bluuebunny/crossref_metadata_2025 huggingface dataset:
Femtosecond Laser Maskless Optical Projection Lithography of Cartilage PCM Inspired 3D Protein Matrix to Chondrocyte Phenotype
Authors: Li Teng , Liu Jie , Guo Min , Bin Fan‐Chun , Duan Qi , Dong Xian‐Zi , Jin Feng , Fujita Katsumasa , Zheng Mei‐Ling
Published: April 2024

Hydrogels containing chondrocytes have exhibited excellent potential in regenerating hyaline cartilage. However, chondrocytes are vulnerable to dedifferentiation during in vitro culture, leading to fibrosis and mechanical degradation of newly formed cartilage. It is proposed to modulate cartilage formation via the developed chondrocyte pericellular matrix (PCM) ‐like scaffolds for the first time, in which the S, M, and L‐sized scaffolds are fabricated by femtosecond laser maskless optical projection lithography (FL‐MOPL) of bovine serum albumin‐glyceryl methacrylate hydrogel. Chondrocytes on the M PCM‐like scaffold can maintain round morphology and synthesize extracellular matrix (ECM) to induce regeneration of hyaline cartilage microtissues by geometrical restriction. A series of M PCM‐like scaffolds is fabricated with different stiffness and those with a high Young's modulus are more effective in maintaining the chondrocyte phenotype. The proposed PCM‐like scaffolds are effective in modulating cartilage formation influenced by pore size, depth, and stiffness, which will pave the way for a better understanding of the geometric cues of mechanotransduction interactions in regulating cell fate and open up new avenues for tissue engineering.
Stretchable Metal Halide Perovskite Color Conversion Layers with Block Copolymer Dispersant
Authors: Cheon Jaehui , Park Jeong‐Min , Son Jeonghyeon , Lee Minsub , Lee Sumin , Park Chanwoo , Kim Hyo Jung , Kim Jae‐Hyuk , Park Jong S. , Jeong Beomjin
Published: April 2024

Stretchable luminescent nanocomposites with metal halide perovskite (MHP) emitters are in high demand as deformable color‐conversion layers (CCLs) for vivid‐colored form‐factor free displays. However, the immiscibility of the MHP crystals with an elastomeric polymer matrix induces particle aggregation with resultant luminescence quenching, hindering the development of MHP‐based CCLs. Herein, a simple method is proposed to produce highly luminescent MHP nanoparticles (NPs) and stably disperse them in an elastomeric poly(dimethylsiloxane) (PDMS) polymer matrix with block copolymer (BCP) dispersant. The nanocomposites are developed through sequential steps of synthesis of MHP‐NP dispersion solution with BCP and blending with PDMS followed by thermal curing. It is revealed that Lewis basic poly(2‐vinylpyridine)‐block‐poly(dimethylsiloxane) (P2VP‐b‐PDMS) BCP added in the synthesis step promotes crystallization of the MHPs as nanocrystals with an average diameter of 5.9 ± 1.2 nm, whereas MHPs with hundreds of nm are produced without BCP. The resultant MHP‐NPs with P2VP‐b‐PDMS exhibit excellent photophysical properties, such as narrow band emission, high photoluminescence (PL) quantum yield, and long PL lifetime. The MHP‐NPs are stably dispersed in the PDMS matrix by P2VP‐b‐PDMS without particle aggregation, leading to highly deformable and stretchable nanocomposites with stable PL emission upon repetitive stretching, and excellent environmental stability.
Efficacy and Safety of Resveratrol in the Treatment of Bladder Cancer Derived Organoids
Authors: Liu Guang‐Yao , Xiao Kang‐Hua , Li Hong , Chen Xiang , Ye Hai‐Shan , Liu Lin‐Jie , Li Ting‐Ting , Li Sheng , Lu Jun‐Lin , Chen Xu , Liu Jia
Published: April 2024

Intravesical instillation is a prevalent approach in bladder cancer (BC) management, yet it often causes adverse reactions and drug resistance. Safer and more effective alternative is therefore in urgent need, and resveratrol (RES) emerges as a promising candidate. However, the effectiveness of RES against BC remains unexplored. In this study, BC‐derived organoids (BCOs) are established to evaluate the efficacy of RES in comparison to conventional anti‐BC drugs (epirubicin (EPI), cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR)). After a 96‐h treatment, RES demonstrates superior anti‐BCOs efficacy (64.00%; 16/25) compared to the other chemotherapeutics (15.38% to 53.85%). Eighteen BCOs are treated with RES, EPI, or a combination of RES and EPI (RES/EPI) in short‐term (3 h per day for four times) to mimic intravesical instillation. RES exhibits the stronger efficacy (44.44%; 8/18) than EPI against BCOs, and the RES/EPI enhances sensitivity of a single drug (50.00%; 9/18). RES inhibits the activation of β‐catenin/CD44 axis in RES‐sensitive BCOs. The organoid‐forming potential of mouse bladder is preserved after intravesical instillation of RES, and 200 × 10−6 m RES demonstrates no adverse effects on patient‐derived bladder urothelial organoids. The findings highlight the potential of RES, particularly in combination with EPI, to improve intravesical instillation outcomes in BC management.
Progress in Biomass Electro‐Valorization for Paired Electrosynthesis of Valuable Chemicals and Fuels
Authors: Abderrahmane Amira Ben , Tingry Sophie , Cornu David , Holade Yaovi
Published: April 2024

Environmental and energy concerns surrounding the use of fossil fuels are driving an increasingly rapid transition to sustainable and eco‐responsible processes. Electrochemical processes can provide the necessary sustainability and economic roadmap for storing intermittent and renewable electricity by synthesizing, in cogeneration electrolyzers, energy carriers and/or synthetic chemicals (hydrogen, ammonia, etc.) via flagship reduction reactions (hydrogen evolution reaction (HER), nitrogen reduction reaction (NRR), etc.). To balance the electrochemical process, these cathodic processes have long been coupled to the oxygen evolution reaction (OER), which ultimately consumes almost 90% of the energy input. Recent years have witnessed an overwhelming development of anode scenarios based on biomass substrates, because OER cannot be driven below a certain potential threshold, while organics are thermodynamically more favorable. Therefore, paired electrolysis, which refers to cases where electrochemical oxidation and reduction are desired, embraces the electrocatalysis community for the electrolytic production of hydrogen, ammonia, etc. (cathode side), in parallel with value‐added chemicals (anode side), all with a modest electricity input. The trade‐off is selectivity at relevant current densities. This review discusses, the progress, challenges, and potential of biomass‐fueled paired electrosynthesis of valuable chemicals and fuels. Fundamental principles, main biomass solubilization methods, and different scenarios for paired electrosynthesis are presented.
Expansion of the core features of VACTERL association to include genital anomalies
Authors: Forero Laura T. , Henderson Riley , Galarreta Carolina , Swee Steven , Bird Lynne M.
Published: April 2024

Genital anomalies have been reported with VACTERL association but not considered a core feature. Acute and chronic complications stemming from unrecognized genital anomalies have been reported in adolescents and young adults with VACTERL association. We sought to determine the frequency and severity of genital anomalies in VACTERL patients and identify which core features were more frequently associated with genital anomalies. A retrospective chart review from January 2010 to October 2021 identified 211 patients with two or more core VACTERL features, 34% of whom had a genital anomaly. The majority of genital anomalies (83% of those in males and 90% in females) were classified as functionally significant (requiring surgical intervention or causing functional impairment). The frequency of genital anomalies in the VACTERL cohort was higher if anorectal malformations or renal anomalies were present in both males and females and if vertebral anomalies were present in females. Due to their functional significance, genital anomalies should be assessed in all patients with two or more core features of VACTERL association, especially in those with anorectal or renal anomalies. Most genital anomalies in males will be detected on physical examination but additional investigation is often needed to detect genital anomalies in females. The timing and type of investigation are subjects for future study.
In vivo validation of late‐onset Alzheimer's disease genetic risk factors
Authors: Sasner Michael , Preuss Christoph , Pandey Ravi S. , Uyar Asli , Garceau Dylan , Kotredes Kevin P. , Williams Harriet , Oblak Adrian L. , Lin Peter Bor‐Chian , Perkins Bridget , Soni Disha , Ingraham Cindy , Lee‐Gosselin Audrey , Lamb Bruce T. , Howell Gareth R. , Carter Gregory W.
Published: April 2024

INTRODUCTION

Genome‐wide association studies have identified over 70 genetic loci associated with late‐onset Alzheimer's disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.

METHODS

Candidate genetic risk variants were informatically prioritized and individually engineered into a LOAD‐sensitized mouse model that carries the AD risk variants APOE ε4/ε4 and Trem2*R47H. The potential disease relevance of each model was assessed by comparing brain transcriptomes measured with the Nanostring Mouse AD Panel at 4 and 12 months of age with human study cohorts.

RESULTS

We created new models for 11 coding and loss‐of‐function risk variants. Transcriptomic effects from multiple genetic variants recapitulated a variety of human gene expression patterns observed in LOAD study cohorts. Specific models matched to emerging molecular LOAD subtypes.

DISCUSSION

These results provide an initial functionalization of 11 candidate risk variants and identify potential preclinical models for testing targeted therapeutics.

Highlights

A novel approach to validate genetic risk factors for late‐onset AD (LOAD) is presented.

LOAD risk variants were knocked in to conserved mouse loci.

Variant effects were assayed by transcriptional analysis.

Risk variants in Abca7, Mthfr, Plcg2, and Sorl1 loci modeled molecular signatures of clinical disease.

This approach should generate more translationally relevant animal models.
Purely Organic Room‐Temperature Phosphorescence Molecule for High‐Performance Non‐Doped Organic Light‐Emitting Diodes
Authors: Peng Xiaoluo , Zou Peng , Zeng Jiajie , Wu Xing , Xie Dian , Fu Yan , Yang Dezhi , Ma Dongge , Tang Ben Zhong , Zhao Zujin
Published: April 2024

Purely organic molecules with room‐temperature phosphorescence (RTP) are potential luminescent materials with high exciton utilization for organic light‐emitting diodes (OLEDs), but those exhibiting superb electroluminescence (EL) performances are rarely explored, mainly due to their long phosphorescence lifetimes. Herein, a robust purely organic RTP molecule, 3,6‐bis(5‐phenylindolo[3,2‐a]carbazol‐12(5H)‐yl)‐xanthen‐9‐one (3,2‐PIC‐XT), is developed. The neat film of 3,2‐PIC‐XT shows strong green RTP with a very short lifetime (2.9 μs) and a high photoluminescence quantum yield (72 %), and behaviors balanced bipolar charge transport. The RTP nature of 3,2‐PIC‐XT is validated by steady‐state and transient absorption and emission spectroscopies, and the working mechanism is deciphered by theoretical simulation. Non‐doped multilayer OLEDs using thin neat films of 3,2‐PIC‐XT furnish an outstanding external quantum efficiency (EQE) of 24.91 % with an extremely low roll‐off (1.6 %) at 1000 cd m−2. High‐performance non‐doped top‐emitting and tandem OLEDs are also achieved, providing remarkable EQEs of 24.53 % and 42.50 %, respectively. Delightfully, non‐doped simplified OLEDs employing thick neat films of 3,2‐PIC‐XT are also realized, furnishing an excellent EQE of 17.79 % and greatly enhanced operational lifetime. The temperature‐dependent and transient EL spectroscopies demonstrate the electrophosphorescence attribute of 3,2‐PIC‐XT. These non‐doped OLEDs are the best devices based on purely organic RTP materials reported so far.
Electrochemically‐Driven 1,4‐Aryl Migration via Radical Fluoromethylation of N‐Allylbenzamides: a Straightforward Access to Functionalized β‐Arylethylamines
Authors: Derat Etienne , Masson Géraldine , Claraz Aurélie
Published: April 2024

An electrochemical radical Truce Smiles rearrangement of N‐allylbenzamides is documented herein. The selective 1,4‐aryl migration was triggered by the radical fluoromethylation of the alkene providing a direct route to fluoro derivatives of the highly privileged β‐arylethylamine pharmacophore. This practical transformation utilizes readily available starting materials and employs an electrical current to drive the oxidative process under mild reaction conditions. It accommodates a variety of migratory aryl groups with different electronic properties and substitution patterns. Careful selection of the protecting group on the nitrogen atom of the N‐allylbenzamide is crucial to outcompete the undesired 6‐endo cyclization and achieve high level of selectivity towards the 1,4‐aryl migration. DFT calculations support the reaction mechanism and unveil the origin of selectivity between the two competitive pathways.
Consolidation of the Oxidant‐Free Au(I)/Au(III) Catalysis Enabled by the Hemilabile Ligand Strategy
Authors: Font Pau , Valdés Hugo , Ribas Xavi
Published: April 2024

In this minireview we survey the challenges and strategies in gold redox catalysis. Gold's reluctance to oxidative addition reactions due to its high redox potential limits its applicability. Initial attempts to overcome this problem focused on the use of sacrificial external oxidants in stoichiometric amounts to bring Au(I) compounds to Au(III) reactive species. Recently, innovative approaches focused on employing hemilabile ligands, which are capable of coordinating to Au(I) and stabilizing square‐planar Au(III) intermediates, thus facilitating oxidative addition steps and enabling oxidant‐free catalysis. Notable examples include the use of the (P^N) bidendate MeDalphos ligand to achieve various cross‐coupling reactions via oxidative addition Au(I)/Au(III). Importantly, hemilabile ligand‐enabled catalysis allows merging oxidative addition with π‐activation, such as oxy‐ and aminoarylation of alkenols and alkenamines using organohalides, expanding gold‘s versatility in C−C and C‐heteroatom bond formations and unprecedented cyclizations. Moreover, recent advancements in enantioselective catalysis using chiral hemilabile (P^N) ligands are also surveyed. Strikingly, versatile bidentate (C^N) hemilabile ligands as competitors of MeDalphos have appeared recently, by designing scaffolds where phosphine groups are substituted by N‐heterocyclic or mesoionic carbenes. Overall, these approaches highlight the evolving landscape of gold redox catalysis and its tremendous potential in a broad scope of transformations.
Investigation of liquid crystal epoxy resin composites for application in cryogenic environments
Authors: Li Na , Ma Jun‐Li , Liu Yu , Huang Gui‐Wen , Qu Cheng‐Bing , Li Meng , Xiao Hong‐Mei
Published: April 2024

It is well accepted that the intrinsic thermal conductivity is extremely important in achieving excellent thermal conductivity composite and can be improved via incorporation of mesogens. In this work, an azomethine type liquid crystal epoxy (LCE) with aliphatic ether was designed and synthesized with expected structure, and the liquid crystal epoxy resin (LCER), together with KH‐550‐modified boron nitride (K‐BN)/LCER composites, has been obtained. Results show an increase of 31.6% in the thermal conductivity of the matrix, which could result in an enhancement of 57.7% for the composites when compared with E‐51. Additionally, the coefficient of thermal expansion (CTE), dielectric properties, and shear strength of LCER and K‐BN/LCER composites were assessed across a broad temperature range. Remarkably, the 30 wt% K‐BN/LCER composites showed a maximum decrease of 37.8% in CTE, while maintaining adequate shear strength to fulfill the bonding requirement and high thermal conductivity at both RT and −196°C.
A dual amplified gold nanoparticle‐based biosensor for ultrasensitive and selective detection of fibrin
Authors: Gong Wenyue , Zhang Yuanfu , Chen Yawei , Zhao Xue , Wang Shuhao
Published: April 2024

Ultrasensitive, selective, and non‐invasive detection of fibrin in human serum is critical for disease diagnosis. So far, the development of high‐performance and ultrasensitive biosensors maintains core challenges for biosensing. Herein, we designed a novel ribbon nanoprobe for ultrasensitive detection of fibrin. The probe contains gold nanoparticles (AuNPs) that can not only link with homing peptide Cys‐Arg‐Glu‐Lys‐Ala (CREKA) to recognize fibrin but also carry long DNA belts to form G‐quadruplex‐based DNAzyme, catalyzing the chemiluminescence of luminol–hydrogen peroxide (H2O2) reaction. Combined with the second amplification procedure of rolling circle amplification (RCA), the assay exhibits excellent sensitivity with a detection limit of 0.04 fmol L−1 fibrin based on the 3‐sigma. Furthermore, the biosensor shows high specificity on fibrin in samples because the structure of antibody‐fibrin‐homing peptide was employed to double recognize fibrin. Altogether, the simple and inexpensive approach may present a great potential for reliable detection of biomarkers.
Smartphone app for lifestyle improvement improves brain health and boosts the vitality and cognitive function of healthy middle‐aged adults
Authors: Kokubun Keisuke , Nemoto Kiyotaka , Yamakawa Yoshinori
Published: April 2024

Introduction

The number of smartphone apps for brain training is increasing, and the number of people who are working on brain training is also increasing. However, researchers disagree about the effectiveness of brain training.

Methods

Therefore, in this study, we conducted an intervention test with the participation of 70 healthy middle‐aged men and women and measured the effect of smartphone apps on lifestyle improvement using brain healthcare quotient calculated from brain imaging data.

Results

As a result, in the intervention group, significant improvements were seen in fractional anisotropy (FA) of the whole brain, corpus callosum, internal capsule, corona radiata, posterior thalamic radiation, external capsule, and superior longitudinal fasciculus. Additionally, in the intervention group, these FA increments correlated with improvements in cognitive function as measured by the trail‐making test and vigor as measured by the Profile of Mood States 2nd Edition.

Conclusion

The results of this study suggest that improving lifestyle habits through smartphone apps can improve brain health and cognitive and emotional performance of healthy middle‐aged adults. This is consistent with previous research that suggests that FA integrity in the limbic‐thalamo‐cortical pathway influences cognitive function and emotion regulation.
Case report—Depression with psychotic features as an atypical presentation of neurosyphilis
Authors: Aytulun Aykut , Grannemann Laura Sophie , MacKenzie Colin R. , Dimitrakopoulos Alexandros , Pessanha‐Schlegel Francesca , Kamp Daniel , Schilbach Leonhard
Published: April 2024

Key Clinical Message

Recurrent depression with psychotic features is an atypical presentation of neurosyphilis. This case emphasizes the polymorphic clinical presentation of neurosyphilis and how it mimics affective disorders with psychotic symptoms.
Molecular regulation of calcium‐sensing receptor (CaSR)‐mediated signaling
Authors: Tian Li , Andrews Corey , Yan Qiuyun , Yang Jenny J.
Published: April 2024

Calcium‐sensing receptor (CaSR), a family C G‐protein‐coupled receptor, plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca2+, Mg2+, amino acids (e.g., L‐Trp and L‐Phe), small peptides, anions (e.g., HCO3− and PO43−), and pH. CaSR‐mediated intracellular Ca2+ signaling regulates a diverse set of cellular processes including gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission. Dysfunction of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. CaSR also influences calciotropic disorders, such as osteoporosis, and noncalciotropic disorders, such as cancer, Alzheimer's disease, and pulmonary arterial hypertension. This study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands, as well as exogenous positive allosteric modulators and negative allosteric modulators. The establishment of the first CaSR protein–protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum, trafficking, cell surface expression, endocytosis, degradation, and signaling pathways. The roles of these proteins in Ca2+‐dependent cellular physiological processes and in CaSR‐dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G‐protein‐coupled receptors.
Unveiling blood pressure‐associated genes in aortic cells through integrative analysis of GWAS and RNA modification‐associated variants
Authors: Zhang Huan , Chen Yuxi , Xu Peng , Liu Dan , Wu Naqiong , Wang Laiyuan , Mo Xingbo
Published: April 2024

Background

Genome‐wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell‐type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification‐associated single‐nucleotide polymorphisms (RNAm‐SNPs).

Methods

Utilizing large‐scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm‐SNPs and BP. The association between RNAm‐SNPs, gene expression, and BP were examined.

Results

A total of 355 RNAm‐SNPs related to m6A, m1A, m5C, m7G, and A‐to‐I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m6A‐SNPs, highlighting the potential functional relevance of m6A in physiological processes influencing BP. Notably, m6A‐SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO‐overexpression and METTL14‐knockdown vascular smooth muscle cells were detected. RNAm‐SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA‐seq study, we identified ARID5A, HLA‐DPB1, HLA‐DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells.

Conclusion

The present study identified RNAm‐SNPs in BP loci and elucidated the associations between the RNAm‐SNPs, gene expression, and BP. The identified BP‐associated genes in aortic cells were associated with AD.
Transforming Cigarette Wastes into Oxygen Reduction Reaction Electrocatalyst: Does Each Component Behave Differently? An Experimental Evaluation
Authors: Zuccante Giovanni , Muhyuddin Mohsin , Ficca Valerio C. A. , Placidi Ernesto , Acciarri Maurizio , Lamanna Niccolò , Franzetti Andrea , Zoia Luca , Bellini Marco , Berretti Enrico , Lavacchi Alessandro , Santoro Carlo
Published: April 2024

Trillion of cigarette butts are annually littered without being recycled. This work aims at valorizing the whole cigarette butts and their components (paper, filter and tobacco) into Fe‐Nx‐C electrocatalysts for oxygen reduction reaction (ORR) in acid and alkaline media. The pristine wastes were pyrolyzed at 450 °C, activated with KOH at 700 °C, blended with iron phthalocyanine (FePc) precursor, and heat‐treated at 600 °C to produce a robust Fe‐Nx‐C material with ORR active units. The effect of the cigarette components on the final electrocatalytic activity was evaluated by thoroughly investigating the surface chemistry with XPS. The electrocatalysts displayed similar results among the different components in both media due to comparable surface chemistry, especially concerning the nitrogen functional groups. The highest performance was obtained in alkaline where the electrocatalysts from whole cigarettes and paper (CIGF_450 and CIGPF_450) showed an E1/2 of 0.89 V vs RHE, slightly larger than that of Pt/C with 40 wt % of Pt, which encouraged to replace Pt‐based electrocatalysts in alkaline fuel cells.
The effects of public health and social measures (PHSM) implemented during the COVID‐19 pandemic: An overview of systematic reviews
Authors: Fadlallah Racha , El‐Jardali Fadi , Karroum Lama Bou , Kalach Nour , Hoteit Reem , Aoun Andrew , Al‐Hakim Lara , Verdugo‐Paiva Francisca , Rada Gabriel , Fretheim Atle , Lewin Simon , Ludolph Ramona , Akl Elie A.
Published: April 2024

Introduction

To systematically review the effectiveness and unintended health and socioeconomic consequences of public health and social measures (PHSM) aimed at reducing the scale and risk of transmission of coronavirus disease 2019 (COVID‐19).

Methods

This review followed guidance about overviews of reviews in the Cochrane handbook for systematic reviews of interventions and used the Epistemonikos database's COVID‐19 Living Overview of Evidence repository as a primary search source. Methodological quality was evaluated using the Measurement Tool to Assess Systematic Reviews (AMSTAR 2) checklist.

Results

A total of 94 reviews were included, of which eight (9%) had “moderate” to “high” confidence ratings on the AMSTAR 2. Of 16 reviews (17%) reporting applying the GRADE framework, none found high certainty evidence for any of our outcomes of interest. Across the 94 reviews, the most frequently examined PHSM were personal protection (n = 18, 19%). Within multicomponent interventions, so‐called “lockdown” was the most frequently examined component (n = 39, 41%). The most frequently reported outcome category was non‐COVID‐19‐related health outcomes (n = 58, 62%). Only five (5%) reviews reported on socioeconomic outcomes. Findings from the eight reviews with moderate or high confidence ratings on AMSTAR 2 are narratively summarized. There is low‐certainty evidence that multicomponent interventions may reduce the transmission of COVID‐19 in different settings. For active surveillance and response measures, low‐certainty evidence suggests that routine testing of residents and staff in long‐term care facilities may reduce the number of infections, hospitalizations, and deaths among residents. We found very low‐certainty evidence about the effectiveness of personal protection measures, travel‐related control measures, and environmental measures. Unintended consequences were rarely examined by those eight reviews.

Conclusion

We found predominantly low‐ to very low‐certainty evidence regarding the effectiveness and unintended consequences of PHSM in controlling the risk and scale of COVID‐19 transmission. There is a need to improve the conduct and reporting of systematic reviews.
Multifunctional Amino Acid Derivative Coordination Compounds: Novel Contrast Agent and Luminescence Materials
Authors: Echenique‐Errandonea Estitxu , Rojas Sara , Ortuño Ana M. , Cepeda Javier , Ramos‐Cabrer Pedro , Vitórica‐Yrezábal Íñigo J. , Cuerva Juan M. , Seco José M. , Rodríguez‐Diéguez Antonio
Published: April 2024

In this work a family of multidimensional (2‐(1H‐tetrazol‐5‐yl)ethyl) amino acid coordination compounds have been synthesized and thoroughly characterized. For this purpose, glycine, valine, phenylalanine and tyrosine have been selected as starting amino acids and Mn2+, Zn2+ and Cd2+ as metallic nodes. From one side, for Mn2+ based dimer magnetic resonance imaging studies have been conducted, prompted by the number and disposition of the coordinated water molecules and taking into consideration the promising future of manganese‐based coordination compounds as bio‐compatible substitutes to conventional Gd based contrast agents. From another side, d10 block metal‐based complexes allowed exploring photoluminescence properties derived by in situ synthesized ligands. Finally, amino acid preserved structural chirality allowed us to examine chiroptical properties, particularly focusing on circularly polarized luminescence.
Gut‐lung axis and asthma: A historical review on mechanism and future perspective
Authors: Song Xiu‐Ling , Liang Juan , Lin Shao‐Zhu , Xie Yu‐Wei , Ke Chuang‐Hong , Ao Dang , Lu Jun , Chen Xue‐Mei , He Ying‐Zhi , Liu Xiao‐Hua , Li Wen
Published: April 2024

Background

Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut‐lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic.

Body

This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut‐lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed.

Conclusion

The gut‐lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.
N‐Pyrazolyl‐ and N‐Triazolylamines and ‐Ureas as Antileishmanial and Antitrypanosomal Drugs
Authors: Winge Tobias , Imberg Lukas , Perry Ben , Matheeussen An , Caljon Guy , Kalinin Dmitrii , Wünsch Bernhard
Published: April 2024

Three types of modifications of antileishmanial pyrazole lead compounds 7 and 8 were conducted to expand understanding of the relationships between structural features and antileishmanial/antitrypanosomal activity: (1) the pyrazole core was retained or replaced by a 1,2,4‐triazole ring; (2) various aryl moieties including 2‐fluorophenyl, pyridin‐3‐yl and pyrazin‐2‐yl rings were attached at 3‐position of the core azole; (3) either arylmethylamino or ureido substituents were introduced at 5‐position of the azole core. The synthesis followed established routes starting with esters 9 or 15 and anhydride 21. The synthesized 3‐arylpyrazoles and 3‐aryl‐1,2,4‐triazoles had only very low antileishmanial activity. The 2‐fluorophenyl‐substituted pyrazole 18c revealed the highest antileishmanial activity of this series of compounds, but its IC50 value (20 μM) still indicates low activity. However, low micromolar antitrypanosomal activity was detected for the pyridin‐3‐yl‐substituted pyrazoles 12b (IC50=4.7 μM) and 14a (IC50=2.1 μM). Their IC50 values are comparable with the IC50 values of the reference compounds benznidazole and nifurtimox. Whereas only low unspecific cytotoxicity at the primary peritoneal mouse macrophages (PMM) was detected, considerable cytotoxicity at MRC‐5 human fibroblast cells was found for both pyrazoles 12b an 14a. The activity of pyrazole 12b against T. cruzi is 4‐fold higher than its unspecific MRC‐5 cytotoxicity.
Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures
Authors: Bielamowicz Kevin , Dimitrion Peter , Abla Oussama , Bomken Simon , Campbell Patrick , Collin Matthew , Degar Barbara , Diamond Eli L. , Eckstein Olive S. , El‐Mallawany Nader , Fluchel Mark , Goyal Gaurav , Henry Michael M. , Hermiston Michelle , Hogarty Michael , Jeng Michael , Jubran Rima , Lubega Joseph , Kumar Ashish , Ladisch Stephan , McClain Kenneth L. , Merad Miriam , Mi Qing‐Sheng , Parsons D. Williams , Peckham‐Gregory Erin , Picarsic Jennifer , Prudowsky Zachary D. , Rollins Barrett J. , Shaw Peter H. , Wistinghausen Birte , Rodriguez‐Galindo Carlos , Allen Carl E. ,   North American Consortium for Histiocytosis
Published: April 2024

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a‐positive/Langerin (CD207)‐positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life‐threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard‐of‐care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long‐term morbidity, including the risk of LCH‐associated neurodegeneration. Historically, the nature of LCH—whether a reactive condition versus a neoplastic/malignant condition—was uncertain. Over the past 15 years, seminal discoveries have broadly defined LCH pathogenesis; specifically, activating mitogen‐activated protein kinase pathway mutations (most frequently, BRAFV600E) in myeloid precursors drive lesion formation. LCH therefore is a clonal neoplastic disorder, although secondary inflammatory features contribute to the disease. These paradigm‐changing insights offer a promise of rational cures for patients based on individual mutations, clonal reservoirs, and extent of disease. However, the pace of clinical trial development behind lags the kinetics of translational discovery. In this review, the authors discuss the current understanding of LCH biology, clinical characteristics, therapeutic strategies, and opportunities to improve outcomes for every patient through coordinated agent prioritization and clinical trial efforts.
Insights into Carbon Dioxide Capture over Glycine‐Functionalized Metal–Organic Framework‐808 from DFT Calculations
Authors: Wansa Chomphunuch , Sittiwong Jarinya , Srifa Pemikar , Maihom Thana , Limtrakul Jumras
Published: April 2024

Metal‐organic framework‐808 (MOF‐808), functionalized with amino acids, is a promising class of materials for carbon dioxide (CO2) capture. In this study, we employed density functional theory calculations to investigate the mechanism of CO2 capture by glycine‐functionalized MOF‐808 (MOF‐808‐Gly). MOF‐808 was treated with one, two, three, or four glycine molecules to investigate the effect of glycine functionalization. It is proposed that the capture reaction proceeds in a single step involving proton transfer and C−N bond formation. With increasing glycine loading, the reaction barriers decreased, whereas the observed rate increased. When considering the substitution of different tetravalent metal centers (Zr and Hf) on the MOF‐808 node, it is found that substituting these tetravalent metal centers does not affect the capture activity. The capture reaction under humid conditions was also studied by introducing explicit and implicit amounts of water. The presence of a water molecule led to reduced barriers and more stable capture product formation, indicating the enhanced performance of MOF‐808‐Gly in CO2 capture.
Pearcey universality at cusps of polygonal lozenge tilings
Authors: Huang Jiaoyang , Yang Fan , Zhang Lingfu
Published: April 2024

We study uniformly random lozenge tilings of general simply connected polygons. Under a technical assumption that is presumably generic with respect to polygon shapes, we show that the local statistics around a cusp point of the arctic curve converge to the Pearcey process. This verifies the widely predicted universality of edge statistics in the cusp case. Together with the smooth and tangent cases proved by Aggarwal‐Huang and Aggarwal‐Gorin, these are believed to be the three types of edge statistics that can arise in a generic polygon. Our proof is via a local coupling of the random tiling with nonintersecting Bernoulli random walks (NBRW). To leverage this coupling, we establish an optimal concentration estimate for the tiling height function around the cusp. As another step and also a result of potential independent interest, we show that the local statistics of NBRW around a cusp converge to the Pearcey process when the initial configuration consists of two parts with proper density growth, via careful asymptotic analysis of the determinantal formulas.
Zibotentan Can Be Co‐administered with Contraceptives Containing Ethinyl Estradiol and Levonorgestrel: A Pharmacokinetic Drug–Drug Interaction Study
Authors: Mercier Anne‐Kristina , Kois Abigail K. , Karsanji Deeyen , Baldry Richard , Birve Filip , Hedwall Maria , Molodetskyi Oleksandr , Gillen Michael
Published: April 2024

The endothelin A receptor antagonist zibotentan, combined with the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin, is being investigated for the treatment of chronic kidney disease with high proteinuria. To allow women of childbearing potential access to this treatment, highly effective contraception is required and drug interactions compromising contraception reliability must be avoided. This study investigated the risk of pharmacokinetic (PK) interaction between zibotentan and the contraceptives ethinyl estradiol and levonorgestrel. A single‐sequence, within‐participant comparison study was conducted in 24 healthy women of non‐childbearing potential, comparing the PK of ethinyl estradiol/levonorgestrel alone and with zibotentan. Single oral doses of 0.06 mg ethinyl estradiol/0.3 mg levonorgestrel were administered on Days 1 and 15; zibotentan 10 mg was dosed orally, once‐daily through Days 6–19. PK profiles were determined and ethinyl estradiol/levonorgestrel PK was compared between Day 1 and 15 based on geometric least‐squares mean ratios of PK parameters, including maximum observed concentration (Cmax) and area under the plasma concentration–time curve from zero to infinity (AUCinf). Co‐administration with zibotentan did not affect ethinyl estradiol PK (geometric mean ratio [90% confidence interval] Cmax 1.05 [0.99–1.11], AUCinf 1.00 [0.96–1.05]), while a weak interaction (increased exposure) was observed for levonorgestrel (Cmax 1.12 [1.02–1.23], AUCinf 1.30 [1.21–1.39]), which was regarded as without clinical relevance. Plasma exposure of ethinyl estradiol/levonorgestrel was not reduced by multiple‐dose zibotentan. In conclusion, contraception containing ethinyl estradiol/levonorgestrel is regarded possible under zibotentan‐containing treatments. This expands choices for women of childbearing potential, supporting diversity in the ZENITH High Proteinuria trial.
The Orthogonal α‐meso‐Linked bisBODIPY Photosensitizers Demonstrate Effective Two‐Photon Fluorescence Imaging and Photodynamic Therapy
Authors: Guo Luying , Guo Xing , Zuo Huiquan , Li Heng , Lv Fan , Wu Qinghua , Jiao Lijuan , Hao Erhong
Published: April 2024

Hypoxic tumor microenvironments pose significant challenges to the clinical translation of cancer photodynamic therapy (PDT). While heavy atom‐free Type‐I boron dipyrromethenes (BODIPYs) photosensitizers can alleviate this challenge by reducing oxygen dependency, but they remain scarce. Herein, heavy‐atom‐free α,meso‐linked bisBODIPYs were designed and synthesized. These bisBODIPYs exhibit remarkable red‐shifted emission (λemmax ~670 nm), large Stokes shifts (~4480 cm−1) and they are capable of producing both superoxide anion (O2⋅−) and singlet oxygen (1O2) in solution and cells. Additionally, they offer a wide PDT treatment window, ranging from 0.26 to 83.5 μM. Furthermore, these bisBODIPYs also demonstrate superior two‐photon fluorescence, promising for surgical navigation and integrating diagnosis with treatment.
A Zero‐Gap Gas Phase Photoelectrolyzer for CO2 Reduction with Porous Carbon Supported Photocathodes
Authors: Zhao Yujie , Merino‐Garcia Ivan , Albo Jonathan , Kaiser Andreas
Published: April 2024

A modified Metal‐Organic Framework UiO‐66‐NH2‐based photocathode in a zero‐gap gas phase photoelectrolyzer was applied for CO2 reduction. Four types of porous carbon fiber layers with different wettability were employed to tailor the local environment of the cathodic surface reactions, optimizing activity and selectivity towards formate, methanol, and ethanol. Results are explained by mass transport through the different type and arrangement of carbon fiber support layers in the photocathodes and the resulting local environment at the UiO‐66‐NH2 catalyst. The highest energy‐to‐fuel conversion efficiency of 1.06 % towards hydrocarbons was achieved with the most hydrophobic carbon fiber (H23C2). The results are a step further in understanding how the design and composition of the photoelectrodes in photoelectrochemical electrolyzers can impact the CO2 reduction efficiency and selectivity.
Impact of the COVID‐19 pandemic on the treatment of acute cholangitis caused by choledocholithiasis: A single‐center retrospective study in Japan
Authors: Hanatani Jun‐ichi , Kitagawa Koh , Tomooka Fumimasa , Asada Shohei , Mitoro Akira , Fujinaga Yukihisa , Nishimura Norihisa , Sato Shinya , Shibamoto Akihiko , Fujimoto Yuki , Kubo Takahiro , Iwai Satoshi , Tsuji Yuki , Namisaki Tadashi , Akahane Takemi , Kaji Kosuke , Tanaka Misako , Koizumi Aritoshi , Yorioka Nobuyuki , Matsuda Takuya , Masuda Hiroyuki , Takami Masayoshi , Kikuchi Mayuko , Kawanishi Mariya , Ohoka Kazutaka , Watanabe Daisuke , Kawasaki Akane , Yoshiji Hitoshi
Published: April 2024

Objectives

This study aimed to determine the impact of the coronavirus disease 2019 (COVID‐19) pandemic on the treatment of acute cholangitis caused by choledocholithiasis.

Methods

The Japanese government declared a state of emergency in April 2020 due to the COVID‐19 pandemic. We retrospectively reviewed the medical records of 309 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis caused by choledocholithiasis between April 2017 and December 2022.

Results

Patients were categorized into a pregroup (n = 134) and a postgroup (n = 175), depending on whether they were diagnosed before or after the state of emergency declaration. The total number of ERCP cases and the number of ERCP cases with endoscopic stone removals increased after the state of emergency declaration. Compared with the pregroup, the numbers of patients with performance status of 0–1 and surgically altered anatomy increased, whereas the numbers of patients taking oral antiplatelets or anticoagulants and those with cerebrovascular disease decreased in the postgroup. The number of single‐stage endoscopic stone removals increased and hospital stays were significantly shorter in the postgroup. No differences in adverse event rates were detected between the two groups.

Conclusions

Although our hospital provides tertiary care, the number of patients with cholangitis in good general condition and no underlying disease increased after the state of emergency declaration. The COVID‐19 pandemic resulted in an increase in the number of single‐stage endoscopic treatments and shortened hospital stays for patients with acute cholangitis caused by choledocholithiasis. No safety issues with ERCP were detected, even during the pandemic.
Endoscopic ultrasound‐guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms
Authors: Takano Yuichi , Tamai Naoki , Yamawaki Masataka , Noda Jun , Azami Tetsushi , Niiya Fumitaka , Nishimoto Fumiya , Maruoka Naotaka , Yamagami Tatsuya , Nagahama Masatsugu
Published: April 2024

Objective

This study aimed to investigate the usefulness of endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms.

Methods

Among patients who underwent EUS‐TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS‐TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS‐TA.

Results

This study included 16 patients (median age, 73 [33–90] years), the median tumor size was 32 (6–51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS‐TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS‐TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure.

Conclusion

EUS‐TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.
Evaluating haemodynamic changes: vericiguat in patients with heart failure with reduced ejection fraction
Authors: Suzuki Hideaki , Inoue Takumi , Terui Yousuke , Takeuchi Kouki , Susukita Kai , Arai Marina , Sato Haruka , Satoh Taijyu , Yamamoto Saori , Yaoita Nobuhiro , Tatebe Shunsuke , Hayashi Hideka , Nochioka Kotaro , Takahama Hiroyuki , Yasuda Satoshi
Published: April 2024

Aims

Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline‐directed medical therapies. The haemodynamic effects of vericiguat remain unclear.

Methods and results

This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II–IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline‐recommended therapies between March and December 2022, with follow‐ups completed in June 2023. A balloon‐tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5 mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5 mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30 min after (both P < 0.05). Reduction in PAWP was also found from 14.5 [9.5, 19.5] mmHg on day 1 to 9.5 [6.5, 12.5] mmHg on day 105 (37, 168) (P < 0.05), when vericiguat was titrated to 2.5 mg 25% (N = 3), 5 mg 50% (N = 6), and 10 mg 25% (N = 3).

Conclusions

The consistent reduction in PAWP underscores the well‐tolerated nature of vericiguat and its potential to enhance cardiac performance in patients with HFrEF.