bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower Thermospheric Temperature Response to Geomagnetic Activity at High Latitudes
Authors: Yamazaki Y. , Stolle C. , Stephan C. , Mlynczak M. G.
Published: June 2024

The magnetosphere‐ionosphere‐thermosphere system is externally driven by the energy input from the solar wind. A part of the solar wind energy deposited in the magnetosphere during geomagnetically active periods dissipates into the thermosphere. Previous studies have reported temperature perturbations in the lower thermosphere during geomagnetic storms. The present study aims to assess the climatological spatial pattern of the lower thermospheric response to geomagnetic activity at high latitudes based on 21 years of temperature measurements by the SABER (Sounding of the Atmosphere using Broadband Emission Radiometry) instrument onboard the TIMED (Thermosphere Ionosphere Mesosphere Energetics and Dynamics) satellite and their comparison with the recently developed half‐hourly geomagnetic activity index Hp30. The temperature response to geomagnetic activity, evaluated at different seasons and altitudes, is better organized in magnetic coordinates than in geographic coordinates. At 110 km, the temperature increases with Hp30 at all magnetic local times, but with a prominent dusk‐dawn asymmetry in the magnitude. That is, the temperature variation per unit Hp30 is larger in the dusk sector than in the dawn sector. At 106 km, the response in the dawn sector is further reduced or even negative. These results provide observational evidence to support earlier theoretical predictions; according to which, both storm‐induced vertical wind and Joule heating contribute to the temperature increase in the dusk sector, while in the dawn sector, the vertical wind acts to cool the air and thus counteracts Joule heating.
Diffusive‐Convection Staircase Merger Events Mediated by Subsurface Eddies in the Canada Basin
Authors: Chai Xia , Zhou Sheng‐Qi , Wang Yan
Published: June 2024

Diffusive‐convection (DC) staircases, characterized by interleaving well‐mixed layers and high‐gradient interfaces of thermohaline properties, are commonly observed in the Canada Basin, Arctic. Previous studies suggested a quasi‐steady state of the thermohaline structures of these staircases. In this work, we employ mooring and Ice‐Tethered Profiler (ITP) data to show emergent merger events of staircases mediated by subsurface eddies with warm cores located at 300–500 m depths in 2005, 2007 and 2009. Two types of merger events, the B‐merger (resulting from strengthening of stronger interfaces at the expense of weaker ones) and the H‐merger (produced by vertical drift and collision of staircase interfaces), are documented during the passage of subsurface eddies. The merging staircases are located at 320–450 m depths, with layers of up to 70 m thick and high‐gradient interfaces thinner than 5 m. Mooring measurements reveal the emergence of staircase mergers associated with a background Richardson number dropping from a typical magnitude of – to , indicating the persistence of DC staircases in the presence of strong shears. In parallel, ITP data suggest the formation of B‐mergers (H‐mergers) to be favored within the eddy core (flank). The vertical heat fluxes associated with the B‐merger (H‐merger) staircases are estimated to be ∼3 W/m2 (∼1.5 W/m2), which substantially exceed the typical staircase‐driven heat fluxes of W/m2. These observations imply the significance of subsurface eddies in shaping the halocline structures and thus the vertical heat fluxes in the Arctic Ocean, particularly in a warming climate.
TNIP3 protects against pathological cardiac hypertrophy by stabilizing STAT1
Authors: Shi Hongjie , Yu Yongjie , Li Dajun , Zhu Kun , Cheng Xu , Ma Tengfei , Tao Zhangqian , Hong Ying , Liu Zhen , Zhou Siyi , Zhang Jianqing , Chen Yun , Zhang Xiao-Jing , Zhang Peng , Li Hongliang
Published: June 2024

Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. Here, we identified the first evidence that TNFAIP3 interacting protein 3 (TNIP3) was a negative regulator of pathological cardiac hypertrophy. We observed a significant upregulation of TNIP3 in mouse hearts subjected to transverse aortic constriction (TAC) surgery and in primary neonatal rat cardiomyocytes stimulated by phenylephrine (PE). In Tnip3-deficient mice, cardiac hypertrophy was aggravated after TAC surgery. Conversely, cardiac-specific Tnip3 transgenic (TG) mice showed a notable reversal of the same phenotype. Accordingly, TNIP3 alleviated PE-induced cardiomyocyte enlargement in vitro. Mechanistically, RNA-sequencing and interactome analysis were combined to identify the signal transducer and activator of transcription 1 (STAT1) as a potential target to clarify the molecular mechanism of TNIP3 in pathological cardiac hypertrophy. Via immunoprecipitation and Glutathione S-transferase assay, we found that TNIP3 could interact with STAT1 directly and suppress its degradation by suppressing K48-type ubiquitination in response to hypertrophic stimulation. Remarkably, preservation effect of TNIP3 on cardiac hypertrophy was blocked by STAT1 inhibitor Fludaradbine or STAT1 knockdown. Our study found that TNIP3 serves as a novel suppressor of pathological cardiac hypertrophy by promoting STAT1 stability, which suggests that TNIP3 could be a promising therapeutic target of pathological cardiac hypertrophy and heart failure.
Epigenetic roles of KDM3B and KDM3C in tumorigenesis and their therapeutic implications
Authors: Yoo Jung , Kim Go Woon , Jeon Yu Hyun , Lee Sang Wu , Kwon So Hee
Published: June 2024

Advances in functional studies on epigenetic regulators have disclosed the vital roles played by diverse histone lysine demethylases (KDMs), ranging from normal development to tumorigenesis. Most of the KDMs are Jumonji C domain-containing (JMJD) proteins. Many of these KDMs remove methyl groups from histone tails to regulate gene transcription. There are more than 30 known KDM proteins, which fall into different subfamilies. Of the many KDM subfamilies, KDM3 (JMJD1) proteins specifically remove dimethyl and monomethyl marks from lysine 9 on histone H3 and other non-histone proteins. Dysregulation of KDM3 proteins leads to infertility, obesity, metabolic syndromes, heart diseases, and cancers. Among the KDM3 proteins, KDM3A has been largely studied in cancers. However, despite a number of studies pointing out their importance in tumorigenesis, KDM3B and KDM3C are relatively overlooked. KDM3B and KDM3C show context-dependent functions, showing pro- or anti-tumorigenic abilities in different cancers. Thus, this review provides a thorough understanding of the involvement of KDM3B and KDMC in oncology that should be helpful in determining the role of KDM3 proteins in preclinical studies for development of novel pharmacological methods to overcome cancer.
Myelin-reactive B cells exacerbate CD4+ T cell-driven CNS autoimmunity in an IL-23-dependent manner
Authors: Fazazi Mohamed Reda , Doss Prenitha Mercy Ignatius Arokia , Pereira Resel , Fudge Neva , Regmi Aryan , Joly-Beauparlant Charles , Akbar Irshad , Yeola Asmita Pradeep , Mailhot Benoit , Baillargeon Joanie , Grenier Philippe , Bertrand Nicolas , Lacroix Steve , Droit Arnaud , Moore Craig S. , Rojas Olga L. , Rangachari Manu
Published: June 2024

B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH[MOG] mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG[35-55], IgH[MOG] mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH[MOG] meninges and by CD4+ T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH[MOG] CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH[MOG] mice. In the CNS parenchyma and dura mater of IgH[MOG] mice, we observe an increased frequency of CD4+PD-1+CXCR5- T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH[MOG] mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner.
Catalytic [4+2]- and [4+4]-cycloaddition using furan-fused cyclobutanone as a privileged C4 synthon
Authors: Hong Kemiao , Liu Mengting , Qian Lixin , Bao Ming , Chen Gang , Jiang Xinyu , Huang Jingjing , Xu Xinfang
Published: June 2024

Cycloaddition reactions play a pivotal role in synthetic chemistry for the direct assembly of cyclic architectures. However, hurdles remain for extending the C4 synthon to construct diverse heterocycles via programmable [4+n]-cycloaddition. Here we report an atom-economic and modular intermolecular cycloaddition using furan-fused cyclobutanones (FCBs) as a versatile C4 synthon. In contrast to the well-documented cycloaddition of benzocyclobutenones, this is a complementary version using FCB as a C4 reagent. It involves a C-C bond activation and cycloaddition sequence, including a Rh-catalyzed enantioselective [4 + 2]-cycloaddition with imines and an Au-catalyzed diastereoselective [4 + 4]-cycloaddition with anthranils. The obtained furan-fused lactams, which are pivotal motifs that present in many natural products, bioactive molecules, and materials, are inaccessible or difficult to prepare by other methods. Preliminary antitumor activity study indicates that 6e and 6 f exhibit high anticancer potency against colon cancer cells (HCT-116, IC50 = 0.50 ± 0.05 μM) and esophageal squamous cell carcinoma cells (KYSE-520, IC50 =  0.89 ± 0.13 μM), respectively.
Rapid summer Russian Arctic sea-ice loss enhances the risk of recent Eastern Siberian wildfires
Authors: Luo Binhe , Luo Dehai , Dai Aiguo , Xiao Cunde , Simmonds Ian , Hanna Edward , Overland James , Shi Jiaqi , Chen Xiaodan , Yao Yao , Duan Wansuo , Liu Yimin , Zhang Qiang , Xu Xiyan , Diao Yina , Jiang Zhina , Gong Tingting
Published: June 2024

In recent decades boreal wildfires have occurred frequently over eastern Siberia, leading to increased emissions of carbon dioxide and pollutants. However, it is unclear what factors have contributed to recent increases in these wildfires. Here, using the data we show that background eastern Siberian Arctic warming (BAW) related to summer Russian Arctic sea-ice decline accounts for ~79% of the increase in summer vapor pressure deficit (VPD) that controls wildfires over eastern Siberia over 2004-2021 with the remaining ~21% related to internal atmospheric variability associated with changes in Siberian blocking events. We further demonstrate that Siberian blocking events are occurring at higher latitudes, are more persistent and have larger zonal scales and slower decay due to smaller meridional potential vorticity gradients caused by stronger BAW under lower sea-ice. These changes lead to more persistent, widespread and intense high-latitude warming and VPD, thus contributing to recent increases in eastern Siberian high-latitude wildfires.
Redirecting electron flow in Acetobacterium woodii enables growth on CO and improves growth on formate
Authors: Moon Jimyung , Poehlein Anja , Daniel Rolf , Müller Volker
Published: June 2024

Anaerobic, acetogenic bacteria are well known for their ability to convert various one-carbon compounds, promising feedstocks for a future, sustainable biotechnology, to products such as acetate and biofuels. The model acetogen Acetobacterium woodii can grow on CO2, formate or methanol, but not on carbon monoxide, an important industrial waste product. Since hydrogenases are targets of CO inhibition, here, we genetically delete the two [FeFe] hydrogenases HydA2 and HydBA in A. woodii. We show that the ∆hydBA/hydA2 mutant indeed grows on CO and produces acetate, but only after a long adaptation period. SNP analyzes of CO-adapted cells reveal a mutation in the HycB2 subunit of the HydA2/HydB2/HydB3/Fdh-containing hydrogen-dependent CO2 reductase (HDCR). We observe an increase in ferredoxin-dependent CO2 reduction and vice versa by the HDCR in the absence of the HydA2 module and speculate that this is caused by the mutation in HycB2. In addition, the CO-adapted ∆hydBA/hydA2 mutant growing on formate has a final biomass twice of that of the wild type.
Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development
Authors: Dwivedi Deepanjali , Dumontier Dimitri , Sherer Mia , Lin Sherry , Mirow Andrea M. C. , Qiu Yanjie , Xu Qing , Liebman Samuel A. , Joseph Djeckby , Datta Sandeep R. , Fishell Gord , Pouchelon Gabrielle
Published: June 2024

During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian “fire together, wire together” precept. However, select connections, essential for circuit development, are transient. They are effectively connected early in development, but strongly diminish during maturation. The mechanisms by which transient connectivity recedes are unknown. To investigate this process, we characterize transient thalamocortical inputs, which depress onto somatostatin inhibitory interneurons during development, by employing optogenetics, chemogenetics, transcriptomics and CRISPR-based strategies in mice. We demonstrate that in contrast to typical activity-dependent mechanisms, transient thalamocortical connectivity onto somatostatin interneurons is non-canonical and involves metabotropic signaling. Specifically, metabotropic-mediated transcription, of guidance molecules in particular, supports the elimination of this connectivity. Remarkably, we found that this process impacts the development of normal exploratory behaviors of adult mice.
Evolution of STAT2 resistance to flavivirus NS5 occurred multiple times despite genetic constraints
Authors: Veit Ethan C. , Salim Madihah S. , Jung Mariel J. , Richardson R. Blake , Boys Ian N. , Quinlan Meghan , Barrall Erika A. , Bednarski Eva , Hamilton Rachael E. , Kikawa Caroline , Elde Nels C. , García-Sastre Adolfo , Evans Matthew J.
Published: June 2024

Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences.
Structure of an RNA G-quadruplex from the West Nile virus genome
Authors: Terrell J. Ross , Le Thao T. , Paul Ananya , Brinton Margo A. , Wilson W. David , Poon Gregory M. K. , Germann Markus W. , Siemer Jessica L.
Published: June 2024

Potential G-quadruplex sites have been identified in the genomes of DNA and RNA viruses and proposed as regulatory elements. The genus Orthoflavivirus contains arthropod-transmitted, positive-sense, single-stranded RNA viruses that cause significant human disease globally. Computational studies have identified multiple potential G-quadruplex sites that are conserved across members of this genus. Subsequent biophysical studies established that some G-quadruplexes predicted in Zika and tickborne encephalitis virus genomes can form and known quadruplex binders reduced viral yields from cells infected with these viruses. The susceptibility of RNA to degradation and the variability of loop regions have made structure determination challenging. Despite these difficulties, we report a high-resolution structure of the NS5-B quadruplex from the West Nile virus genome. Analysis reveals two stacked tetrads that are further stabilized by a stacked triad and transient noncanonical base pairing. This structure expands the landscape of solved RNA quadruplex structures and demonstrates the diversity and complexity of biological quadruplexes. We anticipate that the availability of this structure will assist in solving further viral RNA quadruplexes and provides a model for a conserved antiviral target in Orthoflavivirus genomes.
Solvent concentration at 50% protein unfolding may reform enzyme stability ranking and process window identification
Authors: Sorgenfrei Frieda A. , Sloan Jeremy J. , Weissensteiner Florian , Zechner Marco , Mehner Niklas A. , Ellinghaus Thomas L. , Schachtschabel Doreen , Seemayer Stefan , Kroutil Wolfgang
Published: June 2024

As water miscible organic co-solvents are often required for enzyme reactions to improve e.g., the solubility of the substrate in the aqueous medium, an enzyme is required which displays high stability in the presence of this co-solvent. Consequently, it is of utmost importance to identify the most suitable enzyme or the appropriate reaction conditions. Until now, the melting temperature is used in general as a measure for stability of enzymes. The experiments here show, that the melting temperature does not correlate to the activity observed in the presence of the solvent. As an alternative parameter, the concentration of the co-solvent at the point of 50% protein unfolding at a specific temperature T in short $${c}_{{U}_{50}}^{T}$$

c

U

50

T

is introduced. Analyzing a set of ene reductases, $${c}_{{U}_{50}}^{T}$$

c

U

50

T

is shown to indicate the concentration of the co-solvent where also the activity of the enzyme drops fastest. Comparing possible rankings of enzymes according to melting temperature and $${c}_{{U}_{50}}^{T}$$

c

U

50

T

reveals a clearly diverging outcome also depending on the specific solvent used. Additionally, plots of $${c}_{{U}_{50}}$$

c

U

50

versus temperature enable a fast identification of possible reaction windows to deduce tolerated solvent concentrations and temperature.
Subsurface A-site vacancy activates lattice oxygen in perovskite ferrites for methane anaerobic oxidation to syngas
Authors: He Jiahui , Wang Tengjiao , Bi Xueqian , Tian Yubo , Huang Chuande , Xu Weibin , Hu Yue , Wang Zhen , Jiang Bo , Gao Yuming , Zhu Yanyan , Wang Xiaodong
Published: June 2024

Tuning the oxygen activity in perovskite oxides (ABO3) is promising to surmount the trade-off between activity and selectivity in redox reactions. However, this remains challenging due to the limited understanding in its activation mechanism. Herein, we propose the discovery that generating subsurface A-site cation (Lasub.) vacancy beneath surface Fe-O layer greatly improved the oxygen activity in LaFeO3, rendering enhanced methane conversion that is 2.9-fold higher than stoichiometric LaFeO3 while maintaining high syngas selectivity of 98% in anaerobic oxidation. Experimental and theoretical studies reveal that absence of Lasub.-O interaction lowered the electron density over oxygen and improved the oxygen mobility, which reduced the barrier for C-H bond cleavage and promoted the oxidation of C-atom, substantially boosting methane-to-syngas conversion. This discovery highlights the importance of A-site cations in modulating electronic state of oxygen, which is fundamentally different from the traditional scheme that mainly credits the redox activity to B-site cations and can pave a new avenue for designing prospective redox catalysts.
Quantifying soil accumulation of atmospheric mercury using fallout radionuclide chronometry
Authors: Landis Joshua D. , Obrist Daniel , Zhou Jun , Renshaw Carl E. , McDowell William H. , Nytch Christopher J. , Palucis Marisa C. , Del Vecchio Joanmarie , Montano Lopez Fernando , Taylor Vivien F.
Published: June 2024

Soils are a principal global reservoir of mercury (Hg), a neurotoxic pollutant that is accumulating through anthropogenic emissions to the atmosphere and subsequent deposition to terrestrial ecosystems. The fate of Hg in global soils remains uncertain, however, particularly to what degree Hg is re-emitted back to the atmosphere as gaseous elemental mercury (GEM). Here we use fallout radionuclide (FRN) chronometry to directly measure Hg accumulation rates in soils. By comparing these rates with measured atmospheric fluxes in a mass balance approach, we show that representative Arctic, boreal, temperate, and tropical soils are quantitatively efficient at retaining anthropogenic Hg. Potential for significant GEM re-emission appears limited to a minority of coniferous soils, calling into question global models that assume strong re-emission of legacy Hg from soils. FRN chronometry poses a powerful tool to reconstruct terrestrial Hg accumulation across larger spatial scales than previously possible, while offering insights into the susceptibility of Hg mobilization from different soil environments.
Difluoroester solvent toward fast-rate anion-intercalation lithium metal batteries under extreme conditions
Authors: Wang Yao , Dong Shuyu , Gao Yifu , Lee Pui-Kit , Tian Yao , Meng Yuefeng , Hu Xia , Zhao Xin , Li Baohua , Zhou Dong , Kang Feiyu
Published: June 2024

Anion-intercalation lithium metal batteries (AILMBs) are appealing due to their low cost and fast intercalation/de-intercalation kinetics of graphite cathodes. However, the safety and cycliability of existing AILMBs are constrained by the scarcity of compatible electrolytes. Herein, we showcase that a difluoroester can be applied as electrolyte solvent to realize high-performance AILMBs, which not only endows high oxidation resistance, but also efficiently tunes the solvation shell to enable highly reversible and kinetically fast cathode reaction beyond the trifluoro counterpart. The difluoroester-based electrolyte demonstrates nonflammability, high ionic conductivity, and electrochemical stability, along with excellent electrode compatibility. The Li| |graphite AILMBs reach a high durability of 10000 cycles with only a 0.00128% capacity loss per cycle under fast-cycling of 1 A g−1, and retain ~63% of room-temperature capacity when discharging at −65 °C, meanwhile supply stable power output under deformation and overcharge conditions. The electrolyte design paves a promising path toward fast-rate, low-temperature, durable, and safe AILMBs.
Ligand control of regioselectivity in palladium-catalyzed heteroannulation reactions of 1,3-Dienes
Authors: Rodina Dasha , Vaith Jakub , Paradine Shauna M.
Published: June 2024

Olefin carbofunctionalization reactions are indispensable tools for constructing diverse, functionalized scaffolds from simple starting materials. However, achieving precise control over regioselectivity in intermolecular reactions remains a formidable challenge. Here, we demonstrate that using PAd2nBu as a ligand enables regioselective heteroannulation of o-bromoanilines with branched 1,3-dienes through ligand control. This approach provides regiodivergent access to 3-substituted indolines, showcasing excellent regioselectivity and reactivity across a range of functionalized substrates. To gain further insights into the origin of selectivity control, we employ a data-driven strategy, developing a linear regression model using calculated parameters for phosphorus ligands. This model identifies four key parameters governing regioselectivity in this transformation, paving the way for future methodology development. Additionally, density functional theory calculations elucidate key selectivity-determining transition structures along the reaction pathway, corroborating our experimental observations and establishing a solid foundation for future advancements in regioselective olefin difunctionalization reactions.
Data-driven approaches linking wastewater and source estimation hazardous waste for environmental management
Authors: Xie Wenjun , Yu Qingyuan , Fang Wen , Zhang Xiaoge , Geng Jinghua , Tang Jiayi , Jing Wenfei , Liu Miaomiao , Ma Zongwei , Yang Jianxun , Bi Jun
Published: June 2024

Industrial enterprises are major sources of contaminants, making their regulation vital for sustainable development. Tracking contaminant generation at the firm-level is challenging due to enterprise heterogeneity and the lack of a universal estimation method. This study addresses the issue by focusing on hazardous waste (HW), which is difficult to monitor automatically. We developed a data-driven methodology to predict HW generation using wastewater big data which is grounded in the availability of this data with widespread application of automatic sensors and the logical assumption that a correlation exists between wastewater and HW generation. We created a generic framework that used representative variables from diverse sectors, exploited a data-balance algorithm to address long-tail data distribution, and incorporated causal discovery to screen features and improve computation efficiency. Our method was tested on 1024 enterprises across 10 sectors in Jiangsu, China, demonstrating high fidelity (R² = 0.87) in predicting HW generation with 4,260,593 daily wastewater data.
A safe and potentiated multi-type HPV L2-E7 nanoparticle vaccine with combined prophylactic and therapeutic activity
Authors: Zhao Xueer , Zhang Yueru , Trejo-Cerro Oscar , Kaplan Ecem , Li Zhe , Albertsboer Femke , El Hammiri Neyla , Mariz Filipe Colaço , Banks Lawrence , Ottonello Simone , Müller Martin
Published: June 2024

Persistent infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers. There are six licensed prophylactic vaccines available against HPV, but none of them shows any significant therapeutic effect on pre-existing infections or lesions. Thus, a prophylactic vaccine also endowed with therapeutic activity would afford protection regardless of the vaccine recipients HPV-infection status. Here, we describe the refinement and further potentiation of a dual-purpose HPV nanoparticle vaccine (hereafter referred to as cPANHPVAX) relying on eight different HPV L2 peptide epitopes and on the E7 oncoantigens from HPV16 and 18. cPANHPVAX not only induces anti-HPV16 E7 cytotoxic T-cell responses in C57BL/6 mice, but also anti-HPV18 E7 T-cell responses in transgenic mice with the A2.DR1 haplotype. These cytotoxic responses add up to a potent, broad-coverage humoral (HPV-neutralizing) response. cPANHPVAX safety was further improved by deletion of the pRb-binding domains of E7. Our dual-purpose vaccine holds great potential for clinical translation as an immune-treatment capable of targeting active infections as well as established HPV-related malignancies, thus benefiting both uninfected and infected individuals.
Bridge RNAs direct programmable recombination of target and donor DNA
Authors: Durrant Matthew G. , Perry Nicholas T. , Pai James J. , Jangid Aditya R. , Athukoralage Januka S. , Hiraizumi Masahiro , McSpedon John P. , Pawluk April , Nishimasu Hiroshi , Konermann Silvana , Hsu Patrick D.
Published: June 2024

Genomic rearrangements, encompassing mutational changes in the genome such as insertions, deletions or inversions, are essential for genetic diversity. These rearrangements are typically orchestrated by enzymes that are involved in fundamental DNA repair processes, such as homologous recombination, or in the transposition of foreign genetic material by viruses and mobile genetic elements1,2. Here we report that IS110 insertion sequences, a family of minimal and autonomous mobile genetic elements, express a structured non-coding RNA that binds specifically to their encoded recombinase. This bridge RNA contains two internal loops encoding nucleotide stretches that base-pair with the target DNA and the donor DNA, which is the IS110 element itself. We demonstrate that the target-binding and donor-binding loops can be independently reprogrammed to direct sequence-specific recombination between two DNA molecules. This modularity enables the insertion of DNA into genomic target sites, as well as programmable DNA excision and inversion. The IS110 bridge recombination system expands the diversity of nucleic-acid-guided systems beyond CRISPR and RNA interference, offering a unified mechanism for the three fundamental DNA rearrangements—insertion, excision and inversion—that are required for genome design.
Chemical reservoir computation in a self-organizing reaction network
Authors: Baltussen Mathieu G. , de Jong Thijs J. , Duez Quentin , Robinson William E. , Huck Wilhelm T. S.
Published: June 2024

Chemical reaction networks, such as those found in metabolism and signalling pathways, enable cells to process information from their environment1,2. Current approaches to molecular information processing and computation typically pursue digital computation models and require extensive molecular-level engineering3. Despite considerable advances, these approaches have not reached the level of information processing capabilities seen in living systems. Here we report on the discovery and implementation of a chemical reservoir computer based on the formose reaction4. We demonstrate how this complex, self-organizing chemical reaction network can perform several nonlinear classification tasks in parallel, predict the dynamics of other complex systems and achieve time-series forecasting. This in chemico information processing system provides proof of principle for the emergent computational capabilities of complex chemical reaction networks, paving the way for a new class of biomimetic information processing systems.
VHEE FLASH sparing effect measured at CLEAR, CERN with DNA damage of pBR322 plasmid as a biological endpoint
Authors: Wanstall Hannah C. , Korysko Pierre , Farabolini Wilfred , Corsini Roberto , Bateman Joseph J. , Rieker Vilde , Hemming Abigail , Henthorn Nicholas T. , Merchant Michael J. , Santina Elham , Chadwick Amy L. , Robertson Cameron , Malyzhenkov Alexander , Jones Roger M.
Published: June 2024

Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as ‘FLASH’. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.08 Gy/s), intermediate (96 Gy/s) and ultra-high dose rates (UHDR, (2 × 109 Gy/s) at the CERN Linear Electron Accelerator (CLEAR) user facility. UHDRs were used to determine if the biological FLASH effect could be measured in the plasmid model, within a hydroxyl scavenging environment. Two different concentrations of the hydroxyl radical scavenger Tris were used in the plasmid environment to alter the proportions of indirect damage, and to replicate a cellular scavenging capacity. Indirect damage refers to the interaction of ionising radiation with molecules and species to generate reactive species which can then attack DNA. UHDR irradiated plasmid was shown to have significantly reduced amounts of damage in comparison to conventionally irradiated, where single strand breaks (SSBs) was used as the biological endpoint. This was the case for both hydroxyl scavenging capacities. A reduced electron energy within the VHEE range was also determined to increase the DNA damage to pBR322 plasmid. Results indicate that the pBR322 plasmid model can be successfully used to explore and test the effect of UHDR regimes on DNA damage. This is the first study to report FLASH sparing with VHEE, with induced damage to pBR322 plasmid DNA as the biological endpoint. UHDR irradiated plasmid had reduced amounts of DNA single-strand breaks (SSBs) in comparison with conventional dose rates. The magnitude of the FLASH sparing was a 27% reduction in SSB frequency in a 10 mM Tris environment and a 16% reduction in a 100 mM Tris environment.
Lead-free Cs2Ag1−xNaxIn1 − yBiyCl6 perovskite films with broad warm-yellow emission for lighting applications
Authors: Wang Haiyan , Chen Jin , Sun Yu , Wang Fengchao , Yang Jing , Zhang Canyun , Kong Jinfang , Li Lan
Published: June 2024

Lead-free halide double perovskite Cs2AgInCl6 has been extensively studied in recent years due to the lead toxicity and poor stability of common lead halide perovskites. In this study, sodium (Na+) and bismuth (Bi3+) doped into Cs2AgInCl6 double perovskite, then Cs2Ag1−xNaxIn1 − yBiyCl6 films with broadband warm-yellow emissions were achieved by the blade coating method. Herein, Na and Bi content were changed as variables at a series of parameter optimization experiments, respectively. In the Cs2Ag1−xNaxIn1 − yBiyCl6 systems, Na+ broke the parity-forbidden transition of Cs2AgInCl6, and Bi3+ suppressed non-radiative recombination. The partial replacement of Ag+ with Na+ ions and doping with Bi3+ cations were crucial for increasing the intensity of the PL emission. The experimental results showed that the photoluminescence quantum yield of the Cs2Ag0.4Na0.6In0.8Bi0.2Cl6 film was 66.38%, which was the highest data among all samples. It demonstrated remarkable stability under heat and ultraviolet conditions. After five thermal cycles, the PL intensity of the Cs2Ag0.4Na0.6In0.8Bi0.2Cl6 film is only reduced to approximately 5.7% of the initial value. After 720 h continuous ultraviolet irradiation, there occurred 31.9% emission decay of the film.
Introducing the antibacterial and photocatalytic degradation potentials of biosynthesized chitosan, chitosan–ZnO, and chitosan–ZnO/PVP nanoparticles
Authors: Aouadi Abdelatif , Hamada Saud Djamila , Rebiai Abdelkrim , Achouri Abdelhak , Benabdesselam Soulef , Mohamed Abd El-Mordy Fatma , Pohl Pawel , Ahmad Sheikh F. , Attia Sabry M. , Abulkhair Hamada S. , Ararem Abderrahmane , Messaoudi Mohammed
Published: June 2024

The development of nanomaterials has been speedily established in recent years, yet nanoparticles synthesized by traditional methods suffer unacceptable toxicity and the sustainability of the procedure for synthesizing such nanoparticles is inadequate. Consequently, green biosynthesis, which employs biopolymers, is gaining attraction as an environmentally sound alternative to less sustainable approaches. Chitosan-encapsulated nanoparticles exhibit exceptional antibacterial properties, offering a wide range of uses. Chitosan, obtained from shrimp shells, aided in the environmentally friendly synthesis of high-purity zinc oxide nanoparticles (ZnO NPs) with desirable features such as the extraction yield (41%), the deacetylation (88%), and the crystallinity index (74.54%). The particle size of ZnO NPs was 12 nm, while that of chitosan–ZnO NPs was 21 nm, and the bandgap energies of these nanomaterials were 3.98 and 3.48, respectively. The strong antibacterial action was demonstrated by ZnO NPs, chitosan–ZnO NPs, and chitosan–ZnO/PVP, particularly against Gram-positive bacteria, making them appropriate for therapeutic use. The photocatalytic degradation abilities were also assessed for all nanoparticles. At a concentration of 6 × 10–5 M, chitosan removed 90.5% of the methylene blue (MB) dye, ZnO NPs removed 97.4%, chitosan-coated ZnO NPs removed 99.6%, while chitosan–ZnO/PVP removed 100%. In the case of toluidine blue (TB), at a concentration of 4 × 10–3 M, the respective efficiencies were 96.8%, 96.8%, 99.5%, and 100%, respectively. Evaluation of radical scavenger activity revealed increased scavenging of ABTS and DPPH radicals by chitosan–ZnO/PVP compared to individual zinc oxide or chitosan–ZnO, where the IC50 results were 0.059, 0.092, 0.079 mg/mL, respectively, in the ABTS test, and 0.095, 0.083, 0.061, and 0.064 mg/mL in the DPPH test, respectively. Moreover, in silico toxicity studies were conducted to predict the organ-specific toxicity through ProTox II software. The obtained results suggest the probable safety and the absence of organ-specific toxicity with all the tested samples.
Investigation of deformation behavior and strain-induced precipitations in Al–Zn–Mg–Cu alloys across a wide temperature range
Authors: Zhang Qingdong , Zuo Jinrong , Yang Chen , Xia Yingxiang , Shu Xuedao , Mei Bizhou , Wang Ying , Cui Long
Published: June 2024

This study explores the hot deformation behavior of Al–Zn–Mg–Cu alloy through uniaxial hot compression (200 °C–450°C) using the Gleeble-1500. True stress–strain curves were corrected, and three models were established: the Arrhenius model, strain compensated (SC) Arrhenius model, and strain compensated recrystallization temperature (RT) segmentation-based (TS-SC) Arrhenius model. Comparative analysis revealed the limited predictive accuracy of the SC Arrhenius model, with a 25.12% average absolute relative error (AARE), while the TS-SC Arrhenius model exhibited a significantly improved to 9.901% AARE. Material parameter calculations displayed variations across the temperature range. The SC Arrhenius model, utilizing an average slope method for parameter computation, failed to consider temperature-induced disparities, limiting its predictive capability. Hot processing map, utilizing the Murty improved Dynamic Materials Model (DMM), indicated optimal conditions for stable forming of the Al–Zn–Mg–Cu alloy. Microstructural analysis revealed MgZn2 precipitation induced by hot deformation, with crystallographic defects enhancing nucleation rates and precipitate refinement.
FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer
Authors: Lorito Nicla , Subbiani Angela , Smiriglia Alfredo , Bacci Marina , Bonechi Francesca , Tronci Laura , Romano Elisabetta , Corrado Alessia , Longo Dario Livio , Iozzo Marta , Ippolito Luigi , Comito Giuseppina , Giannoni Elisa , Meattini Icro , Avgustinova Alexandra , Chiarugi Paola , Bachi Angela , Morandi Andrea
Published: June 2024

Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA). Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 by both genetic interference and pharmacological approach renders those tumors ferroptosis-resistant while unbalancing PUFA/MUFA ratio by the supplementation of exogenous PUFA sensitizes resistant tumors to ferroptosis induction. Last, inhibiting lipid droplet (LD) formation and turnover suppresses the buffering capacity of LD and potentiates iron-dependent cell death. These findings have been validated in vitro and in vivo in mouse- and human-derived clinically relevant models and in a retrospective cohort of TNBC patients.
High-throughput light-induced immunoassay with milliwatt-level laser under one-minute optical antibody-coating on nanoparticle-imprinted substrate
Authors: Kanoda Masatoshi , Hayashi Kota , Takagi Yumiko , Tamura Mamoru , Tokonami Shiho , Iida Takuya
Published: June 2024

The efficient detection of protein biomarkers is critical for public health. However, the sensitivity of conventional antigen test kits is relatively low for early diagnosis, and laboratory immunoassays require complex pretreatment processes overnight. If target nanomaterials could be remotely guided to the detection site, simpler and faster methods would be developed. Here, we reveal the mechanism of light-induced immunoassay that anti-spike-protein antibodies for SARS-CoV-2 were coated on our developed nanoparticle-imprinted plasmonic substrate (NPI-PS) over the submillimeter area within one minute and nanoparticles modified with spike proteins can be selectively detected within a few minutes at one or two orders of higher sensitivity via a two-step optical condensation using NPI-PS. NPI-PS exhibits high-performance optical condensation with high photothermal properties even under milliwatt-class nonresonant laser irradiation, enabling a wide range of quantitative measurements. These findings support an innovative strategy to mitigate pandemic threats and various diseases through the high-throughput detection of protein biomarkers.
Enabling technologies applied to glycosylation
Authors: Ferry A. , Gallier F. , Gonzalez S. , Lubin-Germain N. , Soter de Mariz e Miranda L. , Uziel J.
Published: June 2024

The chapter deals with new activation conditions and technologies for glycosylation reactions with stereochemical and large-scale control. We describe new green activation conditions (electrochemistry, mechanochemistry, biocatalysis, continuous flow and photocatalysis) developed for increasing the efficiency of the chemical reactions and applied to glycosylation. Mechanochemistry and electrochemistry were applied to the synthesis of C-, N-, O-glycosides and nucleoside analogues. These conditions can be developed iteratively, without protection from glycosylated substrates. We also describe the use of continuous flow allowing better selectivity, shorter reaction times and easier scale-up, for example in the case of Remdesivir synthesis. Biocatalyzed reactions and photon-starved large-scale photo-redox reactions can be conducted under these conditions. Finally, automated synthesis is definitely entering glycomics. The opportunities for glycosylation provided by these new technologies are significant and respond to the increasing complexity of glycosidic targets.
Automation and machine learning augmented by large language models in a catalysis study
Authors: Su Yuming , Wang Xue , Ye Yuanxiang , Xie Yibo , Xu Yujing , Jiang Yibin , Wang Cheng
Published: June 2024

AI and automation are revolutionizing catalyst discovery, shifting from manual methods to high-throughput digital approaches, enhanced by large language models.
A dual-labeling fluorescent probe to track lysosomal polarity and endoplasmic reticulum dynamics during ferroptosis
Authors: Zhao Zhao , Jin Wendong , Wu Mengfan , Lin Qingyu , Duan Yixiang
Published: June 2024

An ER/lysosome dual-labeling fluoroprobe (DRHB) was developed, allowing for tracking of ER dynamics and ratiometric imaging of lysosomal polarity during ferroptosis.
f-Block hydride complexes – synthesis, structure and reactivity
Authors: Drummond Turnbull Richard , Bell Nicola L.
Published: June 2024

A perspective on complexes of the heaviest and lightest elements; we elucidate how the f-element environment can affect hydride formation, oligomerisation and reactivity, including in catalysis and expose differences between the Ln and An series.
New airborne research facility observes sensitivity of cumulus cloud microphysical properties to aerosol regime over the great barrier reef
Authors: Hernandez-Jaramillo Diana C. , Medcraft Chris , Braga Ramon Campos , Butcherine Peter , Doss Adrian , Kelaher Brendan , Rosenfeld Daniel , Harrison Daniel P.
Published: June 2024

The new research aircraft, Cessna 337, is equipped with a meteorological, aerosol, and cloud microphysical instrumentation. A case study from its first campaign is presented showing the sensitivity of cumulus cloud microphysical properties to the aerosol regime over the Great Barrier Reef.
Advances in the quality characteristics of fried potato products with air frying technology: a mini review
Authors: Téllez-Morales José A. , Arce-Ortiz Abel
Published: June 2024

Hot air frying is a relatively new technology for producing fried foods, therefore, the objective of this review is to know the impact of this frying technology on the quality properties of fried potato products.
Effect of cis/trans isomerization on the photochromic performances of triphenylethylene
Authors: Li Zhuo-Cheng , Cui Hao , Xu Su-Hang , Zhang Zi-Hang , Liang Zuo-Qin , Ye Chang-Qing , Wang Xiao-Mei
Published: June 2024

Monohalogenated triphenylethylene derivatives exhibit different photocolorabilities and fatigue processes, which are closely related to their trans-isomers.
Construction of semiconductor nanocomposites for room-temperature gas sensors
Authors: Zhang Wenjian , Chen Xinyi , Chen Yuexi , Li Hua-Yao , Liu Huan
Published: June 2024

The development of room temperature gas sensors will be achieved by combining nanomaterials with different dimensions, along with modifying the surface properties in terms of both the chemical composition and electrical attributes of these materials.
Formation of a low-symmetry Pd8 molecular barrel employing a hetero donor tetradentate ligand, and its use in the binding and extraction of C70
Authors: Prajapati Dharmraj , Clegg Jack K. , Mukherjee Partha Sarathi
Published: June 2024

A tetradentate ligand with two different donor groups gave unsymmetrical molecular barrel UNMBvia self-assembly. The stronger binding affinity of UNMB towards C70 over C60 was used to extract C70 from a mixture of C60/C70 in high purity.
With or without a co-solvent? highly efficient ultrafast phenanthrenequinone-electron rich alkene (PQ-ERA) photoclick reactions
Authors: Doze Anna M. , Fu Youxin , Di Donato Mariangela , Hilbers Michiel F. , Luurtsema Gert , Elsinga Philip H. , Buma Wybren Jan , Szymanski Wiktor , Feringa Ben L.
Published: June 2024

The commonly used solubilizing co-solvent DMSO was found to quench the triplet state of PQ in PQ-ERA photoclick reactions. DMSO-free conditions lead to exceptionally high photoreaction quantum yields and rate constants.
Unraveling the atomic structure and dissociation of interfacial water on anatase TiO2(101) under ambient conditions with solid-state NMR spectroscopy
Authors: Yang Longxiao , Huang Min , Feng Ningdong , Wang Meng , Xu Jun , Jiang Ying , Ma Ding , Deng Feng
Published: June 2024

41.2% of the adsorbed water spontaneously dissociated under ambient conditions on the TiO2surface at a loading of 0.3 mmol H2O/gcat, due to the delicate interplay between water–surface and water–water interactions.
A highly selective chromo-fluorogenic probe for specific detection of sarin gas simulant diethylchlorophosphate in liquid and vapor phases
Authors: Sultana Tuhina , Mahato Manas , Ahamed Sabbir , Tohora Najmin , Chourasia Jyoti , Ali Shreya , Das Sudhir Kumar
Published: June 2024

A highly selective chromo-fluorogenic probe, TSB has been developed for the recognition of diethyl chlorophosphate (DCP), a sarin gas surrogate, in both gas and solution phases, respectively having detection limit in the μM range.
Droplet tilings in precessive fields: hysteresis, elastic defects, and annealing
Authors: Molina Anton , Prakash Manu
Published: June 2024

A global gravitational field can disrupt a droplet tiling governed by vapor mediated interactions. The transition to field-dominated behavior sees the emergence of grain boundaries and domains.