bluuebunny/crossref_metadata_2025 huggingface dataset:
m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways
Authors: Wu Xi , Wang Shiyang , Pan Yuwei , Li Mengzhen , Song Manyu , Zhang Hanfu , Deng Min , Yang Xu , Xu Jiuzhi , Zhang Shuo , Zhang Jinhua , Wang Fengchao , Plikus Maksim V. , Lv Cong , Yu Lu , Yu Zhengquan
Published: November 2024

Colorectal cancer (CRC) is the third most common cancer type and the second highest mortality rate among cancers. However, the mechanisms underlying CRC progression remain to be fully understood. In this work, a recently identified m6A‐modified RNA reader protein Proline‐rich Coiled‐coil 2a (PRRC2A) is markedly upregulated in CRC, and intestinal epithelium‐specific deletion of Prrc2a significantly suppressed tumor cell growth, stemness, and migratory capacity, while its overexpression promoted these behaviors. Through multiomics analysis, PRRC2A directly targeted CSNK1E (encoding CK1ε), maintaining its RNA stability in an m6A‐dependent manner, and that elevated CK1ε can concomitantly result in activation of the WNT and YAP signaling pathways. Interestingly, PRRC2A is directly regulated by the transcription factor ATF1 in its promoter. In summary, the work reveals a novel mechanism by which m6A reader PRRC2A promotes colorectal cancer progression via CK1ε and aberrant upregulation of WNT and YAP signaling. Therefore, PRRC2A and CK1ε can be potential therapeutic targets for treating CRC.
Smart Driving Hardware Augmentation by Flexible Piezoresistive Sensor Matrices with Grafted‐on Anticreep Composites
Authors: Chen Kaifeng , Yang Hua , Wang Ang , Tang Linsen , Zha Xin , Iita Ndeutala Selma , Zhang Hong , Li Zhuoxuan , Wang Xinyu , Yang Wei , Qu Shaoxing , Wang Zongrong
Published: November 2024

Signal drift and hysteresis of flexible piezoresistive sensors pose significant challenges against the widespread applications in emerging fields such as electronic skin, wearable equipment for metaverse and human‐AI (artificial intelligence) interfaces. To address the creep and relaxation issues associated with pressure‐sensitive materials, a highly stable piezoresistive composite is proposed, using polyamide‐imide (PAI) fibers as the matrix and in situ grafted‐polymerized polyaniline (PANI) as the semi‐conducting layer. The PAI with large rigid fluorenylidene groups exhibits a high glass transition temperature of 372 °C (PAI 5‐5), which results in an extremely long relaxation time at room temperature and consequently offers outstanding anti‐creep/relaxation performances. The enhancement of PAI‐PANI interfacial bonding through in situ grafting improves the sensor reliably. The sensor presents high linear sensitivity of 35.3 kPa−1 over a pressure range of 0.2–20 kPa, outstanding repeatability, and excellent dynamic stability with only a 3.8% signal deviation through ≈10 000 cycles. Real‐time visualization of pressure distribution is realized by sensor matrices, which demonstrate the capability of tactile gesture recognition on both flat and curved surfaces. The recognition of sitting postures is achieved by two 12 × 12 matrices facilitated by machine learning, which prompts the potential for the augmentation of smart driving.
Calcium Channel Blocker Lacidipine Promotes Antitumor Immunity by Reprogramming Tryptophan Metabolism
Authors: Sheng Yuwen , Qiao Chong , Zhang Zhonghui , Shi Xiaoke , Yang Linhan , Xi Ruiying , Yu Jialing , Liu Wanli , Zhang Guolin , Wang Fei
Published: November 2024

Dysfunction of calcium channels is involved in the development and progression of some cancers. However, it remains unclear the role of calcium channel inhibitors in tumor immunomodulation. Here, calcium channel blocker lacidipine is identified to potently inhibit the enzymatic activity and expression of indoleamine 2,3‐dioxygenase 1 (IDO1), a rate‐limiting enzyme in tryptophan metabolism. Lacidipine activates effector T cells and incapacitates regulatory T cells (Tregs) to augment the anti‐tumor effect of chemotherapeutic agents in breast cancer by converting immunologically “cold” into “hot” tumors. Mechanistically, lacidipine targets calcium channels (CaV1.2/1.3) to inhibit Pyk2‐JAK1‐calmodulin complex‐mediated IDO1 transcription suppression, which suppresses the kynurenine pathway and maintains the total nicotinamide adenine dinucleotide (NAD) pool by regulating NAD biosynthesis. These results reveal a new function of calcium channels in IDO1‐mediated tryptophan metabolism in tumor immunity and warrant further development of lacidipine for the metabolic immunotherapy in breast cancer.
Unusual Thermo‐Enhanced Second Harmonic Generation in Organic Configurationally‐Locked Polyene Crystals
Authors: Liu Yi , Zhu Pengfei , Fan Qingshun , Zhao Zihao , Wei Linjie , Ma Yu , Xu Haojie , Guo Wuqian , Luo Junhua , Sun Zhihua
Published: November 2024

To modulate nonlinear optical (NLO) effects of crystalline material holds great application potential in the photoelectronic and optical fields. Organic configurationally‐locked polyene represents an exciting NLO family with large second harmonic generation (SHG) effects, whereas it is a huge blank to switch and modulate their NLO property through external stimuli. For the first time, here present unusual thermo‐enhanced SHG activities are presented in a polyene‐based NLO compound, 2‐{3‐[2‐(4‐pyrrolidinphenyl)vinyl]‐5,5‐dimethylcyclohex‐2‐enylidene}malononitrile (1), giving a record‐high magnitude of SHG enhancement up to ≈170% during its isomorphic phase transition. Theoretical analysis discloses this behavior stems from the reduced degree of torsion in the π‐conjugated structures in 1, as verified by dihedral angles between its pyrrolidine and phenyl planes. As the first study on thermo‐enhanced SHG properties of organic crystals, this work affords a new avenue of modulating physical properties to fabricate high‐performance photoelectronic and optical devices.
Synergistic Configuration of Binary Rhodium Single Atoms in Carbon Nanofibers for High‐Performance Alkaline Water Electrolyzer
Authors: Logeshwaran Natarajan , Kim Gyuchan , Thangavel Pandiarajan , Jeon Sun Seo , Thiyagarajan Kaliannan , Kishore Kampara Roopa , Lee Hyunjoo , Seo Inseok , Yun Hongseok , Lee Sungho , Kim Byung‐Hyun , Lee Young Jun
Published: November 2024

Electrochemical alkaline water electrolysis offers significant economic advantages; however, these benefits are hindered by the high kinetic energy barrier of the water dissociation step and the sluggish kinetics of the hydrogen evolution reaction (HER) in alkaline media. Herein, the ensemble effect of binary types of Rh single atoms (Rh‐Nx and Rh‐Ox) on TiO2‐embedded carbon nanofiber (Rh‐TiO2/CNF) is reported, which serves as potent active sites for high‐performance HER in anion exchange membrane water electrolyzer (AEMWE). Density functional theory (DFT) analyses support the experimental observations, highlighting the critical role of binary types of Rh single atoms facilitated by the TiO2 sites. The Rh‐TiO2/CNF demonstrates an impressive areal current density of 1 A cm−2, maintaining extended durability for up to 225 h in a single‐cell setup. Furthermore, a 2‐cell AEMWE stack utilizing Rh‐TiO2/CNF is tested under industrial‐scale conditions. This research makes a significant contribution to the commercialization of next‐generation high‐performance and durable AEMWE stacks for clean hydrogen production.
Evolution of Dissipative Regimes in Atomically Thin Bi2Sr2CaCu2O8 + x Superconductor
Authors: Shokri Sanaz , Ceccardi Michele , Confalone Tommaso , Saggau Christian N. , Lee Yejin , Martini Mickey , Gu Genda , Vinokur Valerii M. , Pallecchi Ilaria , Nielsch Kornelius , Caglieris Federico , Poccia Nicola
Published: November 2024

Thermoelectric transport is widely used to study Abrikosov vortex dynamics in unconventional superconductors. However, only a few thermoelectric studies have been conducted near the dimensional crossover that occurs when the vortex‐vortex interaction length scale becomes comparable to the sample size. Here, the effects of finite size on the dissipation mechanisms of the Nernst effect in the optimally doped Bi2Sr2CaCu2O8 + x high‐temperature superconductor are reported, down to the atomic length limit. To access this regime, a new generation of thermoelectric chips based on silicon nitride microprinted circuit boards is developed. These chips ensure optimized signals while preventing sample deterioration. The results demonstrate that lateral confinement at the nanoscale can effectively reduce vortex dissipation. Investigating vortex dissipation at the micro‐ and nano‐scale is essential for creating stable, miniaturized superconducting circuits.
Bifunctional Al Dopant for Enhancing Bulk and Grain Boundary Conductivities in Sodium Ion Conducting NASICON Ceramics
Authors: Xun Bowei , Wang Jian , Sato Yukio , Jia Shufan , Ohno Saneyuki , Akamatsu Hirofumi , Hayashi Katsuro
Published: November 2024

Compared to Li+ and Na+ ion‐conducting sulfides with conductivities of ≈10⁻2 S cm⁻1 at room temperature, oxide ceramics typically exhibit conductivities an order of magnitude lower, rendering them less attractive as electrolytes for all‐solid‐state batteries (ASSBs). This study presents NASICON‐based electrolyte, achieving a remarkable conductivity of 6.0 × 10⁻3 S cm⁻1 at room temperature, rivaling that of sulfide‐based electrolytes. This is accomplished by optimizing the composition in the range Na3+x+yZr2−yAlySi2+xP1−xO12 (0.10 ≤ x ≤ 0.50, 0 ≤ y ≤ 0.1). Despite the issue of reduced sinterability with increasing Si/P ratio due to the formation of a viscous SiO2‐rich grain boundary interphase, the addition of Al2O3 effectively reduces the viscosity and improves the sinterability. In other words, a strategy of engineering the liquid phase that is in situ generated from the host phase is viable. The enhanced conductivity is attributed not only to the lowered grain boundary resistivity but also to lattice expansion from modified Na occupations in the crystal structure. Furthermore, this material demonstrates a wide electrochemical window, suppressed partial electronic conductivity, low polarization voltage in direct contact with a Na anode, and charge‐discharge cycles with minimal polarization when directly interfaced with a NASICON‐type cathode, repositioning it as a promising electrolyte for ceramic ASSBs.
Changing behavior and promoting clinical empathy through a patient experience curriculum for health profession students
Authors: Nelson Sara W. , Germann Carl , Yudkowsky Rachel , Pare Benjamin , Wendell Lauren , Blackie Michael , Strout Tania , Hirshfield Laura E.
Published: November 2024

Objectives

The authors sought to explore how a curriculum that uses a patient experience simulation followed by reflection can lead to clinical empathy in learners and whether this experience leads to behavioral change. Further, in response to critiques of common pragmatic approaches to clinical empathy teaching in which empathy is operationalized and taught through formal trainings and checklists, the study aimed to contribute insights regarding how clinical empathy may best be taught to health profession students.

Methods

Twenty‐six senior medical students participated in an in situ patient experience simulation during a 4‐month period in 2021–2022 in an academic emergency department. The simulation was followed by a written reflection and a structured debrief. A thematic analysis was performed on transcripts of the group debriefs.

Results

In the group debriefs, learners described several empathetic behavioral changes they made after this intervention. First, learners discussed performing more small acts of kindness to improve patient care and humanize the patient experience. Second, learners discussed seeking to improve their communication through acknowledgment and validation of the patient experience. Finally, learners described actions to keep patients informed through frequent check‐ins and setting expectations on time.

Conclusions

The findings suggest that empathy may not be simply transactional for health profession students and that an understanding of the patient experience leads to actions that improve the patient experience and alleviate suffering.
Unlocking electrodialysis efficiency with spacer mesh geometry and material conductivity via finite element analysis
Authors: Yao Yuyang , Mu Junjie , Lu Yueyue , Ang Edison Huixiang , Shen Jiangnan
Published: November 2024

Spacer meshes in electrodialysis (ED) play a crucial role in influencing fluid and electric field distributions during mass transfer. This study employed finite element analysis using real‐world parameters to explore how spacer mesh geometry and material affect mass transport. Comparisons among different wire mesh configurations revealed increased fluid velocity near mesh wires and reduced electric field intensity nearby, enhancing overall transport efficiency. Increasing mesh count or wire diameter notably improves transport, with optimal results achieved when wire orientation aligns with fluid flow. Additionally, the study showed that spacer mesh conductivity significantly influences ED transport, particularly when it exceeds the conductivity of the solution. These findings advance the design and application of spacer meshes, offering valuable insights for future developments in ED technology.
Stature and Its Association With Physiological Stress Exposure in a Pediatric Autopsy Sample
Authors: Wyatt Bronwyn , McPherson Cait , O'Donnell Lexi
Published: November 2024

Introduction and Background

Experiencing illnesses or other stressors may disrupt processes of growth and development throughout the different stages of prepubertal development. Stunted stature for age is one potential outcome from such disruption, with both the nature and timing of stressors playing a role in the development of stunting. This study explores whether stress events in utero or during birth, and prepubertal development have an impact on stature, by examining associations between experience of prenatal or birth issues, postnatal stressor exposure by severity, and stature at time‐of‐death, with the impact of different stress experiences compared.

Methods

A coronial pediatric dataset of individuals aged 0–20.9 years (280 male, 195 female) who died in the state of New Mexico from years 2011 to 2019 was assessed for presence/absence of stunting associated with physiological stress exposure type whilst controlling for low socioeconomic status (as inferred by housing type) and sex using two multiple logistic regression models for ages < 12, and for ages 12+. Broad postnatal condition categories were then investigated, again controlling for socioeconomic status and sex for these two cohorts. A linear regression model was also used to assess relationships between stunting, physiological stress, low socioeconomic status housing, and age‐at‐death.

Results and Discussion

For both groups aged < 12 and 12+, experiencing moderate to severe illness prior to 12 years of age increased the odds of being stunted at death. Only experience of prenatal or birth issues was associated with younger age‐at‐death, but stunting itself was not, potentially reflecting the prolonged exposure to severe stressors necessary for stunted growth.
Enhancement of a Mathematical Model for Predicting Puberty Stage in Boys: A Cross‐Sectional Study
Authors: de Almeida‐Neto Paulo Francisco , Baxter‐Jones Adam Dominic George , Arrais Ricardo Fernando , de Azevedo Jenner Christian Veríssimo , Dantas Paulo Moreira Silva , Cabral Breno Guilherme de Araújo Tinôco , Medeiros Radamés Maciel Vitor
Published: November 2024

Background

Previously, we developed a mathematical model capable of predicting pubertal development (PD) through seven anthropometric variables, with an accuracy of 75%. We believe that it is possible to develop a similar model that uses fewer anthropometric measurements and provides greater precision.

Objective

Develop a mathematical model capable of predicting PD through anthropometric variables.

Methods

We evaluated the anthropometric profile and PD by medical analysis in 203 boys (Age = 12.6 ± 2.6). Subsequently, we divided the boys into groups: development (n = 121) and cross‐validation (n = 82). Data from the development group were subjected to discriminant analysis to identify which anthropometric indicators would be potential predictors of PD. We subsequently developed an equation based on the indicated indicators and tested its validation using data from the cross‐validation group.

Results

Discriminant analyses showed that age and sitting‐height were the variables with the greatest power to predict PD (p < 0.05). Consequently, the mathematical model was developed: Puberty‐score = −17.357 + (0.603 × Age [years]) + (0.127 × Sitting‐height [cm]). Based on the scores generated, we classified PD into stage‐I (score ≤ −1.815), stage‐II (score = −1.816 to −0.605), stage‐III (score = −0.606 to 0.695), stage‐IV (score = 0.696–3.410), and stage‐V (score > 3.410). No differences were found between PD assessments performed by doctors and assessments using the mathematical model (p > 0.5). The prediction model showed high agreement (R
2 = 0.867; CCC = 0.899; ICC = 0.900; Kappa = 0.922; α‐Krippendorff = 0.885; Bland–Altman LoAs = −2.0, 2.0; pure error = 0.0009) with accuracy of 82.8% and precision of 82%. Analyses in the cross‐validation group confirmed the reliability of the prediction model.

Conclusion

The developed mathematical model presents high reliability, validity and accuracy and precision above 80% for determining PD in boys.
Allosteric CDC37 Inhibitor Disrupts Chaperone Complex to Block CDK4/6 Maturation
Authors: Zhang Lixiao , Liu Wei , Zheng Zhen , Zhang Qiuyue , He Yanyi , Gu Jinying , Wang Danni , Shu Huangliang , Yu Jia , Liu Jianfeng , Yin Xingyu , Zhang Lianshan , Zhang Jian , You Qidong , Wang Lei
Published: November 2024

Cell division cycle 37 (CDC37) is a member of the molecular chaperone family and acts as a cochaperone of heat shock protein 90 (HSP90), which is overexpressed in many cancer types as a regulator of protein kinase maturation. In this process, CDC37 selectively recognizes and stabilizes protein kinases by forming a HSP90‐CDC37‐kinase chaperone complex. The protein‐protein interactions (PPIs) of HSP90‐CDC37 and CDC37‐kinase complexes contribute to malignant tumors, as oncogenic kinases in malignant cells depend upon CDC37 expression. Thus, inhibiting CDC37 to disrupt HSP90‐CDC37‐kinase chaperone complex reveals as a promising way to achieve selective inhibition of oncogenic kinase maturation. Herein, we report a small‐molecule CDC37 inhibitor called DDO‐6079 that simultaneously inhibits HSP90‐CDC37 and CDC37‐CDK4/6 chaperone complex by binding to an allosteric site on CDC37. DDO‐6079 selectively inhibited the maturation of multiple oncogenic kinases to escape heat shock response (HSR). Furthermore, DDO‐6079 decreased the thermostability of CDK6, reversed the resistance of CDK6 to palbociclib (a successful CDK4/6 inhibitor) in colorectal cancer cells and exhibited efficacy in vivo. Together, the results revealed that DDO‐6079 is a first‐in‐class small molecule CDC37 inhibitor that disrupts the HSP90‐CDC37‐kinase chaperone complex and provides a new way to block kinase maturation.
A Chlorine‐Resistant Self‐Doped Nanocarbon Catalyst for Boosting Hydrogen Peroxide Synthesis in Seawater
Authors: Wang Xinyu , Shen Wangqiang , Zhang Chang , Huang Yuzhong , Zhang Jian , Lv Jun , Lu Xing
Published: November 2024

Developing seawater‐compatible hydrogen peroxide (H2O2) electroproduction technologies is crucial for advancing marine resource utilization in coastal regions. However, designing efficient and highly stable non‐noble metal catalysts for two‐electron oxygen reduction reaction (2e− ORR) in seawater environment remains a challenging task due to the corrosive and toxic nature of chloride ions (Cl−). Herein, we present, for the first time, a novel nitrogen and oxygen self‐doped defect‐rich nanocarbon (NO‐DC700) catalyst, derived from silk fiber, which addresses these challenges with low toxicity, cost‐effectiveness, and high adaptability. The obtained NO‐DC700 catalyst demonstrates an impressive H2O2 production rate of up to 4997 mg L−1 h−1, a high Faradaic efficiency of 96.5 %, and produces 4.3 wt % H2O2 after 20 hours of stable operation, placing it among the highest‐performing catalysts reported in neutral electrolytes. Theoretical calculations reveal that NO‐DC700′s superior 2e− ORR performance is due to the synergistic effect of graphitic nitrogen and C‐OH, which inhibits Cl− adsorption and promotes *OOH adsorption. Additionally, integrating 2e− ORR with Fenton‐like technology enables rapid degradation of organic pollutants and effective inactivation of seawater algae, offering significant potential for mitigating coastal eutrophication and red tide pollution. This work provides valuable insights into H2O2 electrosynthesis in seawater solution and promises advancements in ocean‐energy applications.
Dicyanocarbene‐Induced Metal‐Free Efficient Quinoidization for the Development of Fused N‐Type Organic Semiconductors
Authors: Wu Runshi , Huang Fei , Xu Renjie , Liu Wuyue , Zhang Cheng , Zhu Xiaozhang
Published: November 2024

Dicyanomethylene‐terminated quinoidal materials are promising n‐type organic semiconductors featuring excellent electron mobilities and air stability. Traditional synthetic methods of these materials such as Takahashi reaction, require the use of expensive palladium catalyst and halogenated substrates. However, for electron‐rich fused aromatic compounds, the poor stability after halogenation renders their halogenated derivatives unsuitable as reaction precursors. To address this issue, we present a new metal‐free synthetic approach using 2‐(dimethylsulfaneylidene)malononitrile as the quinoidization reagent, which is successfully applied to various electron‐rich fused aromatic compounds, leading to the corresponding quinoidal compounds with high yields up to 94 %. We proposed the reaction mechanism, and investigated the physical properties of four fused quinoidal materials based on highly electron‐rich fused aromatic compounds, which are scarce to be synthesized by the traditional method. Furthermore, these fused quinoidal materials were utilized in field‐effect transistors, achieving high electron mobilities up to 1.33 cm2 V−1 s−1. We provide an effective synthetic approach to expand the library of high‐performance n‐type small‐molecule semiconductors.
Bottom‐up Synthesis of Piezoelectric Covalent Triazine‐based Nanotube for Hydrogen Peroxide Production from Water and Air
Authors: Guan Lijiang , Li Zhi , Wang Kai , Gong Li , Fang Yuanyuan , Yu Guipeng , Zhu Mingshan , Jin Shangbin
Published: November 2024

Carbon nanotubes (CNTs) are nanoscale tubular materials with superior mechanical strength and electronic properties. However, the conventional CNTs are inherently non‐piezoelectric, mainly due to the lack of polar structures with pure carbon elements. The direct synthesis of fully conjugated and polarized organic nanotubes with desired piezoelectric properties remains a challenge. Herein, we report the bottom‐up synthesis of a new type of covalent triazine‐based nanotube (CTN‐1) as a novel piezoelectric material. The CTN‐1 comprises of high surface area, nitrogen‐rich and fully conjugated structure, which provides a series of merits for piezoelectric catalytic processes. These structural features combined with one‐dimensional tubular morphology endow CTN‐1 with excellent mechanical stimuli response and thus displaying prominent piezoelectric properties via pronounced nanocurvature effect. We further show that the CTN‐1 enables the efficient synthesis of H2O2 from water in the air via mechanical energy conversion, with an excellent piezocatalytic H2O2 evolution rate of 4115 μmol g−1 h−1, which exceeds other reported piezoelectric materials. The piezocatalysis by the CTN‐1 can be practically integrated into a self‐Fenton system, which exhibits excellent pollutant degradation capability. This work demonstrates the enormous potential of a new type of piezoelectric synthetic nanotube from organic frameworks for the in situ synthesis valuable chemicals.
Locking up G‐Quadruplexes with Light‐Triggered Staples Leads to Increased Topological, Thermodynamic, and Metabolic Stability
Authors: Barr Jack , Cadoni Enrico , Schellinck Sofie , Laudadio Emiliano , Martins José C. , Madder Annemieke
Published: November 2024

G‐quadruplexes (G4 s) are secondary, tetraplexed DNA structures abundant in non‐coding regions of the genome, implicated in gene transcription processes and currently firmly recognised as important potential therapeutic targets. Given their affinity for human proteins, G4 structures are investigated as potential decoys and aptamers. However, G4 s tend to adopt different conformations depending on the exact environmental conditions, and often only one displays the specifically desired biological activity. Their less intensively studied counterparts, the elusive tetraplexed intercalated‐motifs (IMs) are typically unstable at neutral pH, hampering the investigation of their potential involvement in a biological context. We herein report on a photochemical method for “stapling” such tetraplexed‐structures, to increase their stability, lock their topology and enhance their enzymatic resistance, while maintaining biological activity. The chemical structure and topology of the stapled Thrombin Binding Aptamer (TBA) was spectroscopically characterised and rationalised in silico. The method was then extended to other biologically relevant G4‐ and IM‐prone sequences, hinting towards potential application of such stapled structures in a therapeutic context.
Visualization and Quantification of Single‐Base m6A Methylation
Authors: Zhang Qiushuang , Dai Yicong , Teng Xucong , Li Jinghong
Published: November 2024

N6‐methyladenosine (m6A) has emerged as the most prevalent form of RNA modification found across various RNA classes. The detection and quantification of m6A RNA modifications under various physiological conditions are crucial for elucidating disease mechanisms and identifying potential therapeutic targets. However, visualizing intracellular m6A modifications at single‐base resolution remains a significant challenge. Existing methods based on high‐throughput sequencing or in vitro assays are not suitable for in situ m6A RNA imaging. In this work, we introduce the TadA8.20‐assisted N6‐methyladenosine RNA imaging at single‐base resolution (TARS) method for precise visualization and quantification of both A and m6A forms at specific RNA sites within single cells. Validation studies using TARS on MALAT1 lncRNA in HeLa cells and CCND1 mRNA in breast cancer cell lines demonstrated its high specificity and efficiency in mapping and quantifying m6A modifications at single‐base resolution. TARS represents a novel tool that advances m6A RNA modification research by offering accurate and detailed insights into m6A modifications at the single‐base level.
Structure Prediction and Computational Protein Design for Efficient Biocatalysts and Bioactive Proteins
Authors: Buller Rebecca , Damborsky Jiri , Hilvert Donald , Bornscheuer Uwe T.
Published: November 2024

The ability to predict and design protein structures has led to numerous applications in medicine, diagnostics and sustainable chemical manufacture. In addition, the wealth of predicted protein structures has advanced our understanding of how life's molecules function and interact. Honouring the work that has fundamentally changed the way scientists research and engineer proteins, the Nobel Prize in Chemistry in 2024 was awarded to David Baker for computational protein design and jointly to Demis Hassabis and John Jumper, who developed AlphaFold for machine‐learning‐based protein structure prediction. Here, we highlight notable contributions to the development of these computational tools and their importance for the design of functional proteins that are applied in organic synthesis. Notably, both technologies have the potential to impact drug discovery as any therapeutic protein target can now be modelled, allowing the de novo design of peptide binders and the identification of small molecule ligands through in silico docking of large compound libraries. Looking ahead, we highlight future research directions in protein engineering, medicinal chemistry and material design that are enabled by this transformative shift in protein science.
Unraveling the Configuration Modulation in Spiro‐Based Through‐Space Charge Transfer Materials
Authors: Qu Yang‐Kun , Zheng Qi , Zhou Dong‐Ying , Cui Lin‐Song , Liao Liang‐Sheng , Jiang Zuo‐Quan
Published: November 2024

Thermally activated delayed fluorescence (TADF) materials hold promise for optoelectronic applications. Among various design strategies, through‐space charge transfer (TSCT) systems offer the potential for enhanced performance. However, the relationship between molecular configuration and TSCT properties remains unclear compared to traditional through‐band charge transfer materials. In this study, we investigated the influence of spatial configuration on TSCT features and electronic properties of triplet excited states in these TSCT materials. By manipulating the spatial arrangement between donor and acceptor segments using different spiro skeletons, a series of TSCT materials (DMB2‐DMB5) was synthesized. Together with the parent molecule, DM‐B, these materials exhibited completely different TADF characteristics, demonstrating the impact of spatial arrangements on their optoelectronic properties. Thus, the external quantum efficiency of these materials ranged from as high as 28.0 % (DMB2) to as low as 3.6 % (DMB5) due to variations in their TADF characteristics. Our findings highlight the significance of spatial configuration, beyond distance alone, in influencing TSCT properties when donor and acceptor segments are sufficiently close. This insight provides valuable guidance for developing advanced TSCT materials and advancing TADF systems with improved performance and functionality.
Subtle Modifications in Interface Configurations of Iron/Cobalt Phthalocyanine‐Based Electrocatalysts Determine Molecular CO2 Reduction Activities
Authors: Xin Yinger , Musgrave Charles B. , Su Jianjun , Li Jiangtong , Xiong Pei , Meng‐Jung Li Molly , Song Yun , Gu Qianfeng , Zhang Qiang , Liu Yong , Guo Weihua , Cheng Le , Tan Xuefeng , Jiang Qiu , Xia Chuan , Zhong Tang Ben , Goddard William A. , Ye Ruquan
Published: November 2024

Strain engineering has emerged as a powerful approach in steering material properties. However, the mechanism and potential limitations remain poorly understood. Here we report that subtle changes in molecular configurations can profoundly affect, conducively or adversely, the catalytic selectivity and product turnover frequencies (TOFs) of CO2 reduction reaction. Specifically, introducing molecular curvature in cobalt tetraaminophthalocyanine improves the multielectron reduction activity by favorable *CO hydrogenation, attaining methanol Faradaic efficiency up to 52 %. In stark contrast, strained iron phthalocyanine exacerbates *CO poisoning, leading to decreased TOFCO by >50 % at −0.5 VRHE and a rapid current decay. The uniform dispersion is crucial for optimizing electron transfer, while activity is distinctly sensitive to the local atomic environment around the active sites. Specifically, local strain either enhances binding to intermediates or poisons the catalytic sites. Our comprehensive analysis elucidates the intricate relationship between molecular structure and activities, offering insights into designing efficient heterogeneous molecular interfaces.
Highly Conductive Multifunctional Iron‐Incorporated Polythiophene Nanocomposite: A Nanocatalyst for Nitrobenzene Reduction in Aqueous Medium and an Efficient Room Temperature Methanol Gas Sensor
Authors: Devi Shrutipriya , Kalita Amar Jyoti , Chetia Rupkamal , Mazumder Lakhya J. , Guha Ankur K. , Chetia Bolin , Konwer Surajit
Published: November 2024

This study reports the synthesis and application of a polythiophene–iron oxide (PTh‐Fe0‐Fe2O3) nanocomposite as a highly effective catalyst for the selective reduction of nitro aromatics in an aqueous environment. The nanocomposite was synthesized using in situ chemical polymerization, with Fe0‐Fe2O3 nanoparticles created from ferric chloride solution using Camellia sinensis leaf extract as a reducing and stabilizing agent at room temperature. Characterization techniques, including XRD, FTIR, SEM–EDX, TEM, XPS, and UV–Vis spectroscopy, confirmed the successful integration of Fe0‐Fe2O3 into the polythiophene matrix. The nanocomposite demonstrated higher electrical conductivity compared to PTh alone, ranging from 20 S/cm at 313 K to 53 S/cm at 373 K. Magnetic studies indicated a saturation magnetization of 23.1 emu/g, lower than the 42.6 emu/g of Fe0‐Fe2O3 nanoparticles, attributed to the non‐magnetic nature of PTh. Under optimal conditions (4‐nitrobenzaldehyde [1 mmol], catalyst [0.04 g], and water [5 mL] in air), the catalyst achieved a 94% yield in the reduction of nitrobenzenes within 7 h, demonstrating broad applicability and retaining significant catalytic activity over six cycles. Furthermore, the PTh‐ Fe0‐Fe2O3 nanocomposite exhibited notable methanol gas sensing capabilities, with a sensitivity of 52.6 at 200‐ppm methanol. The sensor exhibited a response time of 60 s and a recovery time of 80 s, attributed to its n‐type semiconductor characteristics and abundant oxidative‐reductive sites. Computational studies supported the methanol sensing mechanism, highlighting significant O… S interactions and stable non‐covalent interactions between methanol and the nanocomposite. This study is the first to introduce a novel magnetic nanocatalyst for the cost‐effective and eco‐friendly reduction of nitroarenes, while also demonstrating its applicability in gas sensing. The research highlights an environmentally sustainable synthesis process and enhanced material properties, showcasing the nanocatalyst's potential for diverse applications.
Discovery of Imidazo[1,2‐a]pyrimidine–Schiff Base Derivatives as Potent Antifungal Agents Against Fusarium oxysporum f. sp. albedinis: Synthesis, Crystal Structure, Biological Evaluation, Homology Modeling, and Docking Analysis
Authors: Azzouzi Mohamed , El Hadad Salah Eddine , Ouchaoui Abderrahim Ait , Benabbes Redouane , Neffa Mounsef , Abboud Mohamed , Touzani Rachid , Hammouti Belkheir , Oussaid Adyl , Salghi Rachid , Chaouiki Abdelkarim
Published: November 2024

Bayoud disease, which is caused by the fungus Fusarium oxysporum f. sp. albedinis (FOA), is a severe threat to date palm cultivation in North Africa and the Middle East; thus, effective antifungal treatments are urgently required. In response to this, the present study develops, characterizes, and tests imidazo[1,2‐a]pyrimidine–Schiff base derivatives as potential antifungal compounds. A series of these derivatives (labeled IMP‐1 to IMP‐6) was obtained using a facile conventional synthetic route that holds the potential for scalable production. The structures of the samples were characterized using traditional spectroscopic techniques, while IMP‐1 and IMP‐3 were subjected to single‐crystal X‐ray diffraction analysis to verify the structural assignment of the synthesized compounds. Screening analysis of the antifungal activity of the IMPs against FOA demonstrated remarkable inhibition effects, with IC50 values ranging from 4.7 to 2.6 μg/mL. In particular, IMP‐6 demonstrated exceptional potency, with an inhibition rate exceeding 97% at a low concentration of only 16.42 μM, thus outperforming many previously reported antifungal compounds. Homology modeling and molecular docking analysis were also conducted to understand how these novel antifungal agents interact with their target, with the experimental and theoretical approaches producing consistent results.
Enhanced Energy Storage Properties of PP/PA11 Dielectric Composite Films With PP‐g‐MAH as Compatibilizer
Authors: Liu Xiaomeng , Xie Junhao , Zhong Shaoyuan , Sun Shulin
Published: November 2024

As an energy storage capacitor film material, polypropylene (PP) suffers from its low dielectric constant and limited energy density. To overcome the defects of pure PP, the PP‐based all‐organic composite films with multiple interfaces have been constructed to enhance the dielectric and energy storage properties. In this research, PA11 was used to blend with PP with polypropylene grafted maleic anhydride (PP‐g‐MAH) as compatibilizer. The prepared PP/PP‐g‐MAH/PA11 composites formed the typical “sea‐island” structure and double interfaces between PP/PP‐g‐MAH and PP‐g‐MAH/PA11. The higher molecular polarity of PP‐g‐MAH, PA11, and interfacial polarization significantly increases the dielectric constant of the composite films. Furthermore, the formation of interface traps suppressed the migration of charge carriers, resulting in lower leakage current and higher breakdown strength of the PP/PP‐g‐MAH/PA11 composite films. Density functional theory (DFT) simulation further proved the confinement of space charges. Energy storage results showed the optimal PP/PP‐g‐MAH/PA11‐2 film achieved high energy density (4.49 J/cm3) and excellent charge/discharge efficiency (97.4%), which behaved good application prospect in the field of thin film capacitors.
Design of Hydrolysis, Enzymatic and Soil‐Degradation Diglycolate‐Based Copolyesters With Good Mechanical and Thermal Properties
Authors: Dong Liming , Li Deling , Zhuang Wenchang , Ding Yue
Published: November 2024

In this paper, a series of poly(butylene diglycolate‐co‐succinate‐co‐furandicarboxylate) (PBSFD) and poly(butylene diglycolate‐co‐adipate‐furandicarboxylate) (PBAFD) copolymers were synthesized to enhance the degradation rate of PBAF and PBSF. The structure and properties were tested. PBAFD and PBSFD copolymers display impressive biodegradability when catalyzed by candida antarctica lipase B. The weight loss of copolymers was more than 75% after 14 days degradation. Compared to PBSFD copolymers, the PBAFDs owned better soil degradability, resulting in weight loss was 89.1% when the molar ratio of diglycolic acid was 30% after 70 days degradation. Also, the stress of PBAFD30 was 17.1 Mpa, and the elongation at break was more than 900%. The temperature of 5% mass loss of PBAFD30 was as high as 371.3°C. Thus, PBAFD and PBSFD copolymers have good application prospects in single‐use packaging materials.
Tunable Luminescence of Glyoxylic Acid Modified Poly (Vinyl Alcohol) Film Codoped With Eu2+ and Eu3+
Authors: Chen Wanping , Wang Ke , Ren Baoru
Published: November 2024

Poly(vinyl alcohol) (PVA), a high‐consumption polymer, is currently facing the problem of overcapacity. The development of modified PVA with novel properties is an alternative way to solve this problem. In this work, glyoxylic acid was used as a bridging agent to indirectly bond europium ions to PVA molecule chain. The luminescence properties of the modified PVA materials were investigated by adjusting the reaction conditions such as pH value, heating treatment methods, reaction temperature, and doping concentration. Upon excitation at 394 nm, a strong and tunable luminescence is achieved due to the existence of both blue emission from Eu2+ and red emission from Eu3+. The luminescence properties are explained based on the reduction of Eu3+, the existence form of europium ions, and the arranged regulation of PVA molecules. The modified PVA materials have potential applications in the fields of displaying and lighting if their luminescence properties are further improved in the future.
Effect of Bio‐Based Plasticizers From Modified Vegetable Oils in a New Formulation of PVC Materials
Authors: Akter Sharmin , Rahman Md Mahbubur , Auerbach Marcel , Langer Beate
Published: November 2024

This study investigates the performance of polyvinyl chloride (PVC) plasticized with diisononyl phthalate (DINP), rapeseed oil epoxidized ester (ROE), and rapeseed oil carbonated ester (ROC). The formulations were evaluated for surface resistance, wettability, migration, mechanical properties, and resistance to aging and thermal degradation. PVC/ROC exhibited the highest surface resistance of 1.5 × 1016 Ω, indicating superior electrical insulation. Wettability tests showed PVC/ROE with the highest contact angle at 63°, while PVC/ROC and PVC/DINP demonstrated lower contact angles of 44° and 43°, respectively. Migration tests revealed that PVC/ROC had the lowest migration rates: 0.1% in distilled water and 1.5% in 95% ethanol. Mechanical testing under algae exposure demonstrated that PVC/ROC achieved the highest tensile strength of 43 MPa and a strain at break of 200%. After 1008 h of thermo‐oxidative aging, PVC/ROC retained superior tensile strength and hardness, while PVC/ROE showed a slight decrease. PVC/ROC also demonstrated improved thermal stability at 255°C compared with DINP (245°C). These results confirm that ROC is an effective bio‐based plasticizer, providing enhanced mechanical properties, reduced migration, and greater durability compared to conventional DINP, offering a sustainable alternative for diverse PVC applications in medical, automotive, and packaging industries.
Accelerating Drug Discovery With High‐Throughput Crystallographic Fragment Screening and Structural Enablement
Authors: Fearon Daren , Powell Ailsa , Douangamath Alice , Dias Alexandre , Tomlinson Charles W. E. , Balcomb Blake H. , Aschenbrenner Jasmin C. , Aimon Anthony , Barker Isabel A. , Brandão‐Neto José , Collins Patrick , Dunnett Louise E. , Fairhead Michael , Gildea Richard J. , Golding Mathew , Gorrie‐Stone Tyler , Hathaway Paul V. , Koekemoer Lizbé , Krojer Tobias , Lithgo Ryan M. , Maclean Elizabeth M. , Marples Peter G. , Ni Xiaomin , Skyner Rachael , Talon Romain , Thompson Warren , Wild Conor F. , Winokan Max , Wright Nathan David , Winter Graeme , Shotton Elizabeth J. , von Delft Frank , Bertram Felicity , Coe Paul A. , Mikolajek Halina , Nidamarthi Kutumbarao H. V. , O'Donnell Garry , Watt Grant , Williams Mark A.
Published: November 2024

Fragment‐based drug discovery is a well‐established method for the identification of chemical starting points for development into clinical candidates. Historically, crystallographic fragment screening was perceived to be low‐throughput and time consuming. However, thanks to advances in synchrotron capabilities and the introduction of dedicated facilities, such as the XChem platform at Diamond Light Source, there have been substantial improvements in throughput and integration between sample preparation, data collection and hit identification. Herein we share our experiences of establishing a crystallographic fragment screening facility, our learnings from operating a user programme for ten years and our perspective on applying structural enablement to rapidly progress initial fragment hits to lead‐like molecules.
Giant Inverse Barocaloric Effect of Ferroelectric Salts Driven by Negative Thermal Expansion
Authors: Dai Yin , Wu Menghao
Published: November 2024

Refrigeration technologies based on the barocaloric effect have garnered significant attention, while their potential applications are limited by the poor performance of current materials. Here it is proposed that ferroelectric ionic salts with covalent‐like bondings like LiI may become ideal candidates. The pressure‐induced phase transition between two phases with distinct densities and entropies leads to tremendous negative thermal expansion (with volume reduced by 13%) and inverse barocaloric effect, which are facilitated by the low transition barriers due to the long‐range Coulomb interaction. Using ab initio‐based training database, we trained the machine learning potential of LiI based on a deep neutral network‐based mode, and this simulations of its barocaloric effect reveal a high entropy change and thermal conductivity, and in particular, the estimated adiabatic temperature change, pressure sensitivity and relative cooling power are all unprecedented. This prediction provides a high‐performance barocaloric mechanism for practical applications and also expands the scope of barocaloric materials to simple and facile binary salts.
Synapsids and sensitivity: Broad survey of tetrapod trigeminal canal morphology supports an evolutionary trend of increasing facial tactile specialization in the mammal lineage
Authors: Miyamae Juri A. , Benoit Julien , Ruf Irina , Sibiya Zoleka , Bhullar Bhart‐Anjan S.
Published: November 2024

The trigeminus nerve (cranial nerve V) is a large and significant conduit of sensory information from the face to the brain, with its three branches extending over the head to innervate a wide variety of integumentary sensory receptors, primarily tactile. The paths of the maxillary (V2) and mandibular (V3) divisions of the trigeminus frequently transit through dedicated canals within the bones of the upper and lower jaws, thus allowing this neuroanatomy to be captured in the fossil record and be available to interpretations of sensory ability in extinct taxa. Here, we use microCT and synchrotron scans from 38 extant and fossil species spanning a wide phylogenetic sample across tetrapods to investigate whether maxillary and mandibular canal morphology can be informative of sensory biology in the synapsid lineage. We found that in comparison to an amphibian and sauropsid outgroup, synapsids demonstrate a distinctive evolutionary pattern of change from canals that are highly ramified near the rostral tip of the jaws to canals with increasingly simplified morphology. This pattern is especially evident in the maxillary canal, which came to feature a shortened infraorbital canal terminating in a single large infraorbital foramen that serves as the outlet for branches of V2 that then enter the soft tissues of the face. A comparison with modern analogues supports the hypothesis that this morphological change correlates to an evolutionary history of synapsid‐specific innovations in facial touch. We interpret the highly ramified transitional form found in early nonmammalian synapsids as indicative of enhanced tactile sensitivity of the rostrum via direct or proximal contact, similar to tactile specialists such as probing shorebirds and alligators that possess similar proliferative ramifications of the maxillary and mandibular canals. The transition toward a simplified derived form that emerged among Mid‐Triassic prozostrodont cynodonts and is retained among modern mammals is a unique configuration correlated with an equally unique and novel tactile sensory apparatus: mobile mystacial whiskers. Our survey of maxillary and mandibular canals across a phylogenetic and ecological variety of tetrapods highlights the morphological diversity of these structures, but also the need to establish robust form‐function relationships for future interpretations of osteological correlates for sensory biology.
Ruthenium(II)‐Catalyzed C−H/C−H (4+2) Annulation of 2‐Aryl‐N‐heterocycles with Vinylene Carbonate
Authors: Nipate Dhananjay S. , Swami Prakash N. , Gadekar Amol B. , Jangir Tarun , Rangan Krishnan , Kumar Anil
Published: November 2024

A ruthenium(II)‐catalyzed direct C−H/C−H (4+2) annulation of 2‐aryl‐N‐heterocycles such as 2‐aryl‐4H‐pyrido[1,2‐a]pyrimidin‐4‐ones, 2‐arylimidazo[1,2‐a]pyridines, 2‐aryl‐2H‐indazoles and 2‐arylquinolin‐4(1H)‐ones with vinylene carbonate has been described. This one‐pot cascade strategy provided the diversely substituted fused‐polyheterocycles such as 7H‐benzo[h]pyrido[2,1‐b]quinazolin‐7‐ones, naphtho[1′,2′:4,5]imidazo[1,2‐a]pyridines, indazolo[2,3‐a]quinolines and benzo[c]acridin‐7(12H)‐ones in moderate to excellent yields. The developed protocol exhibited a broad substrate scope with good functional group tolerance and acid/base‐free conditions. Based on a preliminary mechanistic investigation, a tentative mechanism of Ru(II)‐catalyzed (4+2) annulation reaction has been proposed.