctional manipulation of various microstructures. These methods include 3D turnover, fixed‐point rotation, and 3D ejection. By harnessing the combined principles of the effect of the heat flow field and surface tension of an optothermally generated bubble, the bubble microrobot can perform tasks such as flipping an SIA humanoid structure, rotating a bird‐like structure, and launching a hollow rocket‐like structure. The proposed multi‐mode operation of bubble microrobots enables diverse attitude adjustments of microstructures with different sizes and shapes in both 2D and 3D spaces. As a demonstration, a biological microenvironment of brain glioblastoma is constructed by the bubble microrobot. The simplicity, versatility, and flexibility of this proposed method hold great promise for applications in micromanipulation, assembly, and tissue engineering.
A Journey of Challenges and Victories: A Bibliometric Worldview of Nanomedicine since the 21st Century
Authors: Wang Jingyu , Zhao Wenling , Zhang Zhao , Liu Xingzi , Xie Tong , Wang Lan , Xue Yuzhou , Zhang Yuemiao
Published: January 2024

Nanotechnology profoundly affects the advancement of medicine. Limitations in diagnosing and treating cancer and chronic diseases promote the growth of nanomedicine. However, there are very few analytical and descriptive studies regarding the trajectory of nanomedicine, key research powers, present research landscape, focal investigative points, and future outlooks. Herein, articles and reviews published in the Science Citation Index Expanded of Web of Science Core Collection from first January 2000 to 18th July 2023 are analyzed. Herein, a bibliometric visualization of publication trends, countries/regions, institutions, journals, research categories, themes, references, and keywords is produced and elaborated. Nanomedicine‐related academic output is increasing since the COVID‐19 pandemic, solidifying the uneven global distribution of research performance. While China leads in terms of publication quantity and has numerous highly productive institutions, the USA has advantages in academic impact, commercialization, and industrial value. Nanomedicine integrates with other disciplines, establishing interdisciplinary platforms, in which drug delivery and nanoparticles remain focal points. Current research focuses on integrating nanomedicine and cell ferroptosis induction in cancer immunotherapy. The keyword “burst testing” identifies promising research directions, including immunogenic cell death, chemodynamic therapy, tumor microenvironment, immunotherapy, and extracellular vesicles. The prospects, major challenges, and barriers to addressing these directions are discussed.
Simple and Effective Patterning Method of Liquid‐Metal‐Infused Sponge Electrode for Fabricating 3D Stretchable Electronics
Authors: Kim Seonghyeon , Yoo Dongwoo , Lim Jongkyeong , Kim Joonwon
Published: January 2024

Stretchable electrodes have emerged as a promising technology for soft robotics and wearable devices. One fabrication method that guarantees sustained elasticity and high conductivity is directly filling or printing an elastic substrate with liquid metal (LM). However, it is difficult to create patterns with complex or 3D shapes, such as hole patterning, integration electrodes, and flexible breadboards. Therefore, a simple and effective patterning method for fabricating 3D stretchable electronics using LM electrodes is proposed in this study. The LM‐infused sponge electrode is fabricated by loading LM onto a polydimethylsiloxane (PDMS) sponge, which is fabricated using the salt‐leaching method in PDMS patterned by replica molding. The LM‐infused sponge electrode exhibits a minimal change in terms of resistivity under strain, bending, and twisting (∆R < 0.01 Ω cm−1). This enables various devices to be driven by the production of flexible breadboards, which makes it possible to integrate the proposed model into commercial electronics. Finally, a stretchable tactile sensor (self‐capacitive and self‐powered) is fabricated by integrating stretchable electrodes using only the LM‐infused sponges. In the future, stretchable electrodes fabricated in this manner can be used in various applications, such as soft robots and wearable devices.
Construction of 3D Patterns Through Modified Electrochemical Replication and Transfer
Authors: Chen Zijian , Fu Jingjing , Chen Fan , Xie Chuan , Zhuang Qiuna , Huang Qiyao , Zheng Zijian
Published: January 2024

As the development of flexible electronics continuously progresses, so does the demand for fabricated 3D electrodes via patterning technology. Electrochemical replication and transfer (ERT) has emerged as an efficient patterning technique, which deposits materials of interest on a predefined template via electroplating and subsequently transfers them onto target substrates. ERT can pattern large‐area 2D electrodes on nontraditional substrates whilst maintaining adequate flexibility, stretchability, and complex surface structures. This study extends the capability of ERT from 2D into 3D patterning. Via the rational design of a 3D SiO2/Si template, in which conductive Si trenches or holes are patterned with insulating SiO2 banks, electroplating of materials only occurs in the exposed Si surfaces so that both continuous and isolated 3D patterns with high aspect ratios up to 4:1 are realized. 3D‐ERT offers a high‐throughput and low‐cost approach to fabricating high Figure of Merit (>30 000) flexible transparent electrodes. Also, the application of 3D‐ERT in constructing highly sensitive, and self‐powered pressure sensors is showcased.
Efficient Blue Thermally Activated Delayed Fluorescence Molecules with Sandwich‐Structured Through‐Space Charge Transfer for Fabricating High‐Performance OLEDs
Authors: Yang Zuguo , Qiu Nuoling , Dong Xiaobin , Li Jinshi , Zou Peng , Yang Dezhi , Ma Dongge , Tang Ben Zhong , Zhao Zujin
Published: January 2024

Exploring robust blue luminescent materials is of high significance but challenging for the commercialization application of organic light‐emitting diodes (OLEDs). In this work, it is wished to report two blue thermally activated delayed fluorescence (TADF) molecules with a through‐space charge transfer feature. They have sandwich‐structured molecular backbones comprised of one triphenyltriazine acceptor and two 9‐phenylcarbazole or 3,6‐di(tert‐butyl)‐9‐phenylcarbazole donors that are linked at the 1,8,9‐positions of a 3,6‐di(tert‐butyl)carbazole holder, and exhibit high thermal stability and strong blue delayed fluorescence with high photoluminescence quantum yields and fast reverse intersystem crossing. The blue OLEDs use 2TBCTC as an emitter and provide outstanding maximum external quantum efficiencies (EQEmaxs) of up to 32.76% with Commission Internationale de I'Eclairage coordinates of (0.160, 0.206). To the best of knowledge, 2TBCTC is the most efficient blue TADF emitter based on through‐space charge transfer in the literature. Moreover, the interlayer‐sensitizing OLED employs 2TBCTC as a sensitizer for blue multi‐resonance TADF (MR‐TADF) molecule (v‐DABNA) as guest emitter attains an excellent EQEmax of 32.69% with a narrow full width at half maximum of 18 nm, validating the excellent potential of 2TBCTC as sensitizer for MR‐TADF emitters and the feasibility and effectiveness of the interlayer sensitization strategy for blue hyperfluorescence OLEDs.
Perfect Absorption with Independent Electric and Magnetic Lattice Resonances in Metallo‐Dielectric Arrays
Authors: Cerdán Luis , Deop‐Ruano Juan R. , Alvarez‐Serrano Juan J. , Manjavacas Alejandro
Published: January 2024

Lattice resonances are collective modes supported by periodic arrays of nanostructures. They originate from the coherent interaction between the localized modes of the individual constituents of the array, which, for systems made of metallic nanostructures, usually correspond to the electric dipole plasmon. Unfortunately, fundamental symmetry reasons preclude a two‐dimensional (2D) arrangement of electric dipoles from absorbing more than half the incident power, thus imposing a strong limitation on the performance of conventional lattice resonances. This work introduces an innovative solution to overcome this constraint, which is based on using an array made of a unit cell containing one metallic and one dielectric nanostructure. Using a rigorous coupled dipole model, it is shown that this system can support two independent lattice resonances associated, respectively, with the electric and magnetic dipole modes of the nanostructures. By adjusting the geometrical characteristics of the array, these two lattice resonances can be meticulously aligned in the spectral domain, leading to the total absorption of the incident power. The results of this work provide clear, yet general, guidelines for the rational design of arrays sustaining lattice resonances capable of producing perfect absorption, thus leveraging the potential of these modes for applications requiring an efficient absorption of light.
Giant Apparent Optical Circular Dichroism in Thin Films of Bismuth‐Based Hybrid Organic–Inorganic Metal Halide Semiconductor Through Preferred Orientation
Authors: Yan Liang , Xie Yi , Mitzi David B. , Sercel Peter C. , Phillips Alan J. , Blackburn Jeffrey L. , You Wei
Published: January 2024

Introducing chirality into organic/inorganic hybrid materials can impart chiroptical properties such as circular dichroism. The ability to tune chiroptical properties in self‐assembled materials can have important implications for spintronic and optoelectronic applications. Here, a chiral organic cation, (R/S)‐4‐methoxy‐α‐methylbenzylammonium, is incorporated to synthesize the bismuth‐based hybrid organic–inorganic metal halide semiconductor, (R/S‐MeOMePMA)BiI4. Thin films of this Bi‐based compound demonstrate large chiroptical responses, with circular dichroism anisotropy (gCD) values up to ≈0.1, close to the highest value observed in another chiral metal‐halide semiconductor, (R‐MBA2CuCl4). Detailed investigation reveals that this large gCD in (R/S‐MeOMePMA)BiI4 is caused by the apparent CD effect. Careful selection of deposition conditions and the concomitant thin‐film orientation enables the control of gCD, with maximum value observed when its thin film has a well‐crystallized preferred (001) orientation parallel to the substrate. The results support a growing body of evidence that low symmetry plays an important role in achieving unusually large gCD in these chiral metal–halide materials and provides design rules for achieving large chiroptical response via morphology control.
Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis‐Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment
Authors: Zhi Yuan , Wang Qian , Zi Moxin , Zhang Shanshan , Ge Junshang , Liu Keyue , Lu Linsong , Fan Chunmei , Yan Qijia , Shi Lei , Chen Pan , Fan Songqing , Liao Qianjin , Guo Can , Wang Fuyan , Gong Zhaojian , Xiong Wei , Zeng Zhaoyang
Published: January 2024

In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.
Hierarchical Self‐Assembly of Capsule‐Shaped Zirconium Coordination Cages with Quaternary Structure
Authors: Du Shunfu , Sun Shihao , Ju Zhanfeng , Wang Wenjing , Su Kongzhao , Qiu Fenglei , Yu Xuying , Xu Gang , Yuan Daqiang
Published: January 2024

Biological macromolecules exhibit emergent functions through hierarchical self‐assembly, a concept that is extended to design artificial supramolecular assemblies. Here, the first example of breaking the common parallel arrangement of capsule‐shaped zirconium coordination cages is reported by constructing the hierarchical porous framework ZrR‐1. ZrR‐1 adopts a quaternary structure resembling protein and contains 12‐connected chloride clusters, representing the highest connectivity for zirconium‐based cages reported thus far. Compared to the parallel framework ZrR‐2, ZrR‐1 demonstrated enhanced stability in acidic aqueous solutions and a tenfold increase in BET surface area (879 m2 g−1). ZrR‐1 also exhibits excellent proton conductivity, reaching 1.31 × 10−2 S·cm−1 at 353 K and 98% relative humidity, with a low activation energy of 0.143 eV. This finding provides insights into controlling the hierarchical self‐assembly of metal–organic cages to discover superstructures with emergent properties.
Reliable Memristive Switching Empowered by Ag/NiO/W ReRAM Configuration for Multi‐Level Non‐Volatile Memory Applications
Authors: Chauhan Manvendra , Choudhary Sumit , Sharma Satinder K.
Published: January 2024

Resistive random‐access memories (ReRAM) are promising candidates for next‐generation non‐volatile memory, logic components, and bioinspired neuromorphic computing applications. The analog resistive switching (RS) tuning with a sizable memory window is crucial for realizing multi‐level storage devices. This work demonstrates the multi‐level storage capability of fabricated Ag/NiO/W ReRAM architecture, controlled through voltage modulations. The fabricated ReRAM structures exhibit stable bipolar analog RS, non‐overlapping resistance, and endurance of ≈104 cycles, respectively, with marginal statistical variations/fluctuations. Also, the fabricated ReRAM offers highly controlled and stable retention characteristics tested up to ≈104 s with significantly controlled statistical variations/fluctuations. Adjacent thereto, it offers a substantially lower operating SET and RESET voltage of 1 and −1 V, respectively. Moreover, the non‐overlapping multiple resistive states are observed with the voltage pulse modulation schemes. Furthermore, the current switching mechanism is described using a model proposed for the conductive filament growth and the contribution of the NiO/W interface layer (IL) toward notable RS of fabricated Ag/NiO/W structures.
Effects of Grain Boundaries and Surfaces on Electronic and Mechanical Properties of Solid Electrolytes
Authors: Xie Weihang , Deng Zeyu , Liu Zhengyu , Famprikis Theodosios , Butler Keith T. , Canepa Pieremanuele
Published: January 2024

Extended defects, including exposed surfaces and grain boundaries (GBs), are critical to the properties of polycrystalline solid electrolytes in all‐solid‐state batteries (ASSBs). These defects can alter the mechanical and electronic properties of solid electrolytes, with direct manifestations in the performance of ASSBs. Here, by building a library of 590 surfaces and grain boundaries of 11 relevant solid electrolytes—including halides, oxides, and sulfides— their electronic, mechanical, and thermodynamic characteristics are linked to the functional properties of polycrystalline solid electrolytes. It is found that the energy required to mechanically “separate” grain boundaries can be significantly lower than in the bulk region of materials, which can trigger preferential cracking of solid electrolyte particles in the grain boundary regions. The brittleness of ceramic solid electrolytes, inferred from the predicted low fracture toughness at the grain boundaries, contributes to their cracking under local pressure imparted by lithium (sodium) penetration in the grain boundaries. Extended defects of solid electrolytes introduce new electronic interfacial states within bandgaps of solid electrolytes. These states alter and possibly increase locally the availability of free electrons and holes in solid electrolytes. Factoring effects arising from extended defects appear crucial to explain electrochemical and mechanical observations in ASSBs.
Women farmers and community well‐being under modeling uncertainty
Authors: Schmidt Claudia , Deller Steven C. , Goetz Stephan J.
Published: January 2024

We examine the association between woman farmers and community well‐being using U.S. county‐level data. We address modeling uncertainty around three measures of community well‐being by using a spatial Bayesian model averaging approach and find that a higher share of farms operated or owned by women in a county is associated with higher rates of new business formation, longer life expectancies, and lower poverty rates. The results are consistent with a growing literature that finds women business owners approach their businesses more holistically, with positive community spillovers.
Improved quality of life in patients with chronic rhinosinusitis with nasal polyps associated with expanded types of endoscopic sinus surgery: A 2‐year retrospective study
Authors: Martin‐Jimenez Daniel I , Moreno‐Luna Ramon , Callejon‐Leblic Amparo , Del Cuvillo Bernal Alfonso , Ebert Charles S. , Maza‐Solano Juan M , Gonzalez‐Garcia Jaime , Sanchez‐Gomez Serafin
Published: January 2024

Key points

Expanded types of functional endoscopic sinus surgery (FESS) significantly improve quality of life and reduce revision surgeries rates, supporting their early application for moderate‐to‐severe cases.

Minimal clinically important difference may play as a crucial role in defining surgical treatment response (i.e., responder and super‐responder conditions).

Expanded FESS benefits patients with chronic rhinosinusitis with nasal polyps but more data are required to have a clearer understanding of its uses due to varied approaches and reported outcomes in the literature.
Tapcin, an In Vivo Active Dual Topoisomerase I/II Inhibitor Discovered by Synthetic Bioinformatic Natural Product (Syn‐BNP)‐Coupled Metagenomics
Authors: Wang Zongqiang , Kasper Amanda , Takahashi Mai , Morales Amador Adrian , Bhattacharjee Abir , Kan Jingbo , Hernandez Yozen , Ternei Melinda , Brady Sean F.
Published: January 2024

DNA topoisomerases are attractive targets for anticancer agents. Dual topoisomerase I/II inhibitors are particularly appealing due to their reduced rates of resistance. A number of therapeutically relevant topoisomerase inhibitors are bacterial natural products. Mining the untapped chemical diversity encoded by soil microbiomes presents an opportunity to identify additional natural topoisomerase inhibitors. Here we couple metagenome mining, bioinformatic structure prediction algorithms, and chemical synthesis to produce the dual topoisomerase inhibitor tapcin. Tapcin is a mixed p‐aminobenzoic acid (PABA)‐thiazole with a rare tri‐thiazole substructure and picomolar antiproliferative activity. Tapcin reduced colorectal adenocarcinoma HT‐29 cell proliferation and tumor volume in mouse hollow fiber and xenograft models, respectively. In both studies it showed similar activity to the clinically used topoisomerase I inhibitor irinotecan. The study suggests that the interrogation of soil microbiomes using synthetic bioinformatic natural product methods has the potential to be a rewarding strategy for identifying potent, biomedically relevant, antiproliferative agents.