bluuebunny/crossref_metadata_2025 huggingface dataset:
The meningeal transcriptional response to traumatic brain injury and aging
Authors: Bolte Ashley C , Shapiro Daniel A , Dutta Arun B , Ma Wei Feng , Bruch Katherine R , Kovacs Michael A , Royo Marco Ana , Ennerfelt Hannah E , Lukens John R
Published: December 2022

Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.
Calcium dependence of both lobes of calmodulin is involved in binding to a cytoplasmic domain of SK channels
Authors: Halling David B , Philpo Ashley E , Aldrich Richard W
Published: December 2022

KCa2.1–3 Ca2+-activated K+-channels (SK) require calmodulin to gate in response to cellular Ca2+. A model for SK gating proposes that the N-terminal domain (N-lobe) of calmodulin is required for activation, but an immobile C-terminal domain (C-lobe) has constitutive, Ca2+-independent binding. Although structures support a domain-driven hypothesis of SK gate activation by calmodulin, only a partial understanding is possible without measuring both channel activity and protein binding. We measured SK2 (KCa2.2) activity using inside-out patch recordings. Currents from calmodulin-disrupted SK2 channels can be restored with exogenously applied calmodulin. We find that SK2 activity only approaches full activation with full-length calmodulin with both an N- and a C-lobe. We measured calmodulin binding to a C-terminal SK peptide (SKp) using both composition-gradient multi-angle light-scattering and tryptophan emission spectra. Isolated lobes bind to SKp with high affinity, but isolated lobes do not rescue SK2 activity. Consistent with earlier models, N-lobe binding to SKp is stronger in Ca2+, and C-lobe-binding affinity is strong independent of Ca2+. However, a native tryptophan in SKp is sensitive to Ca2+ binding to both the N- and C-lobes of calmodulin at Ca2+ concentrations that activate SK2, demonstrating that the C-lobe interaction with SKp changes with Ca2+. Our peptide-binding data and electrophysiology show that SK gating models need deeper scrutiny. We suggest that the Ca2+-dependent associations of both lobes of calmodulin to SKp are crucial events during gating. Additional investigations are necessary to complete a mechanistic gating model consistent with binding, physiology, and structure.
Coordinated cadherin functions sculpt respiratory motor circuit connectivity
Authors: Vagnozzi Alicia N , Moore Matthew T , Lin Minshan , Brozost Elyse M , KC Ritesh , Agarwal Aambar , Schwarz Lindsay A , Duan Xin , Zampieri Niccolò , Landmesser Lynn T , Philippidou Polyxeni
Published: December 2022

Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here, we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation in mice during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.
The ‘ForensOMICS’ approach for postmortem interval estimation from human bone by integrating metabolomics, lipidomics, and proteomics
Authors: Bonicelli Andrea , Mickleburgh Hayley L , Chighine Alberto , Locci Emanuela , Wescott Daniel J , Procopio Noemi
Published: December 2022

The combined use of multiple omics allows to study complex interrelated biological processes in their entirety. We applied a combination of metabolomics, lipidomics and proteomics to human bones to investigate their combined potential to estimate time elapsed since death (i.e., the postmortem interval [PMI]). This ‘ForensOMICS’ approach has the potential to improve accuracy and precision of PMI estimation of skeletonized human remains, thereby helping forensic investigators to establish the timeline of events surrounding death. Anterior midshaft tibial bone was collected from four female body donors before their placement at the Forensic Anthropology Research Facility owned by the Forensic Anthropological Center at Texas State (FACTS). Bone samples were again collected at selected PMIs (219-790-834-872days). Liquid chromatography mass spectrometry (LC-MS) was used to obtain untargeted metabolomic, lipidomic, and proteomic profiles from the pre- and post-placement bone samples. The three omics blocks were investigated independently by univariate and multivariate analyses, followed by Data Integration Analysis for Biomarker discovery using Latent variable approaches for Omics studies (DIABLO), to identify the reduced number of markers describing postmortem changes and discriminating the individuals based on their PMI. The resulting model showed that pre-placement metabolome, lipidome and proteome profiles were clearly distinguishable from post-placement ones. Metabolites in the pre-placement samples suggested an extinction of the energetic metabolism and a switch towards another source of fuelling (e.g., structural proteins). We were able to identify certain biomolecules with an excellent potential for PMI estimation, predominantly the biomolecules from the metabolomics block. Our findings suggest that, by targeting a combination of compounds with different postmortem stability, in the future we could be able to estimate both short PMIs, by using metabolites and lipids, and longer PMIs, by using proteins.
Las consecuencias civiles del estado de necesidad justificante en Chile
Authors: Céspedes Muñoz Carlos , Mendoza-Alonzo Pamela , Escobar Veas Javier
Published: December 2022

El objetivo de esta investigación es determinar si existen consecuencias civiles en los casos de estado de necesidad justificante en Chile ante ausencia de norma expresa. Así, hemos sistematizado las opiniones de la doctrina chilena penal y civil sobre este problema, las cuales se contraponen. En nuestra opinión, el estado de necesidad justificante es una causal de justificación que exime tanto de responsabilidad penal como civil al autor del daño. Sin embargo, teniendo a la vista los ordenamientos que han regulado la materia expresamente, así como la opinión de la doctrina civil chilena, afirmamos que es posible aceptar la procedencia de la reparación de los daños producidos a través de las denominadas indemnizaciones o compensaciones por sacrificio.
Federalismo y Estado empresario a nivel subnacional: características y conformación reciente del sector de las empresas públicas provinciales en Argentina
Authors: Yañez Manuel
Published: December 2022

El trabajo busca abordar las características principales del escenario reciente de las empresas públicas provinciales en Argentina en el marco de las transformaciones del rol estatal y el federalismo en las últimas décadas. Se parte de una caracterización general del sector público empresarial provincial a partir de diferentes dimensiones relevantes y se identifican los orígenes de las empresas provinciales existentes en la actualidad en vistas a esbozar algunas claves explicativas sobre su conformación y derrotero reciente. Con ese fin, se utilizaron fuentes primarias y secundarias de diversa índole que derivaron en la construcción de una base de datos propia de empresas públicas provinciales. Como resultado, se identificaron algunas características relevantes (distribución territorial desigual, amplia variedad de actividades económicas y predominio de formatos jurídicos flexibles). Asimismo, se examinaron las sucesivas etapas de surgimiento de las empresas provinciales actualmente existentes y sus posibles vinculaciones con los cambios producidos a nivel general.
El ejercicio de la acusación por parte de la víctima coadyuvante en el nuevo proceso penal cubano: posibilidades y límites
Authors: López Rojas Dayan Gabriel
Published: December 2022

La presente contribución aborda un aspecto concreto del estatuto procesal de la víctima en la nueva Ley del Proceso Penal cubano: su participación como coadyuvante de la acusación. El objetivo central ha sido clarificar las posibilidades y límites de su intervención frente a la postura acusatoria del fiscal, en concreto, respecto a los distintos elementos que componen el objeto del proceso y el objeto del debate. En esa línea, se contrasta el modelo implantado por el legislador de 2021 con otros sistemas que, en Derecho comparado, permiten a la víctima participar en el ejercicio de la acción penal pública; ello como paso previo para ofrecer luego pautas interpretativas orientadas a despejar algunas dudas sobre el alcance de la actuación del acusador coadyuvante. Salvo error involuntario, se trata del primer estudio que encara la cuestión en el ámbito nacional y, por tanto, inaugura el debate sobre una figura que, por su novedad, no ha tenido aún suficiente recorrido práctico.
Nocardia farcinica as a Cause of Complicated Chronic Suppurative Otitis Media: A Case Report
Authors: Lijitha SG , Abarna V , Pradha V , Dhanaleha P , Vaishnavadevi G
Published: December 2022

Nocardia belongs to the order Actinomycetales suborder Corynebacteriaceae, family Nocardiaceae. It causes infections mostly in immunocompromised individuals. It primarily causes pulmonary infections, followed by central nervous system infections, cutaneous and disseminated infections. Cutaneous infections are reported in immunocompetent individuals also. Because of the growth characteristics, it is difficult to recover the organisms in culture. The recent advanced molecular technology has made identification of the organism to species level possible. Chronic Suppurative Otitis Media (CSOM) due to Nocardia spp is rarely reported. Here, authors report a case of CSOM caused by Nocardia farcinica in a 47-year-old female. The patient was on steroid therapy for bronchial asthma. Culture of ear discharge isolated Nocardia spp, identified as Nocardia farcinica by mass spectrometry. Appropriate antibiotic treatment was administered and good treatment response was obtained. Early diagnosis and appropriate antibiotic treatment is critical for nocardial infections. Difficulty in recovering and identifying the organism, with delay in initiating appropriate treatment can result in poor prognosis and treatment failure.
Prevalence of Post Traumatic Stress Disorder among all Emergency Workers at Saudi Tertiary Care Center in Riyadh, Saudi Arabia
Authors: Alkharashi Yasser M. , Alrasheed Faisal , Alhussaini Nawaf , Almosa Abdulaziz , Alkharashi Nawaf , Alsalamah Majid
Published: December 2022

Aims: Our objective for this study is to assess post traumatic stress disorder and its severity point prevalence among all emergency department workers.

Study Design: A cross-sectional model is most appropriate for this study’s aims, objectives and time frame.

Place and Duration of Study: This study took place at the emergency department of King AbdulAziz Medical City (KAMC) in Riyadh, Saudi Arabia, between December 2021 and November 2022.

Methodology: Our study concluded 202 emergency department workers (94 men, 108 women: age range 24-60). A self-administered questionnaire consisting of two parts was distributed. The first part was demographic variables. The second part was the PTSD Checklist for DSM-5 - Civilian Version (PCL-5).

Results: From our 202 ER employees, 26.7% met the criteria for PSTD. Using logistic regression, we found a relation between PTSD and verbal or physical abuse with a P value of 0.004. we also observed a significant P value of 0.018 between the age groups, indicating the younger population of our study were more prone to develop PTSD.

Conclusion: There is a concerning high prevalence of self-reported post-traumatic stress disorder among the emergency medicine department workers, including an increased number of employees having been a victim of physical assault or verbal abuse. It is crucial at the organizational level to prioritize prevention of workplace violence.
Study on restoration and sharing method on town space in devastated area
Authors: Tsukihashi Osamu , Yamada Kyohei , Nakamura Akika , Hirao Morifumi
Published: December 2022

After the tsunami of the Great East Japan Earthquake, various projects have been pushed forward for early restoration while they do not necessarily restore former townscapes which were entirely transformed. Some local people are worried about losing their memories of hometown in course of recovery. This essay examines, how they could retrieve and transmit memories of their lost towns to next generations through the workshops to build 1:500 restoration models on the central districts (Machikata area) at Otsuchi town in Iwate prefecture. The result enables us to explore memories of town space and means to share and utilize them.
TESOL Technology Standards
Authors: Healey Deborah
Published: December 2022

The TESOL Technology Standards offer guidance for learners, teachers, teacher educators, researchers, and administrators who use technology in English language learning and teaching. The Standards incorporate two complementary sets of standards. The Standards for Language Learners focus on what learners need to know in order to use technology productively, safely, appropriately, legally, and with a critical eye. The Standards for Language Teachers address how teachers can help learners achieve the Learner Standards, be personally productive and creative with technology, and continue to develop expertise in teaching with technology. The Teacher Standards recognize a general and an “expert” level. All teachers are expected to meet the general standards. The expert level describes those with additional skills and who deserve appropriate recognition for sharing those skills with others. Checklists for self‐assessment, program assessment, and online teaching are part of
TESOL Technology Standards, Description, Implementation, Integration
(Healey et al., 2011).
Resurrection, Zoroastrianism
Authors: Timuş Mihaela
Published: December 2022

This entry defends the idea of the antiquity of the Zoroastrian doctrine of bodily resurrection. It was attested in the Young Avesta, dated before the Christian era, and confirmed by the testimonies of the Greek historians, such as Theopomp, who was writing by the fourth century
bce
. The entry is mainly based on the Middle Persian (MP) sources, written down by the ninth century
ce
, but also reflecting ideas which circulated before that date. It discusses the main MP terminology, as well as the ideas related to this doctrine, such as the universal versus selective character of bodily resurrection, the analogy between micro‐ and macro‐cosmos, and the individuality of eschatological bodies. It also briefly presents the mythology associated with this doctrine and the main mythological characters, as well as the specific notions and images used to designate the resurrection. The comparison with Manichaeism and the relation between doctrine and funerary customs are also addressed.
Yang Xiong
Authors: Chapman Jesse J. , Nylan Michael
Published: December 2022

Yang Xiong (53bce–18ce), a court poet who initially won renown for hisfupoems, was a central figure in arguing for a “classical turn” that took place at the late Western Han courts (206bce–9ce) in his later neoclassical works. At Han emperor Cheng's (r. 33–7bce) court, Yang became a protégé of Liu Xiang (79–8bce), and under his direction worked for two decades in the Palace Library project collecting, collating, and revising manuscripts. This position, which allowed Yang exceptional access to the riches of the palace holdings, doubtless shaped the style of his later works, all of which are allusion‐laden. He spent his later years teaching and writing, but during the Xin (9ce–23ce), Yang was implicated, though ultimately exonerated, in a plot against Wang Mang. Yang's surviving works include severalfu, other poetic compositions, and three major neoclassical works:Regional Expressions(Fangyan),Exemplary Figures(Fayan), and theCanon of Supreme Mystery(Taixuan jing), modeled, respectively, on theErya, theAnalects, and theChanges. Yang was regarded as one of the supreme masters of classical learning, until the Southern Song (1129–1279), when he became a target of criticism by Zhu Xi (1130–1200).
Liu Xiang
Authors: Chapman Jesse J. , Nylan Michael
Published: December 2022

Liu Xiang, a statesman, historian, omen expert, and poet in theChuci‐style, first came to prominence for his poetic skill under Emperor Xuan of Han (r. 74–48bce). In 51bce, he championed theGuliang Traditionsfor theAnnalsclassic at the Stone Canal court conference. Then, under Emperor Yuan (r. 48–33bce), Liu became embroiled in factional conflicts led by the eunuch Shi Xian (d. after 33bce), which jeopardized his place at court. When Shi's faction lost favor, under Emperor Cheng (r. 33–7bce), Liu was soon promoted to a ministerial position responsible for overseeing the members of the Liu ruling house. Liu's biography includes memorials criticizing the project to construct a second massive mausoleum for Emperor Cheng at Changling, warning of the Wang clan's gradual arrogation of the imperial powers, and reading baleful signs. But Liu is most famous in history for his supervision of the court‐sponsored Palace Library project, which for decades collected, collated, and revised manuscripts found throughout the empire, and was responsible for creating and cataloguing many of the texts we hold in our hands today. Possibly in connection with that project, Liu produced three major anecdotal collections, theNew Orders(Xinxu),Garden of Eloquence(Shuoyuan), andBiographies of Exemplary Women(Lienü zhuan), to provide hallowed models of behavior for the ruler and the members of his court.
Controlled Synthesis of Sub‐Millimeter Nonlayered WO2 Nanoplates via a WSe2‐Assisted Method
Authors: Lyu Chongguang , Zhang Linghai , Zhang Xu , Zhang Hongmei , Xie Hongguang , Zhang Jianhong , Liu Yufeng , Liu Yu , Wu Ruixia , Zhang Junran , Zha Chenyang , Wang Wei , Wan Zhong , Li Bo , Zhu Chao , Ma Huifang , Duan Xidong , Wang Lin
Published: December 2022

2D metal oxides (2DMOs) have stimulated tremendous attention due to their distinct electronic structures and abundant surface chemistry. However, it remains a standing challenge for the synthesis of 2DMOs because of their intrinsic 3D lattice structure and ultrahigh synthesis temperature. Here, a reliable WSe2‐assisted chemical vapor deposition (CVD) strategy to grow nonlayered WO2 nanoplates with tunable thickness and lateral dimension is reported. Optical microscopy and scanning electron microscopy studies demonstrate that the WO2 nanoplates exhibit a well‐faceted rhombic geometry with a lateral dimension up to the sub‐millimeter level (≈135 µm), which is the largest size of 2DMO single crystals obtained by CVD to date. Scanning transmission electron microscopy studies reveal that the nanoplates are high‐quality single crystals. Electrical measurements show the nanoplates exhibit metallic behavior with strong anisotropic resistance, outstanding conductivity of 1.1 × 106 S m−1, and breakdown current density of 7.1 × 107 A cm−2. More interestingly, low‐temperature magnetotransport studies demonstrate that the nanoplates show a quantum‐interference‐induced weak‐localization effect. The developed WSe2‐assisted strategy for the growth of WO2 nanoplates can enrich the library of 2DMO materials and provide a material platform for other property explorations based on 2D WO2.
Bilirubin Nanomedicine Alleviates Inflammation and Angiogenesis in a Rosacea Mouse Model
Authors: Choi Chong Won , Keum Hyeongseop , Yang Seoyun , Kang Bo Mi , Kim Dohyeon , Piao Haiying , Kim Jee Woo , Kim Bo Ri , Youn, Sang Woong , Jon Sangyong
Published: December 2022

Rosacea is a common chronic inflammatory facial disorder. Reactive oxygen species (ROS) have a key role in the pathogenesis of rosacea. In this study, the antioxidant and anti‐inflammatory effects of bilirubin‐based nanoparticles (BRNPs) are investigated in the LL‐37‐induced rosacea‐like mouse model. Effects of BRNPs on rosacea‐like skin inflammation and ROS level of the skin are determined using histological analysis. The expression of genes encoding rosacea‐associated cytokines and chemokines is assessed and the molecular mechanisms of BRNPs against rosacea are investigated using RNA sequencing (RNAseq) analysis. This study reveals that BRNPs significantly alleviate LL‐37‐induced inflammatory manifestation in the rosacea mouse model and reduce the expression of proinflammatory cytokines (interleukin [IL]‐1β, IL‐6, and tumor necrosis factor [TNF]‐α) and chemokines (C‐X‐C motif chemokine ligand 8 [CXCL8] and CXCL10). Moreover, BRNPs preferentially localize at the inflammatory skin lesion, decrease the level of ROS in the skin, and ameliorate the vascular endothelial growth factor expression and vascular changes in the skin induced by LL‐37. Furthermore, these findings provide a mechanism for the efficacy of BRNPs in this experimental model and support BRNPs as a potential therapeutic option for rosacea and other related inflammatory skin disorders.
Erythrocyte‐Inspired Functional Materials for Biomedical Applications
Authors: Luo Zhiqiang , Sun Lingyu , Bian Feika , Wang Yu , Yu Yunru , Gu Zhuxiao , Zhao Yuanjin
Published: December 2022

Erythrocytes are the most abundant cells in the blood. As the results of long‐term natural selection, their specific biconcave discoid morphology and cellular composition are responsible for gaining excellent biological performance. Inspired by the intrinsic features of erythrocytes, various artificial biomaterials emerge and find broad prospects in biomedical applications such as therapeutic delivery, bioimaging, and tissue engineering. Here, a comprehensive review from the fabrication to the applications of erythrocyte‐inspired functional materials is given. After summarizing the biomaterials mimicking the biological functions of erythrocytes, the synthesis strategies of particles with erythrocyte‐inspired morphologies are presented. The emphasis is on practical biomedical applications of these bioinspired functional materials. The perspectives for the future possibilities of the advanced erythrocyte‐inspired biomaterials are also discussed. It is hoped that the summary of existing studies can inspire researchers to develop novel biomaterials; thus, accelerating the progress of these biomaterials toward clinical biomedical applications.
Inflammation‐Controlled Anti‐Inflammatory Hydrogels
Authors: Helmecke Tina , Hahn Dominik , Matzke Nadine , Ferdinand Lisa , Franke Lars , Kühn Sebastian , Fischer Gunter , Werner Carsten , Maitz Manfred F.
Published: December 2022

While autoregulative adaptation is a common feature of living tissues, only a few feedback‐controlled adaptive biomaterials are available so far. This paper herein reports a new polymer hydrogel platform designed to release anti‐inflammatory molecules in response to the inflammatory activation of human blood. In this system, anti‐inflammatory peptide drugs, targeting either the complement cascade, a complement receptor, or cyclophilin A, are conjugated to the hydrogel by a peptide sequence that is cleaved by elastase released from activated granulocytes. As a proof of concept, the adaptive drug delivery from the gel triggered by activated granulocytes and the effect of the released drug on the respective inflammatory pathways are demonstrated. Adjusting the gel functionalization degree is shown to allow for tuning the drug release profiles to effective doses within a micromolar range. Feedback‐controlled delivery of covalently conjugated drugs from a hydrogel matrix is concluded to provide valuable safety features suitable to equip medical devices with highly active anti‐inflammatory agents without suppressing the general immunosurveillance.
A Symmetric Aqueous Magnesium Ion Supercapattery Based on Covalent Organic Frameworks
Authors: Zou Guodong , Tian Zhengnan , Kale Vinayak S. , Wang Wenxi , Kandembeth Sharath , Cao Zhen , Guo Jing , Czaban‐Jóźwiak Justyna , Cavallo Luigi , Shekhah Osama , Eddaoudi Mohamed , Alshareef Husam N.
Published: December 2022

Aqueous magnesium ion‐based batteries have attracted significant research interest due to the two‐electron transfer process, small cation radius, low reduction potential as well as the inert hydrogen evolution reaction. However, the high surface charge density of divalent Mg2+ ions results in sluggish solid‐state diffusion kinetics, which significantly limits the number of host materials suitable for effective Mg2+ ion storage. Here, for the first time, covalent organic frameworks (COFs) are explored as host materials for high‐rate aqueous Mg2+ ion batteries. Combining electrochemical and spectral characterization with theoretical simulation, a synergistic charge storage mechanism involving the reaction of nitrogen and oxygen bridged by Mg2+ ions is revealed. Using electrochemical analysis, it is shown that the Mg2+ ion diffusion kinetics are dominated by the surface pseudocapacitive behavior in COFs, which achieves a favorable rate performance and durable cyclic stability. This work offers a new perspective on the storage of Mg2+ ions in COF host materials.
A Biocompatible Probe for the Detection of Neutrophil Elastase Free from the Interference of Structural Changes and Its Application to Ratiometric Photoacoustic Imaging In Vivo
Authors: Huang Ling , Su Wanting , Zhu Lin , Li Jiangfeng , Quan Wei , Yoon Juyoung , Lin Weiying
Published: December 2022

Neutrophil elastase (NE) plays a key role in chronic inflammation and acute responses to infection and injury. Effective disease interventions thus call for precise identification of NE to aid the clinical treatment of such diseases. However, the detection process suffers from the interference of structural changes of NE. Herein, we introduce a molecular probe with high biocompatibility to overcome the interference, which was achieved by combining theoretical calculations and experimental studies, that permits highly specific and sensitive detection of NE in cells and in vivo. The upregulated NE accumulation was specifically measured in inflammation by ratiometric photoacoustic and near‐infrared fluorescence imaging, providing a new method for developing more specific fluorogenic probes for other enzymes.
Thermodynamic Control of Intramolecular Singlet Fission and Exciton Transport in Linear Tetracene Oligomers
Authors: Nakamura Shunta , Sakai Hayato , Fuki Masaaki , Ooie Rikuto , Ishiwari Fumitaka , Saeki Akinori , Tkachenko Nikolai V. , Kobori Yasuhiro , Hasobe Taku
Published: December 2022

We newly synthesized a series of homo‐ and hetero‐tetracene (Tc) oligomers to propose a molecular design strategy for the efficient exciton transport in linear oligomers by promoting correlated triplet pair (TT) dissociation and controlling sequential exciton trapping process of individual doubled triplet excitons (T+T) by intramolecular singlet fission. First, entropic gain effects on the number of Tc units are examined by comparing Tc‐homo‐oligomers [(Tc)n: n=2, 4, 6]. Then, a comparison of (Tc)n and Tc‐hetero‐oligomer [TcF3‐(Tc)4‐TcF3] reveals the vibronic coupling effect for entropic gain. Observed entropic effects on the T+T formation indicated that the exciton migration is rationalized by number of possible TT states increased both by increasing the number of Tc units and by the vibronic levels at the terminal TcF3 units. Finally, we successfully observed high‐yield exciton trapping process (trapped triplet yield: ΦTrT=176 %).
Liquid Metal as Bioinspired and Unusual Modulator in Bioorthogonal Catalysis for Tumor Inhibition Therapy
Authors: Zhang Lu , Sang Yanjuan , Liu Zhenqi , Wang Wenjie , Liu Zhengwei , Deng Qingqing , You Yawen , Ren Jinsong , Qu Xiaogang
Published: December 2022

Bioorthogonal catalysis mediated by Pd‐based transition metal catalysts has sparked increasing interest in combating diseases. However, the catalytic and therapeutic efficiency of current Pd0 catalysts is unsatisfactory. Herein, inspired by the concept that ligands around metal sites could enable enzymes to catalyze astonishing reactions by changing their electronic environment, a LM‐Pd catalyst with liquid metal (LM) as an unusual modulator has been designed to realize efficient bioorthogonal catalysis for tumor inhibition. The LM matrix can serve as a “ligand” to afford an electron‐rich environment to stabilize the active Pd0 and promote nucleophilic turnover of the π‐allylpalladium species to accelerate the uncaging process. Besides, the photothermal properties of LM can lead to the enhanced removal of tumor cells by photo‐enhanced catalysis and photothermal effect. We believe that our work will broaden the application of LM and motivate the design of bioinspired bioorthogonal catalysts.
Verifying the Charge‐Transfer Mechanism in S‐Scheme Heterojunctions Using Femtosecond Transient Absorption Spectroscopy
Authors: Cheng Chang , Zhang Jianjun , Zhu Bicheng , Liang Guijie , Zhang Liuyang , Yu Jiaguo
Published: December 2022

The S‐scheme heterojunction is flourishing in photocatalysis because it concurrently realizes separated charge carriers and sufficient redox ability. Steady‐state charge transfer has been confirmed by other methods. However, an essential part, the transfer dynamics in S‐scheme heterojunctions, is still missing. To compensate, a series of cadmium sulfide/pyrene‐alt‐difluorinated benzothiadiazole heterojunctions were constructed and the photophysical processes were investigated with femtosecond transient absorption spectroscopy. Encouragingly, an interfacial charge‐transfer signal was detected in the spectra of the heterojunction, which provides solid evidence for S‐scheme charge transfer to complement the results from well‐established methods. Furthermore, the lifetime for interfacial charge transfer was calculated to be ca. 78.6 ps. Moreover, the S‐scheme heterojunction photocatalysts exhibit higher photocatalytic conversion of 1,2‐diols and H2production rates than bare cadmium sulfide.
Synthesis of bio‐diamine derived main‐chain type benzoxazine resins with low surface free energy
Authors: Liu Jiamei , Sheng Weichen , Yang Rui , Liu Yu , Lu Yin , Zhang Kan
Published: December 2022

A series of bio‐based fluorin‐free main‐chain type benzoxazine precursors were synthesized via bisphenol A/bisphenol F/diallyl bisphenol A, Priamine 1074 and paraformaldehyde by Mannich condensation reaction. Chemical structures of these obtained main‐chain type precursors were characterized by FT‐IR and NMR spectroscopies. The polymerization processes were studied by differential scanning calorimeter (DSC) and in situ FT‐IR analysis. Besides, the contact angle and surface free energy of polybenzoxazine coatings were measured by water contact angle instrument. Moreover, the thermal performance of the resulting polybenzoxazine thermosets were evaluated by dynamic mechanical analyzer (DMA) and thermogravimetric analysis (TGA). Through the above various measurements, the newly developed bio‐based main‐chain type polybenzoxazine resins show good thermal stability and low surface free energy, suggesting great potential for applications as high‐performance resin matrix.
Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome‐Wide Imputation
Authors: Rothwell Simon , Amos Christopher I. , Miller Frederick W. , Rider Lisa G. , Lundberg Ingrid E. , Gregersen Peter K. , Vencovsky Jiri , McHugh Neil , Limaye Vidya , Selva‐O'Callaghan Albert , Hanna Michael G. , Machado Pedro M. , Pachman Lauren M. , Reed Ann M. , Molberg Øyvind , Benveniste Olivier , Mathiesen Pernille , Radstake Timothy , Doria Andrea , De Bleecker Jan L. , De Paepe Boel , Maurer Britta , Ollier William E. , Padyukov Leonid , O'Hanlon Terrance P. , Lee Annette , Wedderburn Lucy R. , Chinoy Hector , Lamb Janine A. ,   the Myositis Genetics Consortium
Published: December 2022

Objective

The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed variants from the ImmunoChip array using a large reference panel to fine‐map associations and identify novel associations in IIM.

Methods

We analyzed 2,565 Caucasian IIM patient samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically matched control samples. We imputed 1,648,116 variants from the ImmunoChip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM and clinical and serologic subgroups.

Results

The HLA locus was consistently the most significantly associated region. Four non‐HLA regions reached genome‐wide significance, SDK2 and LINC00924 (both novel) and STAT4 in the whole IIM cohort, with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A‐BLK loci in PM, and for CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells.

Conclusion

We found novel and strong associations in IIM and PM and localized signals to single genes and immune cell types.
Swapping Copper‐Catalytic Process: Selective Access to Pyrazoles and Conjugated Ketimines from Oxime Acetates and Cyclic Sulfamidate Imines
Authors: Prakash Meher , Halder Sajal , Guin Soumitra , Samanta Sampak
Published: December 2022

A powerful CuCl‐catalyzed sequential one‐pot reaction of aryl methyl ketoxime acetates with cyclic N‐sulfonyl imines followed by elimination in the presence of base is reported. This hydrazine‐free method conveniently makes C−C and N−N bonds via a radical cleavage of the N−O bond, delivering a special class of C3‐hydroxyarylated pyrazoles in good yields. Surprisingly, while employing CuI as a catalyst instead of CuCl, the reaction proceeds through a non‐radical pathway which embodies a new tactic for the high‐yielding access to value‐added conjugated N‐unsubstituted ketimines. Moreover, additive‐free approach to sulfamidate‐fused‐pyrazoles was achieved by successfully catalyzing addition and oxidative N−N bond‐making reactions by CuI and CuCl, respectively. Significantly, our novel technique could convert the prepared ketimines into the pharmacologically recognized 6H‐benzo[c]chromene frameworks.
Resolution tests for ΛCDM: A comparison of three cosmological codes
Authors: Lozano‐Rodríguez Flor , Hernández‐Aguayo César , Arturo Ureña‐López Luis
Published: December 2022

We present a series of resolution tests of the Modified Gravity‐Parallel Implementation of the Comoving Lagrangian Acceleration method (MG‐PICOLA) code for the Λ Cold Dark Matter (ΛCDM) model. The tests are a previous step in the analysis of modified gravity models implemented in the code. We measure the non‐linear matter power spectrum of the model and compare it with the prediction obtained with the Boltzmann code CLASS. We also compare the mass power spectrum with results from another N‐body simulation code, Modified Gravity GaLAxy Mocks (MG‐GLAM), to obtain information on the capabilities and performance of MG‐PICOLA for the optimal values of its input parameters.
Design and simulation of a novel integrated microfluidic chip for cell isolation and culture
Authors: Tabatabaei Seyed Ali , Javaherchian Javane
Published: December 2022

The lab on a chip is utilized as a background and a substrate for creating a proper flow for cellular processes in medicine. In this study, the concepts of cell isolation and cell transfer methods have been discussed. After that, the device of separation and transfer systems has been designed, simulated, and verified by placing the frequency of particle separation and droplet formation, which is tried to introduce a new device that can be used in cellular studies. The optimal operation conditions for the problem have also been investigated. High separation efficiency (99%) could be achieved when the velocity of the sample inlet in the microchannel separator is 180 μm/s. Also, a microfluidic device for droplet generation has been designed to transfer the isolated cells to the culture medium. For this purpose, the frequency of droplet production must be synchronized with particle ejection frequency and equals 9.09 Hz.
Compassionate use of recombinant human IL‐7‐hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma
Authors: Ahn Stephen , Park Jae‐Sung , Kim Heewon , Heo Minkyu , Sung Young Chul , Jeun Sin‐Soo
Published: December 2022

Purpose

Addressing lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin‐7 (IL‐7) is necessary for proliferation of lymphocytes and to increase total lymphocyte count (TLC), IL‐7 therapy has been attempted in various cancers. Here, we describe the clinical results of treatment of recurrent glioblastoma (GBM) with a long‐acting engineered version of recombinant human IL‐7 (rhIL‐7‐hyFc).

Methods

This prospective case series based on compassionate use was approved by the Ministry of Food and Drug Safety in South Korea. Primary outcomes were safety profile and TLC. Secondary outcomes were overall survival (OS) and progression‐free survival (PFS).

Results

Among the 18 patients enrolled, 10 received rhIL‐7‐hyFc with temozolomide, 5 received rhIL‐7‐hyFc with bevacizumab, 1 received rhIL‐7‐hyFc with PCV chemotherapy, and 2 received rhIL‐7‐hyFc alone. Mean TLC of the enrolled patients after the first rhIL‐7‐hyFc treatment increased significantly from 1131 cells/mm3 (330–2989) at baseline to 4356 cells/mm3 (661–22,661). Higher TLCs were maintained while rhIL‐7‐hyFc was repeatedly administered. Median OS and PFS were 378 days (107–864 days) and 231 days (55–726 days), respectively.

Conclusion

Our study reports that IL‐7 immunotherapy can restore and maintain TLC during treatment with various salvage chemotherapies in recurrent GBM patients without serious toxicity.
Quinoline Alkaloids from the Roots of Orixa japonica with the Anti‐Pathogenic Fungi Activities
Authors: Jian Jun‐You , Fan Yi‐Min , Liu Qian , Jin Jun , Yuan Chun‐Mao , Gu Wei , Hu Zhan‐Xing , Huang Lie‐Jun , Hao Xiao‐Jiang
Published: December 2022

A new quinoline alkaloid, 5‐hydroxy‐6‐methoxy‐N‐methyl‐2‐phenylquinoline‐4‐one (1), and seventeen known quinoline alkaloids (2–18) were isolated from the roots of Orixa japonica. The structure of 1 was determined by analysis of spectroscopic data. Among them, compounds 2, 3, and 13 were isolated from this plant for the first time. All isolates were screened for the anti‐pathogenic fungi activities, including Rhizoctonia solani, Magnaporthe oryzae, and Phomopsis sp. The results showed that five compounds (4, 8, 10, 11, and 12) exhibited significant anti‐pathogenic fungi effects at 50.0 μg/mL. In special, compound 10 exhibited the best antifungal activities toward R. solani and M. oryzae with the IC50 values of 37.86 and 44.72 μM, respectively, better than that of the positive control, hymexazol (IC50 121.21 and 1518.18 μM, respectively). Moreover, eleven new quinoline alkaloids derivatives (12a–12k) were designed and synthesized to investigate the structure−activity relationships (SARs). The SARs analysis indicated that the furo[2,3‐b]quinoline skeleton and the methoxy at C‐7 (compounds 8, 11, and 12) played a key role for improving the antifungal activities.
Bifidobacterial GH146 β‐l‐Arabinofuranosidase (Bll4HypBA1) as the Last Enzyme for the Complete Removal of Oligoarabinofuranosides from Hydroxyproline‐Rich Glycoproteins
Authors: Ishiwata Akihiro , Tsunomachi Hanako , Kameyama Kyohei , Sophon Kaeothip , Nakamura Masayuki , Kitahara Kanefumi , Tanaka Katsunori , Ito Yukishige , Fujita Kiyotaka
Published: December 2022

In plant cell walls, the hydroxyproline‐rich glycoproteins (HRGPs) such as extensin contain oligoarabinofuranoside linked to a hydroxyproline (Hyp) residue. The mature arabinooligosaccharide was revealed to be a tetrasaccharide (α‐l‐Araf‐(1→3)‐β‐l‐Araf‐(1→2)‐β‐l‐Araf‐(1→2)‐β‐l‐Araf, l‐Araf4), whose linkages are targets of the bifidobacterial and Xanthomonas arabinooligosaccharide‐degrading enzymes. The l‐Araf4 motif was cleaved by GH43 α‐l‐arabinofuranosidase (Arafase) and converted to an l‐Araf3‐linked structure. The latter is then cleaved by GH121 β‐l‐arabinobiosidase (HypBA2), producing β‐l‐Araf‐(1→2)‐l‐Ara (β‐l‐arabinobiose) and mono‐β‐l‐Araf linked to the HRGP backbone. In bifidobacteria, the β‐l‐arabinobiose is then hydrolyzed by GH127 β‐l‐Arafase (Bll1HypBA1), a mechanistically unique cysteine glycosidase. We recently identified the distantly related homologue from Xanthomonas euvesicatoria as GH146 β‐l‐Arafase along with paralogues from Bifidobacterium longum, one of which, Bll4HypBA1 (BLLJ_0089), can degrade l‐Araf1‐Hyp in a similar way to that of GH146. As the chemical synthesis of the extensin hydrophilic motif 1 a, which possesses three distinct linkages that connect four oligoAraf residues [Hyp(l‐Arafn) (n=4, 3, 1)], was achieved previously, we precisely monitored the step‐wise enzymatic cleavage of 1 a in addition to that of potato lectin. The results unequivocally revealed that this enzyme specifically degrades the Hyp(l‐Araf1) motif.
Recognizing the Minimum Structural Units Driving the Crystallization of SAPO‐34 in a Top‐Down Process
Authors: Zhang Xiaosi , Yang Miao , Wang Li , Han Jingfeng , Lou Caiyi , Xu Shutao , Zhang Yanyu , Wu Ren'an , Tian Peng , Liu Zhongmin
Published: December 2022

Recognizing the structure and nature of the nuclei for zeolites crystallization on an atomic level is of great importance, which can provide guidance on the control of crystallization kinetics and the rational synthesis of zeolites. However, it remains a long‐standing challenge due to the difficulty in characterization of amorphous precursor with limited crystal nuclei. Herein, a top‐down synthesis system was designed for SAPO‐34 molecular sieve and well investigated. A clear precursor solution with abundant SAPO‐34 crystal nuclei was obtained under a depolymerization‐dominant condition. The species in the liquid precursor were identified by FT‐ICR MS, solid‐state MAS NMR and atomic pair distribution function analyses. In combination with various designed experiments, it is revealed that both the formation of small species containing Si−O−Al bonds and reaching a certain concentration, is crucial for driving the crystallization of SAPO‐34, rather than structural units with specific spatial conformation. This work provides an important understanding on the (pre)nucleation of SAPO‐34 and sheds light on the synthesis control of SAPO molecular sieves.
Customizable 2D Covalent Organic Frameworks for Optoelectronic Applications
Authors: Shao Mingchao , Liu Yunqi , Guo Yunlong
Published: December 2022

Comprehensive Summary

2D covalent organic framework (2D‐COF), a modular three‐dimensional material, is easily influenced by the component module. The assembly of different functionalized modules gives 2D‐COF unique performance. The modular structure not only allows for customization but also allows for variety, which gives 2D‐COF a wide range of functions. Hence, many building blocks with catalytic, ligand, semiconductor, luminescent, and redox centers are integrated into the COF scaffold. The connection and assembly of such modules determine the nature of the final block material. The intra‐layer connections of the modules form a monolayer mesh chemical structure, and the subsequent stacking of the monolayer mesh structure produces the final crystalline porous material—2D‐COF. This review describes in detail the potential of COF materials as optoelectronic materials and our understanding of optoelectronic processes, starting from monolayer reticulation chemistry to final 3D stacked structures, thus establishing a new paradigm for the rational design of well‐defined novel 2D‐COF optoelectronic materials and devices.
Efficient Small‐Molecule Organic Solar Cells by Modulating Fluorine Substitution Position of Donor Material
Authors: Zhang Tao , Lv Qianglong , Peng Zhongxiang , An Cunbin , Bi Pengqing , Xu Ye , Yang Ni , Wang Jingwen , Xian Kaihu , Ye Long , Zhang Shaoqing , Hou Jianhui
Published: December 2022

Comprehensive Summary

The fluorine substitution position in organic semiconductors is critical in improving device performance for organic solar cells (OSCs). Herein, two similar small‐molecule donors, B3T‐PoF and B3T‐PmF, are designed and synthesized, which only differ on the fluorine substitution position on the pendent benzene unit. Although both small‐molecule donors exhibit similar absorption profiles and molecular energy levels, B3T‐PmF has stronger crystallinity and lower energetic disorder than B3T‐PoF. After blending with the non‐fullerene acceptor of BO‐4Cl, B3T‐PmF shows better phase separation and more ordered molecular packing in blend film. As a result, the B3T‐PoF:BO‐4Cl‐based OSC shows a power conversion efficiency (PCE) of 12.3%. In contrast, the B3T‐PmF:BO‐4Cl‐based cell demonstrates obviously increased JSC and FF values, thus yielding an excellent PCE of 14.7%. This study indicates that reasonable selection of fluorine atom substitution position in conjugated side chains is one of the promising strategies for achieving high‐performance SM‐OSCs.