bluuebunny/crossref_metadata_2025 huggingface dataset:
Customization of Ethylene Glycol (EG)‐Induced BmoR‐Based Biosensor for the Directed Evolution of PET Degrading Enzymes
Authors: Li Min , Chen Zhenya , Zhang Wuyuan , Wu Tong , Qi Qingsheng , Huo Yi‐Xin
Published: February 2025

The immense volume of plastic waste poses continuous threats to the ecosystem and human health. Despite substantial efforts to enhance the catalytic activity, robustness, expression, and tolerance of plastic‐degrading enzymes, the lack of high‐throughput screening (HTS) tools hinders efficient enzyme engineering for industrial applications. Herein, we develop a novel fluorescence‐based HTS tool for evolving polyethylene terephthalate (PET) degrading enzymes by constructing an engineered BmoR‐based biosensor targeting the PET breakdown product, ethylene glycol (EG). The EG‐responsive biosensors, with notably enhanced dynamic range and operation range, are customized by fluorescence‐activated cell sorting (FACS)‐assisted transcription factor engineering. The ingeniously designed SUMO‐MHETase‐FastPETase (SMF) chimera successfully addresses the functional soluble expression of MHETase in Escherichia coli and mitigates the inhibitory effect of mono‐(2‐hydroxyethyl) terephthalic acid (MHET) intermediate commonly observed with PETase alone. The obtained SMM3F mutant demonstrates 1.59‐fold higher terephthalic acid (TPA) production, with a 1.18‐fold decrease in Km, a 1.29‐fold increase in Vmax, and a 1.52‐fold increase in kcat/Km, indicating stronger affinity and catalytic activity toward MHET. Furthermore, the SMM3F crude extract depolymerizes 5 g L−1 bis‐(2‐hydroxyethyl) terephthalic acid (BHET) into TPA completely at 37 °C within 10 h, which is then directedly converted into value‐added protocatechuic acid (PCA) (997.16 mg L−1) and gallic acid (GA) (411.69 mg L−1) at 30 °C, establishing an eco‐friendly ‘PET‐BHET‐MHET‐TPA‐PCA‐GA’ upcycling route. This study provides a valuable HTS tool for screening large‐scale PET and MHET hydrolases candidates or metagenomic libraries, and propels the complete biodegradation and upcycling of PET waste.
High‐Impulse, Modular, 3D‐Printed CubeSat Electrospray Thrusters Throttleable via Pressure and Voltage Control
Authors: Kim Hyeonseok , Velásquez‐García Luis Fernando
Published: February 2025

This study reports the proof‐of‐concept demonstration of novel, additively manufactured, droplet‐emitting electrospray emitter arrays for CubeSat thruster applications. The modular thruster design incorporates multiscale features by employing two different vat photopolymerization technologies, i.e., digital light processing for defining mesoscale features, and two‐photon polymerization for creating microscale features. The thruster design includes optimized, 50 µm‐diameter microfluidic channels to attain uniform emitter array operation. Devices with up to 8 modules of 4 emitters were tested in a vacuum to assess their performance. Stable and uniform electrospray emission was achieved across all emitters, with a near 100% transmission across the extractor. Both pressure (flow rate) and voltage modulation are investigated as methods for controlling the emitted current and, by extension, the thrust generated by the devices. The per‐emitter current followed a well‐known square root relationship with flow rate; in addition, a linear relationship between per‐emitter current and extractor voltage is observed. Compared to pressure control, modulating thrust via voltage control simplifies system design, eliminating the need for complex valves and enabling a wider throttle range. Estimated thrust and specific impulse are comparable to, or better than reported droplet‐emitting electrospray thrusters. These findings demonstrate the potential of additive manufacturing to implement electrospray propulsion hardware.
One‐Pot Construction of NHS‐Activated Magnetic Particles for Chemoselective Capture of Carboxyl Metabolites
Authors: Liu Shuai , Yu Meng , Luo Xin‐Yao , Liu Jie , Zou Zhong‐Mei
Published: February 2025

Chemoselective probes immobilize on magnetic materials show great promise in simplifying sample handling and enhancing detection sensitivity. However, their complicated preparation and associated expense limit broader application. In this study, novel magnetic particles with abundant N‐hydroxysuccinimide (NHS) esters on the surface are conveniently synthesized using a one‐pot method without carbodiimide activation carboxylate molecules. Subsequently, multifunctional probes are synthesized by immobilizing high‐density chemical probes on the surface of the magnetic materials through a postsynthetic modification strategy. This versatile probe facilitates the rapid capture of carboxylated compounds from complex matrices, with the labeled metabolites release from the magnetic materials subsequently analyzed using ultra‐high performance liquid chromatography‐mass spectrometry (UHPLC‐MS). The advantages of this innovative chemical biological tool include the simplicity and low cost of the synthesis, as well as the capability to analyze polar and volatile carboxylated metabolites via LC‐MS. This new strategy is successfully applied to analyze short‐chain fatty acids (SCFAs) in rat cecal contents, demonstrating the reliability of the analytical method. This study presents a cost‐effective and easy‐to‐implement approach for preparing NHS‐activated magnetic particles and offers a versatile probe with chemoselective extraction and labeling capabilities, providing a practical tool for analyzing SCFAs in the gut.
Thermoplastic Elastomer‐Reinforced Hydrogels with Excellent Mechanical Properties, Swelling Resistance, and Biocompatibility
Authors: Liu Zhanqi , Zhang Hechuan , Zhou Ruigang , Gao Haiyang , Wu Yongchuan , Wang Yuqing , Wu Haidi , Guan Cheng , Wang Ling , Tang Longcheng , Song Pingan , Xue Huaiguo , Gao Jiefeng
Published: February 2025

Strong and tough hydrogels are promising candidates for artificial soft tissues, yet significant challenges remain in developing biocompatible, anti‐swelling hydrogels that simultaneously exhibit high strength, fracture strain, toughness, and fatigue resistance. Herein, thermoplastic elastomer‐reinforced polyvinyl alcohol (PVA) hydrogels are prepared through a synergistic combination of phase separation, wet‐annealing, and quenching. This approach markedly enhances the crystallinity of the hydrogels and the interfacial interaction between PVA and thermoplastic polyurethane (TPU). This strategy results in the simultaneous improvement of the mechanical properties of the hydrogels, achieving a tensile strength of 11.19 ± 0.80 MPa, toughness of 62.67 ± 10.66 MJ m−3, fracture strain of 1030 ± 106%, and fatigue threshold of 1377.83 ± 62.78 J m−2. Furthermore, the composite hydrogels demonstrate excellent swelling resistance, biocompatibility, and cytocompatibility. This study presents a novel approach for fabricating strong, tough, stretchable, biocompatible, and fatigue‐ and swelling‐resistant hydrogels with promising applications in soft tissues, flexible electronics, and load‐bearing biomaterials.
Structure‐Guided Engineering of a Versatile Urethanase Improves Its Polyurethane Depolymerization Activity
Authors: Li Zhishuai , Han Xu , Cong Lin , Singh Parinita , Paiva Pedro , Branson Yannick , Li Wenshuo , Chen Yangyang , Jaradat Da'san M. M. , Lennartz Frank , Bayer Thomas , Schmidt Louis , Garscha Ulrike , You Song , Fernandes Pedro Alexandrino , Ramos Maria João , Bornscheuer Uwe T. , Weber Gert , Wei Ren , Liu Weidong
Published: February 2025

Polyurethane (PUR), the fifth most prevalent synthetic polymer, substantially contributes to the global plastic waste problem. Biotechnology‐based recycling methods have recently emerged as innovative solutions to plastic waste disposal and sparked interest among scientific communities and industrial stakeholders in discovering and designing highly active plastic‐degrading enzymes. Here, the ligand‐free crystal structure of UMG‐SP2, a metagenome‐derived urethanase with depolymerization activities, at 2.59 Å resolution, as well as its (co‐)structures bound to a suicide hydrolase inhibitor and a short‐chain carbamate substrate at 2.16 and 2.40 Å resolutions, respectively, is reported. Structural analysis and molecular dynamics simulations reveal that the flexible loop L3 consisting of residues 219–226 is crucial for regulating the hydrolytic activity of UMG‐SP2. The semi‐rational redesign of UMG‐SP2 reveals superior variants, A141G and Q399A, exhibiting over 30.7‐ and 7.4‐fold increased activities on polyester‐PUR and a methylene diamine derivative of PUR, respectively, compared to the wild‐type enzyme. These findings advance the understanding of the structure–function relationship of PUR‐hydrolyzing enzymes, which hold great promise for developing effective industrial PUR recycling processes and mitigating the environmental footprint of plastic waste.
Simultaneous Achievement of Enhanced Nonlinear Optical Absorption and Nonlinear Refraction in Highly Crystalline 2D Covalent Organic Frameworks Ultrathin Films
Authors: Dong Tianyang , Wen Xingyuan , Li Junyi , Wu Xingzhi , Wang Chong , Zhou Wenfa , Yu Lingmin , Song Yinglin , Wang Chunru , Jiang Li , Bai Chunli
Published: February 2025

Large enhancement of nonlinear absorption and nonlinear refraction are achieved simultaneously in highly ordered two dimensional (2D) covalent organic framework (COF) films prepared by solidliquid interface one‐step method to overcome the weakness of COF powders in solubility. In the intrinsic nonlinear optical response obtained at 532 nm with 5 ns pulse, the nonlinear absorption coefficients (β) of two COF films are −4.87 × 10−5 and −1.29 × 10−5 m W−1, respectively. Simultaneously, the fitted closed‐aperture curves also show large nonlinear refractive indexes (n2), −5.62 × 10−12 m2 W−1 and −0.76 × 10−12 m2 W−1. The 4f coherent imaging performed at the same condition with a single‐shot pulse further verifies the outstanding nonlinear optical response without any damage probably experienced in the Z‐scan technique. Moreover, the differences in framework electronic structure and photoexcited states between two COF films are compared to explain the difference in nonlinear optical response. All the results indicate that two COF crystalline films with intrinsic giant nonlinear optical response can be capable of modulating both amplitude and phase of light, providing huge potential in all‐optical manipulating and switching at the nanoscale as outstanding nonlinear optical materials.
Electronic Modulation and Built‐in Electric Field Strategies in Heterostructures Together Induce 1T‐Rich MoS2 Conversion for Advanced Sodium Storage
Authors: Peng Hui , Miao Wenxing , Zeng Jingtian , Wang Zihao , Yan Chenhui , Ma Guofu , Lei Ziqiang
Published: February 2025

1T‐MoS2 is considered an attractive energy storage material due to its large layer spacing and excellent electrical conductivity. Unfortunately, 1T‐MoS2 is difficult to synthesize directly due to the substability, which limits its development and application. Electron‐filling engineering of Mo 4d orbitals is the core idea to induce an efficient conversion of 2H to 1T phase. Based on this theory, a homogeneous CuS@MoS2 heterogeneous nanosheet is successfully constructed based on electron‐rich CuS as an electron donor. Both density functional theory (DFT) and X‐ray absorption fine structure analysis (XAFS) illustrate that part of the electrons from Cu at the heterogeneous interface are transferred to Mo, which triggers the reorganization of Mo 4d orbitals and the formation of a strong built‐in electric field at the interface, and induces an irreversible phase transition from 2H to 1T in MoS2. Based on its structural features, CuS@MoS2 heterogeneous nanosheets have a high first discharge capacity of 725 mAh g−1 at 0.1 A g−1, excellent rate performance (466.73 mAh g−1 at 10 A g−1), and long cycle stability (506.03 mAh g−1 after 3200 cycles at 5 A g−1). This work provides new perspectives for the development of high‐performance sodium storage anode materials based on 1T‐rich MoS2.
Ultra‐Fast Synthesis of Composite Oxide‐Supported Transition Metal Alloy as an Advanced Catalyst for Ammonia Decomposition
Authors: Li Yuou , Wang Ke , Wang Zijian , Wang Xiaomei , Chu Xiang , Zhang Rui , Song Shuyan , Zhang Hongjie , Wang Xiao
Published: February 2025

Ammonia decomposition reaction (ADR) has been extensively used to generate clear hydrogen in industry. Despite ruthenium (Ru) being the most active catalyst component for ADR, its exceptionally high price imposes severe limitations on its large‐scale application. Therefore, the development of cost‐effective and robust noble‐metal‐free ADR catalysts is highly desired, but it remains a challenge. Herein, a spray pyrolysis‐assisted method is reported for the ultra‐fast synthesis of strongly coupled composite oxide supports and transition metal alloy centers. The optimized catalyst, La0.75Sr0.25(FeCoNi)1.7O3‐δ, exhibits outstanding ADR performance, achieving ≈98% ammonia conversion at 600 °C with remarkable stability over a period of 150 h. Further investigations reveal that the composite oxide support is enriched with numerous medium to strong basic sites. These sites play a crucial role in transferring electrons to the supported transition metal alloy, thus contributing to the rapid recombination and desorption of nitrogen atoms.
meta‐Hydroxylation of Pyridines, Quinolines, and Isoquinolines Using Dearomatized Intermediates
Authors: Bhattacharya Debkanta , Studer Armido
Published: February 2025

The functionalization of C−H bonds in heterocycles holds considerable importance in chemical synthesis and drug discovery. Recently, the regioselective introduction of various functionalities at the meta‐position of azines, utilizing readily accessible dearomatized intermediates, has emerged as a highly attractive approach. Along these lines, the meta‐hydroxylation of azines is an appealing but challenging transformation due to the inherent electronic nature of these heterocycles. Herein, we report a meta‐selective hydroxylation of pyridines, quinolines and isoquinolines through easily accessible oxazinoaza‐arene intermediates. The nucleophilic C3‐position of these dienamine‐type intermediates engages in highly regioselective hydroxylation upon treatment with electrophilic peroxides.
Ligand‐Enabled Nondirected and Regioselective Arylation of Internal Alkenes with Simple Arenes
Authors: Liu Tianming , Deng Xi , Gao Yue , Li Haofan , Du Yu , Su Weiping
Published: February 2025

Regioselective functionalization of internal alkenes has become a highly efficient approach for preparing stereochemically defined multi‐substituted olefins. Unlike traditional methods that require directing groups, activating groups, or active chemical bonds (e.g., halide, pseudo halide, organometallic reagent, etc.), there remains a strong demand for nondirected and selective functionalization of unactivated alkenes with simple coupling partners, both in academic research or industrial applications. Herein, we report the development of a pyridone‐oxazoline (Pyoox) type ligand that combines the features of both pyridone and pyridine‐oxazoline in assisting Pd‐catalyzed olefination. This ligand enables the activation of simple (hetero) arenes and internal alkenes within a single reaction system. A nondirected and regioselective arylation from simple raw materials has been achieved, providing a straightforward route to various trisubstituted olefins in moderate to excellent yields, with excellent regio‐/stereocontrol. Experimental and computational studies on mechanisms offer insight into the distinctive properties and performance of this ligand‐promoted catalysis. The synthetic utility of this method is further demonstrated by the simplified synthesis and late‐stage diversification of bioactive molecules.
Self‐Accelerated Controllable Phase Transformation for Practical Liquid Metal Electrode
Authors: Qin Chichu , Huang Li , Zhong Xuan , Xia Zhiyong , Li Guanwu , Cheng Guanqing , Huang Lu , Wu Yingpeng
Published: February 2025

Despite the high theoretical capacity, the deposition of solid alkali metals can trigger dendrites growth, causing safety risk, capacity and life decay. While liquid NaK alloy is dendrite‐free, their fluidity may cause leakage or even short circuit. In this work, a novel controllable phase transformation strategy was proposed enabled NaK anode to be processed in near‐solid and work in liquid, effectively overcoming the challenges of dendrite formation and leakage. Specifically, a near‐solid anode was fabricated by liquid metal (LM)‐assisted mechanochemistry reaction, which can be easily shaped and integrated into batteries without leakage risk. Then self‐accelerated phase transformation continues within the battery, driven by an LM‐mediated in‐situ replacement reaction, converts the near‐solid electrode into liquid state and enabling dendrite‐free operation. For the first time, a cylindrical cell with liquid NaK alloy anode was successfully matched and demonstrated excellent electrochemical performances. This innovation not only enhances safety but also advancing the practical application of liquid metal electrodes in energy storage systems.
Broadband‐Light‐Induced [2+2] Cycloaddition and Thermoinduced Cycloreversion‐Powered Dynamic Molecular Crystals
Authors: Naumov Pance , Zhong Jiangbin , Sun Jingbo , Chen Chao , Yang Xiqiao , Ye Kaiqi , Li Liang , Lu Ran
Published: February 2025

Photomechanically responsive dynamic molecular crystals are central to developing efficient, rapid, and robust materials capable of conversion of light energy to mechanical work. However, unlike some other, mainly photochromic molecular solar thermal energy storage (MOST) systems, solids in which the photoinduced [2+2] cycloaddition undergoes have not been explored to power reversible actuation, despite that this reaction system carries an unexplored potential in the heavily strained bonds of the cyclobutane ring, the common chemical moiety in the natural products. In this study, we propose that broadband‐light‐induced [2+2] cycloaddition can be used to store energy and actuate dynamic organic crystals by irradiation with visible light. The prototypical material, pyrenylvinylpyrylium tetrafluoroborate (1‐PVPyL), undergoes a topochemical [2+2] cycloaddition induced not only by ultraviolet radiation (365 nm) but also by monochromatic green light (532 nm), red light (620 nm) and broadband visible light in a single‐crystal‐to‐single‐crystal manner, causing its crystals to bend. The crystals effectively act as energy depots, where the reverse deformation can be initiated by heating and the stored energy is released via thermal cycloreversion reaction. Given the ubiquity of the [2+2] cycloaddition in the solid state, the current study invites the development of new dimeric architectures that utilize sunlight for energy storage.
Halogen Modulation: Novel Fluoropyridylphenylurea Derivatives as Potent Molluscicides Unveiling Snail‐Killing Mechanisms
Authors: Liang Jinsong , Lu Yuxun , Wang Weisi , Zhao Yu‐Qiang , Yu Le , Chen Ying , Duan Liping , Zhou Ying
Published: February 2025

Pomacea canaliculata is an invasive species that poses significant threats to agriculture and human health. The development of environmentally friendly molluscicides is crucial for its management. In this study, we synthesized 17 fluoropyridylphenylurea derivatives using a halogen modulation strategy to explore their potential as molluscicides. Compounds L‐1 and L‐2 demonstrated notable molluscicidal activity, with LC50 values of 1.377 mg/L and 1.001 mg/L, respectively. Among these, L‐2 exhibited superior efficacy while causing minimal harm to other aquatic organisms, particularly fish. The molluscicidal mechanism of L‐2 was investigated using Tandem Mass Tags (TMT)‐labeled quantitative proteomic analysis and non‐targeted metabolic analysis. These analyses revealed that L‐2 significantly affected the liver metabolism of P. canaliculata by disrupting the transaminase, gluconeogenesis, and glycolysis pathways. This metabolic disruption is likely a contributing factor to the mortality observed in the snails. Our findings suggest that compound L‐2 is a promising molluscicide, offering high efficiency and minimal environmental impact. These insights could guide future research and development in molluscicide applications.
Artificial Neural Network: Optimization and Characterization of α‐Amylase Production from Bacillus velezensis Species
Authors: Bhimana Sasidhar , Ravindran Saravanan
Published: February 2025

This article delves into the application of design of experiments methodologies for the integration of a second‐order definitive screening design (DSD) and artificial neural network (ANN) to comprehensively assess and predict nine operational variables aimed at increasing the yield of α‐amylase from Bacillus velezensis species. By utilizing environmentally friendly and cost‐effective agro‐solid substrates such as moong husk and soya bean cake, the physical and chemical parameters influencing α‐amylase biosynthesis from B. velezensis species were optimized, gathering early data from experiments conducted in shake flasks through the standard one‐factor‐at‐a‐time (OFAT) technique. In the realm of response surface methodology (RSM) utilizing the DSD model, nine process variables were taken into account, including pH, temperature, carbon source, nitrogen source, K2PO4, MgSO4, NaCl, fructose, and NaNO3. Furthermore, optimization based on ANN modeling was employed to enhance the enzyme yield further. Experiments were then executed under the optimal conditions as defined by RSM and ANN to corroborate the predicted optimized enzyme activity. As a result, B. velezensis species exhibited enzyme activity of 1092.49 U/mL under the optimal process variables identified by both RSM and ANN optimization methods, which included pH 5.48, temperature (34.28°C), carbon source (4.09%), nitrogen source (2.02%), K2PO4 (0.34%), MgSO4 (0.14%), NaCl (0.23%), fructose (1.54%), and NaNO3 (0.53%). To encapsulate, compared to the OFAT technique, where the enzyme activity was 418.25 U/mL, a 2.6‐fold increase in enzyme activity was achieved by integrating DSD and ANN optimization, considering only nine significant process parameters for the proliferation of B. velezensis species and the maximization of α‐amylase activity. The α‐amylase enzyme from the B. velezensis species was further purified and characterized. The purification process achieved a 71.77‐fold increase in specific activity, with the purified enzyme exhibiting optimal activity at pH 5.5 and 55°C. The enzyme displayed high thermal stability, with minimal activity loss up to 4°C. Kinetic analysis revealed a KM of 0.85 mg/mL and a Vmax of 250 U/mg/min. The enzyme was found to be metal‐independent, with inhibition observed for certain metal ions.
Assessing the Adjuvant Potential of Chinese Hamster Ovary Host Cell Proteins Using an In Vitro Dendritic Cell Assay
Authors: Panikulam Sherin , Morgan Hannah , Gutknecht Michael , Karle Anette , Rajaratnam Atchaya , Muntwyler Jennifer , Anderka Oliver , Lebesgue Nicolas , Villiger Thomas K.
Published: February 2025

Host cell proteins (HCPs) are process‐related impurities of therapeutic protein production and may affect product quality or patient safety. In clinical trials, certain HCPs (e.g., PLBL2 or CCL2) that co‐purify with the therapeutic protein have been associated with immune reactions in patients. In this study, we examined the adjuvant potential of six commonly detected HCPs from CHO cells (PRDX1, S100A4, PLBL2, CCL2, CLU, and YWHAE) using an in vitro dendritic cell (DC) maturation assay. Recombinant HCPs were expressed in CHO cells to mimic manufacturing conditions. PRDX1, S100A4, and PLBL2 caused a slight increase in the expression of maturation markers on DCs, while YWHAE, CLU, and CCL2 did not. Interestingly, CLU and CCL2 reduced the DC maturation induced by rituximab. In addition, we observed that process parameters such as elution conditions during chromatographic purification can influence HCP aggregation, which in turn can mask or enhance the intrinsic adjuvant potential of an HCP. These findings not only provide initial insights into the adjuvant potential of individual HCPs but also indicate that the quantity as well as the degree of aggregation of HCPs might influence adjuvanticity.
Enhanced Natural Killer Cell Proliferation by Stress‐Induced Feeder Cells
Authors: Lee Donghyun , Song Myeongkwan , Kwon Soonjo
Published: February 2025

Natural killer (NK) cells, integral to the innate immune system, are notable in cell therapies because of their applicability in allogeneic treatments, distinguishing them from T cells typically employed in conventional cell therapies. However, their limited half‐life (proliferative capability) poses a challenge for therapy. The limited half‐life creates difficulties in obtaining a sufficient number of cells for in vitro adoptive therapy. Gene modification is commonly employed to address this limitation. However, due to concerns such as genetic instability and unintended gene expression, its suitability for long‐term cultivation is uncertain. Consequently, safer alternatives are needed. We aimed to promote NK cell proliferation through feeder cells rather than genetic modification. These cells are designed to interact with NK cells without adverse effects, aiming to promote NK cell proliferation more safely. In our study, during the tailoring of feeder cells, we excluded genetic modification and instead applied chemical‐based extracellular stress. The extracellular stress applied consisted of hypoxia and cytochalasin D. By treating the feeder cells with these stressors, we were able to inhibit feeder cell proliferation, enabling them to function more efficiently as feeder cells. Furthermore, we observed that the feeder cells subjected to extracellular stress exhibited upregulated expression of 4‐1BBL, which enhances the 4‐1BB/4‐1BBL interaction with NK cells. The upregulated 4‐1BBL binds to 4‐1BB on the surface of NK cells, promoting their proliferation. Additionally, following coculture with feeder cells exposed to extracellular stress, we observed an upregulation of CD56 expression on the surface of NK cells. These CD56bright NK cells influence NK cell proliferation through enhanced cytokine release. We further validated this process under dynamic conditions where shear stress is applied, demonstrating that the feeder cell‐mediated enhancement of NK cell proliferation is applicable under dynamic conditions such as those found in bioreactors.
A Selective and Sensitive Method Development and Validation for Impurity Quantification in Cysteamine Bitartrate Bulk and Formulation by RP‐HPLC
Authors: Katakam Prasanth , Pathak Umesh N. , Chollety Vijay Kumar , Tripuramallu Bharat Kumar
Published: February 2025

RP‐HPLC was used to develop and validate a simple, selective, and sensitive impurity quantification method for cysteamine bitartrate formulation. Chromatographic separation was achieved using Shim‐pack Sceptre HD‐C18‐5 μm 4.6 × 250 mm column. The mobile phase‐A was 43 mM 1‐hexane sulfonic acid sodium salt monohydrate buffer adjusted to pH 2.2 with 0.1% orthophosphoric acid. Mobile phase‐B was acetonitrile. The column oven temperature was 40°C, and gradient elution was done at 0.8 mL per minute, and the gradient program was T/A: 0/100, 12/100, 12.1/90, 30/80, 35/70, 45/70, 45.1/100, and 60/100. To measure component quantities, a 200 nm wavelength and 10 μL injection volumes were utilized. The drug product and drug substance were subjected to the stress conditions such as acid, base, oxidation, heat, and photolysis as per the recommendations of the International Conference on Harmonization (Q2) methodology. Stress research shows that the approach is stable and peak homogeneous. High accuracy (97%–103% recoveries), precision (≤ 1.0%), specificity (R2 > 0.999), and linearity (R2  > 0.999) were achieved with the approach. The detection limit (LOD) was 0.3 μg mL−1, whereas the quantification limit (LOQ) was 1.0 μg mL−1. The analytical method was validated according to ICH and USP < 1225 > guidelines. For quality control, the method was exact, particular, linear, accurate, and resilient.
The Continued Mismeasurement of Plasma Serotonin: A Systematic Review
Authors: Pillalamarri Saketh , Anderson George M.
Published: February 2025

Studies reporting on the analysis of free plasma (platelet‐poor plasma, PPP) serotonin (5‐hydroxytryptamine, 5‐HT) in plasma obtained from healthy humans have been systematically reviewed. The review covered the period from 2010 to July 2024 and is a follow‐up of a similar review published in 2011 which found that nearly all published reported of PPP 5‐HT were clearly and markedly erroneously high. This problem has persisted unabated with nearly all retrieved 47 reports from the past 14 years also apparently being erroneously high. Possible causes and consequences of the problem are discussed along with potential approaches to improving the analysis and reporting of plasma 5‐HT. Most of the errors appear to arise from pre‐analytical problems that occur during the preparation of PPP due to residual platelets and/or due to the release of platelet 5‐HT. The large number of fields interested in plasma 5‐HT and the disparate publication venues appear to have contributed to a general lack of awareness of the difficulties with analyzing plasma 5‐HT. The reporting of erroneous plasma 5‐HT values has led to unsupported conclusions about possible alterations in plasma 5‐HT and about the role of plasma 5‐HT across a wide range of biomedical research areas.
Millennial Consumers' Intention to Purchase Organic Food: Do Environmental Concerns Matter?
Authors: Cavite Harry Jay M.
Published: February 2025

While the organic food market continues to grow globally, millennials' purchase intentions for organic products often lag behind their expressed interest in sustainability. This study investigates the factors influencing millennials' purchase intentions and examines the moderating role of environmental concerns in the organic food context, addressing business strategy gaps in leveraging environmental concerns for increased organic food consumption. Using a unified framework based on the theory of planned behaviour (TPB), data were collected from 499 millennial consumers through structured online surveys. Structural equation modelling (SEM) was employed to validate the proposed direct and moderating hypotheses. The results reveal that attitude, perceived behavioural control and trust in organic food are significant predictors of purchase intention. Moreover, environmental concerns moderate the relationship between subjective norms and purchase intention, suggesting that societal expectations combined with ecological awareness drive millennials toward sustainable consumption. This study offers a new lens to understand sustainable consumption patterns among younger generations globally and provides actionable insights for business managers to align sustainability strategies with evolving consumer preferences, particularly those of millennials. The findings highlight the importance of emphasising the environmental benefits of organic food, improving product accessibility and strengthening community engagement programs to drive sustainability, promote market growth promote market growth and reinforce trust in the organic food sector.
The Future of Circular Economy: Person‐Narrative and Scenario Planning on Self‐Sustained Circular Business Ecosystem in Minimizing Plastic Waste
Authors: Pambudi Noorhan Firdaus , Samarakoon Samindi M. K. , Ratnayake R. M. Chandima , Simatupang Togar Mangihut , Mulyono Nur Budi
Published: February 2025

This study focuses on plastic waste and the need for a circular economy approach to reduce its exploitation. The aim of the study is to explore alternative future scenarios for implementing a circular business ecosystem for plastic products or waste. The research uses scenario planning to address the uncertainty surrounding sustainability aspects. We conduct multiple interviews with individuals involved in plastic waste collection, recycling, and reduction. The study also creates personas through cluster analysis of questionnaire responses from 1000 respondents in six Indonesian regions. The research identifies four personas: the pure eco‐consumer, the market‐rational eco‐consumer, the exploitative consumer, and the eco‐consumer pragmatist. We use these personas to shape future scenarios for the circular business ecosystem, with a focus on consumer or community conditions. The research presents four scenarios for the future of plastic waste management: reducing plastic waste through a reuse model, recycling plastic waste for new material sources, recovering energy from plastic waste, and a throw‐away society. The findings emphasize the importance of safe working conditions and fair wages for waste workers, and they suggest that the private sector can contribute by formalizing public waste facilities. Policymakers and business initiators can use the research findings to develop policies and strategies that encourage the adoption of a circular economy business ecosystem for plastic waste management.
Tumor‐Associated Macrophages: Key Players in the Non‐Small Cell Lung Cancer Tumor Microenvironment
Authors: Lv Tongtong , Fan Rui , Wu Jiaqi , Gong Haolan , Gao Xiaoru , Liu Xin , Gong Yixin , Luo Bo , Zhang Yanhua , Peng Xiaochun , Liang Gai
Published: February 2025

Background

Lung cancer is among the most common and deadliest malignant tumors worldwide. It is often detected at late stages, resulting in unfavorable outcomes, with tumor cell heterogeneity and medication resistance. Tumor‐associated macrophages are among the key cells contributing to cancer progression. They are categorized into two primary phenotypes: Proinflammatory (M1) and anti‐inflammatory (M2) which are involved in the onset and progression of NSCLC. The role of common cytokines secreted by macrophages in the progression of lung cancer are described, and the effects of various substances such as RNA or protein on the differentiation and polarization of two phenotypes of macrophages are highlighted to characterize the impact of the immune state of tumors on therapeutic effect of treatments and patient prognosis. Researchers have primarily aimed to investigate innovative carriers and strategies based on macrophages to modify the tumor microenvironment.

Objectives

These approaches are often integrated with other treatments, particularly immunotherapy, to enhance therapeutic efficacy.

Methods

A comprehensive review was carried out by systematically synthesizing existing literature on PubMed, using the combination of the keywords “TAMs”, “NSCLC”, “Drug resistance”, and “therapy”. The available studies were screened for selection based on quality and relevance.

Conclusions

TAMs promote tumor invasion, growth, and metastasis by promoting angiogenesis and EMT. In addition, they contribute to the development of drug resistance and the immunosuppressive microenvironment establishment. The immunosuppressive factors secreted by TAM can weaken the activity of immune cells, inhibit their killing effect on tumors, leading to immune suppression and hindering the effectiveness of treatment. Therefore, TAM is a key target for the development of cancer immunotherapy. Various strategies are being explored, including reducing the recruitment of TAMs and influencing their polarization to treat NSCLC. In addition, TAMs based treatment systems can achieve precise delivery of drugs or gene interfering molecules without causing side effects.
Advances in Cytosolic Delivery of Proteins: Approaches, Challenges, and Emerging Technologies
Authors: Zhang Wenyan , Liu Huiling , Zhu Bingdong , Li Wen , Han Xue , Fu Jiaojiao , Luo Renjie , Wang Haiyan , Wang Jinxia
Published: February 2025

Although therapeutic proteins have achieved recognized clinical success, they are inherently membrane impermeable, which limits them to acting only on extracellular or membrane‐associated targets. Developing an efficient protein delivery method will provide a unique opportunity for intracellular target‐related therapeutic proteins. In this review article, we summarize the different pathways by which cells take up proteins. These pathways fall into two main categories: One in which proteins are transported directly across the cell membrane and the other through endocytosis. At the same time, important features to ensure successful delivery through these pathways are highlighted. We then provide a comprehensive overview of the latest developments in the transduction of covalent protein modifications, such as coupling cell‐penetrating motifs and supercharging, as well as the use of nanocarriers to mediate protein transport, such as liposomes, polymers, and inorganic nanoparticles. Finally, we emphasize the existing challenges of cytoplasmic protein delivery and provide an outlook for future progress.
JET EDGE Technique: Results of a Single‐Center Retrospective Study of Jetstream Atherectomy Using the Guidewire Bias Method for Eccentric Severely Calcified Lesions
Authors: Iwata Shuko , Tan Michinao , Miwa Takashi , Sasaki Wataru , Urasawa Kazushi
Published: February 2025

Background

The Jetstream device is an effective treatment option for debulking calcified lesions; however, it carries a risk of damaging the healthy vessel wall. This study aimed to evaluate the safety and efficacy of the Jetstream device combined with wire bias adjustments for treating eccentric calcified lesions.

Aims

The aim of this study was to evaluate the safety and efficacy of JET EDGE technique for treating eccentric calcified lesions.

Methods

This single‐center, retrospective, nonrandomized observational study was conducted at a cardiovascular department in Japan. It included patients aged ≥ 20 years with eccentric calcified lesions (Rutherford classification 3−6) who underwent endovascular therapy using the Jetstream catheter for femoropopliteal disease between October 2022 and September 2024.

Results

Twenty‐eight lesions in 28 patients (28.6% female; mean age: 76.9 ± 7.3 years) with a mean follow‐up period of 409 ± 174 days were analyzed. All lesions were graded 3 or 4 on the peripheral arterial calcium scoring system. The procedural success rate was 96.4%. No vascular perforations or medial layer damage were observed on imaging following the use of the Jetstream catheter. The 1‐year Kaplan–Meier estimates for primary patency, freedom from major adverse limb events, and freedom from target lesion revascularization were 88.6%, 88.1%, and 91.3%, respectively.

Conclusions

This retrospective study demonstrates that eccentric calcified lesions, which pose a risk of damaging the healthy vessel wall during treatment with the Jetstream catheter, can be safely treated by adjusting the wire bias during the procedure.
Onset of Fibromyalgia Symptoms Following Parvovirus B19 Infection: A Case Report and Review of the Literature
Authors: Nigro Angelo
Published: February 2025

This case report identifies parvovirus B19 as a potential trigger for fibromyalgia, underscoring the contribution of viral infections to the pathogenesis of chronic pain syndromes. Awareness of this association may prompt clinicians to consider infectious agents in the differential diagnosis of new‐onset fibromyalgia, facilitating timely recognition and personalized management strategies.
Sarcomatoid Hepatocellular Carcinoma: A Case Report and Review of Literature
Authors: Gao Bo , Liu Yan , Duan Wendu
Published: February 2025

Sarcomatoid hepatocellular carcinoma (SHC), which contains variable proportions of sarcomatous and carcinomatous components, is a rare variant of hepatocellular carcinoma and is a special variant of hepatocellular carcinoma. It is highly malignant, progresses rapidly, and has an extremely poor prognosis. However, the molecular pathogenesis of SHC remains unknown. We report a case of a 35‐year‐old male, previously healthy with no liver disease history, who presented with intermittent fever. Imaging examination during hospitalization revealed focal liver lesions. Without obvious surgical contraindications, right hemihepatectomy, cholecystectomy, and regional lymph node dissection were performed. Postoperative pathology and immunohistochemistry confirmed the diagnosis of SHC. However, due to the financial burden of the disease, the patient and his family chose traditional Chinese medicine as postoperative supplementary treatment rather than targeted drug combined with immunotherapy or other adjuvant therapies. Unfortunately, the patient passed away due to tumor recurrence 8 months after surgery.
Physicochemical Properties of New Ionic Liquids and Plastic Crystal Based on Huckel Anions
Authors: Sourjah Azra , Mikus Agnieszka , Forsyth Craig M. , Wieczorek Wladyslaw , O'Dell Luke A. , Pringle Jennifer M.
Published: February 2025

There is increasing interest in ionic liquid electrolytes for battery applications due to their potential as safer alternatives to conventional liquid electrolytes. By carefully selecting cations and anions, the physicochemical properties of these salts can be optimised. However, investigation of new cations and anions is still required to achieve the desired electrolyte properties such as high conductivity, electrochemical stability and low corrosivity. Thus, here a new series of room temperature ionic liquids (RTILs) and an organic ionic plastic crystal (OIPC) were synthesized and characterized based on N−ethyl−N−methylpyrrolidinium ([C2mpyr]+) and N−ethyl−N−methyloxazolidinium ([C2moxa]+) cations, paired with 4,5‐dicyano‐2‐(trifluoromethyl)imidazolide ([TDI]−) and 4,5‐dicyano‐2‐(pentafluoroethyl)imidazolide ([PDI]−) anions, forming [C2mpyr][TDI] (OIPC), [C2mpyr][PDI] (IL), [C2moxa][TDI] (IL), and [C2moxa][PDI] (IL). Thermal properties were analysed using DSC and TGA. The plastic phase of the OIPC [C2mpyr][TDI] is wide and spans most electrolyte application temperatures, extending from −40 to 56 °C. All salts exhibit thermal stability above 200 °C. The temperature dependence of the transport properties (viscosity, ionic conductivity, self‐diffusion coefficient) were measured and fitted by the Vogel‐Fulcher‐Tamman (VFT) equation, and the ionicity of the ILs is reported. The electrochemical stability windows of the salts were analysed by CV, and the [C2mpyr]+ cation‐based ILs showed the widest window of ~5 V.
Unveiling Quantum Coherence Effects in Modulating Electron Transfer in Platinum (II) Donor‐Acceptor‐Donor Systems
Authors: Li Juanjuan , Shi Yuqing , Cui Can , Li Yefan , Ruan Chenluwei , Cheng Tao
Published: February 2025

Quantum coherence effects (QCEs), arising from the interference of wave‐like amplitudes, are crucial in controlling the electron transfer function of molecular systems. Here, we report a coherence phenomenon associated with charge separation (CS) in a range of Pt (II) cis‐acetylide donor‐acceptor‐donor (D‐A‐D) systems, where the photogenerated Pt (III) center acts as an acceptor connecting two (R)phenothiazine (R = H or tBu) donors. Femtosecond transient absorption spectroscopy revealed that CS rates in D‐A‐D systems with double CS paths were accelerated by 4–8 times compared to their donor‐acceptor (D‐A) counterparts with a single path. An enhancement factor of 2–3 in electronic coupling, within the context of interference between CS paths, is derived, providing a clear signature of QCEs. This enhancementin CS processes closely correlates with the strength of coupling between donors. This study highlights the significant impact of QCEs on the photophysical properties of molecular systems and offers insights into charge and energy transport mechanisms in both natural and artificial systems.
Halogen Modulation and Physical Property Variation in Two Novel Mixed‐Cation Organic‐Inorganic Hybrid Perovskites†
Authors: Fu Xiaomei , Zhou Zining , Yang Yawen , He Lei , Mu Jie , Ye Qiong
Published: February 2025

Comprehensive Summary

Organic‐inorganic hybrid perovskites (OIHPs) offer precise control over material properties through the substitution of organic cations and halogens. In this study, two OIHPs, [(C6H10P)(n‐BA)]Sb2X9 ([C6H10P]+ = [Me3PCH2CH2CH3]+, [n‐BA]+ = n‐butylamine cation, X = I (1), Br (2)), were synthesized by varying halogens within a mixed‐cation system. The halogen substitution induced a shift from compound 1, which remains stable without phase transitions, to compound 2, which undergoes a ferroelastic phase transition (mmmF2/m). Compound 1 crystallizes in the non‐centrosymmetric Pca21 space group and demonstrates a second harmonic generation (SHG) response, while compound 2 displays elasticity in nanoindentation tests. Halogen substitution alters Sb—X bond lengths, inducing structural distortions in the inorganic framework and influencing the spatial configuration of organic cations and inorganic anions. These changes lead to distinct crystallization behaviors, resulting in different physical properties for compounds 1 and 2. This work contributes to the development of multifunctional materials based on halogen regulation in mixed‐cation OIHPs.
Recent Natural Product Total Syntheses Involving Cycloadditions of Allenes
Authors: Gu Chen‐Chen , Long Xiong‐En , Chen Xiuping , Liu Junyang , Li Chuang‐Chuang
Published: February 2025

Comprehensive Summary

Allenes, characterized by their cumulated carbon–carbon double bonds, have emerged as indispensable synthons in the construction of complex natural products. Their unique reactivity and stereochemical properties render allenes a powerful tool for the efficient and streamlined total synthesis of structurally intricate natural products. This review comprehensively summarizes the total syntheses of complex natural products involving allene cycloaddition reactions reported over the past decade (2014—2024). Among the nearly 20 total syntheses reviewed, the [2+1], [2+2], [3+2], [4+2], [4+3], [5+1] and [2+2+1] cycloaddition reactions of allenes are the most important transformations to construct the key skeleton. This is because of their ability to form multiple bonds in a single step with high atom economy, stereoselectivity, and regioselectivity, often under mild conditions. The strategic application of these reactions in forming key carbon–carbon bonds and controlling stereochemistry makes them practical for the efficient assembly of complex molecular frameworks. With the ongoing exploration of methods for allene generation, particularly the enantioselective approaches, and the continued discovery of novel cyclization reactions of allenes, allene chemistry will maintain its crucial and indispensable role in the total synthesis of natural products.

Key Scientists
Nickel‐Cobalt Bimetallic Strategy Enables Regioselective C8–H Alkylation of Polyaromatics with Inert Alkyl Chlorides
Authors: Song Wanbin , Shi Ximeng , Li Wen , Yao Shuang , Mao Yujian , Zhang Yinan
Published: February 2025

Comprehensive Summary

A regioselective C8−H alkylation of polyaromatics exampled with inert alkyl chloride is reported. The reaction proceeds via the synergistic participation of inexpensive transition metals nickel and cobalt. This approach enables the coupling of various substituted polyaromatic rings with a broad range of primary and secondary alkyl chlorides. Further synthetic applications provide a series of simple conversions to useful building blocks, suggesting its potency in the late‐stage functionalization of complex molecules. Mechanistic investigation illustrates that the reaction goes through a radical process with an unusual Ni(II)→Ni(III)→Ni(I) cycle being responsible for the rate‐determining C−H insertion of alkyl radicals, which are generated by the homolysis of chloroalkane with 2‐electrons oxidative addition of Co(I).