bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometric Phase Flat Optical Gratings with High Diffraction Angle Based on Dual‐Frequency Nematic Liquid Crystal
Authors: Nys Inge , Liu Sunqian , Huang Yu‐Nung , Strzeżysz Olga , Kula Przemysław , Neyts Kristiaan
Published: June 2023

Diffractive optical elements (DOEs) are increasingly used as lightweight and compact solutions in photonic devices. Steering of light and manipulation of the polarization can be efficiently obtained with the help of photo‐aligned liquid crystal (LC) devices. 1D LC diffraction gratings are studied that are based on the geometric phase principle and demonstrate that the optical functionality can be substantially broadened by using dual frequency LC. Switching between a highly efficient diffractive and a transmissive state is obtained by adjusting the frequency of the applied electric field. Compared to commonly studied 1D nematic LC diffraction gratings, the steering efficiency over large diffraction angles is strongly increased. By using an appropriate electric‐field treatment, the efficiency for first‐order diffraction of red light over an angle of 12.6° increases from 60% to 90%. Moreover, additional switching phenomena are observed at intermediate voltage treatments, leading to enhanced tunability of the DOEs. The origin of this behavior is explained with the help of finite element Q‐tensor simulations for the director configuration.
Hydrogels in Dental Medicine
Authors: Chen Wener , Zhang Chengfei , Peng Simin , Lin Yifan , Ye Zhou
Published: June 2023

Oral diseases are a prevalent global health problem that are primarily characterized by microbial infections, inflammation, and destruction of oral tissues. Maintaining good oral health is essential for a high quality of life, but the effective treatment of oral diseases and the regeneration of lost dental tissues remain challenging. Hydrogels have emerged as promising biomaterials in modern dental medicine. Their 3D network structures, high water content, good biocompatibility, and various bioactivities enable them to serve as drug delivery platforms, antimicrobial materials, tissue regeneration scaffolds, and biosensors. This review provides an overview of the formation mechanisms, structures, and functions of hydrogels, and highlights their latest applications in treating oral and maxillofacial diseases, such as periodontal diseases, caries, pulp diseases, oral cancer, and mucosal diseases.
Location and Concentration of Aromatic‐Rich Segments Dictates the Percolating Inter‐Molecular Network and Viscoelastic Properties of Ageing Condensates
Authors: Blazquez Samuel , Sanchez‐Burgos Ignacio , Ramirez Jorge , Higginbotham Tim , Conde Maria M. , Collepardo‐Guevara Rosana , Tejedor Andres R. , Espinosa Jorge R.
Published: June 2023

Maturation of functional liquid‐like biomolecular condensates into solid‐like aggregates has been linked to the onset of several neurodegenerative disorders. Low‐complexity aromatic‐rich kinked segments (LARKS) contained in numerous RNA‐binding proteins can promote aggregation by forming inter‐protein β‐sheet fibrils that accumulate over time and ultimately drive the liquid‐to‐solid transition of the condensates. Here, atomistic molecular dynamics simulations are combined with sequence‐dependent coarse‐grained models of various resolutions to investigate the role of LARKS abundance and position within the amino acid sequence in the maturation of condensates. Remarkably, proteins with tail‐located LARKS display much higher viscosity over time than those in which the LARKS are placed toward the center. Yet, at very long timescales, proteins with a single LARKS—independently of its location—can still relax and form high viscous liquid condensates. However, phase‐separated condensates of proteins containing two or more LARKS become kinetically trapped due to the formation of percolated β‐sheet networks that display gel‐like behavior. Furthermore, as a work case example, they demonstrate how shifting the location of the LARKS‐containing low‐complexity domain of FUS protein toward its center effectively precludes the accumulation of β‐sheet fibrils in FUS‐RNA condensates, maintaining functional liquid‐like behavior without ageing.
Small Extracellular Vesicle‐Derived vWF Induces a Positive Feedback Loop between Tumor and Endothelial Cells to Promote Angiogenesis and Metastasis in Hepatocellular Carcinoma
Authors: Wong Samuel Wan Ki , Tey Sze Keong , Mao Xiaowen , Fung Hiu Ling , Xiao Zhi‐Jie , Wong Danny Ka Ho , Mak Lung‐Yi , Yuen Man‐Fung , Ng Irene Oi‐Lin , Yun Jing Ping , Gao Yi , Yam Judy Wai Ping
Published: June 2023

Hepatocellular carcinoma (HCC) is a hypervascular malignancy by which its growth and dissemination are largely driven by the modulation of tumor‐derived small extracellular vesicles (sEVs). Proteomic profiling of circulating sEVs of control individuals and HCC patients identifies von Willibrand factor (vWF) to be upregulated progressively along HCC stages. Elevated sEV–vWF levels are found in a larger cohort of HCC–sEV samples and metastatic HCC cell lines compared to their respective normal counterparts. Circulating sEVs of late‐stage HCC patients markedly augment angiogenesis, tumor–endothelial adhesion, pulmonary vascular leakiness, and metastasis, which are significantly compromised by anti‐vWF antibody. The role of vWF is further corroborated by the enhanced promoting effect of sEVs collected from vWF‐overexpressing cells. sEV–vWF modulates endothelial cells through an elevated level of vascular endothelial growth factor A (VEGF‐A) and fibroblast growth factor 2 (FGF2). Mechanistically, secreted FGF2 elicits a positive feedback response in HCC via the FGFR4/ERK1 signaling pathway. The co‐administration of anti‐vWF antibody or FGFR inhibitor significantly improves the treatment outcome of sorafenib in a patient‐derived xenograft mouse model. This study reveals mutual stimulation between HCC and endothelial cells by tumor‐derived sEVs and endothelial angiogenic factors, facilitating angiogenesis and metastasis. It also provides insights into a new therapeutic strategy involving blocking tumor–endothelial intercellular communication.
Automatic Multiparametric Magnetic Resonance Imaging‐Based Prostate Lesions Assessment with Unsupervised Domain Adaptation
Authors: Dai Jing , Wang Xiaomei , Li Yingqi , Liu Zhiyu , Ng Yui-Lun , Xiao Jiaren , Fan Joe King Man , Lam James , Dou Qi , Vardhanabhuti Varut , Kwok Ka-Wai
Published: June 2023

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a valuable diagnostic tool in prostate lesion assessment. However, training convolutional neural networks (CNNs) inevitably involves magnetic resonance (MR) images from multiple cohorts. There always exists variation in scanning protocol among cohorts, inducing significant changes in data distribution between source and target domains. This challenge has greatly limited clinical adoption on a large scale. Herein, a coarse mask‐guided deep domain adaptation network (CMD2A‐Net) is proposed to develop a fully automated framework for prostate lesion detection and classification (PLDC). No category or mask label is required from the target domain. A coarse segmentation module is trained to cover the possible lesion‐related regions, so that attention maps can be generated to dedicate the local feature extraction of lesions within those regions. Experiments are performed on 512 mpMRI sets from datasets of PROSTATEx (330 sets) and two cohorts, A (74 sets) and B (108 sets). Using ensemble learning, CMD2A‐Net accomplishes an AUC of 0.921 in cohort A and 0.913 in cohort B, demonstrating its transferability from a large‐scale public dataset PROSTATEx to small‐scale target domains. Results from an ablation study also support its effectiveness in classification between benign and malignant lesions, compared to the state‐of‐the‐art models. An interactive preprint version of the article can be found here:https://doi.org/10.22541/au.166081031.11420810/v1.
EmoSense: Revealing True Emotions Through Microgestures
Authors: Fang Le , Xing Sark Pangrui , Long Yonghao , Lee Kun-Pyo , Wang Stephen Jia
Published: June 2023

Stress is a universally ubiquitous emotional state that takes place everywhere and microgestures (MGs) have been verified to indicate more accurate hidden emotions. However, only limited studies attempted to explore how MGs could reflect stress levels. Herein,EmoSense, an emerging technology for wearable systems containing a three‐layer stress detection mechanism, is proposed: 1) converting the MGs into digital signals; 2) training a machine learning‐based MG detection model; and 3) configuring the stress level based on the MG frequency. To detect the MGs, the swept frequency capacitive sensing technology to is adopted capture the MG signals and the random forest model to detect the MGs effectively is applied. 16 participants are recruited in the pilot study to verify the correlation between stress level and MG frequency. The experimental results further verify that stress level is highly related to other negative emotions that should be studied while handling high stress levels.
Soft Bio‐Microrobots: Toward Biomedical Applications
Authors: Wang Zihan , Klingner Anke , Magdanz Veronika , Misra Sarthak , Khalil Islam S. M.
Published: June 2023

Soft bio‐microrobots have the potential to execute complex tasks in unexpected and harsh environments of the human body due to their dexterity and flexibility. The architectural designs of soft bio‐microrobots either replicate the motion of natural creatures or capitalize on their motility. Based on this design principle, biologically inspired microrobots that imitate the movements and functions of biological systems, such as starfish, bacteria, and sperm cells, as well as biohybrid microrobots that combine motile micro‐organisms or cells with functional components have been developed. Herein, an overview of the design principles, energy sources, and biomedical applications of existing soft bio‐microrobots is presented. It is shown that the incorporation of externally responsive material enables biologically inspired microrobots to change their shapes and imitate the motion of living organisms under external stimuli, and it is interpreted how biohybrid microrobots are guided through the tactic behavior of microorganisms or cells. Finally, perspectives on key challenges that soft bio‐microrobots must overcome to achieve in vivo biomedical applications are given.
A Redox‐Based Ion‐Gating Reservoir, Utilizing Double Reservoir States in Drain and Gate Nonlinear Responses
Authors: Wada Tomoki , Nishioka Daiki , Namiki Wataru , Tsuchiya Takashi , Higuchi Tohru , Terabe Kazuya
Published: June 2023

Herein, physical reservoir computing with a redox‐based ion‐gating reservoir (redox‐IGR) comprising LixWO3thin film and lithium‐ion conducting glass ceramic (LICGC) is demonstrated. The subject redox‐IGR successfully solves a second‐order nonlinear dynamic equation by utilizing voltage pulse driven ion‐gating in a LixWO3channel to enable reservoir computing. Under the normal conditions, in which only the drain current (ID) is used for the reservoir states, the lowest prediction error is 8.15 × 10−4. Performance is enhanced by the addition ofIGto the reservoir states, resulting in a significant lowering of the prediction error to 5.39 × 10−4, which is noticeably lower than other types of physical reservoirs (memristors and spin torque oscillators) reported to date. A second‐order nonlinear autoregressive moving average (NARMA2) task, a typical benchmark of reservoir computing, is also performed with the IGR and good performance is achieved, with a normalized mean square error (NMSE) of 0.163. A short‐term memory task is performed to investigate an enhancement mechanism resulting from theIGaddition. An increase in memory capacity, from 2.35 withoutIGto 3.57 withIG, is observed in the forgetting curves, indicating that enhancement of both high dimensionality and memory capacity is attributed to the origin of the performance improvement.
Enantioselective 1,3‐Dipolar Cycloaddition of Aryldiazoalkanes Catalyzed by Chiral Oxazaborolidinium Ions
Authors: Seo Terim , Park Kyung Yee , Kim Jae Yeon , Ryu Do Hyun
Published: June 2023

Non‐stabilized aryldiazoalkanes were utilized for highly enantioselective catalytic 1,3‐dipolar cycloaddition reaction in the presence of chiral oxazaborolidinium ion (COBI) as a Lewis acid catalyst. Enantioenriched 2‐pyrazolines were obtained in excellent yields (up to >99%) with excellent enantioselectivities (up to >99%).
The Early‐Onset Alzheimer's Disease Whole‐Genome Sequencing Project: Study design and methodology
Authors: Ray Nicholas R. , Ayodele Temitope , Jean‐Francois Melissa , Baez Penelope , Fernandez Victoria , Bradley Joseph , Crane Paul K. , Dalgard Clifton L. , Kuzma Amanda , Nicaretta Heather , Sims Rebecca , Williams Julie , Cuccaro Michael L. , Pericak‐Vance Margaret A. , Mayeux Richard , Wang Li‐San , Schellenberg Gerard D. , Cruchaga Carlos , Beecham Gary W. , Reitz Christiane
Published: June 2023

INTRODUCTION

Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late‐onset AD although early‐onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations, resulting in a lack of understanding of its molecular etiology.

METHODS

Whole‐genome sequencing and harmonization of clinical, neuropathological, and biomarker data of over 5000 EOAD cases of diverse ancestries.

RESULTS

A publicly available genomics resource for EOAD with extensive harmonized phenotypes. Primary analysis will (1) identify novel EOAD risk loci and druggable targets; (2) assess local‐ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits.

DISCUSSION

This novel resource complements over 50,000 control and late‐onset AD samples generated through the Alzheimer's Disease Sequencing Project (ADSP). The harmonized EOAD/ADSP joint call will be available through upcoming ADSP data releases and will allow for additional analyses across the full onset range.

Highlights

Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late‐onset AD although early‐onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations. This results in a significant lack of understanding of the molecular etiology of this devastating form of the disease.

The Early‐Onset Alzheimer's Disease Whole‐genome Sequencing Project is a collaborative initiative to generate a large‐scale genomics resource for early‐onset Alzheimer's disease with extensive harmonized phenotype data.

Primary analyses are designed to (1) identify novel EOAD risk and protective loci and druggable targets; (2) assess local‐ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits.

The harmonized genomic and phenotypic data from this initiative will be available through NIAGADS.
Leveraging the Persistent Radical Effect in the Synthesis of trans‐2,3‐Diaryl Dihydrobenzofurans**
Authors: Roldan Bec J. , Hammerstad Travis A. , Galliher Matthew S. , Keylor Mitchell H. , Pratt Derek A. , Stephenson Corey R. J.
Published: June 2023

A simple method for accessing trans‐2,3‐diaryl dihydrobenzofurans is reported. This approach leverages the equilibrium between quinone methide dimers and their persistent radicals. This equilibrium is disrupted by phenols that yield comparatively transient phenoxyl radicals, leading to cross‐coupling between the persistent and transient radicals. The resultant quinone methides with pendant phenols rapidly cyclize to form dihydrobenzofurans (DHBs). This putative biomimetic access to dihydrobenzofurans provides superb functional group tolerance and a unified approach for the synthesis of resveratrol‐based natural products.
Dynamic Kinetic Resolution of 2‐(Quinolin‐8‐yl)Benzaldehydes: Atroposelective Iridium‐Catalyzed Transfer Hydrogenative Allylation
Authors: Carmona José A. , Rodríguez‐Salamanca Patricia , Fernández Rosario , Lassaletta José M. , Hornillos Valentín
Published: June 2023

An atroposelective Ir‐catalyzed dynamic kinetic resolution (DKR) of 2‐(quinolin‐8‐yl)benzaldehydes/1‐naphthaldehydes by transfer hydrogenative coupling of allyl acetate is disclosed. The allylation reaction takes place with simultaneous installation of central and axial chirality, reaching high diastereoselectivities and excellent enantiomeric excesses when ortho‐cyclometalated iridium‐DM‐BINAP is used as the catalyst. The racemization of the substrates occurs through a designed transient Lewis acid‐base interaction between the quinoline nitrogen atom and the aldehyde carbonyl group.
Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late‐Stage Functionalisation
Authors: Krajcovicova Sona , Spring David R.
Published: June 2023

Peptide stapling is a robust strategy for generating enzymatically stable, macrocyclic peptides. The incorporation of biologically relevant tags (such as cell‐penetrating motifs or fluorescent dyes) into peptides, while preserving their binding interactions and enhancing their stability, is highly sought after. Despite the unique opportunities offered by tryptophan‘s indole scaffold for targeted functionalisation, its utilisation in peptide stapling has been limited as compared to other amino acids. Herein, we present an approach for peptide stapling using the tryptophan‐mediated Petasis reaction. This method enables the synthesis of both stapled and labelled peptides and is applicable to both solution and solid‐phase synthesis. Importantly, the use of the Petasis reaction in combination with tryptophan facilitates the formation of stapled peptides in a straightforward, multicomponent fashion, while circumventing the formation of undesired by‐products. Furthermore, this approach allows for efficient and diverse late‐stage peptide modifications, thereby enabling rapid production of numerous conjugates for biological and medicinal applications.
Synthesis and Reactivity of an Anionic Diazoolefin
Authors: Kooij Bastiaan , Dong Zhaowen , Fadaei‐Tirani Farzaneh , Scopelliti Rosario , Severin Kay
Published: June 2023

Bent (hetero)allenes such as carbodicarbenes and carbodiphosphoranes can act as neutral C‐donor ligands, and diverse applications in coordination chemistry have been reported. N‐Heterocyclic diazoolefins are heterocumulenes, which can function in a similar fashion as L‐type ligands. Herein, we describe the synthesis and the reactivity of an anionic diazoolefin. This compound displays distinct reactivity compared to neutral diazoolefins, as evidenced by the preparation of diazo compounds via protonation, alkylation, or silylation. The anionic diazoolefin can be employed as an ambidentate, X‐type ligand in salt metathesis reactions with metal halide complexes. Extrusion of dinitrogen was observed in a reaction with PCl(NiPr2)2, resulting in a stable phosphinocarbene.
Isocyanide Cu(I) complexes with unexpected μ2‐bridging pseudohalides: Synthesis, characterization and catalytic activity towards CuAAC
Authors: Ferraro Valentina , Sole Roberto , Álvarez‐Miguel Lucía
Published: June 2023

Three neutral Cu(I) complexes bearing 2,6‐dimethylphenyl isocyanide (CNXyl) and different triatomic pseudohalogens (SCN−, OCN− and N3−) as ligands were efficiently synthesized and characterized. The solid‐state structures were unambiguously determined through single‐crystal X‐ray diffraction, revealing unexpected bridging coordination modes in the case of OCN− and N3−. All the complexes were tested for azide‐alkyne cycloaddition (CuAAC), showing interesting catalytic activity towards the formation of 1,4‐disubstituted‐1,2,3‐triazoles for the cyanato and the azido Cu(I) complexes. Both species afforded yields above 90% with 0.5 mol% of catalyst at 50°C for 24 h. Several alkynes and azides were tested using the more active azido Cu(I) complex, affording the corresponding triazoles in high yields. The azido Cu(I) complex also induced the intramolecular CuAAC in the presence of dimethyl acetylenedicarboxylate and benzyl bromide/phenylacetylene.
Synthesis and anticancer activities of novel Pt (II) and Pd (II) complexes with 4‐(2,2′:6′,2″‐terpyridin‐4′‐yl)phenol as ligand
Authors: Yu He , Xu Baotong , Yao Wei , Gao Enjun , Fedin Vladimir P.
Published: June 2023

Traditional platinum (Pt)‐based drugs have limited use in cancer treatment because of their toxicity, which generates the need for new Pt complexes with effective anticancer activity. Two potent prospective anticancer small molecule drug complexes, PtLCl (1) and PdLCl (2) (L:4‐[2,2′:6′,2′‐terpyridin‐4′‐yl]phenol), were synthesized via a low‐temperature solvothermal method. The structures of the complexes are characterized by a four‐coordinated rhombus plane, according to single‐crystal X‐ray diffraction studies. The complexes 1 and 2 were further characterized using several techniques including powder X‐ray diffraction, infrared spectroscopy, and cyclic voltammetry. Cytotoxicity was assessed using flow cytometry and morphological observations of HeLa cells. The findings demonstrate that both complexes were highly effective at inducing cell death, and the tumor inhibition rate of 1 was greater than that of 2, with total tumor inhibition of 92.3% and 72.3%, respectively, after 24 h. In addition, fluorescence and UV–vis spectroscopy showed that these complexes interacted with DNA through the embedding methods. The four‐coordinated planar structure and π–π stacking could prevent DNA transfer and replication, which has the potential for more effective cancer cell eradication through intercalation. Therefore, these two complexes are promising candidates for the development of new Pt‐ and Pd‐based anticancer drugs.
A Randomized, Double‐Blind, Sham‐Controlled, Clinical Trial of Auricular Vagus Nerve Stimulation for the Treatment of Active Rheumatoid Arthritis
Authors: Baker Matthew C. , Kavanagh Sarah , Cohen Stanley , Matsumoto Alan K. , Dikranian Ara , Tesser John , Kivitz Alan , Alataris Konstantinos , Genovese Mark C.
Published: June 2023

Objective

Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA); however, prior studies have been small and/or uncontrolled; this study aimed to address that gap.

Methods

This randomized, double‐blind, sham‐controlled trial enrolled patients aged 18 to 75 years with active RA who had failed conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) and were naïve to biologic and/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C‐reactive protein (DAS28‐CRP) and Health Assessment Questionnaire‐Disability Index (HAQ‐DI).

Results

A total of 113 patients (mean age 54 years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation versus 26.9% for sham (difference vs. sham, −1.9; 95% CI, −18.8, 14.9, P = 0.823). The least square mean ± SE change in DAS28‐CRP was −0.95 ± 0.16 for active stimulation and −0.66 ± 0.16 for sham (P = 0.201); in HAQ‐DI it was −0.19 ± 0.06 for active stimulation and −0.02 ± 0.06 for sham (P = 0.044). Adverse events occurred in 17 patients (15%); all were mild or moderate.

Conclusion

Auricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility.
Synovial Tissue Heterogeneity in Japanese Patients With Rheumatoid Arthritis Elucidated Using a Cell‐Type Deconvolution Approach
Authors: Nakajima Sotaro , Tsuchiya Haruka , Ota Mineto , Ogawa Megumi , Yamada Saeko , Yoshida Ryochi , Maeda Junko , Shirai Harumi , Kasai Taro , Hirose Jun , Ninagawa Keita , Fujieda Yuichiro , Iwasaki Takeshi , Aizaki Yoshimi , Kajiyama Hiroshi , Matsushita Masakazu , Kawakami Eiryo , Tamura Naoto , Mimura Toshihide , Ohmura Koichiro , Morinobu Akio , Atsumi Tatsuya , Tanaka Yoshiya , Takeuchi Tsutomu , Tanaka Sakae , Okamura Tomohisa , Fujio Keishi
Published: June 2023

Objective

Recent advances in single‐cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype.

Methods

Synovial tissues were obtained from East Asian patients in Japan with RA (n = 41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single‐cell–based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin–sequencing.

Results

We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA‐DRAhigh synovial fibroblasts, autoimmune‐associated B cells, GZMK+ GZMB+ CD8+ T cells, interleukin (IL)1‐β+ monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)‐α, interferons (IFNs), and IL‐6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL‐6 signaling, and expression of molecules associated with degeneration, respectively.

Conclusion

This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology.
Color‐Tunable Ultralong Organic Phosphorescence: Commercially Available Triphenylmethylamine for UV‐Light Response and Anticounterfeiting
Authors: Gao Wei , Liu Zhenliang , Dai Xianyin , Sun Weitao , Gong Qi , Li Jinwei , Ge Yanqing
Published: June 2023

Due to the unclear mechanism and lack of effective design for color‐tunable ultralong organic phosphorescence (UOP) in a single‐component molecule, the development of new types of single‐component UOP materials with color‐tunable property remains challenging. Herein, commercially available triphenylmethylamine‐based single‐component phosphors featuring color‐tunablity and ultralong lifetime (0.56 s) are reported. The changed afterglow colors from cyan to orange were observed after different wavelengths of UV excitation. Crystal structure and calculation studies show that multiple emission centers in the aggregated states may be responsible for the color‐tunablity. In addition, visual probing of UV light (from 260 to 370 nm) and colorful anti‐counterfeiting were conducted. More importantly, UV light ranging from 350 to 370 nm could be detected with the minimal interval of 2 nm. The findings provide a new type of single‐component color‐tunable UOP materials and shed new light on mechanism and design for such materials.
Pitch Carbon‐coated Ultrasmall Si Nanoparticle Lithium‐ion Battery Anodes Exhibiting Reduced Reactivity with Carbonate‐based Electrolyte
Authors: Schulze Maxwell C. , Fink Kae , Palmer Jack , Carroll Gerard M. , Dutta Nikita S. , Zwiefel Christof , Engtrakul Chaiwat , Han Sang‐Don , Neale Nathan R. , Tremolet de Villers Bertrand J.
Published: June 2023

Silicon anodes for lithium‐ion batteries (LIBs) have the potential for higher energy density compared to conventionally used graphite‐based LIB anodes. However, silicon anodes exhibit poor cycle and calendar lifetimes due to mechanical instabilities and high chemical and electrochemical reactivity with the carbonate‐based electrolytes that are typically used in LIBs. In this work, we synthesize a pitch carbon‐coated silicon nanoparticle composite active material for LIB anodes that exhibits reduced chemical reactivity with carbonate‐based electrolytes compared to an uncoated silicon anode. Silicon primary particle sizes less than 10 nm diameter minimize micro‐scale mechanical degradation of the anode composite, while conformal coatings of pitch carbon minimize the parasitic reactions between the silicon and the electrolyte. When matched with a high voltage NMC622 (LiNi0.6Mn0.2Co0.2O2) cathode, the pitch carbon‐coated silicon anode retains ≈75 % of its initial capacity at the end of 1000 cycles. Increasing the areal loading of the pitch carbon‐coated silicon anodes to realize energy density improvements over graphite anodes results in severe mechanical degradation on the electrode level, highlighting a remaining challenge to be addressed in future work.
Ascertainment of malformations in pregnancy registries: Lessons learned in the North American AED Pregnancy Registry
Authors: Holmes Lewis B. , Quinn Moira , Conant Susan , Lyons Amy , Hauser W. Allen , Yerby Mark , Hernandez‐Diaz Sonia
Published: June 2023

Background

Pregnancy registries, designed to assess the safety of medications and vaccines for the exposed mother and fetus, have been developed since the 1990s. Malformations present in the exposed liveborn or stillborn infant or fetuses in elective terminations are the outcome of greatest concern. The experiences of the North American AED (antiepileptic drug) Pregnancy Registry (NAAPR) can be used to identify the challenges and limitations of a pregnancy registry in identifying congenital malformations.

Methods

The NAAPR enrolls pregnant women who are taking one or more AEDs for any medical condition, but primarily to prevent seizures, and an unexposed comparison group. Participants are interviewed by clinical research coordinators (CRCs) at enrollment, later in pregnancy and postpartum. Malformations are identified in the mother's reports and her infant's medical records through age 12 weeks. A teratologist, blinded to exposure status, evaluates each potential malformation identified.

Results

Among 10,982 pregnancies enrolled between 1997 and 2022, 282 malformations were identified in the 9677 AED‐exposed and 15 among the 1305 unexposed infants. Isolated malformations, such as cleft palate, accounted for 84% of the malformations identified. Increased frequencies of oral clefts and myelomeningocele were associated with exposure to several different AEDs. Copies of reports from many diagnostic studies were not obtained and very few pregnancy losses had autopsies.

Conclusions

The evaluation of the AED‐exposed infants in a pregnancy registry is indirect. Improvements rely on the rapport established with the mothers by the CRCs and the mothers’ willingness to assist in obtaining information from her infants’ physicians.
Noncytotoxic Dy3+‐activated glass emits cool white light for near ultraviolet‐based white light‐emitting diodes, visible lasers, and biomedical applications
Authors: Vijayalakshmi L. , Kumar K. Naveen , Palle Kishor , Baek Jong Dae , Mohammed Abdallah A. A.
Published: June 2023

Using the melt quenching technique, a lithium zinc borate glass (LZB) system with trivalent dysprosium ions (Dy3+) was synthesized, and the luminescence and lasing properties of these materials were examined for the generation of white light. Structural investigation through X‐ray diffraction revealed that the prepared glass had an amorphous nature. The optimized glass containing 0.5 Dy3+ had a direct optical band gap of 2.782 eV and an indirect optical band gap of 3.110 eV. A strong excitation band at 386 nm (6H15/2→4I13/2) was recognized in the ultraviolet (UV) light region of its excitation spectrum. Emission bands could be seen in the photoluminescence spectrum at 659, 573, and 480 nm under the 386 nm excitation. These transitions of emission resembled electronic transitions such as (4F9/2→6H11/2), (4F9/2→6H13/2), and (4F9/2→6H15/2). In a pristine glass matrix, the higher intensity ratio of yellow to blue can result in the production of white light. The optimized Dy3+ ion concentration was observed to be 0.5 mol%. In addition, an analysis of lifetime decay was conducted for all synthesized glasses, and their decay trends were systematically investigated. Noticeably, we assessed the photometric parameters and found that they were close to the white light standard. Furthermore, a cytotoxicity study was carried out using lung fibroblast (WI‐38) cell lines for the optimized 0.5Dy3+‐doped LZB glass and it appeared to be noncytotoxic. It is clear from the results that the noncytotoxic LZB glass doped with 0.5 Dy3+ ions could be a suggestive choice for the manufacture of white light‐emitting diodes and lasers using near‐UVs.
Metabolic engineering of Synechococcus elongatus for photoautotrophic production of mannitol
Authors: Pritam Prem , Sarnaik Aditya P. , Wangikar Pramod P.
Published: June 2023

With multiple applications in food, pharmaceutical, and chemical industries as antioxidant or nonmetabolizable sweetener; the bioproduction of d‐mannitol is gaining global attention, especially with photosynthetic organisms as hosts. Considering the sustainability prospects, the current work encompasses metabolic engineering of a widely used cyanobacterial strain, Synechococcus elongatus PCC 7942, and two newly isolated fast‐growing cyanobacterial strains; S. elongatus PCC 11801 and S. elongatus PCC 11802, for mannitol production. We engineered these strains with a two‐step pathway by cloning genes for mannitol‐1‐phosphate dehydrogenase (mtlD) and mannitol‐1‐phosphatase (mlp), where the mtlD expression was under the control of different promoters from PCC 7942, namely, Prbc225, PcpcB300, PcpcBm1, PrbcLm17, and PrbcLm15. The strains were tested under the “switch conditions,” where the growth conditions were switched after the first 3 days, thereby resulting in differential promoter activity. Among the engineered strains of PCC 11801 and PCC 11802, the strains possessing Prbc225‐mtlD module produced relatively high mannitol titers of 401 ± 18 mg/L and 537 ± 18 mg/L, respectively. The highest mannitol titer of 701 ± 15 mg/L (productivity 60 mg/L.d, yield 895 µM/OD730) was exhibited by the engineered strain of PCC 7942 expressing PcpcB300‐mtlD module. It is by far the highest obtained mannitol yield from the engineered cyanobacteria.
Identification and analysis of anti‐tumor effective substances in Yangzheng Mixture
Authors: Dai Bingling , Cao Hanbing , Hu Yu , Wang Xuemei , Huang Xiaoyue , Su Xinyue , Ma Weina , Chen Yanbin , Peng Xiujuan , Gong Zhengyan , Liu Feng , Zhang Yanmin
Published: June 2023

Yangzheng Mixture is a traditional Chinese medicine used in clinical practice as an adjuvant therapy for tumors. However, little is known about its active components in tumor treatment. The purpose of this study was to explore the potential anti‐tumor components of Yangzheng Mixture to better promote its clinical application. Using LC–MS/MS, 43 components were detected in concentrated Yangzheng Mixture. Six components, comprising astragaloside, calycosin, formononetin, isoquercitrin, ononin, and calycosin‐7‐O‐β‐D‐glucoside, were identified in rat plasma. The cancer cell absorption assay showed that the intracellular concentration of four components, calycosin, calycosin‐7‐O‐β‐D‐glucoside, formononetin, and ononin, increased with extended incubation time and demonstrated potential anti‐tumor effects. The MTT assay results confirmed that Yangzheng Mixture inhibited different tumor cells proliferation. Additionally, the colony formation assay, flow cytometry analysis and wound healing displayed that Yangzheng Mixture and a combination of four components could inhibit colony formation, arrest the cell cycle and impair cell migration of tumor cells, including HCT‐116, MHCC‐97L, MCF‐7 and NCI‐H1299. In summary, our study highlighted the plausible application of Yangzheng Mixture as a potential adjuvant treatment for tumors. Furthermore, it identified effective anti‐tumor components and provided evidences for the further clinical application of Yangzheng Mixture.
Heterogeneity in corporate green supply chain practice adoption: Insights from institutional fields
Authors: Chen Yuan , Zhu Qinghua , Sarkis Joseph
Published: June 2023

Firms adopt different green supply chain management (GSCM) practices at varying levels. Drawing on institutional field theory, this study aims to explore the heterogeneity in GSCM practice adoption considering different firm characteristics, including firm size, industry, and ownership. Secondary data from 394 firms operating in China show that four organizational groupings—brown, light brown, light green, and green—firms exist. Multinomial logistic regression results show that larger firms and firms in the electronics industry are more likely to be greener, indicating that firm size and industry play a strong role in discriminating GSCM practice adoption. Interestingly, no differences between domestic and foreign‐owned firms exist, implying that the gaps in institutional perspectives between Chinese domestic and non‐domestic ownership may be disappearing. This study provides practical implications for strategic benchmarking of GSCM practices. The results also have broader implications for firm operations within China and Chinese firms competing elsewhere.
Glutamine and amino acid metabolism as a prognostic signature and therapeutic target in endometrial cancer
Authors: Zhai Lirong , Yang Xiao , Cheng Yuan , Wang Jianliu
Published: June 2023

Introduction

Endometrial cancer (EC) is the most common female reproductive system cancer in developed countries with growing incidence and associated mortality, which may be due to the growing prevalence of obesity. Metabolism reprogramming including glucose, amino acid, and lipid remodeling is a hallmark of tumors. Glutamine metabolism has been reported to participate in tumor proliferation and development. This study aimed to develop a glutamine metabolism‐related prognostic model for EC and explore potential targets for cancer treatment.

Method

Transcriptomic data and survival outcome of EC were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes related to glutamine metabolism were recognized and utilized to build a prognostic model by univariate and multivariate Cox regressions. The model was confirmed in the training, testing, and the entire cohort. A nomogram combing prognostic model and clinicopathologic features was established and tested. Moreover, we explored the effect of a key metabolic enzyme, PHGDH, on the biological behavior of EC cell lines and xenograft model.

Results

Five glutamine metabolism‐related genes, including PHGDH, OTC, ASRGL1, ASNS, and NR1H4, were involved in prognostic model construction. Kaplan–Meier curve suggested that patients recognized as high risk underwent inferior outcomes. The receiver operating characteristic (ROC) curve showed the model was sufficient to predict survival. Enrichment analysis recognized DNA replication and repair dysfunction in high‐risk patients whereas immune relevance analysis revealed low immune scores in the high‐risk group. Finally, a nomogram integrating the prognostic model and clinical factors was created and verified. Further, knockdown of PHGDH showed cell growth inhibition, increasing apoptosis, and reduced migration. Promisingly, NCT‐503, a PHGDH inhibitor, significantly repressed tumor growth in vivo (p = 0.0002).

Conclusion

Our work established and validated a glutamine metabolism‐related prognostic model that favorably evaluates the prognosis of EC patients. DNA replication and repair may be the crucial point that linked glutamine metabolism, amino acid metabolism, and EC progression. High‐risk patients stratified by the model may not be sufficient for immune therapy. PHGDH might be a crucial target that links serine metabolism, glutamine metabolism as well as EC progression.
Age‐specific cardiovascular disease‐related mortality among patients with major gastrointestinal cancers: A SEER population‐based study
Authors: Liu Gen , Zhang Bo‐fang
Published: June 2023

Background

Studies have reported age as a risk factor for cardiovascular disease (CVD)‐related mortality; however, only a few studies have focused on the relationship between age and CVD‐related mortality, especially among major gastrointestinal cancers.

Method

The present retrospective cohort enrolled patients with colorectal, pancreatic, hepatocellular, gastric, and esophageal cancer between 2000 to 2015 from the Surveillance, Epidemiology and End Results Registry (SEER). Standardized mortality ratio (SMR), competing risk regression, and restricted cubic spline (RCS) analyses were used in our study.

Results

We analyzed 576,713 patients with major gastrointestinal cancers (327,800 patients with colorectal cancer, 93,310 with pancreatic cancer, 69,757 with hepatocellular cancer, 52,024 with gastric cancer, and 33,822 with esophageal cancer). Overall, CVD‐related mortality gradually decreased every year, and the majority were older patients. All cancer patients had a higher CVD‐related mortality rate than the general U.S. population. The adjusted sub‐hazard ratios for middle‐aged with colorectal cancer, pancreatic cancer, hepatocellular cancer, gastric cancer, and esophageal cancer were 2.55 (95% CI: 2.15–3.03), 1.77 (95% CI: 1.06–2.97), 2.64 (95% CI: 1.60–4.36), 2.15 (95% CI: 1.32–3.51), and 2.28 (95% CI: 1.17–4.44), respectively. The adjusted sub‐hazard ratios for older patients with colorectal cancer, pancreatic cancer, hepatocellular cancer, gastric cancer, and esophageal cancer were 11.23 (95% CI: 9.50–13.27), 4.05 (95% CI: 2.46–6.66), 4.47 (95% CI: 2.72–7.35), 7.16 (95% CI: 4.49–11.41), and 4.40 (95% CI: 2.28–8.48), respectively. A non‐linear relationship between age at diagnosis and CVD‐related mortality was found in colorectal cancer, pancreatic cancer, and esophageal cancer; their reference ages were 67, 69, and 66 years old, respectively.

Conclusion

This study demonstrated that age was a risk factor for CVD‐related mortality among major gastrointestinal cancers.
Ce−ZSM‐5: A Highly Capable Catalyst for the Construction of Acridines in Water and Their Computational Study against DNA Gyrase Protein
Authors: Kusampally Uppalaiah , Pagadala Ramakanth , Damera Thirupathi , Puligundla Sateesh Kumar
Published: June 2023

Cerium doped ZSM‐5 (Ce−ZSM‐5) as an environmentally benign and reusable catalyst for the construction of acridines in aqueous medium. This method produced corresponding acridines with good yields and shorter reaction times. Also avoids the use of hazardous solvents and involves a simple work‐up process. The solid catalyst was prepared by doping Ce ions with ZSM‐5 (Zeolite Socony Mobil‐5) and confirmed by XRD, BET SA‐PSD and SEM. The synthesised acridine derivatives were confirmed by 1H‐NMR, 13C‐NMR and FT‐IR spectroscopic data. The docking studies of the synthesised compounds are performed by the PyRx auto dock tool against DNA gyrase protein. The products 5a and 6d are found to be the best fit ligands against DNA gyrase protein.
Fusobacterium bacteremia presenting with inferior mesenteric vein thrombosis
Authors: Sapkota Surendra , Shrestha Suraj , Sharma Sandipa , Sapkota Subash , Solis Lauren A. , Kalla Abhishek
Published: June 2023

Key Clinical Message

Isolated mesenteric vein thrombosis associated with Fusobacterium is rare. Physicians should be aware regarding the association of Fusobacterium with thrombosis at various sites.
Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications
Authors: Gori Alessandro , Lodigiani Giulia , Colombarolli Stella G. , Bergamaschi Greta , Vitali Alberto
Published: June 2023

Cell‐penetrating peptides (CPPs) encompass a class of peptides that possess the remarkable ability to cross cell membranes and deliver various types of cargoes, including drugs, nucleic acids, and proteins, into cells. For this reason, CPPs are largely investigated in drug delivery applications in the context of many diseases, such as cancer, diabetes, and genetic disorders. While sharing this functionality and some common structural features, such as a high content of positively charged amino acids, CPPs represent an extremely diverse group of elements, which can differentiate under many aspects. In this review, we summarize the most common characteristics of CPPs, introduce their main distinctive features, mechanistic aspects that drive their function, and outline the most widely used techniques for their structural and functional studies. We highlight current gaps and future perspectives in this field, which have the potential to significantly impact the future field of drug delivery and therapeutics.
High‐Contrast and Fast‐Removable 19F‐MRI Labels with Perfluoro‐tert‐Butyl Substituents
Authors: Gervits Lev L. , Sigan Andrey L. , Markova Alina A. , Gulyaev Mikhail V. , Pavlova Olga S. , Ozhiganov Ratislav M. , Pirogov Yury A.
Published: June 2023

19F MRI is a unique technique for tracking and quantifying the indicator (19F‐MRI label) in vivo without the use of ionizing radiation. Here we report new 19F‐MRI labels, which are compounds with perfluoro‐tert‐butyl groups: 1,2‐bis(perfluoro‐tert‐butoxy)ethane (C10F18H4O2) and 1,3‐bis(perfluoro‐tert‐butyl)propane (C11F18H6). Both substances contain 18 equivalent 19F atoms, constituting 68.67 % and 71.25 % of the molecule, respectively. The emulsions with 19F molecules were prepared and used in 19F MRI studies in laboratory rats in vivo. The substances demonstrated high contrast properties, good biological inertness and the ability to be rapidly eliminated from the body. We showed that at a dose of 0.34 mg/g of body weight in rats, the time for complete elimination of C10F18H4O2 and C11F18H6 is ∼30 days. The results turned out to be promising for the use of the presented compounds in 19F MRI applications, especially since they are quite easy to synthesize.
Hydrolysable tannins as a potential therapeutic drug for the human fibrosis‐associated disease
Authors: Wang Meiwei , Cao Linghui
Published: June 2023

Fibrosis is a pathological change with abnormal tissue regeneration due to a response to persistent injury, which is extensively related to organ damage and failure, leading to high morbidity and mortality worldwide. Although the pathogenesis of fibrosis has been comprehensively elucidated, there are few effective therapies for treating fibrotic diseases. Natural products are increasingly regarded as an effective strategy for fibrosis with numerous favorable functions. Hydrolysable tannins (HT) are a type of natural products that have the potential to treat the fibrotic disease. In this review, we describe some biological activities and the therapeutic prospects of HT in organ fibrosis. Furthermore, the underlying mechanisms of inhibition of HT on fibrotic organs in relation to inflammation, oxidative stress, epithelial–mesenchymal transition, fibroblast activation and proliferation, and extracellular matrix accumulation are discussed. Understanding the mechanism of HT against fibrotic diseases will provide a new strategy for the prevention and attenuation of fibrosis progression.