bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung‐Specific mRNA Delivery by Ionizable Lipids with Defined Structure‐Function Relationship and Unique Protein Corona Feature
Authors: He Xiaoyan , Wang Runyuan , Cao Yan , Ding Yan , Chang Yan , Dong Haoru , Xie Rong , Zhong Guisheng , Yang Huiying , Li Jianfeng
Published: February 2025

Targeted delivery of mRNA with lipid nanoparticles (LNPs) holds great potential for treating pulmonary diseases. However, the lack of rational design principles for efficient lung‐homing lipids hinders the prevalence of mRNA therapeutics in this organ. Herein, the combinatorial screening with structure‐function analysis is applied to rationalize the design strategy for nonpermanently charged lung‐targeted ionizable lipids. It is discovered that lipids carrying N‐methyl and secondary amine groups in the heads, and three tails originated from epoxyalkanes, exhibiting superior pulmonary selectivity and efficiency. Representative ionizable lipids with systematically variation in chemical structures are selected to study the well‐known but still puzzling “protein corona” adsorbed on the surface of LNPs. In addition to the commonly used corona‐biomarker vitronectin, other arginine‐glycine‐aspartic acid (RGD)‐rich proteins usually involved in collagen‐containing extracellular matrix, such as fibrinogen and fibronectin have also been identified to have a strong correlation with lung tropism. This work provides insight into the rational design of lung‐targeting ionizable lipids and reveals a previously unreported potential function of RGD‐rich proteins in the protein corona of lung‐homing LNPs.
Impact of a Multidisciplinary Approach to Polypharmacy Management in Community‐Dwelling Older Adults: Insights From a Specialized Outpatient Clinic
Authors: Roncal‐Belzunce Victoria , Gutiérrez‐Valencia Marta , Cedeño‐Veloz Bernardo Abel , San Miguel Ramón , Marín‐Epelde Itxaso , Galbete Arkaitz , Preciado Goldaracena Javier , Ezpeleta María Irache , Garaioa‐Aramburu Karmele , Martínez‐Velilla Nicolás
Published: February 2025

Objectives

The increase in polypharmacy among older adults increases the risk of drug‐related problems, making multidisciplinary interventions essential. This study evaluated the impact of a multidisciplinary polypharmacy consultation on medication management and outcomes in older outpatients.

Methods

This prospective observational study at a Spanish teaching hospital involved geriatricians, clinical pharmacists, and nurses. Older adults (≥ 75 years) with polypharmacy underwent medication review at baseline and at 3 and 6 months. Data on medication use, adherence to Screening Tool of Older Person's Prescriptions (STOOP) criteria, and anticholinergic burden were analyzed.

Results

The study included 104 older adults (mean age 86.2 years; 66% female). An average of 3.6 recommendations per participant was made (63.8% acceptance rate). Common drug‐related problems were adverse effects (20%), non‐adherence (18.1%), and incorrect dose/regimen (14.4%). Interventions led to an average reduction of 1.7 medications per patient, with 1.3 dosage or regimen changes and 1.1 new prescriptions. The mean number of medications decreased from 9.6 at baseline to 8.9 at 3 months (p < 0.001) and remained below baseline at 6 months. STOPP criteria violations per patient dropped from 1.2 to 1.0 (p = 0.036). Of the 126 medications flagged by STOPP criteria, 68.3% were addressed, 24.6% discontinued, mainly psychotropics, and 89.3% of these discontinuations were maintained. The anticholinergic burden decreased from 1.3 to 1.1 at 3 months (p = 0.036) and remained below baseline at 6 months.

Conclusions

A multidisciplinary clinic effectively managed polypharmacy in older adults by reducing medication load and improving appropriateness per STOPP criteria, highlighting the importance of proactive medication management.

Trial Registration

ClinicalTrials.gov: NCT05408598 (March 1, 2022)
GACNet: Interactive Prediction of Surrounding Vehicles Behavior under High Collision Risk
Authors: Chai Jingzheng , Liu Jianting , Huang Jingluo , Huang Chunyan
Published: February 2025

Trajectory prediction technology is essential for driving safety in autonomous vehicles and is advancing rapidly. Current research mainly aims to enhance prediction accuracy in typical traffic conditions. However, less attention has been paid to low‐probability, high‐risk safety‐critical events. It is undeniable that multiagent interaction behaviors in safety‐critical events are more complex and difficult to predict. To address this, an interaction mechanism based on generative adversarial networks training, named GACNet, aimed at effectively predicting multiagent interaction behaviors under potential collision risks is proposed. GACNet is a deep learning framework capable of learning and capturing complex interaction patterns between multiple agents from real vehicle trajectory data. In addition, A conflict analysis module, which analyzes the predicted future trajectories and assesses potential collisions to provide a more detailed characterization of the interaction behaviors in safety‐critical events is designed and incorporated. This design enables the model to predict vehicle trajectory behaviors in safety‐critical events more accurately, aligning them more closely with real‐world trajectory distributions. This mechanism is validated in various highly interactive roundabout and urban road scenarios. The results demonstrate that GACNet accurately learns vehicle behavior characteristics from real traffic data and makes precise predictions of multiagent interaction behaviors in safety‐critical events.
Voltage‐Summation‐Based Compute‐in‐Memory Technology with Capacitive Synaptic Devices
Authors: Kim Jung Nam , Kim Yong Woo , Kim Boram , Kim Doo‐Hyun , Lee Gil Sung , Chae Dong‐Hyuk , Je Minkyu , Koo Minsuk , Kim Yoon
Published: February 2025

Previous compute‐in‐memory (CIM) technologies use current summation for executing matrix–vector multiplication (MVM) operations and are gaining attention as next‐generation artificial intelligence (AI) computing systems. Despite their advantages, these technologies encounter significant difficulties, such as managing wide current ranges in large arrays, overcoming substantial “IR (current‐resistance)‐drop” issues, and integrating with complementary metal–oxide–semiconductor operating circuits. Herein, an innovative voltage‐summation‐based CIM (V‐CIM) technology is introduced; this technology represents a paradigm shift that employs capacitive coupling at a floating voltage summation node for MVM operations. By using a differential pair of input voltages (|ΔV|) with opposite signs relative to the reference voltage, the accumulated MVM results at the floating summation node cancel out, eliminating IR‐drop. Representing the MVM result as an analog voltage simplifies the neuron circuit design and significantly reduces energy consumption. V‐CIM technology is reported with two types of capacitive synaptic devices: read‐only and programmable. A prototype V‐CIM chip using read‐only capacitors is developed, demonstrating the superiority of V‐CIM in image classification applications. For programmable capacitive synaptic devices, a memcapacitor device based on logic‐compatible embedded flash memory is introduced. The work sheds light on ultralow‐power, highly integrated, and highly reliable AI computing systems based on CIM technology.
Differential Sex Trends in Infant, Neonatal, and Child Mortality Before and After Decentralization in Pakistan
Authors: Ibupoto Mukhtiar Hussain , Shah Athar Ali , Sang Anqi
Published: February 2025

Background

Differential sex child mortality is an important indicator of gender‐based discrimination. Decentralization refers to the distribution of power from the federal to the provincial governments in Pakistan. Present research highlights the sex differential sex trends in infant, neonatal, and child mortality before and after decentralization.

Methodology

The research utilizes the four waves of the Demographic and Health Survey from 1990 to 2018, applying Cox proportional regression in STATA. The sample size includes 164 005 total live births and 24 089 deaths across all years, with 8204 neonatal, 5107 infants, and 11 778 child deaths.

Results

This study provides crucial insights into the gendered patterns of neonatal, infant, and child mortality in Pakistan before and after key policy reforms. This study reveals persistent gender disparities in neonatal, infant, and child mortality in Pakistan before and after policy reforms. While girls initially had a biological survival advantage, this diminished at higher birth orders, where they faced increased mortality risks. Despite some improvements post‐reform, gender‐based discrimination and son preference continue to disadvantage female children, particularly in larger families.

Conclusion

The findings highlight the need for targeted policies to address healthcare inequities and discriminatory practices. Strengthening gender‐sensitive interventions is crucial to improving female child survival and achieving long‐term progress in reducing mortality disparities.
Development of Rhesus Macaque (Macaca mulatta) Facial Musculature: Implications for Macaque Social Behavior Ontogeny
Authors: Pater Jordan T. , Kimock Clare M. , Downing Sarah E. , Waller Bridget M. , Burrows Anne M.
Published: February 2025

Rhesus macaques (Macaca mulatta) have long been used as a model for the evolution of some aspects of human social behavior and they are among the most completely understood species of the macaque genus. Rhesus macaques have a despotic dominance hierarchy with a well‐documented facial display repertoire. However, we know little about the ontogenetic changes in gross facial musculature and how this might relate to corresponding facial display behavior. In an effort to illuminate our understanding, we dissected facial masks from 13 M. mulatta cadavers that died naturally, shortly after birth or were stillborn, and we compared these results to those from adult rhesus macaques. Results reveal that, unlike the adults in the present study, infant rhesus macaques have extrinsic external ear muscles and muscles associated with the lower lip that are very gracile and poorly developed. Musculature associated with the upper lip and nares are well developed, individually distinct, and robust, like those of the adults in our sample and adult M. mulatta. However, we were unable to locate the zygomaticus major muscle in any fetal/infant sample. These results may reflect simple variation in mimetic muscle ontogeny, differences related to facial allometry, or they could reflect a behaviorally meaningful adaptation to different life stages of macaque ontogeny.
A Green and Efficient Recycling Strategy for Spent Lithium‐Ion Batteries in Neutral Solution Environment
Authors: Xu Zhilong , Ye Long , Yu Yun , Gong Haiqiang , Xiao Zhiming , Ming Lei , Zhang Bao , Yao Zhen , Wang Jiexi , Ou Xing
Published: February 2025

Traditional acid or/and ammonia leaching techniques are usually applied to extract valuable metals during hydrometallurgical recovery of spent lithium‐ion batteries. However, the excessive and repeated use of acids and bases inevitably increases the environmental burden and safety threats. Herein, considering the advantages of neutral pH solution system in terms of safety and environmental protection, neutral leaching has been pioneeringly proposed to achieve a low‐cost and harmless hydrometallurgical process. Specifically, benefited from the ligand complexation reaction of glycine, the valuable metals can be efficiently leached within neutral environment. More importantly, a strategy of solid‐solid reduction with primary batteries effect is employed to achieve an efficient neutral leaching within rapid time, breaking through the reaction limitation of shrinking core model. As anticipated, an efficient leaching of 99.99 % Li, 96.86 % Ni, 92.35 % Co, and 90.59 % Mn can be achieved within 15 minutes, which has extended applications for various kinds of layered cathodes. Therefore, it is sturdily confirmed that the intractable problem, the effective extraction is available only under the aggressive acid/alkali‐ion conditions, is well‐solved within a mild leaching atmosphere. This green and efficient strategy in neutral solution environment opens a new pathway to realize the large‐scale pollution‐free recycling of spent batteries.
Profiling Allosteric Modulators of CB1R with an Allosteric Fluoroprobe
Authors: Carreira Erick Moran , Kosar Miroslav , Perera Themiya , Ganzoni Rudolf Liun Zaccaria , Sarott Roman Clà , Borrega-Roman Leire , Vitale Rosa Maria , Ligresti Alessia , Rufer Arne , Guba Wolfgang , Grether Uwe , Veprintsev Dmitry , Sykes David
Published: February 2025

Allosteric modulation of cannabinoid receptor type 1 (CB1R) offers a promising alternative to conventional therapeutic approaches using orthosteric ligands (OLs). Currently, CB1R allosteric modulators (AMs) are characterized based on their ability to modulate binding or functional response of OLs, preventing isolation of individual contributions by allosteric and orthosteric ligands. Herein, we develop the first allosteric fluoroprobe and attendant FRET‐based assay allowing for the direct profiling of CB1R AMs without coincubation with an OL. Our allosteric tracer enables differentiation of allosteric and orthosteric ligands as well as their pharmacological profiling at CB1R. The utility of this work is highlighted by addressing ambiguities surrounding the binding of cannabidiol (CBD). CBD was found to interact with both allosteric and orthosteric sites of CB1R with comparable affinity (pKi = 5.34 and 5.67, respectively).
Three‐Electron Uric Acid Oxidation via Interdistance‐Dependent Switching Pathways in Correlated Single‐Atom Catalysts for Boosting Sensing Signals
Authors: Jiang Bowen , Zhang Heng , Pan Rui , Ji Min , Zhu Lin , Zhang Guoju , Liu Jing , Shi Huihui , Huang Huang , Wan Shu , Yin Kuibo , Sun Litao
Published: February 2025

The overly simplistic geometric and electronic structures of single‐atom catalysts have become a significant bottleneck in the field of single‐atom sensing, impeding both the design of highly efficient electrochemical sensors and the establishment of structure‐activity relationships. To address these challenges, we present a novel strategy to boost the sensing performance of single‐atom catalysts by precisely tuning the single‐atomic interdistance (SAD) in correlated single‐atom catalysts (c‐SACs). A series of Ru‐based c‐SACs (Rud=6.2 Å, Rud=7.0 Å, and Rud=9.3 Å) are synthesized with predetermined SAD values, which are comprehensively characterized by various techniques. Electrochemical studies on uric acid (UA) oxidation reveal that Rud=6.2 Å demonstrates an extraordinary sensitivity of 9.83 μA μM‐1cm‐2, which is superior to most of electrochemistry biosensors reported previously. Kinetic analysis and product examination unveil that the 6.2 Å Ru SAD instigates a distinctive three‐electron oxidation of UA, with an extra electron transfer compared to the conventional two‐electron pathway, which fundamentally enhances its sensitivity. Density functional theory calculations confirm the optimal SAD facilitates dual‐site UA adsorption and accelerated charge transfer dynamics. This investigation provides novel insights into the strategic engineering of high‐performance SAC‐based electrochemical sensors by precisely controlling the atomic‐scale structure of active sites.
3D Cluster‐Based Covalent Organic Framework for Efficient CO2 Photoreduction
Authors: Zang Shuang-Quan , Xu Yue , Dong Jian-Peng , Wang Le , Geng Rong-Li , Wang Rui , Si Ya-Nan , Mak Thomas C. W.
Published: February 2025

Copper clusters exhibit superior catalytic activity for the CO2 reduction reaction (CO2RR), and their defined structures endow them with unique advantages for modelling the catalytic mechanism at the atomic level. Additionally, the construction of highly stable and regularly structured covalent organic frameworks (COFs) based on copper clusters still presents significant challenges. Herein, we reported two highly stable and reactive cluster‐based COFs (termed Cu4COF‐1 and Cu4COF‐2) constructed via a stepwise assembly strategy. The epitaxially amino‐modified Cu4 cluster (Cu4‐NH2) was initially synthesized based on coordination bonds. Then, Cu4COFs were obtained by the covalent linkage of Cu4‐NH2 clusters and organic linkers. Compared with isolated Cu4 clusters, the Cu4COFs exhibit greater stability, a narrower band gap, a larger specific surface area, and better charge transfer ability, which endow them with superior photocatalytic CO2RR performance under visible light. In situ infrared spectroscopy and density functional theory (DFT) calculations revealed that the covalently linked Cu4COFs could efficiently lower the energy barrier for the formation of the critical *COOH intermediate, thereby enhancing the photocatalytic activity. This study offers a solid basis for the atomically precise construction of novel metal‐cluster‐based COF catalysts.
Silver Molybdate Nanoparticles for Enhanced Tumor Immunotherapy through Pyroptosis Conversion and Ferroptosis Induction
Authors: Chen Hao , Ding Binbin , Tan Jia , Meng Qi , Li Jing , Zhang Wenying , Zheng Pan , Liu Bin , Ma Ping’an , Lin Jun
Published: February 2025

Pyroptosis hold great potential in tumor therapy due to its strong immunogenicity. Several strategies, including ion interference therapy (IIT), are developed to induce pyroptosis. However, the mechanism by which metal oxoanions induced pyroptosis remained unclear. It was reported that MoO42− ions could stimulate immune responses, but their pyroptosis‐inducing mechanisms were not fully understood. Herein, we synthesized uniform and dispersed silver molybdate (Ag2MoO4) nanoparticles (AMO) via a solvothermal method. AMO responded to H2O2 and glutathione (GSH) stimuli, releasing Ag+ and MoO42− ions, generating reactive oxygen species (ROS), and depleting GSH, thereby inducing ferroptosis and pyroptosis. The MoO42− also inhibited cell migration and upregulated GSDME expression, converting apoptosis into caspase‐3/GSDME‐mediated pyroptosis. Additionally, DNA damage and ROS activated the cGAS‐STING pathway, enhancing innate immunity. In vivo experiments demonstrated that the combination of AMO and the immune checkpoint inhibitor αPD‐1 significantly inhibited tumor growth. This combination promoted dendritic cell (DC) maturation, increased effector T cell numbers, induced M1 macrophage polarization, and alleviated immunosuppression. This study contributed to a deeper understanding of metal oxoanion‐mediated pyroptosis, supporting its potential application in cancer immunotherapy.
Ionic‐fence Effect in Au Nanoparticle‐loaded UiO‐66 Metal–Organic Frameworks for Highly Chemoselective Hydrogenation
Authors: Zhong Yicheng , Liao Peisen , Jiang Pingping , Zhang Yuhao , Kang Jiawei , Xie Sizhuo , Feng Rongyu , Fan Yanan , Liu Qinghua , Li Guangqin
Published: February 2025

The chemoselective reaction are vital for fine chemicals, which requires economical and environmentally friendly catalysts. In order to improve the selectivity of multi‐reaction competition, herein, we propose a novel ionic‐fence strategy to synthesize heterogeneous catalyst for efficient hydrogenation. Practically, UIO‐66 metal‐organic frameworks (MOF) modified with pyridinium‐linker has been constructed through post‐synthetic chains with paired anion via quaternization and ion exchange to form ionic‐fence MOF (IFMOF‐Cl), which can manage the adsorption mode of nitro substrate, further confine the formation of metal nanoparticles with high dispersity. The optimal Au@IFMOF‐Cl catalyst demonstrates satisfactory selectivity for hydrogenation of nitro group compared to acetylene group in 4‐nitrophenylacetylene, specifically, it owns a high yield of 4‐aminophenylacetylene (~97%) with ultra‐high catalytic efficiency (3880 h‐1 TOF) and long stability, far superior to other catalysts without ionic fence effect. Adsorption experiments and density functional theory studies reveal that the incorporation of ionic fence could modulate the adsorption energy of nitro group, which is responsible for the high selectivity enhancement. Notably, this ionic‐fence strategy exhibits comprehensive universality towards a wide range of substrates (23 kinds in total), providing a promising avenue for precisely engineering the internal microenvironments of catalysts to achieve highly selective synthesis of fine chemicals.
Leakage Characteristics of Hydrogen Gas Carrying Alkaline Solution
Authors: Feng Wen , Qiu Xiaojun , Li Xiangbin , Lin Jiancheng , Ma Tie , Lyu Xuefeng , Zhang Shucheng
Published: February 2025

Hydrogen energy, as a green and clean energy source of the 21st century, boasts numerous advantages including excellent combustion performance, no pollution, diverse storage methods, and significant development potential. However, the safety risks associated with hydrogen's combustibility and explosive nature cannot be overlooked. Hydrogen leaks during production and storage pose a serious threat when encountered with an ignition source. To gain a deeper understanding of hydrogen leakage patterns, hydrogen leakage accidents involving alkaline liquid entrainment in typical scenarios of hydrogen production are simulated using the CFD program and analyzed in conjunction with jet theory. The results indicate that the impact of alkaline liquid on hydrogen leakage is primarily in dilution and promotion of dispersion. The concentration of pure hydrogen leakage is generally higher than that of leakage involving alkaline liquid. Under the same break velocity, the range of the combustible zone for leakage involving alkaline liquid is consistent with pure hydrogen leakage in the vertical direction, yet significantly larger in the horizontal direction. Hydrogen leakage involving alkaline liquid also exhibits distinctly different flow patterns at various flow rates. At higher velocities, the overall characteristics are dominated by the momentum jet of hydrogen, presenting a positive buoyant jet flow pattern, whereas at lower velocities, the scenario is dominated by the alkaline liquid, exhibiting a negative buoyant jet flow. The characteristic effects of alkaline liquid on hydrogen also vary with changes in velocity.
Empowering Green Energy: ί‐Carrageenan Based Solid Polymer Electrolytes for Zinc Ion Batteries
Authors: Dhanush P. C. , Ismayil
Published: February 2025

This work investigates the potential of ί‐carrageenan, a natural biopolymer, doped with zinc trifluoromethanesulfonate (Zn(Tf)2) (or zinc triflate), to serve as a solid polymer electrolyte (SPE) films for zinc ion conducting batteries (ZIBs). The solution casting technique is employed to prepare the electrolyte films. The study focuses on examining the impact of the dopant and its concentration on the electrochemical properties of the polymer. The research verifies the effectiveness of this SPE by incorporating it into a Zn/MnO2 primary cell. The results show that the cell achieved an initial open‐circuit voltage (OCV) of 1.55 V and an initial short‐circuit current (SCC) of 1 mA. Furthermore, the SPE demonstrated a conductivity of 10−5 S cm−1, which is two orders higher than the undoped polymer. This significant improvement in conductivity highlights the potential of ί‐carrageenan doped with zinc triflate as SPE for ZIBs.
Investigation of Critical Success Factors for Sustainable Marketing of Malaysian Manufacturing Small and Medium‐Sized Enterprises: A Multi‐Criteria Decision‐Making Approach
Authors: Ijaz Baig Maria , Yadegaridehkordi Elaheh
Published: February 2025

In today's business environment, sustainable marketing has become an essential component for small and medium‐sized enterprises (SMEs) aiming to enhance productivity and maintain competitiveness. However, there is a gap in research regarding the critical factors that contribute to the success of sustainable marketing and the importance and interconnections of these factors from experts' perspectives. Thus, this study aims to provide a comprehensive understanding of the complex relationships among factors contributing to the success of sustainable marketing strategies within manufacturing companies. This study extracted 19 success factors crucial to sustainable marketing within Malaysian manufacturing SMEs from the literature and thoughtfully categorized them into technology, organization, environment, human, and social groups. Data was gathered from 26 experts in Malaysian SME manufacturing using a questionnaire. The decision‐making trial and evaluation laboratory (DEMATEL) method was employed to identify the significant factors and reveal cause‐and‐effect relationships among them. The findings showed that perceived benefits, sustainable strategy, natural resources protection, IT knowledge and expertise, and customer demands were crucial factors within technology, organization, environment, human, and social groups, respectively. Meanwhile, the environment group was ranked as the most important dimension influencing sustainable marketing. This study provides valuable insights for researchers, practitioners, and policymakers, offering a foundation to initiate and boost sustainable practices within the organizations.
Noninvasive monitoring of vascular alterations in mice with acute lower limb ischemia using multimodal photoacoustic imaging
Authors: Wang Heng , Fan Keyi , Ning Yijie , Lu Chuanlong , Zhang Yuhang , Wang Qian , Zhang Hongjiu , Li Yaling , Zhang Zeyu , Jia Xiaohua , Yan Sheng , Zhang Ruijing , Dong Honglin
Published: February 2025

Acute limb ischemia (ALI), especially acute lower limb ischemia (ALLI), is a common clinical vascular emergency with high amputation and mortality rates. However, major challenges exist in rapidly diagnosing and assessing collateral vascular compensatory capacity, leading to appropriate clinical treatment strategies to improve limb preservation and reduce recurrence rates. Traditional imaging methods, such as digital subtraction angiography (DSA) and ultrasound, have high demands on patient kidney function and operator maneuvers and are unable to monitor the temporal and spatial variability of collateral circulation establishment in the limb. In this study, we report the first combined use of real‐time and wide‐field laser speckle imaging (RFLSI), near‐infrared two‐zone imaging (NIR‐II), duplex ultrasound (DUS), and optical coherence tomography angiography (OCTA) for the diagnosis and monitoring of ALLI in male C57 and ICR mice. The RFLSI assesses overall perfusion, the NIR‐II allows rapid diagnosis and monitoring of the establishment of collateral circulation, DUS monitors muscle tenderness and stiffness, and OCTA detects microcirculation in the skin of the limb, which is confirmed by histopathological testing. Overall, the results of this study demonstrate the ability to accurately diagnose and detect ALLI with the help of a variety of optical and acoustic imaging devices, with significant clinical translational implications for intervention in clinical decision‐making preoperatively and prognostic assessment postoperatively.
pH and conductivity transients during elution of IgG from protein A columns
Authors: Hahn Rainer , Berger Lukas , Beck Jürgen , Carta Giorgio
Published: February 2025

The evolution of pH and conductivity waves during elution of IgG from protein A columns is studied for the resin MabSelect PrismA as well as other commercial resins using glycine and acetate buffers as eluents. The effects of buffer composition, IgG load, and residence time are explored. For glycine buffers, conductivity and pH waves travel through the column at different speeds, with the conductivity wave emerging in the column void volume and the pH waves emerging in 1 to 6 column volumes (CV) dependent on the buffer composition. The pH effluent temporarily overshoots the feed value, followed by a sharp drop as the pH approaches the eluent pH. For these conditions, elution of IgG is delayed and, at high loads, most of the IgG loaded elutes from the column at high pH values. Complex pH profiles, involving overshoots and delays between conductivity and pH waves are also observed when eluting with dilute sodium acetate (50 mM) or with acetic acid, but to a lesser extent. No overshoots or delays are observed for more concentrated sodium acetate (100 mM). A mechanistic model is developed to predict elution with glycine buffers. Model predictions agree with the experimental trends. In particular, the model shows that when eluting a partially loaded column, IgG desorbed near the column entrance is re‐adsorbed downstream of the pH front eventually emerging at high concentration and high pH. The model can be used to design optimized buffers and predict the pH of the IgG elution pool.
Mechanistic insights into hypoxia‐induced metabolic reprogramming in colorectal cancer through genome‐scale modeling
Authors: Omer Sonal , Sridhar Subasree , Karunagaran D. , Suraishkumar G. K.
Published: February 2025

The hypoxic colorectal cancer (CRC) microenvironment is a complex niche. Hence, in vivo, the metabolism occurring in the cancer cell is not fully known due to difficulties in estimating metabolic fluxes and metabolite exchanges. Genome‐scale metabolic modeling helps estimate such metabolic fluxes to gain insights into the metabolic behavior of individual cancer cell types under various tumor microenvironments (TME). We developed a simplified approach to apply proteomics data‐based enzyme usage constraints and integrated reactive species (RS) reactions in a context‐specific genome‐scale metabolic model (GSMM) of HCT116, a CRC cell line. The combined modeling approach reproduced several phenotypes of HCT116 under hypoxia such as the Warburg effect. The integration of the RS module with the hypoxic HCT116 context‐specific GSMM highlighted the hypoxia‐mediated dysregulation occurring in important metabolic pathways such as hyaluronan metabolism in which 80% of the reactions from the total reactions corresponding to this metabolic pathway were dysregulated. Similarly, 23% of reactions in the urea cycle, 26% of reactions in eicosanoid metabolism and 38% of reactions in glyoxylate and dicarboxylate metabolism were dysregulated.
Incorporation of Nettle (Urtica dioica L.) Hydrophilic Actives in Alginate Beads: Design of Formulation, Encapsulation Efficiency, Antioxidant Activity and Characterization of Beads
Authors: Toprakçı Gizem , Toprakçı İrem , Şahin Selin
Published: February 2025

In this study, nettle (Urtica dioica L.) bioactives was extracted using an environmentally friendly method, and then encapsulated in alginate via ionic gelation. The research aimed to optimize encapsulation efficiency (EE), antioxidant activity (in vitro DPPH scavenging activity), and bead morphology (sphericity factor (SF) and the roundness (Rn)) with Box‐Behnken design under Response Surface Method (RSM) based on 3 parameters (CaCl2 and sodium alginate concentration, and time). The optimal points were determined as almost 12% CaCl2, 2% alginate and 10 min for bead hardening in order to obtain the best quality product (31.52 % of EE, 7.31 mg‐TEAC/g‐DB of antioxidant activity, 0.01 of SF and 0.804 of Rn). The most critical factor of EE and Rn was hardening time at p<0.0001, while sodium alginate concentration was the most significant factor for antioxidant activity and SF at p<0.0001.  The findings demonstrate that the proposed method is practical and efficient in producing nearly spherical and stable beads with significant antioxidant properties. This work highlights the potential for alginate‐based microencapsulation to enhance the stability and functionality of plant‐derived bioactives.
Prenylated Chalcones from Roots of Kidney Vetch (Anthyllis vulneraria L.) with Anti‐proliferative Activity
Authors: Lorenz Peter , Conrad Jürgen , Klaiber Iris , Mailänder Lilo K. , Gazafroudi Khadijeh Nosrati , Stintzing Florian C. , Kammerer Dietmar R. , Ablinger Celina C. , Huber-Cantonati Petra C.
Published: February 2025

Kidney vetch (Anthyllis vulneraria L.) is an old medicinal plant, which is mostly known from ethnomedicine. Nowadays, its herbal parts are only scarcely used in phytotherapy, whereas medicinal applications of root parts have not been reported so far. In this study we investigated ethyl acetate extracts, obtained from A. vulneraria roots. A completely different metabolite profile compared to that of aerial parts was detected by HPLC‐ESI‐(HR)MSn , mainly prenylated chalcones, flavones, isoflavones and cinnamic acids . Two main chalcones (23 and 24) were isolated from the EtOAc extracts by preparative chromatography. Based on 1D‐ and 2D‐NMR data 24 was assigned to the known compound kanzonol C, while 23 as a novel chalcone. Moreover, anti‐proliferative activities of the EtOAc extract and of isolated chalcones were investigated in different liver, breast, and thyroid carcinoma cell lines. Interestingly, the EtOAc extract and 24 exhibited the most pronounced decrease of cell viability in the MDA‐MB468 breast carcinoma cell line with an IC50 value of 5.97 µM. Two synthetic derivatives of 24 (hexahydro‐ and triacetyl kanzonol, 30, 31, respectively), 23 and isobavachalcone 18 were less active . Thus, the prenylated chalcones in A. vulneraria roots appear to be promising lead structures for further anti‐proliferative studies.
Chemical constituents of Hernandiaceae plants and their biological activities
Authors: Wang Xijing , Yan Min , Wang Haiwen , Cai Le , Yin Tianpeng
Published: February 2025

The Hernandiaceae family is a resource plant group with great medicinal and economic value that consists of 70 plant species in 4 genera. In recent years, approximately 300 natural products with various structures and significant biological activities, including mainly alkaloids, lignans, terpenes, and butyrolactones, have been reported from the Hernandiaceae family. In terms of the number of compounds and their distribution, aporphine‐type alkaloids can be considered characteristic components of Hernandiaceae plants. In addition to aporphines, arylnaphthalene and dibenzylbutane lignans are characteristic components of Hernandia plants, while menthane monoterpenes and their dimers are characteristic components of Illigera. The natural products in Hernandiaceae plants have antitumor, anti‐inflammatory, antiplatelet aggregation, and antimalarial activities and can serve as substantial resource banks for drug screening and discovery. This paper is the first to review the structural characteristics and biological activities of the chemical components of Hernandiaceae plants and provides a reference for the efficient use of the resources of this plant family.
Beyond Phenolics: Alternative Substrates for Type III Copper Enzymes
Authors: Pretzler Matthias , Rompel Annette
Published: February 2025

The type III copper enzyme family of tyrosinases (TYRs) catalyzes the ortho‐hydroxylation and oxidation of phenols as well as the two‐electron oxidation of catechols to ortho‐quinones. TYRs use copper ions as their tightly bound cofactors and utilize molecular oxygen as their cosubstrate. They are responsible for physiologically important reactions like the formation of melanin, the primary pigment animals apply for protection against UV light. While the reactivity of TYRs on substrates containing aromatic hydroxy groups (i. e. phenols) is well recognized, reports clearly demonstrating that TYRs are active on aromatic amines as well have gone largely unnoticed. In this perspective we aim to bring together the sparse data on non‐phenolic TYR substrates to illustrate the potential of TYRs for the oxidation of aminophenols and anilines. The activity of TYRs on aromatic amines extends the substance classes amenable to biotechnological production with TYRs from catechols to N‐phenyl imines and phenoxazinone derivates and calls for the inclusion of TYRs among the candidates for oxidative modification of aromatic amines in metabolic pathways.
Diboron Reagents in N‐N Bond Cleavage of Hydrazines, N‐Nitrosamines, and Azides: Reactivity and Mechanistic Insights
Authors: Cid Belén , Tortosa Mariola , Valderrama Raúl , Alonso Inés , Vargas Emily
Published: February 2025

Diboron reagents are known for their ability to promote the deoxygenation of amine or pyridine oxides, nitroarenes, and nitrones through the formation of B‐O‐B bonds. In this study, we have investigated the potential of diboron reagents to induce N‐N bond cleavage in hydrazines, N‐nitrosamines and azides. Our findings show that the combination of B2nep2 as diboron source and KOMe as a Lewis base can effectively promote the N‐N cleavage of a wide variety of substrates. For hydrazines and nitrosamines, the presence of an aryl group is essential for the reaction to proceed, probably due to a better stabilization of the negative charge developed during N‐N bond cleavage. Both types of azides, aromatic and aliphatic, are easily reduced, and the resulting amines can be in situ converted into the corresponding amides by simple treatment with a carboxylic acid. Experimental and theoretical calculations suggest a non‐radical mechanism, with concerted B‐B and N‐N bond cleavage in the case of hydrazines and azides, and a stepwise mechanism in the case of N‐nitrosamines, where deoxygenation occurs as the first step, involving the formation of an N‐nitrene intermediate
Development of Acid‐Functionalized Molecularly Imprinted Phenolic Resin for Chiral Recognition of S‐Venlafaxine
Authors: Alnoman Rua B.
Published: February 2025

This article reports the synthesis of a molecularly imprinted phenolic formaldehyde resin for the selective recognition of the cationic S‐enantiomer of venlafaxine. The resin was developed through the condensation polymerization of p‐hydroxybenzoic acid (4‐HBA) and 4‐nitrophenol (4‐NP) with formaldehyde in an acidic medium. The resultant polymer was reduced to introduce amino groups into the polymer to obtain a dual‐functional resin with amino and carboxylic groups (CA‐P). After the uptake of S‐VF, glutaraldehyde cross‐linking stabilized the resin and formed its enantioselective cavities. Adsorption studies showed that optimum conditions occurred at pH 7, whereas the maximum adsorption capacity was 420 mg/g according to the Langmuir isotherm. The selectivity coefficient of S‐VF‐IP was 13 times that of NIP, confirming that the imprinting process indeed occurred. Chiral separation experiments using the SV‐imprinted polymer (S‐VF‐IP) column resulted in 98% enantiomeric excess for R‐VF, whereas the respective NIP did not provide any enantioselectivity. These results show a great possibility of the developed resin in efficient enantioselective separation and offer a promising method for the purification of chiral drugs from racemic mixtures in pharmaceutical applications.
Chiral Porous Frameworks for Enantioselective Separation and Asymmetric Catalysis
Authors: Yan Bing , Song Jin‐Hui , Zhang Da‐Long , Guan Zong‐Jie , Fang Yu
Published: February 2025

Comprehensive Summary

The preparation and resolution of chiral molecules hold significant importance in scientific and industrial domains, such as drug development and manufacturing. In recent years, chiral porous frameworks have attracted increasing attention in asymmetric catalysis and enantiomer resolution due to their excellent performance. The metal‐organic frameworks (MOFs), covalent organic frameworks (COFs), porous organic cages (POCs), and porous coordination cages (PCCs) are important representative of the porous framework family. Significantly, chirality can be easily introduced into these framework materials through simple bottom‐up or post‐modification methods, thereby promoting their applications related to chirality. In this review, we systematically summarize the synthesis strategies of four classes of chiral framework materials and their applications in asymmetric catalysis and enantiomeric resolution. Finally, we present some perspectives on the future development in chiral porous frameworks.

Key Scientists

Significant progress has been made in the development of chiral porous frameworks, primarily driven by the application of chiral molecules. This area of research has seen contributions from many distinguished scientists. A particularly important milestone was reached in 2000, when Kimoon Kim reported the first catalytic Chiral Metal‐Organic Framework (CMOF). In 2001, Lin et al. reported a new generation of recyclable CMOF capable of chiral separation and heterogeneous catalysis. Simultaneously, researchers such as Cui and Duan have made substantial contributions, advancing the field considerably. Furthermore, notable developments have been made in the area of Chiral Covalent Organic Frameworks (CCOFs), with pioneering work by researchers like Jiang, Wang, and Cui. Meanwhile, some groups such as Su and Li have made significant strides in the chiral cages. These remarkable accomplishments have drawn considerable interest.
A comparative genomic study across 396 liver biopsies provides deep insight into FGF21 mode of action as a therapeutic agent in metabolic dysfunction‐associated steatotic liver disease
Authors: Tang Shifang , Borlak Jürgen
Published: February 2025

Background

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a systemic disease with insulin resistance at its core. It affects one‐third of the world population. Fibroblast growth factor (FGF21)‐based therapies are effective in lowering hepatic fat content and fibrosis resolution; yet, its molecular functions remain uncertain. To gain insight into FGF21 mode of action (MoA), we investigated the transcriptomes of MASLD liver biopsies in relation to FGF21 expression.

Methods

We compared N = 66 healthy controls with 396 MASLD patients and considered clinical characteristics relative to NAS disease activity scores (steatosis, lobular inflammation and ballooning), fibrosis grades and sex. We performed comparative genomics to identify FGF21‐responsive DEGs, utilised information from FGF21‐transgenic and FGF21‐knockout mice and evaluated DEGs following FGF21 treatment of MASLD animal models. Eventually, we explored 188 validated FGF21 targets, and for ≥10 patients showing the same changes, we constructed MASLD‐associated networks to determine the effects of FGF21 in reverting metabolic dysfunction.

Results

We identified patients with increased 30% (N = 117), decreased 40% (N = 159) or unchanged 30% (N = 120) FGF21 expression, and the differences are caused by changes in FGF21 transcriptional control with ATF4 functioning as a key regulator. Based on comparative genomics, we discovered molecular circuitries of FGF21 in MASLD, notably FGF21‐dependent induction of autophagy and oxidative phosphorylation/mitochondrial respiration. Conversely, FGF21 repressed hepatic glycogen‐storage, its glucose release and gluconeogenesis, and therefore reduced glucose flux in conditions of insulin resistance. Furthermore, FGF21 repressed lipid transporters, and acetyl‐CoA carboxylase‐β to attenuate hepatic lipid overload and lipogenesis. Strikingly, FGF21 dampened immune response by repressing complement factors, MARCO, CD163, MRC1/CD206, CD4, CD45 and pro‐inflammatory cytokine receptors. It also reverted procoagulant imbalance in MASLD, stimulated extracellular matrix degradation, repressed TGFβ‐ and integrin‐signalling and lessened liver sinusoidal endothelial cell defenestration in support of fibrosis resolution.

Conclusions

We gained deep insight into FGF21‐MoA in MASLD. However, heterogeneity in FGF21 expression calls for molecular stratifications as to identify patients which likely benefit from FGF21‐based therapies.

Key points

Performed comprehensive genomics across liver biopsies of 396 MASLD patients and identified patients with increased, decreased and unchanged FGF21 expression.

Used genomic data from FGF21 transgenic, knock‐out and animal MASLD models treated with synthetic FGF21 analogues to identify FGF21‐mode‐of‐action and metabolic networks in human MASLD.

Given the significant heterogeneity in FGF21 expression, not all patients will benefit from FGF21‐based therapies.
Helical Electric Field‐Assisted Circular Polarised Terahertz Wave Generation in Plasma by Beating of Two Lasers
Authors: Shukla Vivek Kumar , Hussain Saba , Singh Monika , Singh Ram Kishor
Published: February 2025

We have studied the circular polarised Terahertz (THz) wave emission by mixing of two lasers in plasma when an externally applied helical structured electric field is present. A nonlinear transverse current density at difference frequency emerges on the accounts of ponderomotive nonlinearity. This occurs when the electrons moving under the influence of externally applied helical electric field, couples with the nonlinear plasma density at difference frequency. This transverse current density can be decomposed of two mutually perpendicular vector having equal amplitude and phase shift, which drives a circular polarised coherent THz radiation. It turns out that conversion efficiency of THz radiation substantially depends on electron plasma frequency, mismatch phase, polarisation angle between laser beams and externally applied helical electric filed. Numerical simulations show that the conversion efficiency increases as THz frequency approach to plasma frequency.
Integrating Human and Wildlife Dynamics in Co‐Occurrence Modelling
Authors: Rolle F. , Boiani M. V. , Fardone L. , Gaydou F. , Macario M. , Parentela F. , Ruco V. , Sigaudo D. , Marucco F.
Published: February 2025

In shared environments, where different species interact depending on overlapping resources, complex interspecific interactions emerge, with human activities impacting these dynamics and influencing wildlife abundance and distribution. In the Alps, the presence of multiple species of ungulates, such as roe deer and red deer, and a predator, the wolf, creates a web of spatial and behavioral interactions in an area where farming, hunting and tourism have persisted over time, with tourism recently experiencing a substantial growth. Accounting for these multiple interactions, we modelled the co‐occurrence probabilities of roe deer, red deer and wolves in an area of the Maritime Alps using data derived from 60 camera traps. We applied multi‐species occupancy models to investigate (i) the role of species co‐occurrences in explaining the occupancy of model species across the landscape, (ii) the role of human presence and activities on species occupancy and (iii) the potential effect of the hunting season on the species detection probabilities. Among the identified species, roe deer reported the highest frequency of recorded events and were the most widespread species. We provided important evidence of interspecific dependence, revealing that pairwise interactions among species had a greater impact than only considering individual environmental effects. We documented that the setting of cameras on trails increased the likelihood of detecting wolves but decreased the likelihood of detecting ungulates. Most importantly, the hunting season significantly reduced the likelihood of capturing roe deer, while having no effect on either red deer or wolves. Our results confirmed the relevance of including prey, predators, and human dynamics as a whole. Since the sharing of habitat makes human activities significantly important in defining predator–prey mechanisms, our insights are particularly relevant for defining solutions to optimize human‐wildlife coexistence, especially in a highly anthropogenic system such as Europe.