bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractPathological 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

AbstractAdvances 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

AbstractB 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

AbstractCycloaddition 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

AbstractIn 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

AbstractAnaerobic, 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

AbstractDuring 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

AbstractZika 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

AbstractPotential 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

AbstractAs 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

AbstractTuning 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

AbstractSoils 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

AbstractAnion-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

AbstractOlefin 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

AbstractIndustrial 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

AbstractPersistent 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.