bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Killing of Human Colon Cancer Stem Cells by γδ T Lymphocytes
Authors: Todaro Matilde , D'Asaro Matilde , Caccamo Nadia , Iovino Flora , Francipane Maria Giovanna , Meraviglia Serena , Orlando Valentina , La Mendola Carmela , Gulotta Gaspare , Salerno Alfredo , Dieli Francesco , Stassi Giorgio
Published: May 2009

Colon cancer comprises a small population of cancer stem cells (CSC) that is responsible for tumor maintenance and resistant to cancer therapies, possibly allowing for tumor recapitulation once treatment stops. We previously demonstrated that such chemoresistance is mediated by autocrine production of IL-4 through the up-regulation of antiapoptotic proteins. Several innate and adaptive immune effector cells allow for the recognition and destruction of cancer precursors before they constitute the tumor mass. However, cellular immune-based therapies have not been experimented yet in the population of CSCs. Here, we show that the bisphosphonate zoledronate sensitizes colon CSCs to Vγ9Vδ2 T cell cytotoxicity. Proliferation and production of cytokines (TNF-α and IFN-γ) and cytotoxic and apoptotic molecules (TRAIL and granzymes) were also induced after exposure of Vγ9Vδ2 T cells to sensitized targets. Vγ9Vδ2 T cell cytotoxicity was mediated by the granule exocytosis pathway and was highly dependent on isoprenoid production by of tumor cells. Moreover, CSCs recognition and killing was mainly TCR mediated, whereas NKG2D played a role only when tumor targets expressed several NKG2D ligands. We conclude that intentional activation of Vγ9Vδ2 T cells by zoledronate may substantially increase antitumor activities and represent a novel strategy for colon cancer immunotherapy.
CD45-Mediated Fodrin Cleavage during Galectin-1 T Cell Death Promotes Phagocytic Clearance of Dying Cells
Authors: Pang Mabel , He Jiale , Johnson Pauline , Baum Linda G.
Published: May 2009

Disassembly and phagocytic removal of dying cells is critical to maintain immune homeostasis. The factors that regulate fragmentation and uptake of dying lymphocytes are not well understood. Degradation of fodrin, a cytoskeletal linker molecule that attaches CD45 to the actin cytoskeleton, has been described in apoptotic cells, although no specific initiator of fodrin degradation has been identified. CD45 is a glycoprotein receptor for galectin-1, an endogenous lectin that can trigger lymphocyte apoptosis, although CD45 is not required for phosphatidylserine externalization or DNA degradation during galectin-1 death. In this study, we show that fodrin degradation occurs during galectin-1 T cell death and that CD45 is essential for fodrin degradation to occur. In the absence of CD45, or if fodrin degradation is prevented, galectin-1-induced cell death is not accompanied by membrane blebbing, although phosphatidylserine externalization and DNA degradation proceed, indicating that fodrin degradation occurs via a distinct pathway compared with the pathway that leads to these other hallmarks of cell death. Moreover, there is slower phagocytic uptake by macrophages of T cells in which fodrin degradation is prevented, relative to T cells in which CD45-mediated fodrin degradation occurs. These studies identify a novel role for CD45 in regulating cellular disassembly and promoting phagocytic clearance during galectin-1-induced T cell death.
Cooperation between Molecular Targets of Costimulation in Promoting T Cell Persistence and Tumor Regression
Authors: Zhao Baohua , Song Aihua , Haque Rizwanul , Lei Fengyang , Weiler Lauren , Xiong Xiaofang , Wu Yuzhang , Croft Michael , Song Jianxun
Published: May 2009

Costimulation regulates multiple cellular processes of T cells inducing proliferation, expansion, and survival. The molecular targets of costimulation might then be useful to augment T cell activities. Two defined targets of costimulatory signals in primary T cells are the anti-apoptotic bcl-2 family molecule Bcl-xL, and survivin, an inhibitor of apoptosis family member that might regulate both cell division and survival. However, the relative importance of, and relationship between, these molecules in primary T cells is not clear. To understand whether they have overlapping or cooperative functions, we used retrovirus-mediated transduction to introduce Bcl-xL and survivin separately, or together linked by a 2A picornavirus self-cleaving peptide, into Ag-responding CD8+ T cells. We found that CD8+ effector T cells expressing both Bcl-xL and survivin strongly expanded at an early stage and had a long-term survival advantage over cells transduced with either molecule alone. In vivo, with response to tumor-expressed Ag following adoptive T cell transfer, Ag-reactive CD8+ T cells expressing both Bcl-xL and survivin displayed greatly enhanced tumor protective activity compared with CD8+ T cells expressing either molecule introduced separately. These results indicate that Bcl-xL and survivin can critically contribute in a cooperative, nonredundant manner to augment the accumulation and persistence of CD8+ T cells following encounter with Ag. The data provide new insights into why costimulatory signals might need to be sustained over time and suggest a potential novel approach to augment cellular immunotherapy for cancer.
In Situ IL-12/23p40 Production during Mycobacterial Infection Is Sustained by CD11bhigh Dendritic Cells Localized in Tissue Sites Distinct from Those Harboring Bacilli
Authors: Rothfuchs Antonio Gigliotti , Egen Jackson G. , Feng Carl G. , Antonelli Lis R. V. , Bafica Andre , Winter Nathalie , Locksley Richard M. , Sher Alan
Published: May 2009

Although IL-12/23p40 is known to play a major role in host resistance to Mycobacterium spp, the cellular source, tissue localization, and regulation of p40 production during mycobacterial infection in vivo has been unclear. In this study, we used IL-12/23p40eYFP (yet40) reporter mice to track expression of the cytokine following Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. We found that in spleens of these mice, p40 production is initiated by a transient burst from CD11blowCD11c+ dendritic cells (DC) which are later replaced at the onset of granuloma formation by CD11bhighCD11c+ DC as the major source of the cytokine. The latter subset was also found to be the key producer of DC-derived p40 in nonlymphoid tissue and in both spleen and liver optimal production of the cytokine was regulated by endogenous TNF-α. Although BCG and p40-expressing DC were both observed in splenic white pulp, p40+ DC rarely colocalized with bacilli. Indeed, in vitro flow cytometry and confocal microscopy indicated that the presence of intracellular bacteria is not required for p40 production by DC and Transwell experiments confirmed that soluble mycobacterial components are sufficient for inducing cytokine expression by these cells. Moreover, when stimulated with LPS, DC directly infected with BCG showed impaired IL-12p40 production in vitro. Together, our findings establish CD11bhigh DC as a major source of IL-12/23p40 during mycobacterial infection in situ and implicate both soluble mycobacterial products and TNF-α in stimulating sustained production of p40 by these cells.
PD-1-Mediated Suppression of IL-2 Production Induces CD8+ T Cell Anergy In Vivo
Authors: Chikuma Shunsuke , Terawaki Seigo , Hayashi Tamon , Nabeshima Ryusuke , Yoshida Takao , Shibayama Shiro , Okazaki Taku , Honjo Tasuku
Published: May 2009

Accumulating evidence suggests that PD-1, an immuno-inhibitory receptor expressed on activated T cells, regulates peripheral T cell tolerance. In particular, PD-1 is involved in the induction and/or maintenance of T cells’ intrinsic unresponsiveness to previously encountered Ags, although the mechanism is yet to be determined. We used a simple experimental model to dissect the mechanism for anergy establishment, in which 2C TCR transgenic rag2−/− PD-1+/+ mice were anergized by a single injection of a cognate peptide. Interestingly, 2C rag2−/− PD-1−/− mice were totally resistant to anergy induction by the same treatment; thus, PD-1 was responsible for anergy induction. Furthermore, PD-1 expression was induced within 24 h of the initial Ag exposure. The establishment of anergy was associated with a marked down-regulation of IL-2 from the CD8+ T cells. In fact, IL-2 blockade resulted in anergy even in 2C rag2−/−PD-1−/− T cells. Furthermore, the complementation of the IL-2 signal in 2C rag2−/− PD-1+/+ mice reversed the anergy induction. We propose that CD8+ T cell anergy is induced by a reduction of cell-autonomous IL-2 synthesis, which is caused by the quick expression of PD-1 in response to Ag stimulation and the subsequent stimulation of this receptor by its ligands on surrounding cells.
Phenotypic and Functional Analyses of KIR3DL1+ and KIR3DS1+ NK Cell Subsets Demonstrate Differential Regulation by Bw4 Molecules and Induced KIR3DS1 Expression on Stimulated NK Cells
Authors: Morvan Maelig , Willem Catherine , Gagne Katia , Kerdudou Nolwenn , David Gaelle , Sébille Véronique , Folléa Gilles , Bignon Jean-Denis , Retière Christelle
Published: May 2009

Recently, the Z27 mAb was shown to recognize the NK cell-activating receptor KIR3DS1, and several genetic studies suggest that the most probable ligands of KIR3DS1 are HLA class I molecules with the Bw4 motif. Despite these findings, the attempts to establish a functional interaction between KIR3DS1 and its potential ligand have been unsuccessful. Here, we study the proliferation and cytotoxicity of KIR3DS1+ NK cells, compared with KIR3DL1+ NK cells, according to the Bw4+ or Bw4− allogeneic environment. Our results show for the first time that KIR3DS1 expression on NK cells can be induced after exposure to stimulator cells (221, K562, EBV-B cell lines, and B cells), polyinosinic-polycytidylic acid, IL-15, or IL-2. Furthermore, whereas KIR3DL1+ NK cell proliferation and cytotoxicity were inhibited in a Bw4+ but not a Bw4− context, KIR3DS1+ NK cell functions were not influenced by the presence of Bw4 on target cells. Nevertheless, despite the absence of demonstrated regulation of KIR3DS1+ NK cell functions by HLA-Bw4 molecules, we found a higher KIR3DS1+ NK cell frequency and higher levels of KIR3DS1 expression in Bw4+ compared with Bw4− individuals. Altogether, these results suggest that KIR3DS1 does not recognize HLA-Bw4 molecules in a physiological context, and they highlight the induced expression of KIR3DS1 observed on stimulated NK cells and the higher frequency of KIR3DS1+ NK cells in Bw4+ individuals. Because a protective KIR3DS1-Bw4 association has been reported in viral infections, our results further the understanding of the role of KIR3DS1+ NK cells in controlling viral infections.
Dendritic Cells Use Endocytic Pathway for Cross-Priming Class Ib MHC-Restricted CD8αα+TCRαβ+ T Cells with Regulatory Properties
Authors: Smith Trevor R. F. , Tang Xiaolei , Maricic Igor , Garcia Zacarias , Fanchiang Shaohsuan , Kumar Vipin
Published: May 2009

Understanding the mechanisms leading to effective priming of lymphocytes with regulatory properties is crucial for the manipulation of immune responses. CD8αα+TCRαβ+ T cells are a special subset of innate-like lymphocytes that have been shown to be involved in immune regulation. These cells can recognize self-peptides in the context of a class Ib molecule, Qa-1. How self-Ags are processed in the Qa-1 pathway and presented to CD8αα+TCRαβ+ T cells is not understood. In this study we demonstrate a cross-presentation pathway by which bone marrow-derived dendritic cells (DCs) capture apoptotic CD4+ T cells and process and present TCR-derived peptides in the context of Qa-1 to prime CD8αα+TCRαβ+ T cells. The priming ability of the DCs is enhanced following TLR signaling using TLR3, TLR4, and TLR9 agonists. DC-mediated cross-presentation is inhibited in the presence of endosomal and proteasomal Ag-processing antagonists. Importantly, DCs loaded with apoptotic T cells prime CD8αα+TCRαβ+ T cells in vivo, which in turn provides protection from CD4+ T cell-mediated autoimmune disease. These data provide a key insight related to processing and presentation of self-Ags in the Qa-1 pathway for priming of CD8αα+TCRαβ+ T cells and have implications for a DC-based immunotherapeutic approach to inflammatory diseases.
CARMA1 Controls an Early Checkpoint in the Thymic Development of FoxP3+ Regulatory T Cells
Authors: Molinero Luciana L. , Yang Jianying , Gajewski Thomas , Abraham Clara , Farrar Michael A. , Alegre Maria-Luisa
Published: May 2009

Natural regulatory T cells (nTregs) that develop in the thymus are essential to limit immune responses and prevent autoimmunity. However, the steps necessary for their thymic development are incompletely understood. The CARMA1/Bcl10/Malt1 (CBM) complex, comprised of adaptors that link the TCR to the transcription factor NF-κB, is required for development of regulatory T cells (Tregs) but not conventional T cells. Current models propose that TCR-NF-κB is needed in a Treg-extrinsic manner for IL-2 production by conventional T cells or in already precommitted Treg precursors for driving IL-2/STAT5 responsiveness and further maturation into Tregs and/or for promoting cell survival. Using CARMA1-knockout mice, our data show instead that the CBM complex is needed in a Treg-intrinsic rather than -extrinsic manner. Constitutive activity of STAT5 or protection from apoptosis by transgenic expression of Bcl2 in developing Tregs is not sufficient to rescue CARMA1-knockout Treg development. Instead, our results demonstrate that the CBM complex controls an early checkpoint in Treg development by enabling generation of thymic precursors of Tregs. These data suggest a modified model of nTreg development in which TCR-CBM-dependent signals are essential to commit immature thymocytes to the nTreg lineage.
Artificial Intelligence: Revolutionizing the Medicolegal Field
Authors: Brigham Christopher R. , Buttar Waqas A. , Bucksbaum Mark , Talmage James B.
Published: April 2024

Artificial intelligence (AI) is transforming healthcare and holds immense potential for the medicolegal field. It also presents significant challenges for these systems and their participants. This article overviews core AI concepts such as machine learning and large language models. It highlights current medical applications spanning clinical decision support, computer vision, robotics, and predictive analytics. AI can aid research, summarize documents, draft reports, and enhance quality and efficiency in a medicolegal practice. Limitations must be recognized and managed. Human expertise remains irreplaceable for nuanced analysis, and oversight is crucial. With thoughtful adoption, AI can augment medicolegal evaluations and enhance quality and efficiency. But human skills like critical thinking, judgment, and compassion must persist at the heart of this profoundly human profession.
Introduction to Artificial Intelligence (AI) and AI-Related Concepts
Authors: Brigham Christopher R. , Buttar Waqas A. , Bucksbaum Mark , Talmage James B.
Published: April 2024

Artificial intelligence (AI) is transforming health care and holds immense potential for various fields, including the medical field, but it also brings its share of concerns and issues. This article introduces AI and its core concepts, such as deep learning, machine learning, and large language models (LLMs). It also provides examples that were generated using ChatGPT to highlight the use of prompts and the limitations of LLMs in AI. AI is a powerful paradigm for scientific research, and it can and does reduce work effort and enhance results. However, is it the right tool for the selected task? In addition, no matter how powerful, AI is meant to complement humans and does not replace them.
Circulating Tumor HPV DNA in Patients With Stage I and II HPV-Associated Head and Neck Cancer After Surgery
Authors: Naegele Saskia , Das Dipon , Hirayama Shun , Shalhout Sophia Z. , Lee Hang , Richmon Jeremy D. , Faden Daniel L.
Published: April 2024

This cohort study examines the association of posttreatment circulating tumor human papillomavirus DNA (ctHPVDNA) with residual disease and 2-year overall survival and recurrence-free survival in patients with HPV-associated head and neck cancer.
Finite‐Element Analysis Study Comparing Titanium and Polyetheretherketone Caps in a Conometric Connection between Implant and Prosthesis
Authors: Ceddia Mario , Romasco Tea , Comuzzi Luca , Specchiulli Alessandro , Piattelli Adriano , Lamberti Luciano , Di Pietro Natalia , Trentadue Bartolomeo
Published: April 2024

Prosthetic retention relies on the perfect adaptation between the cap and the abutment of a dental implant. The conometric connection ensures retention similar to cemented systems, preventing bacterial infiltration and sustaining a high implant success rate. Furthermore, the material used for the cap plays a crucial role in distributing stress on the implant components and bone. Traditionally, caps use titanium (Ti), but ongoing research investigates polyetheretherketone (PEEK) for its bone‐like qualities and similar elasticity to Ti. In this finite‐element analysis study, stress and strain distributions are compared between crestal and subcrestal implants using Ti and PEEK conometric caps, assessing retention through cap displacement to determine the material best suited for proper retention aligned with implant insertion depth. In the findings, an improvement in stress and strain is indicated on trabecular bone, a reduction in stress on cortical bone, and thus enhanced implant stability due to higher stresses around the implant threads, particularly with PEEK coping and subcrestal placement. Consequently, PEEK emerges as a promising substitute for Ti in conometric caps as it absorbs stress more effectively, distributing it across prosthetics to counter stress shielding and prevent implant failure.
A Simultaneous Modulation Strategy to Construct High Dense and Accessible Co‐N4 Sites for Promoting Oxygen Reduction Reaction in Zn–Air Battery
Authors: Xie Xuan , Peng Hui , Sun Kanjun , Li Wenjuan , Liang Aoji , Ma Guofu , Lei Ziqiang , Xu Yuxi
Published: April 2024

Transition metal‐nitrogen‐carbon single‐atom catalysts (M─N─C SACs) exhibit outstanding catalytic activity for the oxygen reduction reaction (ORR). However, these catalysts still face the dual challenges of low density and low utilization of active sites in practical applications. Hence, a simultaneous modulation strategy to construct high‐density and accessible Co‐N4 sites on nitrogen‐doped porous carbon (CoH SA/NC), is reported. As expected, the optimized CoH SA/NC catalyst exhibits superior ORR activity with a half‐wave potential value of 0.874 V, outperforming that of the benchmark Pt/C catalyst. Importantly, the mass activity and turnover frequency of CoH SA/NC are 14.7 and 13.3 times higher than that of low‐density Co single atom catalyst (CoL SA/NC), respectively. Structural characterization and density functional theory (DFT) reveal that the porous structure and the high dense Co‐N4 sites synergistically improve the ORR performance, in which the high dense Co‐N4 sites induced a redistribution of the d orbital, resulting in dz2 orbital has enough electron to interact with the OOH* specie, thereby facilitating the kinetic process of ORR. Moreover, CoH SA/NC‐based Zn–Air Battery (ZAB) also showed excellent device performance, including a high‐power density (191.7 mW cm−2), high specific capacity, and outstanding stability (250 h), significantly superior to benchmark Pt/C‐based ZABs.
Chemokine‐Based Injectable Navigation System for Enhancing CAR‐T Cell Therapy Against Solid Tumors
Authors: Wan Wenjun , Han Wenqing , Chen Jin , Li Yangjing , Zhao Lei , Gao Mengqian , Shen Cui , Liu Ning , Deng Wenhao , Ma Siqi , Cheng Lifang , Zheng Yiran
Published: April 2024

Chimeric antigen receptor (CAR)‐T cell therapy has demonstrated poor efficacy for solid tumors. The low number and poor functional persistence of CAR‐T cells in tumors are the main limiting factors. Here a Chemokine‐based Injectable platform for enhancing adoptive T cells’ Efficacy (CITE) is presented. CITE consists of peritumorally‐injected immunogel co‐loading chemotactic CXCL9 particles with PD‐1 antibody (aPD1) and intravenously‐infused tumor‐penetrating peptide iRGD. Immunogel formed drug depots and allowed sustained release of cargo peritumorally while iRGD facilitated tumor infiltration of gel‐released drugs, thus remarkably increasing the amount of CXCL9 and aPD1 in the tumor. CITE induced an effective chemotactic gradient to promote the tumor‐specific migration of CAR‐T cells and boosted the function of infiltrated T cells by blocking immunosuppression via a two‐in‐one approach. Consequently, CITE yielded a 218‐fold increase in the intratumoral number of transferred T cells and substantially improved the efficacies of transferred T cell receptor (TCR)‐T cells and CAR‐T cells in multiple syngeneic tumor models, including immunologically “cold” tumors, in immunocompetent mice. More importantly, CITE enhanced systemic antitumor immunity and elicited immune memory, enabling CITE to treat multimodal, metastatic, and recurrent tumors. CITE is broadly applicable to adoptive cell therapies involving CAR‐T or TCR‐T cells.
Polyphenol‐Copper Derived Self‐Cascade Nanozyme Hydrogel in Boosting Oxygenation and Robust Revascularization for Tissue Regeneration
Authors: Wen Mengyao , Wang Tianyi , Li Na , Wu Yifeng , Zhang Lianbing , Xue Yumeng , Shang Li
Published: April 2024

The regeneration of hypoxia‐impaired chronic tissue defects has long been challenging, mainly due to the inefficiency of oxygenation and the limited biological activity of existing oxygen delivery systems in regulating dynamic tissue regeneration process. Herein, a novel polyphenol‐copper coordination strategy to fabricate bioactive superoxide dismutase‐catalase self‐cascade nanozymes (SalB‐CuNCs) is reported, which can serve as an in situ oxygenator and induce angiogenesis simultaneously. The copper‐phenolic hydroxyl coordination structure in SalB‐CuNCs plays a critical role in promoting the enzyme‐like cascade reaction via catechol‐mediated Cu valence state transition and substrate capture mechanism. Furthermore, after incorporating SalB‐CuNCs into a Schiff base hydrogel (COC@SalB‐Cu), the resulting system exhibits outstanding antioxidant and robust oxygenation effect in mitigating the hypoxic microenvironment. Benefiting from the intrinsic angiogenic activity of SalB and copper, COC@SalB‐Cu hydrogel can induce a more complete tube formation by up‐regulating the expression level of vascular endothelial growth factor (VEGF), platelet‐endothelial cell adhesion molecule‐1 (CD31), and endothelial nitric oxide synthase (eNOS). In vivo experiments further demonstrate that the COC@SalB‐Cu hydrogel can significantly restore the oxygen and blood supply, leading to fast tissue regeneration. The present strategy holds enormous promise for the treatment of hypoxia‐related chronic tissue defects and vascular injury in the field of regenerative medicine.
In Situ Exsolution of Quaternary Alloy Nanoparticles for CO2‐CO Mutual Conversion Using Reversible Solid Oxide Cells
Authors: Luo Yao , Zhang Dong , Liu Tong , Chang Xu , Wang Jietao , Wang Yao , Gu Xiang‐Kui , Ding Mingyue
Published: April 2024

Reversible solid oxide cell is a promising energy storage and conversion device for CO2‐CO mutual conversion, with simplified cell configuration and performance stability. One key technical challenge is the lack of catalytically active and carbon‐tolerant fuel electrodes. The other one is still a lack of the kinetics mechanism and the redox stability of the active interface. Herein, the findings of a fuel electrode composed of a Sr2Fe1.0Co0.2Ni0.2Cu0.2Mo0.4O6‐δ medium‐entropy perovskite matrix decorated with in situ exsolved Fe‐Co‐Ni‐Cu quaternary alloy nanoparticles (QA@SFO) are reported. Under a reducing atmosphere, the exsolution of the quaternary alloy is accompanied by a structural transformation from double perovskite to layered perovskite, forming an interface structure where alloy nanoparticles are strongly pinned to the substrate with abundant oxygen vacancies. Electrochemically, the highly active sites provided by the QA@SFO interface greatly enhance the kinetics of CO2‐CO mutual conversion and exhibit outstanding durability for over 300 h at 1.3 V and 800 °C. Moreover, first‐principles calculations and ab initio molecular dynamics simulations from the atomic scale further elucidate the impressive electrocatalytic activity and stability and reveal that Fe and Ni in exsolved nanoparticles enhance the electrocatalytic activity, and the strong binding of Co and Cu to the parent improves the interfacial stability.
Donor–Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR‐II Emission
Authors: Yang Xueqin , Wang Xinyuan , Zhang Xun , Zhang Jianyu , Lam Jacky W. Y. , Sun Haitao , Yang Jinglei , Liang Yongye , Tang Ben Zhong
Published: April 2024

Photosensitizers (PSs) with aggregation‐induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor–acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near‐infrared (NIR‐II) window. By employing dithieno[3,2‐b:2′,3′‐d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP‐In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR‐II region. The reduced energy gap between singlet and triplet states in DTP‐In also increases the reactive oxygen species (ROS) generation rate. Further, DTP‐In can self‐assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP‐In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor–acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.
Optimizing Ionomer Distribution in Anode Catalyst Layer for Stable Proton Exchange Membrane Water Electrolysis
Authors: Liu Han , Wang Xinhui , Lao Kejie , Wen Linrui , Huang Meiquan , Liu Jiawei , Hu Tian , Hu Bo , Xie Shunji , Li Shuirong , Fang Xiaoliang , Zheng Nanfeng , Tao Hua Bing
Published: April 2024

The high cost of proton exchange membrane water electrolysis (PEMWE) originates from the usage of precious materials, insufficient efficiency, and lifetime. In this work, an important degradation mechanism of PEMWE caused by dynamics of ionomers over time in anode catalyst layer (ACL), which is a purely mechanical degradation of microstructure, is identified. Contrary to conventional understanding that the microstructure of ACL is static, the micropores are inclined to be occupied by ionomers due to the localized swelling/creep/migration, especially near the ACL/PTL (porous transport layer) interface, where they form transport channels of reactant/product couples. Consequently, the ACL with increased ionomers at PTL/ACL interface exhibit rapid and continuous degradation. In addition, a close correlation between the microstructure of ACL and the catalyst ink is discovered. Specifically, if more ionomers migrate to the top layer of the ink, more ionomers accumulate at the ACL/PEM interface, leaving fewer ionomers at the ACL/PTL interface. Therefore, the ionomer distribution in ACL is successfully optimized, which exhibits reduced ionomers at the ACL/PTL interface and enriches ionomers at the ACL/PEM interface, reducing the decay rate by a factor of three when operated at 2.0 A cm−2 and 80 °C. The findings provide a general way to achieve low‐cost hydrogen production.
Iron‐Catalyzed C−C and C−N Bond‐Forming Tandem Amidation Offering Access to 3‐Amino‐3‐Aminomethyl‐2‐Oxindole Frameworks
Authors: Ankade Shidheshwar B. , Pradhan Chandini , Paramita Samal Pragnya , Gonnade Rajesh G , Krishnamurty Sailaja , Punji Benudhar
Published: April 2024

An iron‐catalyzed protocol for the synthesis of 3‐amino‐3‐aminomethyl‐2‐oxindole heterocyclic structures is disclosed employing isatins and non‐nucleophilic N‐methoxybenzamides. This reaction class is associated with broad scope and tolerates numerous functionalities, such as fluoro, chloro, bromo, iodo, trifluoromethyl, nitrile, ester, ether, and alkenyl, including heteroaryl – thiophene, benzothiophene, carbazolyl, indolyl, eugenol, and polycyclic cholesterol moieties. Detailed mechanistic investigations reveal that the reaction proceeds via iron‐catalyzed N−O bond cleavage in N‐methoxybenzamides, generating formaldehyde and benzamide, and through the intermediacy of isatin‐ketimines and N‐(hydroxymethyl)benzamides. Overall, this amidation reaction involves one C−C and two C−N bond‐forming tandem processes, providing a range of β‐amino‐aminomethyl‐oxindoles (45 examples) in up to 88% yields.
Value‐Added Cascade Synthesis Mediated by Paired‐Electrolysis Using an Ultrathin Microenvironment‐Inbuilt Metalized Covalent Organic Framework Heterojunction
Authors: Li Qing , Ma Dong‐Dong , Wei Wen‐Bo , Han Shu‐Guo , Zheng Lirong , Zhu Qi‐Long
Published: April 2024

Energy‐saving and value‐added management in advanced catalysis is highly desirable but is challenged by the limitations of multifunctional catalysts and catalytic modules. Herein, an azo‐linked phthalocyanine‐porphyrin covalent organic framework (COF) with the ultrathin layered nanostructure grown on carbon nanotubes (NiPc‐azo‐H2Pp@CNTs) has been designed and synthesized, which can serve as a highly active and stable bifunctional heterojunction electrocatalyst for selective paired‐electrosynthesis through coupling anodic iodide oxidation reaction and cathodic CO2 conversion. Particularly, the inbuilt local microenvironment conferred by the dihydroporphyrin moieties in COF can act as a proton reservoir to promote the proton relay at the heterojunction interface during the electrocatalytic process. Moreover, through the cascade construction of dual electrocatalytic/organocatalytic modules, the cathode‐generated CO can be further converted to dimethyl carbonate with a yield of 6.21 mmol L−1 h−1, while the anode‐produced iodine can be derived into iodoform on the hundred‐milligram scale. It is worth noting that the value‐added cascade synthesis mediated by paired‐electrolysis using the distinctive and high‐powered electrocatalysts will help advance the sustainable development of industrial intelligent manufacturing.
Management of post‐autologous transplant relapse in patients with T‐cell lymphomas
Authors: Veilleux Olivier , Socola Francisco , Arai Sally , Frank Matthew J. , Johnston Laura , Lowsky Robert , Shizuru Judith , Meyer Everett , Muffly Lori , Rezvani Andrew R. , Shiraz Parveen , Sidana Surbhi , Dahiya Saurabh , Miklos David B. , Negrin Robert S. , Weng Wen‐Kai
Published: April 2024

Autologous hematopoietic cell transplantation (AHCT) is often used as a consolidation for patients with peripheral T‐cell lymphomas (PTCLs) due to the poor prognosis associated with this heterogenous group of disorders. However, a significant number of patients will experience post‐AHCT disease relapse. Here, we report a retrospective study of consecutive 124 patients with PTCLs who underwent AHCT from 2008 to 2020. With a median follow‐up of 6.01 years following AHCT, 49 patients (40%) experienced disease relapse. As expected, more patients who were not in first complete remission experienced post‐AHCT relapse. Following relapse, majority of the patients (70%) receiving systemic therapies intended as bridging to curative allogeneic HCT. However, only 18 (53%) patients eventually underwent allogeneic HCT. The estimated 3‐year OS among patients proceeding to allogeneic HCT was 72% (95% CI 46%–87%). Our report details the pattern of post‐AHCT relapse and the management of relapsed disease using different therapeutic modalities.
Veno‐venous extracorporeal membrane oxygenation for acute respiratory distress syndrome caused by nitrogen dioxide inhalation: A case report
Authors: Nishimura Tomoya , Aoki Makoto , Suzuki Hiroyuki , Hagiwara Hiroya , Kawauchi Akira , Fujizuka Kenji , Nakamura Mitsunobu
Published: April 2024

Background

Nitrogen dioxide (NO2) is known to cause lung injury, but there is no established treatment for acute respiratory distress syndrome (ARDS) caused by NO2 inhalation.

Case Presentation

A 35‐year‐old man was accidentally exposed to NO2 fumes and presented to the emergency department. On admission, his oxygen saturation was 87% on ambient air and he was diagnosed with ARDS caused by NO2 inhalation and immediately intubated; however, hypoxemia and hypercapnia were not ameliorated. Hence, veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) was introduced and the ventilator settings were set for lung‐protective ventilation. Methylprednisolone was also administered. After the initiation of these treatments, oxygenation gradually improved. Therefore, ECMO was weaned off on day 11 and he was extubated on day 12.

Conclusion

Lung injury caused by NO2 inhalation can cause ARDS, and lung‐protective ventilation with V‐V ECMO induction, as well as glucocorticoid administration, may be effective for this condition.
Discovery of a Plant 14‐3‐3 Inhibitor Possessing Isoform Selectivity and In Planta Activity
Authors: Nishiyama Kotaro , Aihara Yusuke , Suzuki Takehiro , Takahashi Koji , Kinoshita Toshinori , Dohmae Naoshi , Sato Ayato , Hagihara Shinya
Published: April 2024

Synthetic modulators of plant 14‐3‐3s are promising chemical tools both for understanding the 14‐3‐3‐related signaling pathways and controlling plant physiology. Herein, we describe a novel small‐molecule inhibitor for 14‐3‐3 proteins of Arabidopsis thaliana. The inhibitor was identified from unexpected products in a stock solution in dimethyl sulfoxide (DMSO) of an in‐house chemical library. Mass spectroscopy, mutant‐based analyses, fluorescence polarization assays, and thermal shift assays revealed that the inhibitor covalently binds to an allosteric site of 14‐3‐3 with isoform selectivity. Moreover, infiltration of the inhibitor to Arabidopsis leaves suppressed the stomatal aperture. The inhibitor should provide new insight into the design of potent and isoform‐selective 14‐3‐3 modulators.
Rapid Defect Engineering in FeCoNi/FeAl2O4 Hybrid for Enhanced Oxygen Evolution Catalysis: A Pathway to High‐Performance Electrocatalysts
Authors: Chen Yuhao , Xu Jiang , Chen Yujie , Wang Luqi , Jiang Shuyun , Xie Zong‐Han , Zhang Tianran , Munroe Paul , Peng Shengjie
Published: April 2024

Rational modulation of surface reconstruction in the oxygen evolution reaction (OER) utilizing defect engineering to form efficient catalytic activity centers is a topical interest in the field of catalysis. The introduction of point defects has been demonstrated to be an effective strategy to regulate the electronic configuration of electrocatalysts, but the influence of more complex planar defects (e.g., twins and stacking faults), on their intrinsic activity is still not fully understood. This study harnesses ultrasonic cavitation for rapid and controlled introduction of different types of defects in the FeCoNi/FeAl2O4 hybrid coating, optimizing OER catalytic activity. Theoretical calculations and experiments demonstrate that the different defects optimize the coordination environment and facilitate the activation of surface reconstruction into true catalytic activity centers at lower potentials. Moreover, it demonstrates exceptional durability, maintaining stable oxygen production at a high current density of 300 mA cm−2 for over 120 hours. This work not only presents a novel pathway for designing advanced electrocatalysts but also deepens our understanding of defect‐engineered catalytic mechanisms, showcasing the potential for rapid and efficient enhancement of electrocatalytic performance.
Macrocycle‐Based Charge Transfer Cocrystals with Dynamically Reversible Chiral Self‐Sorting Display Chain Length‐Selective Vapochromism to Alkyl Ketones
Authors: Gu Meng‐Jie , Guo Wei‐Chen , Han Xiao‐Ni , Han Ying , Chen Chuan‐Feng
Published: April 2024

Chirality‐driven self‐sorting plays an essential role in controlling the biofunction of biosystems, such as the chiral double‐helix structure of DNA from self‐recognition by hydrogen bonding. However, achieving precise control over the chiral self‐sorted structures and their functional properties for the bioinspired supramolecular systems still remains a challenge, not to mention realizing dynamically reversible regulation. Herein, we report an unprecedented saucer[4]arene‐based charge transfer (CT) cocrystal system with dynamically reversible chiral self‐sorting synergistically induced by chiral triangular macrocycle and organic vapors. It displays efficient chain length‐selective vapochromism toward alkyl ketones due to precise modulation of optical properties by vapor‐induced diverse structural transformations. Experimental and theoretical studies reveal that the unique vapochromic behavior is mainly attributed to the formation of homo‐ or heterochiral self‐sorted assemblies with different alkyl ketone guests, which differ dramatically in solid‐state superstructures and CT interactions, thus influencing their optical properties. This work highlights the essential role of chiral self‐sorting in controlling the functional properties of synthetic supramolecular systems, and the rarely seen controllable chiral self‐sorting at the solid‐vapor interface deepens the understanding of efficient vapochromic sensors.
A method for assessing student ability to apply anatomical knowledge within a traditional anatomy laboratory examination
Authors: Nolan Michael F. , McNamara John Patrick
Published: April 2024

Fidelity between teaching activities and assessment methods is an important goal of knowledge and performance evaluations in medical education. Ideally, assessment methods provide evidence of learning that reflects the types of knowledge described in the learning objectives of the course. The most reliable assessments involve the same or similar tasks as those used during the instructional components of the course. Our preclinical human anatomy course includes, in addition to traditional lecture and cadaver‐based laboratory learning activities, a series of applied human anatomy learning activities intended to emphasize human anatomy as it is encountered in living human individuals. The learning activities involve psychomotor behaviors including inspection, palpation, and auscultation, techniques used in the physical examination, as well as other activities designed to emphasize anatomical structures and tissues as they may be found in patient populations. We describe here our method for measuring student success in learning human anatomy in this manner, highlighting the direct linkage between the learning activities and the assessment tasks. We describe our performance scoring method and how we include this data in the calculation of an anatomy examination grade. As an indicator of our success with this approach, we include performance scores for the applied anatomy questions included on the laboratory component of our unit examinations for two successive academic years. We conclude with summary comments from students regarding the applied anatomy learning activities and assessment approach and offer suggestions for addressing specific challenges associated with the use of these types of assessment methods.
Semiparametric evaluation of first‐passage distribution for step‐stress accelerated degradation tests
Authors: Palayangoda Lochana , Ng Hon Keung Tony , Li Ling
Published: April 2024

In reliability engineering, different types of accelerated degradation tests have been used to obtain reliability information for evaluating highly reliable or expensive products. The step‐stress accelerated degradation test (SSADT) is one of the useful experimental schemes that can be used to save the resources of an experiment. Motivated by the SSADT data for operational amplifiers collected in Xi'an Microelectronic Technology Institute, in which the underlying degradation mechanism of the operational amplifiers is unknown, we propose a semiparametric approach for SSADT data analysis that does not require strict distributional assumptions. Specifically, the empirical saddlepoint approximation method is proposed to estimate the items' lifetime (first‐passage time) distribution at both stress levels included and not included in the SSADT experiment. Monte Carlo simulation studies are used to evaluate the performance and illustrate the advantages of the proposed approach. Finally, the proposed semiparametric approach is applied to analyze the motivating data set.
A Microporous Gel Polymer Electrolyte with High Mg2+ Ionic Conductivity at Room Temperature
Authors: Liu Jiawei , Yan Yigang , Wicaksana Filicia , Wei Shanghai
Published: April 2024

Rechargeable magnesium batteries have attracted much attention due to the high theoretical volumetric capacity, abundance, and safety. However, solid‐state Mg batteries have been rarely studied because of limited choices of solid‐state electrolyte materials. In this research, poly(vinylidene fluoride)/poly(propylene carbonate) (PVDF/PPC) as matrix were prepared using a simple solution casting method. Ethylene carbonate (EC), diethyl carbonate (DEC), and magnesium(II) bis(trifluoromethanesulfonyl) imide [Mg(TFSI)2] were selected to prepare liquid electrolyte. A classification of novel gel polymer electrolytes (GPEs), PVDF/PPC/Mg(TFSI)2, was synthesized and investigated. The electrochemical measurements show that PVDF/PPC/Mg(TFSI)2 polymer electrolytes exhibit a high ionic conductivity, close to 10−2 S cm−1, at room temperature. The electrochemical stability window of PVDF/PPC‐based GPE was up to 3 V (versus Mg2+/Mg). Materials characterization shows that these GPEs have a porous structure, providing a pathway for magnesium ion transport. Thermal analysis and crystal structure results indicate that PVDF crystallinity was affected by the addition of PPC. Additionally, the ion transport mechanism in the gel polymer electrolyte has been discussed.
The impact of Fintech on corporate carbon emissions: Towards green and sustainable development
Authors: Wang Chang'an , Wang Long , Zhao Shikuan , Yang Cunyi , Albitar Khaldoon
Published: April 2024

Fintech, as the fusion of finance and technology, has not only transformed the traditional financial industry and contributed to reshaping the real economy. But also, it holds the potential to offer a feasible solution for achieving green and sustainable development. This paper investigates the impact of Fintech on corporate carbon emissions (CCEs) by using data from the National Tax Survey Database (NTSD). The results suggest that Fintech development leads to a reduction in CCEs. Our findings remain robust even after using the instrumental variable approach to alleviate endogeneity problems. The mechanism analysis reveals that Fintech reduces CCEs via alleviating financing constraints, improving energy efficiency, and promoting green innovation. Heterogeneity analysis demonstrates that Fintech dramatically decreases CCEs from coal energy consumption, while increasing CCEs from consuming power and gas energy. Additionally, carbon emissions from state‐owned and foreign companies experience a more pronounced reduction through Fintech compared to those from private firms. Furthermore, firms in eastern and middle regions are more vulnerable to Fintech development. Moreover, enterprises in non‐high‐tech industries and high‐polluting industries exhibit noteworthy performance in reducing carbon emissions through Fintech adoption. This research offers policymakers a path to effectively govern CCEs and achieve their carbon reduction targets.
What would an existential approach bring to research supervision in postgraduate psychotherapy and counselling psychology education?
Authors: Wharne Simon , Arnold‐Baker Claire , Hakim‐Dowek Nancy
Published: April 2024

Background

Qualitative/phenomenological research approaches are popular in counselling psychology and psychotherapy post‐graduate training. This article attends to the experience of research supervision in this setting, where there is a need for containment, compassion, clarity and empathy (Counselling and Psychotherapy Research, 2021a, 22, 689).

Aims

This article aims to bring the philosophical development of qualitative/phenomenological research back into focus. It asks what extra value would be brought to the supervision of trainees through existential awareness and phenomenological exploration. The authors offer ways in which existential awareness can be developed and utilised in research supervision.

Materials and Methods

The results of a small survey into the experiences of students are used to ground our observations in practice.

Results

A relational tension is implied, where trust and good communication are essential. An existential anxiety could be prompted, when a trainee's world shifts from being homely, to uncanny and strange. In these experiences of groundlessness, the world no longer provides a sense of certainty about one's possibilities, and one feels estranged and uncomfortably self‐aware. Fostering this awareness can mean that teaching and supervisory relationships are experienced in their intersubjective, free and creative dynamics.

Discussion

Attending to Threshold Concepts can support the transformational nature of professional training, which is often an experience of uncertainty. Likewise, Socratic Questioning and irony contribute to the development of critical thinking, reflexivity and the harnessing of assumptions.

Conclusion

Existential awareness will enable the development of more authentic relationships across the therapeutic and educational encounters of training.
Lysosomal Peptide Self‐Assembly to Control Cell Behavior
Authors: Li Sangshuang , Wang Huaimin
Published: April 2024

Lysosomes are membrane‐enclosed organelles that play key roles in degrading and recycling cellular debris, cellular signaling, and energy metabolism processes. Confinement of amphiphilic peptides in the lysosome to construct functional nanostructures through noncovalent interactions is an emerging approach to tune the homeostasis of lysosome. After briefly introducing the importance of lysosome and its functions, we discuss the advantages of lysosomal nanostructure formation for disease therapy. We next discuss the strategy for triggering the self‐assembly of peptides in the lysosome, followed by a concise outlook of the future perspective about this emerging research direction.
Interplay Between Substrate Polarity and Protein Dynamics in Evolved Kemp Eliminases
Authors: Peccati Francesca , Noey Elizabeth L. , Houk K. N. , Osuna Silvia , Jiménez‐Osés Gonzalo
Published: April 2024

Extensive molecular dynamics (MD) simulations on designed and evolved enzymes for the Kemp Elimination were performed. Over thirty different systems including combinations of three protein scaffolds used in computational design (KE70, KE59 and HG3), several directed evolution variants and ligands (5‐nitrobenzo[d]isoxazole, and 6‐nitro‐1H‐benzo[d][1,2,3]triazole), were screened computationally. The study was focused mostly on computational and evolved variants for which X‐ray structures are available. MD simulations were used to monitor the organization of the active sites over time periods of 100 ns. A general trend was observed in the simulations: the optimal organization of active site residues, corresponding to the most active catalysts, is only maintained with polarized, TS‐like substrates, reinforcing the crucial role of protein dynamics and electrostatic preorganization for efficient biocatalysis. Implications for enzyme design protocols are discussed.