bluuebunny/crossref_metadata_2025 huggingface dataset:
From Batch to Continuous Flow Synthesis in Enzymatic Process Towards Molnupiravir
Authors: Hongnak Siriwat , Vorasin Onanong , Aunbamrung Pornthip , Techapanalai Saharat , Tiyasakulchai Thanat , Sonwong Watcharin , Jaito Nongluck , Thongpanchang Chawanee , Whungsinsujarit Saowalak , Srikun Onsiri , Srimongkolpithak Nitipol
Published: November 2024

Molnupiravir (1) is one among the limited therapeutic options for treating COVID‐19 infection and exhibits pan‐antiviral potency. Because of urgent demands during the COVID‐19 pandemic, a number of methods were developed to offer more efficient routes. In this report, we present a facile 2‐step and scalable synthesis of molnupiravir for batch processing and show the implementation of continuous flow biocatalysis to improve the efficiency in synthesis. Our key step entails immobilized lipase and isobutyric anhydride to facilitate regioselective esterification. In batch process, transamination of cytidine (2) provides N4‐hydroxycytidine (NHC, 3) with 75 % yield followed by esterification of NHC to give molnupiravir with 64 % yield, providing 48 % overall yield and 99.98 % purity (HPLC). Compared to batch approach in the esterification step, the continuous flow process provides similar product yield and purity and highlights the advantages including 2.42‐fold better productivity (mol/day), 2.47‐fold improved reaction time, and 30‐fold higher space‐time‐yield. The optimized batch and continuous flow biocatalysis enhance synthesis efficiency and reduce environmental impact, offering a sustainable approach for industrial molnupiravir production.
Covalent Organic Framework Controls the Aggregation of Metal Porphyrins for Enhanced Photocatalytic H2 Evolution
Authors: Han Yuesheng , Jin Yucheng , Yang Gengxiang , Ma Xiaolin , Wang Xinxin , Qi Dongdong , Wang Tianyu , Jiang Jianzhuang
Published: November 2024

Although different post modifications of covalent organic frameworks (COFs) have been developed for achieving hierarchical nanostructures and improved photocatalytic performance, the co‐assemblies of COFs with small organic molecules were still rarely studied. Herein, COF/porphyrin composites, which were fabricated at room temperature, reveal that COFs surface can modulate the aggregation of metal porphyrins, which subsequently enhance the photocatalytic properties of COFs assemblies. Thus, the surface of COFs was decorated by porphyrins aggregations with varied thickness, dependent on the metal ions of porphyrins. Ni(II) meso‐Tetra (4‐carboxyphenyl) porphine (NiTCPP) formed discontinuous monolayer covering on COFs surface, while Pt(II) meso‐Tetra (4‐carboxyphenyl) porphine (PtTCPP) or Co(II) meso‐Tetra (4‐carboxyphenyl) porphine (CoTCPP) aggregated into multilayer coverage. Notably, even though NiTCPP did not show any advantages in terms of light absorption or HOMO/LUMO energy levels, COF/NiTCPP with the lowest porphyrin loading still exhibited the highest photocatalytic H2 evolution (29.71 mmol g−1 h−1), which is 2.5 times higher than that of COF/PtTCPP or COF/CoTCPP. These results open new possibilities for making highly efficient photocatalysts upon the co‐assemblies of COFs with small organic molecules.
A novel looped functional for stability analysis of asynchronous sampled‐data systems
Authors: Park JunMin , Lee Seok Young
Published: November 2024

This paper is concerned with the stability analysis problems of asynchronous sampled‐data systems via an input‐delay approach. Between two sequential sampling times, a sampled‐data system is controlled by previously sampled states and thus can be modeled as a time‐delay system with a saw‐tooth delay. Inevitably, information at the sampling instants have played essential roles in controlling the systems and reducing the conservatism of the stability criteria. Therefore, to further utilize the information at sampling instants, this paper proposes novel looped functionals consisting of integral state variables and their interval‐normalized terms. Three numerical examples including a practical helicopter system demonstrate the effectiveness of the proposed approaches in terms of allowable sampling intervals.
Skillful seasonal prediction of the boreal summer Pacific–Japan teleconnection pattern
Authors: Yi Kan , Wang Chenqi , Zhang Yunfei , Li Xiang , Wang Jian , Wen Renqiang , Du Mengjiao
Published: November 2024

The Pacific–Japan (PJ) teleconnection pattern, a dominant mode of atmospheric variability over the western North Pacific during boreal summer, is pivotal in shaping regional climate dynamics. Despite its important implications, accurately predicting the PJ pattern remains challenging due to inherent model biases and uncertainties. This study delves into the impact of model biases on the prediction skill of the PJ pattern and evaluates its predictability using outputs from three operational seasonal forecast models. Our findings elucidate that the spatial structure of the PJ pattern simulated by models introduces substantial diversities in prediction skills. By discerning the variance in PJ teleconnection simulation among models, we unveil the high predictability of the PJ pattern, showcasing its capability for accurate forecasts up to 3 months in advance within the current seasonal forecast models. The predictability of the PJ pattern stems from concurrent El Niño–Southern Oscillation‐related sea surface temperature anomalies and its corresponding atmospheric teleconnection processes. Our research underscores the necessity of accounting for model biases in predicting the PJ pattern, and the potential for bolstering seasonal prediction skill through targeted mitigation of these biases.
On a New Point Process Approach to Reliability Improvement Modeling for Repairable Systems
Authors: Finkelstein Maxim , Cha Ji Hwan
Published: November 2024

In this paper, we are the first to consider the combination of the minimal repair with the defined better than minimal repair. With a given probability, each failure of a repairable system is minimally repaired and with complementary probability it is better than minimally repaired. The latter can be interpreted in terms of a reliability growth model when a defect of a system is eliminated on each failure. It turns out that the better than minimal repair can be even better than a perfect one if a perfect repair is understood as a replacement of the whole system or stochastically equivalent operation. We provide stochastic description of the failure/repair process by introducing and describing the corresponding bivariate point process via the concept of stochastic intensity. Distributions for the number of failures for the pooled and marginal processes are derived along with their expected values. The latter can describe the process of reliability growth in applications. Some meaningful special cases are discussed.
Intense Red Fluorescence From Surface Traps in BaSO4:V5+, Eu3+ and Its Applications
Authors: Varalakshmi S. , Lakshmanan Arunachalam , Sangeetha L. , Rathinamala V.
Published: November 2024

BaSO4:V5+ synthesized at 1000°C in air exhibits an intense emission band peaking at 495 nm from surface traps assisted by atmospheric oxygen on excitation at 350 nm due to charge transfer from O2− to V5+ in the (VO4)3− tetrahedral complex. BaSO4:Eu synthesized under similar conditions exhibits both Eu2+ (375 nm) and Eu3+ (619 nm) fluorescence. Vanadium codoping quenches the Eu2+ fluorescence but enhances the Eu3+ fluorescence in BaSO4:V, Eu due to charge compensation. However, Eu codoping quenches the vanadium fluorescence by diffusion of vanadium into the crystal, and V2O5 also serves as a flux enhancing Eu3+ doping efficiency in BaSO4 lattice. The 619nm Eu3+ PL emission intensity in BaSO4:V5+, Eu3+ is comparable to 592nm emission from commercial (Y,Gd) BO3:Eu3+. However, V5+ emission shows strong thermal quenching, while Eu3+ emission shows little thermal quenching up to 210°C, making BaSO4:V5+, Eu3+ a promising new red phosphor for improving the color rendering of blue light‐based white LED. The ratio of Eu3+ to V5+ fluorescence increases with excitation temperature (30°C°C–180°C) enabling BaSO4:V5+, Eu3+ to be used as a non‐contact luminescence thermometer.
The Impact of Board Gender Diversity Commitment on Firm Performance Moderated by Board Characteristics: Evidence From Sustainable European Firms and Financial Orientation
Authors: Bel‐Oms Inmaculada , Grau‐Grau Alfredo J. , Núñez‐Almonte Janny
Published: November 2024

The main goal of this study is to explore the moderating role of board gender diversity on the relationship between CEO duality, board size, board meetings, and firm performance in sustainable companies. This study examines the 120 most sustainable European firms listed in the EuroNext Vigeo Europe 120 Index from 2012 to 2021, with the findings showing that board gender diversity negatively moderates the relationship between CEO duality and firm performance, while positively moderating board meetings' impact. Furthermore, in banking‐oriented countries, board gender diversity positively moderates the relationship between board meetings and firm performance, while these effects are not significant in market‐oriented countries. The paper highlights that despite progress in increasing representation, mechanisms to ensure effective female participation in board decision‐making are required. This study is the first to examine how board gender diversity moderates the impact of board characteristics and CEO duality on sustainable firm performance in different financial orientations.
Highly Conjugated Ergosterols With Anti‐Influenza Virus Activity From the Marine‐Derived Fungus Eutypella Sp. F0219
Authors: Chen Meng‐Ting , Chen Han‐Yu , Luo Yan‐Fang , Zhou Jing , Yang Jing‐Jing , Jiang Zhong‐Ping , Huang Ling
Published: November 2024

One rare 15‐nor‐cadinane sesquiterpenoid (1), one new chromene amide derivative (2), and one new highly conjugated ergosterol steroid (3), along with three known compounds (4–6), were isolated from the marine‐derived fungus Eutypella sp. F0219. Their chemical structures, including absolute configurations, were established by HR–ESIMS, extensive 1D and 2D NMR investigations, and electronic circular dichroism (ECD) calculations. All compounds were evaluated for their anti‐influenza A virus and anti‐influenza B virus activities against the A/PR/8/34 (H1N1), ZX1109 (H1N1, oseltamivir‐resistant virus), HK68 (H3N2), and B/Florida/78/2015 strains. Compounds 3 and 4 showed significant antiviral activities against those four virus strains with EC50 values ranging from 2.07 to 11.3 µM. Most notably, compound 3 exhibited potent anti‐influenza B virus activity against B/Florida/78/2015 strain with EC50 value of 2.27 ± 1.76 µM, versus the postive control (oseltamivir, EC50 = 7.14 ± 1.94 µM).
Improving Retinoic Acid Efficacy: Lipase‐Catalyzed Synthesis of Derivatives with Antiviral Activity
Authors: Bravo Sofía C. , Montalbetti Carlos A. , Freije García Fabricio , Petrera Erina , Liñares Guadalupe García
Published: November 2024

An efficient enzymatic approach was applied to the synthesis of new derivatives of retinoic acid. Nine derivatives, four of them new compounds, were obtained through lipase‐catalysis with excellent yield. In order to find the optimal reaction conditions, the influence of various parameters such as enzyme source, nucleophile : substrate ratio, enzyme : substrate ratio, solvent and temperature was studied. The excellent results obtained by lipase catalysis made the procedure very efficient considering their advantages such as mild reaction conditions and low environmental impact. In addition, several synthesized compounds exhibited lower cytotoxicity than the retinoic acid in Vero cells and a remarkably higher antiviral activity against Herpes simplex virus type 1 (HSV‐1) and Herpes simplex virus type 2 (HSV‐2).
Antigen Presentation in an Artificial and Cell Membrane: Blood Group A Glycan Recognition
Authors: Ryzhov Ivan , Tuzikov Alexander , Obukhova Polina , Sablina Marina , Popova Inna , Anisimova Darya , Galanina Oxana , Shilova Nadezhda , Khaidukov Sergey , Chizhov Alexander , Henry Stephen , Bovin Nicolai
Published: November 2024

Glycosphingolipids (GSL) are functionally important components of the cell membrane and recognition of their glycan “head” by the immune system is a key part of normal and pathological processes. Recognition of glycolipid antigens on a living cell, their structure, “context” (microenvironment and clustering), presentation including orientation and distance from the plasma membrane, as well as molecular dynamics are important. GSL antigens are targets for the development of anticancer vaccines and therapeutic antibodies, therefore, control of the presentation of their glycans by synthetic methods opens up new possibilities in medicine. In this work, we synthesized 13 GSL analogues as function‐spacer‐lipids (FSLs) with the same head (blood group A tetrasaccharide, ABO system) but each either differing in the structure of the lipid tail, or the length of the region between the head and the tail, or cluster organization of the head (from 2 to 4 tetrasaccharides in a cluster). The insertion of these FSLs into an artificial and erythrocyte membranes was compared, and their interaction with antibodies was studied, including erythrocyte agglutination. The results give further insight into knowledge of the membrane presentation of GSLs (some results can be extrapolated to glycoproteins) and factors involved in their interaction with antibodies.
Colonic leiomyosarcoma with lung metastasis or lung cancer: A case report
Authors: Song Tongkun , Xu Kai , Xing JiaDi , Liu Maoxing , Tan Fei , Su Xiangqian
Published: November 2024

Key Clinical Message

Colonic leiomyosarcoma is a tumor with a very low incidence and a high metastasis rate, mainly lung metastasis. This report provides insights into the future treatment. Thoracic puncture is necessary for patients with pulmonary nodules.
Transient Kinetic Investigation of Chain Growth and the Accumulation of Surface Carbon During CO Hydrogenation on Cobalt Catalysts
Authors: Gäßler Max , Hermann Simon , Friedland Jens , Stahl Jakob , Mädler Lutz , Güttel Robert
Published: November 2024

CO hydrogenation is a promising approach for the storage of renewable energy in the form of hydrocarbons via the Fischer–Tropsch synthesis (FTS). Since transient operation of FTS reactors might be necessary and even be beneficial, transient kinetics for a rational catalyst and reactor design are essential. In order to advance the development of such transient kinetics, the periodic transient kinetics (PTK) method was applied to the CO hydrogenation on a Co/TiO2 catalyst under FT‐like conditions. It was revealed that there are two carbon species of different reactivity, Cα and Cβ, present on the catalyst surface during the reaction. Cα forms fast, within a few seconds, and is highly reactive. Whereas Cβ forms slowly, is accumulating on the surface over a longer time, and imposes an inhibiting effect. The results indicate an important role of the Cβ species to chain growth and the formation of C2+ products. Finally, the transient experimental results were evaluated based on a material balance and the amounts of Cα and Cβ present on the catalyst surface during the reaction were determined.
Influence of Ionic Liquid Film Thickness and Flow Rate on Macrocyclization Efficiency and Selectivity in Supported Ionic Liquid‐Liquid Phase Catalysis
Authors: Högler Marc , Kobayashi Takeshi , Kraus Hamzeh , Atwi Boshra , Buchmeiser Michael R. , Fyta Maria , Hansen Niels
Published: November 2024

Supported ionic‐liquid phase (SILP) technology in a biphasic setting with n‐heptane as the transport phase was applied to the Ru‐alkylidene‐N‐heterocyclic carbene (NHC) catalyzed macrocyclization of α,ω‐dienes to elucidate the effect of ionic liquid (IL)‐film thickness, flow rate as well as substrate and product concentration on macrocyclization efficiency, and Z‐selectivity. To understand the molecular‐level behavior of the substrates and products at the n‐heptane/IL interphase, atomistic molecular dynamics simulations were conducted and correlated with experimental observations. The thickness of the IL layer strongly influences the Z/E ratio of the products in that a thin IL layer favors higher Z/E ratios by confining the catalyst between the pore wall and the liquid‐liquid interphase whereas a thick IL layer favors formation of the E‐product and Ru‐hydride catalyzed isomerization reactions. Also, macrocyclization efficiency, expressed by the ratio of oligomers/macromonocycle (O/MMC), is influenced both by the flow rate and the thickness of the IL layer.
NIR Diradical‐Featured Croconaine Nanoagent for Cancer Photoacoustic Imaging and Photothermal Therapy
Authors: Tang Yiru , Li Wanying , Zhou Xiaoling , Hao Na , Zhou Xia , Zhong Zhirong , Jian Yao , Wei Siping , Zheng Xiuli , Yang Lin
Published: November 2024

Radical‐featured organic materials usually demonstrate significantly narrower bandgap than that of regular organic materials, which is beneficial for near‐infrared (NIR) absorption and non‐radiative decay process, making them good candidates for photothermal agents (PTAs) of photothermal therapy (PTT). However, most organic radicals are too short‐lived to be separated and stable. Herein, a stable pyrylium‐croconaine (CR) dye CR845 with high diradical character was synthesized and assembled into CR845 nanoparticles (NPs) to explore the photoacoustic imaging (PAI) and photothermal therapeutic performance under NIR irradiation in vitro and in vivo. CR845 exhibited a stable NIR absorption at 845 nm (ϵ=3.37×105 L mol−1 cm−1) and a relatively high photothermal conversion efficiency (PCE) of 58.8 %. When assembled into nanoparticles, CR845 NPs showed good photostability, good biocompatibility, favorable NIR photoacoustic potential, effective cancer cell killing and complete tumor elimination upon 850 nm laser irradiation. The work demonstrates a diradical‐featured CR PTA with favorable PAI/PTT effects, which can help to provide new ideas for the development of NIR PTAs, and further promote the application of organic radical materials in the field of biomedicine.
Molecular Engineering of Covalent Organic Frameworks for Photocatalytic Hydrogen Evolution from Water
Authors: Su Jie , Li Ping , Duan Feng , Chen Yuxiang , Zhou Yida , Shen Mao , Zhang Li , Ren Shi‐Bin , Chen Mengyang
Published: November 2024

Covalent organic frameworks (COFs) have demonstrated significant potential as photocatalysts for efficiently generating hydrogen through photocatalytic water splitting. However, the design of COFs with distinct organic unit blocks at a molecular level profoundly influences their photocatalytic performance. In this study, we synthesized a series of β‐ketoamine COFs through molecular engineering of nitrogen sites, including phenyl‐structured TpBD, phenylpyridine‐structured TpPpy, phenylpyrimidine‐structured TpPpm, and bipyridine‐structured TpBpy. Advanced characterization techniques reveal that TpPpm and TpBpy with more nitrogen sites exhibit superior efficiencies in electron transfer and charge separation compared to TpBD and TpPpy, thereby endowing them with enhanced photocatalytic performance for hydrogen evolution from water. As a result, the photocatalytic hydrogen production rates of TpPpm (33.80 mmol g−1 h−1) and TpBpy (29.18 mmol g−1 h−1) surpass those of TpBD (20.82 mmol g−1 h−1) and TpPpy (27.49 mmol g−1 h−1). Additionally, due to the different plane symmetries between Ppm and Bpy resulting from the various positions of nitrogen sites, TpPpm displays superior photochemical properties and better photocatalytic performance compared to TpBpy. Moreover, theoretical calculation results further confirm the exceptional intramolecular charge transfer ability of TpPpm among all COFs. This work underscores the significance of precisely controlling N sites in COFs for designing high‐performance photocatalysts.
From a P‐Bridging Phosphaketene to μ‐Phosphinidenide and μ‐Diphosphaurea Units at a Dinickel Core
Authors: Schulz Roland A. , Karaca Uhut S. , Diefenbach Martin , Werthmann Niclas J. A. , Dechert Sebastian , Hansmann Max M. , Holthausen Max C. , Meyer Franc
Published: November 2024

Salt metathesis of dinickel(II) complex LNi2Br (1; L is a dinucleating pyrazolate ligand with two β‐diketiminato chelate arms) with Na(OCP) ⋅ (dioxane)2.5 yielded LNi2(PCO) (2) with a P‐bridging phosphaethynolate. Further reaction of 2 with benzyl isocyanide or with an N‐heterocyclic carbene (NHC) triggered decarbonylation and gave LNi2(PCN‐CH2Ph) (3) and LNi2P(NHC) (4) with P‐bridging cyanophosphide and NHC‐phosphinidenide, respectively. Electronic structure analysis indicated a μ2‐η2 : η1 binding mode of the PCO− anion between the two NiII ions in 2, which is even more pronounced for the [PCN(−CH2Ph)]− anion in 3. DFT assessment of the formation mechanism of 4 showed that attack at the phosphaketene‐C atom is kinetically preferred but reversible and unproductive, while kinetically more demanding back‐side SN2 attack at the phosphaketene‐P atom triggers CO release with 4 as thermodynamic product. Nucleophilic addition at the phosphaketene‐C could be demonstrated by the strongly exergonic reaction of 2 with KPPh2, giving unstable K[LNi2(P(O)CPPh2)] (5) with a P‐bridging and K+‐stabilized diphosphaurea derivative. All new complexes 2–5 have been comprehensively characterized, including by X‐ray diffraction.
Temperature‐Driven Axial‐Equatorial Isomerism and Magnetic Relaxation on Low‐Spin Co(II) Borohydride Complexes
Authors: Wang Jing‐Yu , Li Zhen , Zhang Lu , Chen Yan‐Cong , Ruan Ze‐Yu , Du Shan‐Nan , Deng Wei , Wu Si‐Guo , Liu Jun‐Liang , Tong Ming‐Liang
Published: November 2024

Comprehensive Summary

Crystalline materials with diastereomerism serve as ideal prototypes for investigating the influence of coordination environments on chemophysical properties. In this study, we synthesized a pair of axial‐equatorial isomers [Co(II)(HB(timtBu)3)(cis‐dppen)](BF4)·solv ([HB(timtBu)3]− = hydrotris(3‐tertbutyl‐2‐thioxoimidazol‐1‐yl)borate; cis‐dppen = cis‐1,2‐bis(diphenylphosphino)ethene; solv = 0.5THF·2H2O and 2H2O for ax‐CoHS2P2 and eq‐CoHS2P2, respectively), by varying the crystallization temperatures. Despite both diastereoisomers adopting distorted square pyramidal geometries, the bidentate cis‐dppen ligand chelates to the central Co(II) either in an axial‐equatorial or equatorial‐equatorial manner, with a boron‐hydrogen binding to the metal center. Magnetic studies reveal differences in g‐values between these axial‐equatorial isomers. X‐band electron paramagnetic resonance spectra suggest rapid equilibrium and potential conformational interconversion in response to temperature changes in solution. Magnetic measurements indicate field‐induced slow relaxation of magnetization in this low‐spin S = 1/2 system, with spin‐lattice relaxations dominated by Raman and quantum tunneling of magnetization mechanisms due to the absence of thermally populated excited states.
Long‐term follow‐up of a phase 2 study of all‐trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia
Authors: Jen Wei‐Ying , Marvin‐Peek Jennifer , Kantarjian Hagop M. , Alvarado Yesid , Borthakur Gautam , Jabbour Elias , Wierda William , Kadia Tapan M. , Daver Naval G. , DiNardo Courtney D. , Short Nicholas J. , Jain Nitin , Ferrajoli Alessandra , Kornblau Steven , Yilmaz Musa , Ohanian Maro , McCue David , Burger Jan , Hammond Danielle , Patel Keyur , Issa Ghayas C. , Pemmaraju Naveen , Sasaki Koji , Maiti Abhishek , Abbas Hussein A. , Chien Kelly , Takahashi Koichi , Haddad Fadi , Bose Prithviraj , Masarova Lucia , Montalban‐Bravo Guillermo , Swaminathan Mahesh , Brandt Mark , Pierce Sherry , Garcia‐Manero Guillermo , Ravandi Farhad
Published: November 2024

Background

All‐trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard‐risk acute promyelocytic leukemia (APL). Herein, the authors update their long‐term results with the regimen of ATO‐ATRA and gemtuzumab ozogamicin (GO) in standard‐risk and high‐risk APL.

Methods

This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6–9 mg/m2 was added for high‐risk patients and for standard‐risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO‐ATRA, with GO for patients who had PML::RARA persistence.

Results

One hundred forty‐six patients (median age, 53.0 years; range, 19.3–83.9 years) were treated, including 106 patients (72.6%) with standard‐risk APL and 40 (27.4%) with high‐risk APL. GO was administered to 68 standard‐risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%–98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow‐up of 61.8 months (95% CI, 4.7–128.4 months), the 5‐year event‐free survival, disease‐free survival, and overall survival rates were 92.4% (95% CI, 87.9%–97.1%), 93.6% (95% CI, 89.5%–97.8%), and 93.1% (95% CI, 88.9%–97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno‐occlusive disease.

Conclusions

The combination of ATO‐ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).
Understanding Ion‐specific “Hofmeister” Effects in Enzyme Catalysis through using RNase A as a Paradigm Model
Authors: Taghavi Shahraki Bahareh , Khajehpour Mazdak
Published: November 2024

Biophysical studies in the last two decades have clearly demonstrated that salts affect biomolecules in an ion‐specific manner (i. e., Hofmeister Effects). Studies performed upon such diverse biological processes such as protein folding, protein precipitation, protein coacervation and phase separation, and protein oligomerization, have all shown that this ion specificity is directly related to how individual ions interact with biomolecular surfaces. Interestingly, although ion‐specific effects upon enzyme catalytic processes are well‐known in the literature, a molecular level description of these effects has not yet been made available. For example, it is not clear whether ion‐specific effects observed in enzyme catalysis are directly related to how ions modulate the enzyme's folding free energy, or not. This work attempts to address this need by investigating ion‐specific effects upon the enzymatic activity and folding free energy of a well‐characterized enzyme system, Ribonuclease A (RNase A). To this end we have developed a robust framework to analyze and quantify ion‐specific effects upon the RNase A catalyzed phosphate ring opening reaction of cCMP (Cytidine 2′:3′‐cyclic monophosphate monosodium salt). Our studies show that both the folding thermodynamics and the Michaelis‐Menten kinetic parameters of this enzyme show ion‐specific salt dependence. However, even through salt addition affects the folding free energy and enzyme catalysis of RNase A in an ion‐specific manner, these effects are not necessarily directly related to each other. Ion‐specific effects observed in protein folding reflects mostly how an individual ion interacts with the overall protein surface; while alternatively, ion‐specific effects on enzyme activity indicate how a given ion interacts with the enzyme active site surface or alternatively, how ions interact with the substrate molecule as represented by changes in the substrate thermodynamic activity coefficient.
Understanding the Reactivity and Selectivity of Oxazaborolidium Ion‐Catalyzed Diels‐Alder Reactions Involving Cyclobutenones as Dienophiles
Authors: Portela Susana , Fernández Israel
Published: November 2024

The poorly understood factors controlling the reactivity and selectivity (both stereo‐ and enantioselectivity) of catalyzed Diels‐Alder reactions involving cyclobutenones as dienophiles have been analyzed in detail by means of Density Functional Theory calculations. To this end, the reactions with cyclopentadiene and furan as dienes and 3‐(methoxycarbonyl)cyclobutenone catalyzed by Corey's chiral oxazaborolidium ion (COBI) have been selected and compared to their analogous uncatalyzed transformations. The combined Activation Strain Model of reactivity and Energy Decomposition Analysis methods have been used to quantitatively understand the acceleration and selectivity induced by the catalyst in this reaction.
French‐Speaking Network of Pharmacogenetics (RNPGx) Recommendations for Clinical Use of Mavacamten
Authors: Lebreton Louis , Boyer Jean‐Christophe , Lafay‐Chebassier Claire , Hennart Benjamin , Baklouti Sarah , Cunat Séverine , Vilquin Paul , Medard Yves , Gautier‐Veyret Elodie , Laffitte‐Redondo Clara , Verstuyft Céline , Ait Tayeb Abd El Kader , Haufroid Vincent , Wils Julien , Lamoureux Fabien , Evrard Alexandre , Davaze‐Schneider Julie , Ben‐Sassi Mouna , Picard Nicolas , Quaranta Sylvie , Ayme‐Dietrich Estelle ,   the French‐Speaking Network of Pharmacogenetics (RNPGx)
Published: November 2024

Mavacamten, the first drug in the class of β‐cardiac myosin modulator, is used for the treatment of patients with hypertrophic cardiomyopathy. This orally administered drug demonstrates wide interpatient variability in pharmacokinetics parameters, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 poor metabolizers have increased exposure and are at increased risk of reduced cardiac hypercontractility. To ensure the safety of all patients, European Medicines Agency recommends CYP2C19 preemptive genotyping, and consecutively, to adapt maintenance and initial mavacamten doses, and to manage drug–drug interactions, according to CYP2C19 phenotype. In this article, we summarize evidence from the literature supporting the association between CYP2C19 phenotype and pharmacological features of mavacamten and provide, beyond biologic guidelines, therapeutic recommendations for the use of mavacamten based on CYP2C19 and CYP3A4/CYP3A5 genotype.
Molecular Engineering for Future Thermoelectric Materials: The Role of Electrode and Metal Components in Molecular Junctions
Authors: Park Jiwoo , Park Sohyun
Published: November 2024

As global temperatures increase due to climate change, the accumulation of excess heat on Earth presents a valuable resource that can be harnessed for electricity generation using thermoelectric materials. However, the intricate structures of bulk thermoelectric materials pose significant challenges to their comprehensive understanding and limit performance. Additionally, their relatively high production costs present practical obstacles. A promising solution to these issues lies in molecular control and the use of molecular junctions. Molecules are predicted to surpass the performance of existing bulk materials in energy conversion because they can be chemically tuned to achieve high thermoelectric efficiencies. This review identifies the thermoelectric parameters that affect the performance of molecular junctions. It also explores various experimental platforms for measuring thermoelectric performance from single molecules to assemblies of hundreds of molecules. Finally, it highlights recent advancements in thermoelectric molecular junctions, focusing on the crucial roles of electrodes and metal components within the molecules, such as Ru complexes, metalloporphyrins, metallocenes, conjugated silane wires, and endohedral metallofullerenes. Ultimately, our review provides a comprehensive analysis of strategies to enhance the thermoelectric efficiency of molecular junctions.
CircSpna2 attenuates cuproptosis by mediating ubiquitin ligase Keap1 to regulate the Nrf2‐Atp7b signalling axis in depression after traumatic brain injury in a mouse model
Authors: Du Mengran , Fu Jiayuanyuan , Zhang Jie , Zhu Ziyu , Huang Xuekang , Tan Weilin , Liu Lian , Huang Zhijian , Liu Xin , Tan Qiuhao , Liao ZhengBu , Cheng Yuan
Published: November 2024

Background

Depression is a common but often overlooked consequence in individuals with post‐traumatic brain injury (TBI). Circular RNAs (circRNAs) play essential roles in the nervous system, yet their involvement in the cell death mechanism known as cuproptosis and in TBI‐related depression remains unclear.

Objectives

This study aimed to investigate the role of circRNA, specifically circSpna2, in the regulation of cuproptosis and its association with depression in TBI patients.

Methods

RNA sequencing (RNA‐Seq) was used to assess the differential expression of circRNAs. Depression was evaluated using subjective and objective rating scales, and circSpna2 expression levels in plasma were measured. Further functional experiments were conducted in TBI mouse models, including knockdown and overexpression of circSpna2, to explore its impact on the Keap1‐Nrf2‐Atp7b pathway and cuproptosis.

Results

TBI patients exhibited decreased levels of circSpna2, which correlated with depression (p < 0.0001). Knocking down circSpna2 in TBI mice aggravated depression‐like symptoms (p < 0.0001). Mechanistically, circSpna2 was found to bind ubiquitin ligase Keap1, modulating the Nrf2‐Atp7b signaling pathway and influencing cuproptosis (docking score: −331.88). Overexpression of circSpna2 alleviated cuproptosis after TBI through the Keap1/Nrf2/Atp7b axis.

Conclusions

CircSpna2 plays a regulatory role in cuproptosis and may serve as a novel biomarker and therapeutic target for depression following TBI. Enhancing circSpna2 expression could mitigate depression after TBI by modulating the Keap1/Nrf2/Atp7b pathway.

Key points

This study explores the role of circSpna2 in depression following traumatic brain injury (TBI). It was found that circSpna2 is significantly downregulated in TBI patients, and its expression levels correlate with depressive symptoms. In TBI mouse models, overexpression of circSpna2 alleviated depression‐like behaviours, while its knockdown exacerbated these symptoms, suggesting its potential as both a biomarker and a therapeutic target for post‐TBI depression. Mechanistically, circSpna2 regulates the Nrf2‐Atp7b signalling pathway by binding to the DGR domain of Keap1, which prevents Nrf2 ubiquitination and enhances Nrf2 activity. This in turn promotes the transcription of Atp7b, a copper transport protein, helping to maintain copper homeostasis and mitigate copper‐induced oxidative stress, a key protein of cell death (cuproptosis). The overexpression of circSpna2 also improved mitochondrial function and synaptic integrity, which are typically impaired by copper dysregulation. These findings highlight the therapeutic potential of circSpna2 in managing TBI‐related depression through the regulation of oxidative stress and copper homeostasis.
A Serial Sampling Closed‐Loop System for Transceiver Beam Nulling
Authors: Yang Lei , Yang Dongdong , Wang Yuexian
Published: November 2024

Considering the limited space, power of the unmanned platform, and the inconsistency of the antenna array transceiver beam pattern, we design a serial sampling closed‐loop system for transceiver beam nulling, which has a strong robustness and global convergence. It is mathematically proved that the serial sampling closed‐loop system is capable of adaptively nulling jamming signals by analyzing the system mathematical model for the first time. Our work addresses the issue that the existing transceiver system on unmanned platforms cannot estimate the directions of arrival (DOAs) of jamming signals causing the transmit beam not to be nulled in the DOAs of jammers. Simulation results show that the proposed system can be applied in scenarios with strictly limitations on space, weight, and power (SWaP) to suppress jamming signals when receiving desired signals while covering the transmissions.
Compact UWB Slot Antenna With Dual‐Circular Polarization and Improvement of CP Performance
Authors: Soleimani Leili , Zehforoosh Yashar , Asadpor Loghman
Published: November 2024

This study presents an ultrawideband (UWB) slot antenna with a dual‐circular (left‐ and right‐hand) circular polarization. The presented circularly polarized (CP) antenna involves 45° oriented patches cooperating with I‐ and L‐shaped stubs fed by a directional coupler. Using a directional coupler produces orthogonal electric fields to generate CP operation, and as a result of the cooperation between patches and stubs, antenna CP performance is improved. The fabricated antenna, including two microstrip ports, occupies an area of 50 × 50 × 1.016 mm3. By stimulating each antenna port independently, it is possible to obtain right‐hand circular polarization (RHCP) and left‐hand circular polarization (LHCP). The experiments show that the antenna being presented has an operating frequency of 116.14% (2.87–10.82 GHz) and an axial ratio bandwidth of 33.97% (7.11–10.02 GHz). Furthermore, a stable radiation pattern was also measured for the antenna, which had a maximum gain of 2.77 dBic in the operating frequency band.
Adaptative Variation in a Neotropical Dung Beetle: Females and Gamma Males Present Tunneler Morphology, While Beta and Alpha Males Present Wing Morphology for Velocity
Authors: de Oliveira Ribeiro Pedro Henrique , Camargo Nicholas Ferreira , Frizzas Marina Regina
Published: November 2024

In evolutionary terms, plastic traits can covary, providing adaptive value by compensating for certain characteristic costs or enhancing fitness. This combination of traits is expected in species with significant intrapopulation ecological variation, like insects. In the Phanaeini tribe, males and females have distinct nesting behaviors, and the alpha, beta, and gamma morphotypes of trimorphic males display different reproductive strategies. Although phenotypic integration of wings and protibiae associated with horn size occurs in dung beetles, this study focuses on the morphological and functional variation of these and other structures due to behavioral differences and reproductive strategies between sexes and male morphotypes. We used a geometric and functional morphometric approach to investigate the variation in plasticity of structures (clypeus, protibia, elytra, and membranous wing), their integration with horn size in males, and flight biomechanics in the trimorphic dung beetle Oxysternon palemo (Scarabaeinae: Phanaeini). Comparing different sexes and morphotypes, we tested for significant differences associated with various reproductive and behavioral strategies. Adaptive morphological differences were found in all structures in at least three of the four groups (females and alpha, beta, and gamma males), along with clear sexual dimorphism in the protibia. In alpha males, fossorial structures enhance resource partitioning and confrontations, whereas in females and gamma males, these structures optimize digging and tunnel mobility. We also found integration between the size of pronotal horns and clypeus shape, and between head horn size and wing shape. The variation in elytra morphology, covariation between membranous wings and horns, and flight biomechanics results suggests different reproductive investment and foraging strategies among groups. Alpha and beta males invest in intense flights and rapid resource colonization, whereas gamma males exhibit slower, low‐energy flights with greater reproductive investment. We discuss how trade‐offs between dispersal and reproduction in polyphenic insects shape adaptive variation through plasticity in dung beetle morphotypes.
Levels of Sex Steroids in Plethodontid Salamanders: A Comparative Study Within the Genus Aneides
Authors: Staub Nancy L. , Hayes Stephen G. , Mendonca Mary T.
Published: November 2024

Derived monomorphism is a condition in which males and females are phenotypically similar, but the similarity is derived. Derived monomorphism typically evolves from sexual dimorphism or from a different monomorphic state. We examined the hormonal basis of derived monomorphism in the salamander genus Aneides (Plethodontidae). We reject our hypothesis that circulating levels of androgens explain the derived traits, such as enlarged jaw musculature, in females (some would call them “male‐like traits”). There was no clear pattern of differences in androgen levels or degree of dimorphism in androgen levels, between the sexually dimorphic Aneides hardii and the other, derived monomorphic, species studied. Concentrations of testosterone and dihydrotestosterone were higher in males than in females in all species examined. The degree of sexual dimorphism in androgen level was also consistent among the species studied. Levels of androgens in female plethodontids have not been previously reported.
Parent‐Specific Transgenerational Immune Priming Enhances Offspring Defense—Unless Heat Stress Negates It All
Authors: Schneider Ralf F. , Dubin Arseny , Marten Silke‐Mareike , Roth Olivia
Published: November 2024

Transgenerational immune priming (TGIP) adjusts offspring's immune responses based on parental immunological experiences. It is predicted to be adaptive when parent–offspring environmental conditions match, while mismatches negate those advantages, rendering TGIP potentially costly. We tested these cost–benefit dynamics in the pipefish Syngnathus typhle (Syngnathidae). Because of their unique male pregnancy, egg production and rearing occur in different sexes, providing both parents multiple avenues for TGIP. Parental bacteria exposure in our pipefish was simulated through vaccinations with heat‐killed Vibrio aestuarianus before mating the fish to each other or to controls. The resulting offspring were exposed to V. aestuarianus in control or heat stress environments, after which transcriptome and microbiome compositions were investigated. Transcriptomic TGIP effects were only observed in Vibrio‐exposed offspring at control temperatures, arguing for low costs of TGIP in non‐matching microbiota environments. Transcriptomic phenotypes elicited by maternal and paternal TGIP had limited overlap and were not additive. Parentally induced transcriptomic responses were associated with immune functions, and specifically, the paternal response to the innate immune branch, possibly hinting at trained immunity. TGIP of both parents reduced the relative abundance of the experimental Vibrio in exposed offspring, showcasing its ecological benefits. Despite TGIP's significance in matching biotic environments, no TGIP‐associated phenotypes were observed for heat‐treated offspring, illustrating its limitations. Heat spikes caused by climate change thus threaten TGIP benefits, potentially increasing susceptibility to emerging marine diseases. We demonstrate the urgent need to understand how animals cope with climate‐induced changes in microbial assemblages to assess their vulnerability in light of climate change.
The Cost of Self‐Defense: Browsing Effects in the Rare Plant Species Salix arizonica
Authors: Lencioni Shannon J. , Massatti Rob , Keefover‐Ring Ken , Holeski Liza M.
Published: November 2024

Coevolution between plants and their animal predators has led to diverse defensive adaptations. Multiple theories of defense propose that there are resource allocation costs associated with producing chemical defenses. One leading hypothesis, optimal defense theory (ODT), suggests that natural selection will result in the allocation of resources to defenses that optimize the cost‐to‐benefit ratio between defense and other functional processes. The population decline of the rare subalpine wetland species, Arizona willow (Salix arizonica), has been attributed to various biotic and abiotic factors, with browsing from wild and domestic ungulates as a significant concern for at least three decades. In a field experiment using natural populations, we compare the relationship between phytochemical defense and height in Arizona willows with and without long‐term protection from browsing via browse exclosures. Consistent with the predictions of ODT, individuals with physical protection from ungulate browsing for multiple years had significantly lower phenolic glycoside (PG) concentrations and increased plant height compared to unprotected individuals. A similar pattern was found across all individuals, whereby total PG concentration and height were negatively correlated. In a short‐term experiment in natural populations, changes in levels of defense were not observed when plants received protection for only one growing season. The contrasting pattern of defense plasticity in response to long‐term versus short‐term physical protection suggests a differential plastic response in this long‐lived species. Delayed reduction in PG concentration may serve as a benefit to avoid mismatches between environmental cues and responses. Our research sheds light on the intricate dynamics between plant‐defense strategies, environmental pressures, and evolutionary adaptations in shaping plant–browser interactions.
Temporal Dynamics of Species Richness and Composition in a Peri‐Urban Tropical Frog Community in Central Brazil
Authors: Severgnini Marcos R. , de Oliveira Mônica M. , Valério Luciana M. , Provete Diogo B.
Published: November 2024

Analyzing the temporal dynamics of ecological communities can shed light on coexistence mechanisms and help understand how populations and communities will behave in the face of climate change. However, little is known about how frog communities respond to climate in urban ecosystems, especially in tropical countries. Here, we analyzed how frog species richness and abundance are influenced by weather variables both intra‐ and inter‐annually. We surveyed a peri‐urban area in central Brazil, monthly for 3 years. To test the effect of weather variables on species richness and abundance, we used Generalized Additive Mixed‐effects Models. We assessed seasonality using circular statistics. We also tested for differences in temporal beta diversity within and among years by estimating species disappearance and temporal rank shift, in addition to a multivariate model‐based method to test the effect of year on species composition. Finally, we tested how taxonomic and phylogenetic alpha diversity changed through time using a novel approach based on Hill numbers. We found that species richness varied little among years and was affected only by photoperiod, while species abundance was more variable both between and within years, being mostly affected by humidity, temperature, and photoperiod. Species composition varied little between years, mostly between the first and subsequent years. Conversely, beta diversity was highest within years. Only the effective number of species changed significantly through time. Our results help not only understand temporal mechanisms that allow species coexistence, but also allow to make inferences about the impact of urbanization on biodiversity in recently urbanized landscapes, showing that species composition in peri‐urban sites remains unaltered in a mid‐timescale, especially when climate conditions change little across years.