bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo Performance of a Cell and Factor Free Multifunctional Fiber Mesh Modulating Postinfarct Myocardial Remodeling
Authors: Tung Wing Tai , Maring Janita A. , Xu Xun , Liu Yue , Becker Matthias , Somesh Dipthi Bachamanda , Klose Kristin , Wang Weiwei , Sun Xianlei , Ullah Imran , Kratz Karl , Neffe Axel T. , Stamm Christof , Ma Nan , Lendlein Andreas
Published: May 2022

Guidance of postinfarct myocardial remodeling processes by an epicardial patch system may alleviate the consequences of ischemic heart disease. As macrophages are highly relevant in balancing immune response and regenerative processes their suitable instruction would ensure therapeutic success. A polymeric mesh capable of attracting and instructing monocytes by purely physical cues and accelerating implant degradation at the cell/implant interface is designed. In a murine model for myocardial infarction the meshes are compared to those either coated with extracellular matrix or loaded with induced cardiomyocyte progenitor cells. All implants promote macrophage infiltration and polarization in the epicardium, which is verified by in vitro experiments. 6 weeks post‐MI, especially the implantation of the mesh attenuates left ventricular adverse remodeling processes as shown by reduced infarct size (14.7% vs 28–32%) and increased wall thickness (854 µm vs 400–600 µm), enhanced angiogenesis/arteriogenesis (more than 50% increase compared to controls and other groups), and improved heart function (ejection fraction = 36.8% compared to 12.7–31.3%). Upscaling as well as process controls is comprehensively considered in the presented mesh fabrication scheme to warrant further progression from bench to bedside.
Surface‐Driven Evolution of the Anomalous Hall Effect in Magnetic Topological Insulator MnBi2Te4 Thin Films
Authors: Mazza Alessandro R. , Lapano Jason , MeyerIII Harry M. , Nelson Christopher T. , Smith Tyler , Pai Yun‐Yi , Noordhoek Kyle , Lawrie Benjamin J. , Charlton Timothy R. , Moore Robert G. , Ward T. Zac , Du Mao‐Hua , Eres Gyula , Brahlek Matthew
Published: May 2022

Understanding the effects of the interfacial modification to the functional properties of magnetic topological insulator thin films is crucial for developing novel technological applications from spintronics to quantum computing. Here, a large electronic and magnetic response is reported to be induced in the intrinsic magnetic topological insulator MnBi2Te4 by controlling the propagation of surface oxidation. It is shown that the formation of the surface oxide layer is confined to the top 1–2 unit cells but drives large changes in the overall magnetic response. Specifically, a dramatic reversal of the sign of the anomalous Hall effect is observed to be driven by finite thickness magnetism, which indicates that the film splits into distinct magnetic layers each with a unique electronic signature. These data reveal a delicate dependence of the overall magnetic and electronic response of MnBi2Te4 on the stoichiometry of the top layers. This study suggests that perturbations resulting from surface oxidation may play a non‐trivial role in the stabilization of the quantum anomalous Hall effect in this system and that understanding targeted modifications to the surface may open new routes for engineering novel topological and magnetic responses in this fascinating material.
Breathable and Skin‐Conformal Electronics with Hybrid Integration of Microfabricated Multifunctional Sensors and Kirigami‐Structured Nanofibrous Substrates
Authors: Li Hegeng , Wang Zuochen , Sun Mingze , Zhu Hengjia , Liu Hongzhen , Tang Chuyang Y. , Xu Lizhi
Published: May 2022

Skin‐integrated soft electronics have attracted extensive research attention due to their potential utility for fitness monitoring, disease management, human–machine interfaces, and other applications. Although many materials and device components are explored for the construction of skin‐integrated systems, achieving multifunctional sensor platform combined with good breathability and conformability on the skin remains difficult. This challenge is partly due to the processing incompatibility between planar‐fabricated microelectronics and biocompatible porous substrates. Here, a fabrication strategy that can overcome this limitation, leading to large‐area multifunctional skin electronics with breathability and conformability required for wearable applications, is reported. In this scheme, a hybrid integration of high‐performance microfabricated sensors and nanofibrous soft substrates is made possible with stamp‐based transferring techniques combined with electrospinning. The resulting membrane devices exhibit tissue‐like mechanical properties with high permeability for vapor transport. In addition, kirigami structures can be introduced into these membranes, providing high stretchability and 3D conformability for large‐area integration on the skin. The multifunctional sensors array allow for spatiotemporal measurement of bioelectrical signals, temperature, skin hydration, and potentially many other physiological parameters. The robust performance and manufacturing scalability provided by these multifunctional skin electronics may create further opportunities for the development of advanced wearable systems.
Synergetic Effect of Alkali‐Site Substitution and Oxygen Vacancy Boosting Vanadate Cathode for Super‐Stable Potassium and Zinc Storage
Authors: Zhao Yunxiang , Liang Shuquan , Shi Xiaodong , Yang Yongqiang , Tang Yan , Lu Bingan , Zhou Jiang
Published: May 2022

Layer‐structured metal vanadates have attracted extensive attention as cathode materials due to multi‐electron redox reactions and versatile cations storage capability. Nevertheless, their actual promotion is still hindered by the sluggish reaction kinetics and inferior phase transition upon repeated cations (de)intercalation. Here, large‐sized NH4+ is introduced into the K‐site of K0.43(NH4)0.12V2O5–δ to enable more kinetically favorable oxygen vacancies. The reinforced structure ensures complete solid‐solution phase transition and buffers the dramatic structural change upon potassium storage. The stable presence of NH4+ as pillars during cycling is also confirmed. Meanwhile, the oxygen vacancies induced by alkali‐site substitution can facilitate ion diffusion and enhance the electronic conductivity, as further demonstrated by theoretical calculations. Therefore, it exhibits a high capacity of 117.8 mA g−1 at 20 mA g−1 with smooth profiles and superior capacity retention of 92.5% after 800 cycles at 1000 mA g−1. Such an effective synergetic strategy also promotes its zinc storage capability, which performs negligible self‐discharge behavior and retains a reversible capacity of 216.8 mAh g−1 after 3000 cycles at 10 A g−1. This synergetic strategy may provide novel perspectives to develop layer‐structured cathode and facilitate its practical application in energy storage devices.
Enhancement of Hot Electron Generation in Colloidal Plasmonic Nanocrystals by Adsorption of Pt Clusters
Authors: Yang Yi , Wang Kaiyu , Khan Majid , Hu Ningneng , Ni Weihai
Published: May 2022

Surface scattering of electrons is used to be recognized as a detrimental damping process of the plasmonic oscillation, whereas such electron‐surface scattering generates hot electrons (HEs) inside the metal nanocrystals, being of great significance in practical applications, i.e., photodetection or photocatalytic reactions. However, utilizing surface scattering in colloidal plasmonic nanocrystals in realistic catalytic reactions remains challenging. This work presents a systematic study on the HE rates of colloidal Au nanocrystals, including nanospheres, nanocubes, and nanorods, and their enhancement from the adsorption of Pt clusters. Au nanocubes exhibit the highest single particle‐averaged incident photon‐to‐electron conversion efficiency among the three types of the nanocrystals. The Au nanocrystals are further adsorbed with Pt clusters, and the highest photocurrent enhancement by nearly one order of magnitude is observed. To explain the experimental observations, the contribution of the Pt adsorption to the plasmon damping is characterized by single‐particle dark‐field spectroscopy, and the HE rates are calculated by employing the finite‐element method. The overall significant enhancement of the photocurrent due to the Pt adsorption is finally explained by both electromagnetic and catalytic effects of the Pt clusters.
CF4 Plasma‐Generated LiF‐Li2C2 Artificial Layers for Dendrite‐Free Lithium‐Metal Anodes
Authors: Cao Shengling , He Xin , Nie Lanlan , Hu Jianwei , Chen Manlin , Han Yu , Wang Kangli , Jiang Kai , Zhou Min
Published: May 2022

Lithium metal anodes have long been considered as “holy grail” in the field of energy storage batteries, but dendrite growth and large volume changes hinder their practical applications. Herein, a facile and eco‐friendly CF4 plasma treatment is employed for the surface modification of Li anodes, and an artificial layer consisting of LiF and Li2C2 is fabricated for the first time. Experimental results and theoretical calculations reveal that the high adsorption energy of LiF and low Li+ diffusion barriers in Li2C2 induce uniform nucleation and planar growth of Li, guaranteeing a stable and dendrite‐free Li structure during the repeated plating/stripping process of cycling. Symmetric cells using CF4 plasma‐treated Li operate stably for more than 6500 h (at 2 mA cm−2 and 1 mAh cm−2) or 950 h (at 1 mA cm−2 and 10 mAh cm−2). When paired with a LiFePO4 cathode, full batteries deliver a high reversible capacity of 136 mAh g−1 (at 1 C) with considerable cycling stability (97.2% capacity retention over 200 cycles) and rate performance (116 mAh g−1 up to 5 C). This powerful application of plasma technology toward novel LiF‐Li2C2 artificial layers provide new routes for constructing environment‐friendly and high‐performance energy storage devices.
Synthesis of AAB‐Stacked Single‐Crystal Graphene/hBN/Graphene Trilayer van der Waals Heterostructures by In Situ CVD
Authors: Tian Bo , Li Junzhu , Chen Mingguang , Dong Haocong , Zhang Xixiang
Published: May 2022

van der Waals heterostructures based on graphene and hBN layers with different stacking modes are receiving considerable attention because of their potential application in fundamental physics. However, conventional exfoliation fabrication methods and layer‐by‐layer transfer techniques have various limitations. The CVD synthesis of high‐quality large‐area graphene and hBN multilayer heterostructures is essential for the advancement of new physics. Herein, the authors propose an in situ CVD growth strategy for synthesizing wafer‐scale AAB‐stacked single‐crystal graphene/hBN/graphene trilayer van der Waals heterostructures. Single‐crystal CuNi(111) alloys are prepared on sapphire, followed by the pre‐dissolution of carbon atoms. Single‐crystal monolayer hBN is synthesized on a plasma‐cleaned CuNi(111) surface. Then, a single‐crystal monolayer graphene is epitaxially grown onto the hBN surface to form graphene/hBN bilayer heterostructures. A controlled decrease in the growth temperature allows the carbon atoms to precipitate out of the CuNi(111) alloy to form single‐crystal graphene at the interface between hBN and CuNi(111), thereby producing graphene/hBN/graphene trilayer van der Waals heterostructures. The stacking modes between as‐grown 2D layers are investigated through Raman spectroscopy and transmission electron microscopy. This study provides an in situ CVD approach to directly synthesize large‐scale single‐crystal low‐dimensional van der Waals heterostructures and facilitates their application in future 2D‐material‐based integrated circuits.
Organic Anisotropic Excitonic Optical Nanoantennas
Authors: Kang Evan S. H. , KK Sriram , Jeon Inho , Kim Jehan , Chen Shangzhi , Kim Kyoung‐Ho , Kim Ka‐Hyun , Lee Hyun Seok , Westerlund Fredrik , Jonsson Magnus P.
Published: May 2022

Optical nanoantennas provide control of light at the nanoscale, which makes them important for diverse areas ranging from photocatalysis and flat metaoptics to sensors and biomolecular tweezing. They have traditionally been limited to metallic and dielectric nanostructures that sustain plasmonic and Mie resonances, respectively. More recently, nanostructures of organic J‐aggregate excitonic materials have been proposed capable of also supporting nanooptical resonances, although their advance has been hampered from difficulty in nanostructuring. Here, the authors present the realization of organic J‐aggregate excitonic nanostructures, using nanocylinder arrays as model system. Extinction spectra show that they can sustain both plasmon‐like resonances and dielectric resonances, owing to the material providing negative and large positive permittivity regions at the different sides of its exciton resonance. Furthermore, it is found that the material is highly anisotropic, leading to hyperbolic and elliptic permittivity regions. Nearfield analysis using optical simulation reveals that the nanostructures therefore support hyperbolic localized surface exciton resonances and elliptic Mie resonances, neither of which has been previously demonstrated for this type of material. The anisotropic nanostructures form a new type of optical nanoantennas, which combined with the presented fabrication process opens up for applications such as fully organic excitonic metasurfaces.
Sustainable Upcycling of Spent Lithium‐Ion Batteries Cathode Materials: Stabilization by In Situ Li/Mn Disorder
Authors: Lin Jiao , Fan Ersha , Zhang Xiaodong , Li Zhujie , Dai Ying , Chen Renjie , Wu Feng , Li Li
Published: May 2022

The non‐destructive repair of spent lithium‐ion batteries cathode materials has been the holy grail in the field of waste‐to‐resource research due to the potential for optimal environmental and economic benefits. Here, Mn deficiency and cationic disorder in degraded materials are discovered for the first time and the degraded crystal structure is repaired by the in situ upcycling process using a low‐carbon and economical technique. The repaired disordered LiMn2O4 (LMO) material can contribute higher capacity and greater stability than ordered LMO materials. This unexpected behavior is attributed to the in‐situ upcycling process that enhances the Li/Mn atomic disorder, thereby altering the electrochemical activity as well as the structural stability of the cathode material. Specifically, the Li/Mn disorder can effectively suppress the Jahn–Teller distortion and two‐phase phase transition and activate the activity of disordered Li, contributing to a stable high discharge capacity of upcycled material. The discovery of the Mn‐deficiency mechanism solves many doubts as to the conventional repair technology and can provide a more adequate theoretical guidance of the development of recycling technology together with the Li‐deficiency mechanism. The atomic disorder structure also provides guidance for the design of battery materials and promotes the sustainable development of future green lithium‐ion batteries.
High and normal oleic runner‐type peanut cultivar by year effects on seed germination and vigor response to temperature
Authors: Hurdle Nicholas L. , Grey Timothy L. , Branch William D. , Monfort W. Scott
Published: May 2022

Experiments conducted from 2013 to 2018 evaluated the cultivar by year effects on breeder seed germination and vigor of five high oleic (HO) and five normal oleic (NO) runner‐type peanut (Arachis hypogaea L.) cultivars grown under similar production practices. Seed germination and vigor were evaluated using a thermal gradient at temperatures of 12–36 °C (1.0 °C increments) over 7 d, and included growing degree day (GDD) accumulation. Germination across 6 yr of seed testing over all temperatures were phenotypically similar for HO's: Florida‐07 (59–86%), FloRun 107 (71–85%), Georgia‐09B (73–87%), Georgia‐14N (58–79%), Georgia‐13M (72–88%) and NO's: Georgia‐06G (65–88%), Georgia Greener (65–86%), Tifguard (65–85%), Georgia‐12Y (61–83%), and Georgia‐07W (60–91%). Lorentzian distribution models established the temperature and time (hours) to maximum germination. Analysis indicated the maximum germination across all temperatures: Georgia‐14N (HO) 50.5 h < Georgia Greener (NO) 53.2 h < Tifguard (NO) 54.4 h < Georgia‐07W (NO) 54.6 h < Georgia‐13M (HO) 56.5 h < Georgia‐06G (NO) 58.9 h < Georiga‐09B (HO) 60.4 h < Florida‐07 (HO) 67.8 h < FloRun 107 (HO) 69.7 h < Georgia‐12Y (NO) 72.0 h. Peanut cultivar vigor varied by year with respect to overall GDDs to reach Germ80 and maximum germination (b0). Overall vigor was similar for HO and NO runner‐type peanut cultivars. Peanut seed were consistent in germination, Germ80, and b0 among the 10 evaluated cultivars over the 6 yr of testing.
Evolution and development of inflorescences and floral symmetry in Solanaceae
Authors: Zhang Jingbo , Stevens Peter F. , Zhang Wenheng
Published: May 2022

Premise

The inflorescences of Solanaceae are unique and complex, which has led to long‐standing disputes over floral symmetry mainly due to different interpretations of the cyme‐like inflorescence structure. The main disagreements have been over how the phyllomes associated with the flower were arranged relative to the inflorescence axis especially during early flower initiation.

Methods

Here we investigated the evolution of inflorescences in Solanaceae by analyzing inflorescence structure in the context of phylogeny using ancestral state reconstruction (ASR) to determine the evolutionary transitions between loosely arranged and tightly clustered inflorescences and between monochasial‐like and dichasial‐like cymes. We also reconstructed two‐ and three‐dimensional models for 12 solanaceous species that represent both inflorescence and phylogenetic diversity in the family.

Results

Our results indicate that the most recent common ancestor of Solanaceae had a loosely arranged and monochasial‐like cyme, while tightly clustered inflorescences and dichasial‐like cymes were derived. Compared to the known process of scorpioid cyme evolution, Solanaceae achieved their scorpioid cyme‐like inflorescences through a previously undescribed way. Along the pedicel, the two flower‐preceding prophylls are not in the typical transverse position of dicotyledonous plants; they frequently have axillary buds, and the main inflorescence axis continues in a sympodial fashion. As a result, the plane of symmetry of the flower is 36° from the median, and the inflorescence axis and the two flower‐preceding prophylls are symmetrically located along that plane.

Conclusions

A better understanding of the morphological evolution of solanaceous inflorescence structure helped clarify the floral symmetry of Solanaceae.
A homozygous exonic variant leading to exon skipping in ABCC8 as the cause of severe congenital hyperinsulinism
Authors: Reyes Diaz Jacqueline V. , Jin Yulin , Garber Kathryn , Cossen Kristina M. , Li Yujing , Jin Peng , Li Hong , Ham Jee‐Young Nina
Published: May 2022

Congenital hyperinsulinism (CHI) is genetically heterogeneous, caused by pathogenic variants in multiple known genes regulating insulin secretion from the pancreatic β‐cells. The ABCC8 gene encodes the sulfonylurea receptor 1 (SUR1), a key player in insulin secretion, and pathogenic variants in ABCC8 are the most common cause of CHI. With increased application of genetic testing in clinical practice, variants of unknown clinical significance (VUS) are commonly reported. Additional functional investigation for variant pathogenicity is fundamental in establishing definitive molecular diagnosis and in guiding clinical management. However, due to the lack of ubiquitous tissue expression of these genes, obtaining functional studies on affected tissue has been challenging. We present a case of severe congenital hyperinsulinism which required a near‐total pancreatectomy. CHI gene sequencing identified a homozygous silent variant in ABCC8 located on the last nucleotide of exon 38, c.4608G>A (p.Ala1536Ala). The total RNA was isolated from pancreas resected at the time of pancreatectomy. RNA sequencing and expression analysis demonstrated exon 38 skipping and decreased RNA expression, which supports the pathogenicity of this variant. This case highlights the feasibility of functional studies of VUS on resected pancreatic tissue. The result expands the mutation spectrum in ABCC8 and allows precise genetic counseling to affected families.
Intramolecular C−H Activation as an Easy Toolbox to Synthesize Pyridine‐Fused Bipolar Hosts for Blue Organic Light‐Emitting Diodes
Authors: Wang Fei , Zhang Luoqiang , Han Weiguo , Bin Zhengyang , You Jingsong
Published: May 2022

The development of high‐performance blue organic light‐emitting diodes (OLEDs) remains a challenging task. While exploiting new blue emitters has attracted great interest, developing host materials that considerably determine device performance obviously lags behind. Herein, we present an ease of access to the structurally diverse benzoheteroaromatic‐fused pyridine skeletons by the iridium‐catalyzed intramolecular C−H/C−H coupling reaction, which unlocks an unparalleled opportunity to rapidly assemble a library of pyridine‐fused bipolar host materials. As an illustrated example, the benzo[4,5]thieno[2,3‐b]pyridine skeleton (BTP) has been made to a pseudo‐symmetric host (DCz‐BTP). The merging of a pyridine fragment enables strong intermolecular interactions, leading to satisfactory bipolar transporting properties. Utilizing DCz‐BTP as the host, blue thermally activated delayed fluorescent OLEDs (TADF‐OLEDs) exhibit a low turn‐on voltage of 2.8 V and a high maximum external quantum efficiency (EQEmax) of 29.0 % and blue TADF‐sensitized florescent OLEDs (TSF‐OLEDs) give an EQEmax as high as 20.5 %, revealing the potential of the BTP skeleton for the construction of high‐performance host materials.
Efficiently selective extraction of iron (III) in an aluminum‐based metal–organic framework with native N adsorption sites
Authors: Wang Xu , Long Haijun , Li Lu , Zhan Li , Zhang Xin , Cui Hengqing , Shen Jun
Published: May 2022

Separation and recovery of metal ions from wastewater is greatly significant because of the non‐negligible harm of heavy metal ions in water to human health and environment. A water‐stable aluminum‐based metal–organic framework material (MOF‐303) with native N adsorption sites is proposed for the selective adsorption and separation of the mixture with heavy metal ions (Fe3+ and Cr3+). This type of material comprises the native N adsorption sites, evenly distributing on the organic linking group. It means that the adsorbent has a smoother transport channel for metal ion, resulting in high adsorption capacity and selectivity. The single‐component adsorption results show that MOF‐303 has excellent adsorption capacity for Fe3+, up to a maximum adsorption capacity of 104 mg·g−1, which is about 5 times more than the counterpart capacity of Cr3+. Comprehensive separation studies show that the separation of the mixture with these ions can be achieved in the pH range of 1–3, and the selective adsorption is the most efficient. During 30 min of adsorption process, the removal rate of Fe3+ can be attained by 90%. And the adsorption property of this material can be recovered effectively through pickling process. In addition, the adsorption mechanism of MOF‐303 is characterized by zeta potential analysis, X‐ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT‐IR). Our work shows that MOF‐303 is not only a promising material for effective separation of Fe3+ from industrial wastewater but also providing a new perspective the specific adsorption capacity of MOF materials.
Acute toxicity and antitumor potential of 1,3,4‐trisubstituted‐1,2,3‐triazole dhmtAc‐loaded liposomes on a triple‐negative breast cancer model
Authors: Ramos Jonas P. , Abdel‐Salam Mostafa A. L. , Nobre Daniel A. B. , Glanzmann Nicolas , de Souza Camila P. , Leite Elaine A. , de Abreu Teles Pedro P. , Barbosa Alan S. , Barcelos Luciola S. , dos Reis Diego C. , Cassali Geovanni D. , de Lima Maria E. , de Castro Quênia J. T. , Grabe‐Guimarães Andrea , da Silva Adilson D. , de Souza‐Fagundes Elaine M.
Published: May 2022

For the first time, compounds developed from the 1,2,3‐triazole scaffold were evaluated as novel drugs to treat triple‐negative breast cancer (TNBC). Four organic salts were idealized as nonclassical bioisosteres of miltefosine, which is used in the topical treatment for skin metastasizing breast carcinoma. Among them, derivative dhmtAc displayed better solubility and higher cytotoxicity against the human breast adenocarcinoma cell line and mouse 4T1 cell lines, which are representatives of TNBC. In vitro assays revealed that dhmtAc interferes with cell integrity, confirmed by lactate dehydogenase leakage. Due to its human peripheral blood mononuclear cell (PBMC) toxicity, dhmtAc in vivo studies were carried out with the drug incorporated in a long‐circulating and pH‐sensitive liposome (SpHL‐dhmtAc), and the acute toxicity in BALB/c mice was determined. Free dhmtAc displayed cardiac and pulmonary toxicity after the systemic administration of 5 mg/kg doses. On the other hand, SpHL‐dhmtAc displayed no toxicity at 20 mg/kg. The in vivo antitumor effect of SpHL‐dhmtAc was investigated using the 4T1 heterotopic murine model. Intravenous administration of SpHL‐dhmtAc reduced the tumor volume and weight, without interfering with the body weight, compared with the control group and the dhmtAc free form. The incorporation of the triazole compound in the liposome allowed the demonstration of its anticancer potential. These findings evidenced 1,3,4‐trisubstituted‐1,2,3‐triazole as a promising scaffold for the development of novel drugs with applicability for the treatment of patients with TNBC.
The 2021 EULAR/American College of Rheumatology Points to Consider for Diagnosis, Management and Monitoring of the Interleukin‐1 Mediated Autoinflammatory Diseases: Cryopyrin‐Associated Periodic Syndromes, Tumour Necrosis Factor Receptor‐Associated Periodic Syndrome, Mevalonate Kinase Deficiency, and Deficiency of the Interleukin‐1 Receptor Antagonist
Authors: Romano Micol , Arici Z. Serap , Piskin David , Alehashemi Sara , Aletaha Daniel , Barron Karyl , Benseler Susanne , Berard Roberta A. , Broderick Lori , Dedeoglu Fatma , Diebold Michelle , Durrant Karen , Ferguson Polly , Foell Dirk , Hausmann Jonathan S. , Jones Olcay Y. , Kastner Daniel , Lachmann Helen J. , Laxer Ronald M. , Rivera Dorelia , Ruperto Nicolino , Simon Anna , Twilt Marinka , Frenkel Joost , Hoffman Hal M. , de Jesus Adriana A. , Kuemmerle‐Deschner Jasmin B. , Ozen Seza , Gattorno Marco , Goldbach‐Mansky Raphaela , Demirkaya Erkan
Published: May 2022

Background

The interleukin‐1 (IL‐1) mediated systemic autoinflammatory diseases, including the cryopyrin‐ associated periodic syndromes (CAPS), tumour necrosis factor receptor‐associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL‐1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL‐1 have been life changing and have significantly improved patient outcomes.

Objective

To establish evidence‐based recommendations for diagnosis, treatment and monitoring of patients with IL‐1 mediated autoinflammatory diseases to standardise their management.

Methods

A multinational, multidisciplinary task force consisting of physician experts, including rheumatologists, patients or caregivers and allied healthcare professionals, was established. Evidence synthesis, including systematic literature review and expert consensus (Delphi) via surveys, was conducted. Consensus methodology was used to formulate and vote on statements to guide optimal patient care.

Results

The task force devised five overarching principles, 14 statements related to diagnosis, 10 on therapy, and nine focused on long‐term monitoring that were evidence and/or consensus‐based for patients with IL‐1 mediated diseases. An outline was developed for disease‐specific monitoring of inflammation‐induced organ damage progression and reported treatments of CAPS, TRAPS, MKD and DIRA.

Conclusion

The 2021 EULAR/American College of Rheumatology points to consider represent state‐of‐the‐art knowledge based on published data and expert opinion to guide diagnostic evaluation, treatment and monitoring of patients with CAPS, TRAPS, MKD and DIRA, and to standardise and improve care, quality of life and disease outcomes.
Nrf2 driven macrophage responses in diverse pathophysiological contexts: Disparate pieces from a shared molecular puzzle
Authors: V. Ganesh Goutham , Ganesan Kumar , Xu Baojun , Ramkumar Kunka Mohanram
Published: May 2022

The wide anatomical distribution of macrophages and their vast array of functions match various polarization states and their involvement in homeostasis and disease. The confluence of different cellular signaling networks, including direct involvement in inflammation, at the doorstep of the transcription factor Nuclear Factor‐ erythroid (NF‐E2) p45‐related factor 2 (Nrf2) activation raises the importance of deciphering the molecular circuitry at the background of multiple‐discrete and antagonistic yet flexible and contextual pathways. While we primarily focus on wound healing and repair mechanisms that are affected in diabetic foot ulcers (DFUs), we strive to explore the striking similarities and differences in molecular events including inflammation, angiogenesis, and fibrosis during tissue injury and wound persistence that accumulates pro‐inflammatory senescent macrophages, as a means to identify possible targets or cellular mediators to lessen DFU disease burden. In addition, the role of iron in the modulation of Nrf2 response in macrophages is crucial and reviewed here. Targeted approaches, unlike conventional treatments, in DFU management will require the review and re‐assessment of mediators with relevance to other pathological conditions.
Improved depressive symptoms in patients with refractory Gilles de la Tourette syndrome after deep brain stimulation of posteroventral globus pallidus interna
Authors: Liu Aijun , Jiao Yongcheng , Zhang Shaohui , Kong Haibo
Published: May 2022

Objective

Deep brain stimulation (DBS) has been used on drug‐resistant Gilles de la Tourette syndrome (GTS) for more than two decades until now, but the stimulating targets are still under exploration until now. In this study, the authors reported the efficacy of the bilateral posteroventral globus pallidus interna (GPi) DBS on tic severity and neuropsychiatry symptoms of seven individuals with GTS.

Method

Seven patients with drug‐resistant GTS were enrolled in this study. The severity of these patients was evaluated with Yale Global Tics Severity Scale (YGTSS), Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and Global Assessment of Functioning Scale (GAF). Bilateral posteroventral GPi were selected as the permanent stimulating targets. Follow‐up period was at least 5 years after surgery in the enrolled patients.

Results

After surgery, one patient reported no improvement during the follow‐up period, and a device removal surgery was performed. The other six patients reported minor to significant improvement. The overall YGTSS, YBOCS, HAMA HAMD, and GAF scores of these patients were changed positively after surgery, but only the improvement of the motor tic and HAMD scores had a statistical difference. No surgical complication was reported.

Conclusions

Bilateral posteroventral GPi DBS could relieve the motor tics and depressive symptoms of the enrolled patients significantly, but the vocal tics and other psychiatric symptoms presented a progression without statistical difference during the follow‐up period. The results of this study suggested that bilateral posteroventral GPi are effective targets for the motor tics in GTS patients, especially with prominent depressive symptoms.
Global, regional, and national burden of cancers attributable to tobacco smoking in 204 countries and territories, 1990–2019
Authors: Safiri Saeid , Nejadghaderi Seyed Aria , Abdollahi Morteza , Carson‐Chahhoud Kristin , Kaufman Jay S. , Bragazzi Nicola Luigi , Moradi‐Lakeh Maziar , Mansournia Mohammad Ali , Sullman Mark J. M. , Almasi‐Hashiani Amir , Taghizadieh Ali , Collins Gary S. , Kolahi Ali‐Asghar
Published: May 2022

Background

Cancers are leading causes of mortality and morbidity, with smoking being recognized as a significant risk factor for many types of cancer. We aimed to report the cancer burden attributable to tobacco smoking by sex, age, socio‐demographic index (SDI), and cancer type in 204 countries and territories from 1990 to 2019.

Methods

The burden of cancers attributable to smoking was reported between 1990 and 2019, based upon the Comparative Risk Assessment approach used in the Global Burden of Disease (GBD) study 2019.

Results

Globally, in 2019 there were an estimated 2.5 million cancer‐related deaths (95% UI: 2.3 to 2.7) and 56.4 million DALYs (51.3 to 61.7) attributable to smoking. The global age‐standardized death and DALY rates of cancers attributable to smoking per 100,000 decreased by 23.0% (−29.5 to −15.8) and 28.6% (−35.1 to −21.5), respectively, over the period 1990–2019. Central Europe (50.4 [44.4 to 57.6]) and Western Sub‐Saharan Africa (6.7 [5.7 to 8.0]) had the highest and lowest age‐standardized death rates, respectively, for cancers attributable to smoking. In 2019, the age‐standardized DALY rate of cancers attributable to smoking was highest in Greenland (2224.0 [1804.5 to 2678.8]) and lowest in Ethiopia (72.2 [51.2 to 98.0]). Also in 2019, the global number of DALYs was highest in the 65–69 age group and there was a positive association between SDI and the age‐standardized DALY rate.

Conclusions

The results of this study clearly illustrate that renewed efforts are required to increase utilization of evidence‐based smoking cessation support in order to reduce the burden of smoking‐related diseases.
A novel multimeric sCD19‐streptavidin fusion protein for functional detection and selective expansion of CD19‐targeted CAR‐T cells
Authors: Lian Hui , Jiang Jinhong , Wang Yao , Yu Xiaoxiao , Zheng Rong , Long Jing , Zhou Mengjie , Zhou Shirong , Wei Cheng , Zhao Ai , Gao Jimin
Published: May 2022

Background

CARs are engineered receptors comprising an immunoglobulin single‐chain variable fragment (scFv) that identifies and binds to the target antigen, a transmembrane domain, and an intracellular T‐cell signaling domain. CD19 is a B lineage‐specific transmembrane glycoprotein and is expressed in more than 95% of B‐cell malignancies. Streptavidin (SA) is a homo‐tetrameric protein derived from Streptomyces avidinii, which can bind four biotin molecules with an extremely high affinity at a Kd value of 10‐15 M.

Aims

The aim of the study is to generate a novel soluble multimeric fusion protein, sCD19‐streptavidin (sCD19‐SA) for functional detection and selective expansion of CD19‐targeted CAR‐T cells.

Methods

The fusion proteins CD19‐SA was expressed in CHO cells and purified by use of Ni‐nitrilotriacetic acid agarose beads.

Results

A novel fusion protein (sCD19‐SA) was generated, consisting of the extracellular domain of human CD19 and the core region of SA, and could be used to functionally detect CD19‐targeted CAR‐T cells. Furthermore, this protein was demonstrated to form multimers to activate CAR‐T cells to induce their selective expansion. Importantly, sCD19‐SA‐stimulated CD19‐targeted CAR‐T cells could improve antitumor effects in vivo.

Conclusions

Our study has highlighted the potential of utilizing antigen‐SA fusion proteins such as sCD19‐SA for CAR‐T therapy for the functional detection of CAR expression and selective expansion of CAR‐T cells.
KIF11 manipulates SREBP2‐dependent mevalonate cross talk to promote tumor progression in pancreatic ductal adenocarcinoma
Authors: Gu Xiang , Zhu Qunshan , Tian Guangyu , Song Wenbo , Wang Tao , Wang Ali , Chen Xiaojun , Qin Songbing
Published: May 2022

Cholesterol metabolism is highly correlated with risks of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the underlying mechanisms of activation of cholesterol biogenesis remain inconclusive. KIF11 is a key component of the bipolar spindle and expresses highly in various malignancies. However, its functional role in PDAC tumorigenesis is still unclear. This study aims to elucidate the oncogenic functions of KIF11 in stimulating cholesterol metabolism, thereby driving PDAC progression. We utilized bioinformatics analysis to identify that KIF11 expressed highly in tumor samples versus paired normal tissues and high KIF11 correlated with high clinical stages of patients. Patients with high KIF11 had worse survival outcomes relative to those with low KIF11. Gene set enrichment analysis (GSEA) revealed that KIF11 correlated intensively with the mevalonate (MVA) metabolic pathway. Positive associations were observed between KIF11 and MVA‐signature (HMGCR, FDFT1, SQLE, and MSMO1). KIF11 could elevate the free cholesterol content of PDAC cells and targeting MVA inhibited the in vitro growth of KIF11‐overexpressing cells. Mechanistically, we found KIF11 could interact with SREBP2, the master regulator of MVA. High KIF11 could increase SREBP2 proteins, but not alter their mRNA levels. KIF11 could attenuate the ubiquitination‐mediated degradation of SREBP2, thereby enhancing its stability and accumulation. Accordingly, KIF11 stimulated the expressions of MVA‐signature and free cholesterol contents depending on SREBP2. In addition, KIF11 depended on SREBP2 to promote cell growth, migration, stemness, and colony formation abilities. The subcutaneous xenograft models indicated that targeting MVA biogenesis (atorvastatin) is effective to restrict the in vivo growth of KIF11high PDAC. Taken together, our study identified that KIF11 could activate the MVA cross talk to drive PDAC progression and inhibiting the KIF11/MVA axis provided a therapeutic vulnerability in the treatment of PDAC.
Construction of ovarian metastasis‐related immune signature predicting prognosis of gastric cancer patients
Authors: Gao Jianpeng , Huo Shiying , Zhang Yu , Zhao Zhenxiong , Pan Hongda , Liu Xiaowen
Published: May 2022

Background

Ovarian metastasis (OM) results in poor survival of gastric cancer (GC) patients. While immunotherapy has emerged as a promising approach for late‐stage GC, validated immune‐related prognostic signatures still remain in need. In this study, we constructed an ovarian metastasis‐ and immune‐related prognostic signature (OMIRPS), characterized the molecular and immune features of OMIRPS‐categorized subgroups and predicted their potential response to immunotherapy.

Methods

Three individual cohorts were used to construct and evaluate OMIRPS: RNA‐seq of matched primary GC and OM from Fudan University Shanghai Cancer Center (FUSCC) (discovery cohort, n = 4), The Cancer Genome Atlas (TCGA) (training cohort, n = 544) and GSE84437 (validation cohort, n = 433). Differentially expressed genes (DEGs) identified between primary GC and OM and immune‐related genes (IRGs) from the ImmPort and InnateDB databases were used to identify immune‐related prognostic hub genes, which were further used to construct OMIRPS by using LASSO regression analysis. Prognosis, molecular characteristics, immune features, and differential immunotherapy efficacy between different OMIRPS subgroups were analyzed.

Results

Functional analyses of DEGs revealed the significance of immune‐related signatures and pathways in the OM. Immune‐related prognostic hub genes including TNFRSF18, CARD11, BCL11B, NRP1, BNIP3L, and ATF3 were utilized to construct OMIRPS, which was identified as an independent prognostic factor. Comprehensive analyses unveiled the distinctive molecular and immune characteristics of OMIRPS‐high and ‐low subgroup in regard to enriched pathways, mutation rate, tumor mutation burden, microsatellite instability status, infiltrated immune cell, immune exclusion score, and the prediction of immunotherapy efficacy. Additionally, OMIRPS was associated with Immune Subtypes with borderline significance.

Conclusions

RNA‐seq of paired primary and ovarian metastatic tumors unveiled the significance of immune‐related pathways and tumor immune microenvironment in OM. OMIRPS served as a promising biomarker to predict the prognosis of GC patients and distinguish the molecular features, immune characteristics, and efficacy of immunotherapy between different subgroups.
A real‐world comparison between neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable non‐small cell lung cancer
Authors: Zhang Baihua , Xiao Haifan , Pu Xingxiang , Zhou Chunhua , Yang Desong , Li Xu , Wang Wenxiang , Xiao Qin
Published: May 2022

Background

The impact of neoadjuvant chemoimmunotherapy on pulmonary resection and related outcomes had been poorly reported in previous studies. The present study aims to clarify the efficacy and safety of neoadjuvant chemoimmunotherapy, and intraoperative difficulty in the following surgery, in comparison with chemotherapy alone in non‐small cell lung cancer (NSCLC).

Methods

Patients with newly diagnosed clinical stages IB–IIIB(T3‐4N2) NSCLC, received neoadjuvant chemotherapy + PD‐1 inhibitors (PD‐1 + Chemo group) or chemotherapy alone (Chemo group) followed by surgery between December 2018 and December 2020 were included. The clinicopathological characteristics were retrospectively reviewed and analyzed.

Results

There were 69 NSCLC patients in the PD‐1 + Chemo group and 121 in the Chemo group. The major pathological response (MPR) rate in the PD‐1 + Chemo group was 49.3%, higher than that of 19.0% in the Chemo group (p < 0.001). The 2‐year disease‐free survival (DFS) rate was 79.3% and 60.2%, respectively, in the two groups (p = 0.048). Multivariate analysis identified surgical radicality (hazard ratio (HR), 2.954, 95% confidence interval (CI), 1.527–5.714, p = 0.001), and pathological response (MPR(CR) vs. SD(PD), HR, 0.248, 95% CI, 0.107–0.572, p = 0.001) to be independent prognostic factors for DFS. Lobectomy was performed in 73.9% and 66.1% of patients, respectively, and bronchial sleeve resection/bronchoplasty rate was also comparable (43.4% vs. 40.5%, p = 0.688). More patients in the PD‐1 + Chemo group received vascular sleeve resection/angioplasty (15.9% vs. 6.6%, p = 0.039) and pericardial resection (10.1% vs. 2.5%, p = 0.038). After propensity score matching analysis, pericardial resection rate was still slightly higher in the PD‐1 + Chemo group (9.4% vs. 1.6%, p = 0.05). Perioperative morbidities within 30 days and mortality in 90 days were comparable between groups (p > 0.05).

Conclusions

Neoadjuvant chemoimmunotherapy for NSCLC is safe and feasible, with higher MPR rates, as well as favorable DFS than chemotherapy alone. Surgical complexity might be increased in certain patients, with comparable perioperative morbidity and mortality.
Antimicrobial and Cytotoxic Activities of Selected Hieracium L. s. str. (Asteraceae) Extracts and Isolated Sesquiterpene Lactones
Authors: Milutinović Violeta M. , Matić Ivana Z. , Stanojković Tatjana P. , Soković Marina D. , Ćirić Ana D. , Ušjak Ljuboš J. , Niketić Marjan S. , Petrović Silvana D.
Published: May 2022

Antimicrobial and cytotoxic activities were tested for dried MeOH extracts of Hieracium calophyllum (CAL), H. coloriscapum (COL), H. pseudoschenkii (PSE), H. valdepilosum (VAL) and H. glabratum (GLA) herbs (flowering aerial parts), their 2 sesquiterpene lactones (SLs) 8‐epiixerisamine A and crepiside E, and dried CH2Cl2 extract of H. scheppigianum (SCH) herb. In microdilution test, extracts showed activity on all tested microorganisms (8 bacteria, 10 fungi). The best effect was exhibited by SCH and CAL on Salmonella Typhimurium (MIC=1.7–2.5 mg/mL MBC=3.4–5.0 mg/mL), and SCH and VAL on Candida albicans (MIC=2.5 mg/mL MFC=5.0 mg/mL). SLs showed notable effect on all tested fungi Aspergillus ochraceus, Penicillium funiculosum, C. albicans and C. krusei (MIC=0.15–0.4 mg/mL MFC=0.3–0.8 mg/mL). In MTT test, extracts inhibited growth of all tested cancer cells (HeLa, LS174 and A549), with the best effect on HeLa (IC50=148.1 μg/mL for SCH, and 152.3–303.2 μg/mL for MeOH extracts); both SLs were active against HeLa cells (IC50=46.2 μg/mL for crepiside E and 103.8 μg/mL for 8‐epiixerisamine A). Extracts and SLs showed good safety profile on normal MRC‐5 cells.
Two New Xanthones from the Twigs of Calophyllum membranaceum and Their Anti‐Inflammatory Activities in HESC Cells
Authors: Li Si‐Yuan , Mi Ya‐Hui , Shen Wei , Hu Xiao‐Long , Zhang Jing , Nan Fang , Song Zhe , Zhang Xiao‐Qi , Ye Wen‐Cai , Wang Hao
Published: May 2022

Two new xanthones, calmemxanthone A (1) and calmemxanthone B (2), along with eleven known compounds were isolated from the dried twigs of Calophyllum membranaceum Gardn. et Champ. The structures of compounds 1 and 2 were established by analysis of spectra and mass spectrometry data. The absolute configuration of compound 1 was confirmed by electronic circular dichroism (ECD) spectral analysis. The anti‐inflammation action of these compounds were evaluated on lipopolysaccharide (LPS)‐induced inflammatory damage to human endometrial stromal cells (HESCs), and the structure‐activities of 1–13 were also discussed. Compound 10 presented the anti‐inflammation action with an IC50 value of 20.3 μM, that might be relevant to the regulation of NF‐κB signaling pathway via the suppression of TRIF, IKKα, and IκBα.
Safety and efficacy of 48 mm Xience Xpedition everolimus‐eluting stent for the treatment of long coronary lesions
Authors: Gautier Alexandre , Hovasse Thomas , Arroyo Diego , Unterseeh Thierry , Garot Philippe , Champagne Stéphane , Neylon Antoinette , Sanguineti Francesca , Benamer Hakim , Chevalier Bernard , Lefèvre Thierry
Published: May 2022

Introduction

Long drug‐eluting stents may limit the issue of overlapping multiple stents when treating long coronary lesions.

Aim

The aim of the study was to assess the safety and efficacy of the 48 mm Xience Xpedition everolimus‐eluting stent (48mm‐EES) for the treatment of long coronary lesions, in an all‐comer population.

Methods

Patients receiving at least one 48mm‐EES were prospectively included from March 2014 to December 2018. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization (TLR) at 1 year. The main secondary endpoint was the patient‐oriented composite endpoint (POCE) defined as a composite of death, stroke, myocardial infarction, and reintervention.

Results

A total of 268 patients with 276 long coronary lesions, including 94 chronic total occlusions (CTO), were successfully treated using at least one 48mm‐EES. The total stent length per lesion was 66 ± 22 mm. A single 48mm‐EES was suitable to successfully treat the target lesion in 48% of cases (60% for non‐CTO lesions). One‐year follow‐up rate was 96.3%. TLF occurred in 13 patients (5.3%), mainly driven by TLR (4.1%). Two cardiac death occurred (0.7%). POCE occurred in 30 patients (11.6%) mainly driven by repeat revascularization (9.7%). Definite stent thrombosis was observed in two patients (0.7%). No difference was observed in one‐year outcomes between single 48mm‐EES and multiple stents implantation as well as between CTO and non‐CTO lesions.

Conclusion

The 48mm‐EES is safe and effective to treat long coronary lesions, including CTOs, and provides attractive cost‐effectiveness by limiting multiple stenting.
Isolated psoas abscess caused by Mycobacterium tuberculosis: A rare case report
Authors: Vasigh Mahtab , Karoobi Mohammadreza , Montazeri Mahnaz , Moradi Golnaz , Asefi Hoda , Gilani Abolfazl , Meshkati yazd Seyed mostafa
Published: May 2022

Psoas tuberculosis abscess is very rarely detected primarily without an adjacent vertebral cold abscess. Early diagnosis prevents unnecessary operations and life‐threatening complications.