bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of health status in older patients with transthyretin cardiac amyloidosis: a prospective cohort study
Authors: Fumagalli Carlo , Ponti Lucia , Smorti Martina , Pozza Francesca , Argirò Alessia , Zampieri Mattia , Di Mario Carlo , Marfella Raffaele , Sardu Celestino , Paolisso Giuseppe , Olivotto Iacopo , Perfetto Federico , Ungar Andrea , Marchionni Niccolò , Cappelli Francesco
Published: April 2024

Background

Whether, and to what extent, frailty and other geriatric domains are linked to health status in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown.

Aims

To determine the association of frailty with health status [defined by the Kansas City Cardiomyopathy Questionnaire (KCCQ)] in patients with ATTR-CA.

Methods

Consecutive ATTR-CA patients undergoing cardiovascular assessment at a tertiary care clinic from September 2021 to September 2023 were invited to participate. KCCQ, frailty and social environment were recorded. Frailty was assessed using the modified Frailty Index (mFI), mapping 11 variables from the Canadian Study of Health and Aging (frailty ≥0.36).

Results

Of 168 screened ATTR-CA patients, 138 [83% men, median age of 79 (75–84) years] were enrolled in the study. Median KCCQ was 66 (50–75). wtATTR-CA was the most prevalent form (N = 113, 81.9%). The most frequent cardiac variant was Ile68Leu (17/25 individuals with vATTR-CA). Twenty (14.5%) patients were considered frail, and prevalence of overt disability was 6.5%. At multivariable linear regression analysis, factors associated with worsening KCCQ were age at evaluation, the mFI, NYHA Class, and NAC Score. Gender, ATTR-CA type, phenotype, and LVEF were not associated with health status.

Discussion

In older patients diagnosed with ATTR-CA, frailty, symptoms, and disease severity were associated with KCCQ.

Conclusions

Functional status is a determinant of quality of life and health status in older individuals with a main diagnosis of ATTR-CA. Future research may provide more in-depth knowledge on the association of frailty in patients with ATTR-CA with respect to quality of life and prognosis.
Macroeconomic impacts and co-benefits of deep-decarbonization in Thailand
Authors: Chaichaloempreecha Achiraya , Pradhan Bijay B. , Rajbhandari Salony , Chunark Puttipong , Fujimori Shinichiro , Oshiro Ken , Hanaoka Tatsuya , Limmeechokchai Bundit
Published: April 2024

The updated Nationally Determined Contributions (NDC) in 2022 of Thailand includes an aggressive GHG emission reduction target of 40% in 2030 from its baseline emissions. However, the macroeconomic impacts and co-benefits associated with reducing GHG emissions are not addressed. This study analyzes the macroeconomic implications and co-benefits of GHG emission reduction in Thailand to achieve the NDC and net zero emission (NZE) targets by 2050 using the AIM/Hub-Thailand model. This paper provides co-benefits for Thailand on ambitious long-term GHG emission reduction targets. Considering the co-benefit analysis in the policy documents will provide holistic insights on the positive impacts of GHG mitigation. Results show that Thailand would have to bear a GDP loss of 7.7% in 2050 compared to the BAU level if the net zero emissions need to be achieved. Fuel switching from fossil fuel to electricity in the demand side and improvement of technologies in the power sector also reduces air pollutant emissions. The increasing dependence on domestic energy supply in the NZE scenario will make the country less vulnerable to the fluctuating prices in the international energy market. In terms of trade-offs, the land use for sustainable biomass in both the NDC and NZE scenarios will be larger than in the BAU scenario. Results show better land use for biomass production and higher yields in agricultural production. Moreover, the achievement of NZE pathway will require effective usage of land area and better use of energy resources, thereby making the country more energy secure.
On the Supply Dynamics of Scandium, Global Resources, Production, Oxide and Metal Price, a Prospective Modelling Study Using WORLD7
Authors: Sverdrup Harald Ulrik , Sverdrup Antoniy Elias
Published: April 2024

The scandium production rate and price data for scandium oxide and scandium metal was extracted from various sources. Data for extractable resources of scandium were found and evaluated by application of estimated yields. The feasible extractable resource is about 6.1 million ton, and with present technology, about 676,000 ton scandium appear as potentially extractable. The potential for scandium extraction is about 1500 ton/year at present, but only about 45 ton per year was produced in 2022. With improved extraction and access yields, production could be increased to about 450 ton per year, and the scandium resource would increase to about 1.5 million ton. The investigation suggests that there will be an increased demand for scandium metal in the future, but that it is limited by the high price and the lack of a properly functioning market and by a lack of production infrastructure. The scandium market show signs of being disorganized and unstructured. Modelling of future scandium production was done using the WORLD7 integrated assessment model, after development of a scandium module. Simulations show that the price will remain relatively high, but lower than in the past. The most uncertain factor for predicting the price is the size of the demand. The main limitation for making scandium metal is high energy costs and low extraction yields.
Is promiscuity the key? Multiple paternity in the garden dormouse (Eliomys quercinus)
Authors: Erhardt Stefanie , Förschler Marc I. , Fietz Joanna
Published: April 2024

Many mammals have a promiscuous mating system with multiple sired litters. Promiscuity can increase the genetic variability, reduce the risk of inbreeding, and increase the effective population size, and is therefore crucial for preventing genetic loss and maintaining adaptability. This is particularly true for small and threatened populations. The garden dormouse (Eliomys quercinus) is a threatened species, which exhibited a drastic decline over the last 20–30 years. The aim of this study was therefore to investigate the mating system of the garden dormouse in mountain forest habitat by parentage analyses using 5 polymorphic microsatellite markers combined with morphometric data and information about the nesting behavior. Genetic parentage analyses revealed that 64% (9 of 14) of the litters were sired by at least two males, suggesting that garden dormice have a promiscuous mating system. The genetic findings were further supported by indirect indicators of promiscuity, such as testes, that were nearly four times larger than predicted for a rodent of its body mass and only slight male biased sexual size dimorphism. The finding of a promiscuous mating system in garden dormice should be taken into account in future conservation efforts. Due to its habitat preferences and limited dispersal potential garden dormice are vulnerable to forest fragmentation. The connection of suitable habitats facilitates dispersal and promotes access to potential mating partners, which could be especially important for populations colonizing new habitats. Access to potential mates may also reduce inbreeding, loss of genetic variability which is crucial for populations viability and survival.
Teaching phonics in context—stories of teachers’ practice and students’ outcomes
Authors: Scull Janet , Lyons Damien
Published: April 2024

This article presents the outcomes of a study conducted in Victoria, Australia, that recognised teachers’ knowledge and understanding of phonics teaching, and early literacy acquisition processes more generally. In total, 45 teachers and 220 students from the 18 focus schools who engaged in the reform initiative agreed to participate in this study. The questions posed considered understandings associated with the professional learning programme and processes that support the implementation of the phonics teaching and the impact this had on students’ literacy learning. We share the data used to map teachers’ stories of change and practice and some of the key factors, including structures, practices and attitudes, that influenced the implementation. The impact on students’ reading and writing outcomes throughout the reform process are also reported. Combined, the findings indicate that the teaching of phonic knowledge, integrated into rich contexts for learning, contributed to improvements in teaching and students’ early literacy skills. Furthermore, this study fills an important and common missing gap in professional learning as it explores implementation processes and practice in the classroom. The results inform continuing reform efforts and targeted research necessary to refine phonics teaching practice and further advance students’ literacy outcomes.
Action Understanding
Authors: Lingnau Angelika , Downing Paul
Published: April 2024

The human ability to effortlessly understand the actions of other people has been the focus of research in cognitive neuroscience for decades. What have we learned about this ability, and what open questions remain? In this Element the authors address these questions by considering the kinds of information an observer may gain when viewing an action. A 'what, how, and why' framing organises evidence and theories about the representations that support classifying an action; how the way an action is performed supports observational learning and inferences about other people; and how an actor's intentions are inferred from her actions. Further evidence shows how brain systems support action understanding, from research inspired by 'mirror neurons' and related concepts. Understanding actions from vision is a multi-faceted process that serves many behavioural goals, and is served by diverse mechanisms and brain systems.
Using graph neural networks for wall modeling in compressible anisothermal flows
Authors: Dupuy Dorian , Odier Nicolas , Lapeyre Corentin
Published: April 2024

Compressible anisothermal flows, which are commonly found in industrial settings such as combustion chambers and heat exchangers, are characterized by significant variations in density, viscosity, and heat conductivity with temperature. These variations lead to a strong interaction between the temperature and velocity fields that impacts the near-wall profiles of both quantities. Wall-modeled large-eddy simulations (LESs) rely on a wall model to provide a boundary condition, for example, the shear stress and the heat flux that accurately represents this interaction despite the use of coarse cells near the wall, and thereby achieve a good balance between computational cost and accuracy. In this article, the use of graph neural networks for wall modeling in LES is assessed for compressible anisothermal flow. Graph neural networks are a type of machine learning model that can learn from data and operate directly on complex unstructured meshes. Previous work has shown the effectiveness of graph neural network wall modeling for isothermal incompressible flows. This article develops the graph neural network architecture and training to extend their applicability to compressible anisothermal flows. The model is trained and tested a priori using a database of both incompressible isothermal and compressible anisothermal flows. The model is finally tested a posteriori for the wall-modeled LES of a channel flow and a turbine blade, both of which were not seen during training.
An Orient of One’s Own: Music and Islamic Modernism in the Late Ottoman Empire
Authors: Olley Jacob
Published: April 2024

During the late nineteenth and early twentieth centuries, Muslim intellectuals sought to articulate new forms of Islamic thought and practice that would be suitable for the modern world. Islamic modernist movements drew on concepts of civilization, progress and science that were integral to European imperialism while also constituting a critical response to the latter. In this essay, I examine the views of prominent Ottoman Muslim reformists concerning music, and situate them within a transnational debate about Islam and modernity. While the views of earlier reformers were shaped by Eurocentric notions of musical progress, an oppositional discourse emerged at the end of the nineteenth century. This discourse, associated especially with Rauf Yekta (1871–1935), appropriated the idea of ‘the Orient’ in order to establish a pan-Islamic narrative of music history, which also emphasized the scientific aspects of Islamicate music theory. In the final part of the essay, I discuss how debates about musical reform were related to the political dynamics of the late Ottoman Empire, particularly in terms of religious and ethnic identity. In conclusion, I argue that the discursive categories of the late nineteenth century continue to underly music historiographies both in the West and in other places, precisely as a consequence of the global connections that emerged during this period. In order to write more ‘global’ histories of music, it is therefore necessary to move beyond the analysis of Western colonialist representations by engaging more closely with non-European sources and discourses, which reveal more entangled and ambivalent stories about music, empire and modernity.
Berufsfelder von Psychologinnen und Psychologen
Authors: Antoni Conny H.
Published: April 2024

Zusammenfassung: In dem Beitrag werden vor dem Hintergrund der in den letzten Jahren dynamisch steigenden Studierenden- und Absolventenzahlen im Fach Psychologie die Entwicklung des Arbeitsmarktes und der Berufsfelder von Psychologinnen und Psychologen anhand unterschiedlicher Datenquellen analysiert. Hierzu werden Statistiken des Bundesamts für Arbeit, des Bundesamts für Statistik, der Bundespsychotherapeutenkammer, Analysen von Stellenanzeigen und von Absolventenbefragungen genutzt. Auf Basis dieser Daten werden Zusammenhänge zwischen der Gestaltung von Studiengängen, Studierenden- und Absolventenzahlen und der Entwicklung des Arbeitsmarktes und der Berufsfelder von Psychologinnen und Psychologen diskutiert.
Future Changes in Floods, Droughts, and Their Extents in the Alps: A Sensitivity Analysis With a Non‐Stationary Stochastic Streamflow Generator
Authors: Brunner Manuela I. , Gilleland Eric
Published: April 2024

Spatially compounding droughts and floods challenge water management and may become more severe in a warming climate. However, the influence of climate change on widespread hydrologic extremes remains largely unknown because they are neither well represented in observations nor in models. Here, we present a non‐stationary stochastic streamflow generator that captures streamflow dependencies between different catchments and represents seasonal covariations of streamflow with temperature. We run this model for 925 nearly natural catchments in the Alps to generate daily streamflow time series for a reference period and three warming levels of 1, 2, and 3°C. Then, we identify drought and flood events, determine their spatial extents, and assess changes in all of these characteristics. This sensitivity analysis for different warming levels suggests that changes in flood characteristics and spatial extent are substantially weaker than those in drought characteristics and spatial extent. While floods show changes in their timing toward earlier in the year, simulated changes in magnitude, volume, duration, and spatial extent are negligible. In contrast, droughts show changes not just in timing but also intensity, deficit, duration, and extent. Specifically, droughts are projected to intensify, last longer, and slightly increase in spatial extent, with the magnitude of change increasing with the warming level. These projected changes highlight the need to develop adaptation strategies in particular for droughts. Such adaptation strategies should go beyond local adaptation and consider that extreme events become more widespread in a warming world.
Transformation of Precursor Iron(III) Minerals in Diagenetic Fluids: Potential Origin of Gray Hematite at Vera Rubin Ridge
Authors: Knight A. L. , Mitra K. , Catalano J. G.
Published: April 2024

Coarse‐grained (>3–5 μm) gray hematite particles occur at Vera Rubin ridge (VRR) within Gale crater, Mars. VRR has likely undergone multiple episodes of diagenesis, at least one of which resulted in the formation of gray hematite. The precursor mineralogy and nature of the diagenetic fluids that produced coarse‐grained hematite remain unknown. Analog laboratory experiments were performed on a variety of iron(III) minerals to assess the potential fluid conditions and precursor mineralogy that form coarse‐grained hematite. Gray hematite formed from the transformation of jarosite after 20 days at 200°C. Conversion was complete in chloride‐rich fluids; however, modeling indicates that at lower jarosite‐to‐water ratios, conversion is complete even in chloride‐free, sulfate‐rich conditions. No transformations of jarosite occurred when aged at 98°C. All other precursor minerals (akaganeite, ferrihydrite, goethite, and schwertmannite) did not transform or produced red, fine‐grained hematite under all conditions assessed. Additionally, seeding precursor iron(III) phases with red hematite and coarsening pre‐existing red hematite failed to produce gray hematite. These results suggest that jarosite could have been the precursor of gray hematite at VRR and that transformation is possible in both sulfate‐bearing and chloride‐bearing fluids. Jarosite produces gray hematite because the acidic conditions it generates yield both a low degree of hematite supersaturation, producing few nuclei, and high dissolved iron concentrations, enabling rapid hematite growth. Gray hematite readily forms under oxic conditions and its occurrence at VRR is not a marker for a redox interface. The associated diagenetic event was thus unlikely to have generated substantial new chemical energy for life.
Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia
Authors: Fruchtman Harry , Avigan Zachary M. , Waksal Julian A. , Brennan Nicole , Mascarenhas John O.
Published: April 2024

The emergence of next generation sequencing and widespread use of mutational profiling in acute myeloid leukemia (AML) has broadened our understanding of the heterogeneous molecular basis of the disease. Since genetic sequencing has become a standard practice, several driver mutations have been identified. Accordingly, novel targeted therapeutic agents have been developed and are now approved for the treatment of subsets of patients that carry mutations in FLT3, IDH1, and IDH2 [1, 2]. The emergence of these novel agents in AML offers patients a new modality of therapy, and shifts treatment paradigms toward individualized medicine. In this review, we outline the role of IDH mutations in malignant transformation, focus in on a novel group of targeted therapeutic agents directed toward IDH1- and IDH2-mutant AML, and explore their impact on prognosis in patients with AML.
Combination of bazedoxifene with chemotherapy and SMAC-mimetics for the treatment of colorectal cancer
Authors: Dmello Rhynelle S. , Palmieri Michelle , Thilakasiri Pathum S. , Doughty Larissa , Nero Tracy L. , Poh Ashleigh R. , To Sarah Q. , Lee Erinna F. , Douglas Fairlie W. , Mielke Lisa , Parker Michael W. , Poon Ivan K. H. , Batlle Eduard , Ernst Matthias , Chand Ashwini L.
Published: April 2024

Excessive STAT3 signalling via gp130, the shared receptor subunit for IL-6 and IL-11, contributes to disease progression and poor survival outcomes in patients with colorectal cancer. Here, we provide evidence that bazedoxifene inhibits tumour growth via direct interaction with the gp130 receptor to suppress IL-6 and IL-11-mediated STAT3 signalling. Additionally, bazedoxifene combined with chemotherapy synergistically reduced cell proliferation and induced apoptosis in patient-derived colon cancer organoids. We elucidated that the primary mechanism of anti-tumour activity conferred by bazedoxifene treatment occurs via pro-apoptotic responses in tumour cells. Co-treatment with bazedoxifene and the SMAC-mimetics, LCL161 or Birinapant, that target the IAP family of proteins, demonstrated increased apoptosis and reduced proliferation in colorectal cancer cells. Our findings provide evidence that bazedoxifene treatment could be combined with SMAC-mimetics and chemotherapy to enhance tumour cell apoptosis in colorectal cancer, where gp130 receptor signalling promotes tumour growth and progression.
Thylakoid protein FPB1 synergistically cooperates with PAM68 to promote CP47 biogenesis and Photosystem II assembly
Authors: Zhang Lin , Ruan Junxiang , Gao Fudan , Xin Qiang , Che Li-Ping , Cai Lujuan , Liu Zekun , Kong Mengmeng , Rochaix Jean-David , Mi Hualing , Peng Lianwei
Published: April 2024

In chloroplasts, insertion of proteins with multiple transmembrane domains (TMDs) into thylakoid membranes usually occurs in a co-translational manner. Here, we have characterized a thylakoid protein designated FPB1 (Facilitator of PsbB biogenesis1) which together with a previously reported factor PAM68 (Photosynthesis Affected Mutant68) is involved in assisting the biogenesis of CP47, a subunit of the Photosystem II (PSII) core. Analysis by ribosome profiling reveals increased ribosome stalling when the last TMD segment of CP47 emerges from the ribosomal tunnel in fpb1 and pam68. FPB1 interacts with PAM68 and both proteins coimmunoprecipitate with SecY/E and Alb3 as well as with some ribosomal components. Thus, our data indicate that, in coordination with the SecY/E translocon and the Alb3 integrase, FPB1 synergistically cooperates with PAM68 to facilitate the co-translational integration of the last two CP47 TMDs and the large loop between them into thylakoids and the PSII core complex.
The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus
Authors: Langedijk Annefleur C. , Vrancken Bram , Lebbink Robert Jan , Wilkins Deidre , Kelly Elizabeth J. , Baraldi Eugenio , Mascareñas de Los Santos Abiel Homero , Danilenko Daria M. , Choi Eun Hwa , Palomino María Angélica , Chi Hsin , Keller Christian , Cohen Robert , Papenburg Jesse , Pernica Jeffrey , Greenough Anne , Richmond Peter , Martinón-Torres Federico , Heikkinen Terho , Stein Renato T. , Hosoya Mitsuaki , Nunes Marta C. , Verwey Charl , Evers Anouk , Kragten-Tabatabaie Leyla , Suchard Marc A. , Kosakovsky Pond Sergei L. , Poletto Chiara , Colizza Vittoria , Lemey Philippe , Bont Louis J. ,   on behalf of the INFORM-RSV Study Group, Priante Elena , Komissarova Kseniya , Yun Ki Wook , Clement Pascale , Bauck Monica , Gupta Atul , Wadia Ushma , Rivero-Calle Irene , Lumertz Magalia , Hasimoto Koichi , Madhi Shabir A.
Published: April 2024

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.
Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection
Authors: Giron Leila B. , Liu Qin , Adeniji Opeyemi S. , Yin Xiangfan , Kannan Toshitha , Ding Jianyi , Lu David Y. , Langan Susan , Zhang Jinbing , Azevedo Joao L. L. C. , Li Shuk Hang , Shalygin Sergei , Azadi Parastoo , Hanna David B. , Ofotokun Igho , Lazar Jason , Fischl Margaret A. , Haberlen Sabina , Macatangay Bernard , Adimora Adaora A. , Jamieson Beth D. , Rinaldo Charles , Merenstein Daniel , Roan Nadia R. , Kutsch Olaf , Gange Stephen , Wolinsky Steven M. , Witt Mallory D. , Post Wendy S. , Kossenkov Andrew , Landay Alan L. , Frank Ian , Tien Phyllis C. , Gross Robert , Brown Todd T. , Abdel-Mohsen Mohamed
Published: April 2024

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.
Giant Faraday rotation in atomically thin semiconductors
Authors: Carey Benjamin , Wessling Nils Kolja , Steeger Paul , Schmidt Robert , Michaelis de Vasconcellos Steffen , Bratschitsch Rudolf , Arora Ashish
Published: April 2024

Faraday rotation is a fundamental effect in the magneto-optical response of solids, liquids and gases. Materials with a large Verdet constant find applications in optical modulators, sensors and non-reciprocal devices, such as optical isolators. Here, we demonstrate that the plane of polarization of light exhibits a giant Faraday rotation of several degrees around the A exciton transition in hBN-encapsulated monolayers of WSe2 and MoSe2 under moderate magnetic fields. This results in the highest known Verdet constant of -1.9 × 107 deg T−1 cm−1 for any material in the visible regime. Additionally, interlayer excitons in hBN-encapsulated bilayer MoS2 exhibit a large Verdet constant (VIL ≈ +2 × 105 deg T−1 cm−2) of opposite sign compared to A excitons in monolayers. The giant Faraday rotation is due to the giant oscillator strength and high g-factor of the excitons in atomically thin semiconducting transition metal dichalcogenides. We deduce the complete in-plane complex dielectric tensor of hBN-encapsulated WSe2 and MoSe2 monolayers, which is vital for the prediction of Kerr, Faraday and magneto-circular dichroism spectra of 2D heterostructures. Our results pose a crucial advance in the potential usage of two-dimensional materials in ultrathin optical polarization devices.
Single-cell and spatial RNA sequencing reveal the spatiotemporal trajectories of fruit senescence
Authors: Li Xin , Li Bairu , Gu Shaobin , Pang Xinyue , Mason Patrick , Yuan Jiangfeng , Jia Jingyu , Sun Jiaju , Zhao Chunyan , Henry Robert
Published: April 2024

The senescence of fruit is a complex physiological process, with various cell types within the pericarp, making it highly challenging to elucidate their individual roles in fruit senescence. In this study, a single-cell expression atlas of the pericarp of pitaya (Hylocereus undatus) is constructed, revealing exocarp and mesocarp cells undergoing the most significant changes during the fruit senescence process. Pseudotime analysis establishes cellular differentiation and gene expression trajectories during senescence. Early-stage oxidative stress imbalance is followed by the activation of resistance in exocarp cells, subsequently senescence-associated proteins accumulate in the mesocarp cells at late-stage senescence. The central role of the early response factor HuCMB1 is unveiled in the senescence regulatory network. This study provides a spatiotemporal perspective for a deeper understanding of the dynamic senescence process in plants.
Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis
Authors: Stork Eva Maria , van Rijswijck Danique M. H. , van Schie Karin A. , Hoek Max , Kissel Theresa , Scherer Hans Ulrich , Huizinga Tom W. J. , Heck Albert J. R. , Toes Rene E. M. , Bondt Albert
Published: April 2024

The presence of autoantibodies is a defining feature of many autoimmune diseases. The number of unique autoantibody clones is conceivably limited by immune tolerance mechanisms, but unknown due to limitations of the currently applied technologies. Here, we introduce an autoantigen-specific liquid chromatography-mass spectrometry-based IgG1 Fab profiling approach using the anti-citrullinated protein antibody (ACPA) repertoire in rheumatoid arthritis (RA) as an example. We show that each patient harbors a unique and diverse ACPA IgG1 repertoire dominated by only a few antibody clones. In contrast to the total plasma IgG1 antibody repertoire, the ACPA IgG1 sub-repertoire is characterised by an expansion of antibodies that harbor one, two or even more Fab glycans, and different glycovariants of the same clone can be detected. Together, our data indicate that the autoantibody response in a prominent human autoimmune disease is complex, unique to each patient and dominated by a relatively low number of clones.
A bionic self-driven retinomorphic eye with ionogel photosynaptic retina
Authors: Luo Xu , Chen Chen , He Zixi , Wang Min , Pan Keyuan , Dong Xuemei , Li Zifan , Liu Bin , Zhang Zicheng , Wu Yueyue , Ban Chaoyi , Chen Rong , Zhang Dengfeng , Wang Kaili , Wang Qiye , Li Junyue , Lu Gang , Liu Juqing , Liu Zhengdong , Huang Wei
Published: April 2024

Bioinspired bionic eyes should be self-driving, repairable and conformal to arbitrary geometries. Such eye would enable wide-field detection and efficient visual signal processing without requiring external energy, along with retinal transplantation by replacing dysfunctional photoreceptors with healthy ones for vision restoration. A variety of artificial eyes have been constructed with hemispherical silicon, perovskite and heterostructure photoreceptors, but creating zero-powered retinomorphic system with transplantable conformal features remains elusive. By combining neuromorphic principle with retinal and ionoelastomer engineering, we demonstrate a self-driven hemispherical retinomorphic eye with elastomeric retina made of ionogel heterojunction as photoreceptors. The receptor driven by photothermoelectric effect shows photoperception with broadband light detection (365 to 970 nm), wide field-of-view (180°) and photosynaptic (paired-pulse facilitation index, 153%) behaviors for biosimilar visual learning. The retinal photoreceptors are transplantable and conformal to any complex surface, enabling visual restoration for dynamic optical imaging and motion tracking.
Thermally stable Ni foam-supported inverse CeAlOx/Ni ensemble as an active structured catalyst for CO2 hydrogenation to methane
Authors: Tang Xin , Song Chuqiao , Li Haibo , Liu Wenyu , Hu Xinyu , Chen Qiaoli , Lu Hanfeng , Yao Siyu , Li Xiao-nian , Lin Lili
Published: April 2024

Nickel is the most widely used inexpensive active metal center of the heterogeneous catalysts for CO2 hydrogenation to methane. However, Ni-based catalysts suffer from severe deactivation in CO2 methanation reaction due to the irreversible sintering and coke deposition caused by the inevitable localized hotspots generated during the vigorously exothermic reaction. Herein, we demonstrate the inverse CeAlOx/Ni composite constructed on the Ni-foam structure support realizes remarkable CO2 methanation catalytic activity and stability in a wide operation temperature range from 240 to 600 °C. Significantly, CeAlOx/Ni/Ni-foam catalyst maintains its initial activity after seven drastic heating-cooling cycles from RT to 240 to 600 °C. Meanwhile, the structure catalyst also shows water resistance and long-term stability under reaction condition. The promising thermal stability and water-resistance of CeAlOx/Ni/Ni-foam originate from the excellent heat and mass transport efficiency which eliminates local hotspots and the formation of Ni-foam stabilized CeAlOx/Ni inverse composites which effectively anchored the active species and prevents carbon deposition from CH4 decomposition.
Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons
Authors: Zhou Xiaoting , Lee You-Kyung , Li Xianting , Kim Henry , Sanchez-Priego Carlos , Han Xian , Tan Haiyan , Zhou Suiping , Fu Yingxue , Purtell Kerry , Wang Qian , Holstein Gay R. , Tang Beisha , Peng Junmin , Yang Nan , Yue Zhenyu
Published: April 2024

Autophagy is a conserved, catabolic process essential for maintaining cellular homeostasis. Malfunctional autophagy contributes to neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive. Here we report a systematic investigation of neuronal autophagy targets through integrated proteomics. Deep proteomic profiling of multiple autophagy-deficient lines of human induced neurons, mouse brains, and brain LC3-interactome reveals roles of neuronal autophagy in targeting proteins of multiple cellular organelles/pathways, including endoplasmic reticulum (ER), mitochondria, endosome, Golgi apparatus, synaptic vesicle (SV) for degradation. By combining phosphoproteomics and functional analysis in human and mouse neurons, we uncovered a function of neuronal autophagy in controlling cAMP-PKA and c-FOS-mediated neuronal activity through selective degradation of the protein kinase A - cAMP-binding regulatory (R)-subunit I (PKA-RI) complex. Lack of AKAP11 causes accumulation of the PKA-RI complex in the soma and neurites, demonstrating a constant clearance of PKA-RI complex through AKAP11-mediated degradation in neurons. Our study thus reveals the landscape of autophagy degradation in human neurons and identifies a physiological function of autophagy in controlling homeostasis of PKA-RI complex and specific PKA activity in neurons.
A primary sensory cortical interareal feedforward inhibitory circuit for tacto-visual integration
Authors: Weiler Simon , Rahmati Vahid , Isstas Marcel , Wutke Johann , Stark Andreas Walter , Franke Christian , Graf Jürgen , Geis Christian , Witte Otto W. , Hübener Mark , Bolz Jürgen , Margrie Troy W. , Holthoff Knut , Teichert Manuel
Published: April 2024

Tactile sensation and vision are often both utilized for the exploration of objects that are within reach though it is not known whether or how these two distinct sensory systems combine such information. Here in mice, we used a combination of stereo photogrammetry for 3D reconstruction of the whisker array, brain-wide anatomical tracing and functional connectivity analysis to explore the possibility of tacto-visual convergence in sensory space and within the circuitry of the primary visual cortex (VISp). Strikingly, we find that stimulation of the contralateral whisker array suppresses visually evoked activity in a tacto-visual sub-region of VISp whose visual space representation closely overlaps with the whisker search space. This suppression is mediated by local fast-spiking interneurons that receive a direct cortico-cortical input predominantly from layer 6 neurons located in the posterior primary somatosensory barrel cortex (SSp-bfd). These data demonstrate functional convergence within and between two primary sensory cortical areas for multisensory object detection and recognition.
Manipulating the diffusion energy barrier at the lithium metal electrolyte interface for dendrite-free long-life batteries
Authors: Pokharel Jyotshna , Cresce Arthur , Pant Bharat , Yang Moon Young , Gurung Ashim , He Wei , Baniya Abiral , Lamsal Buddhi Sagar , Yang Zhongjiu , Gent Stephen , Xian Xiaojun , Cao Ye , Goddard William A. , Xu Kang , Zhou Yue
Published: April 2024

Constructing an artificial solid electrolyte interphase (SEI) on lithium metal electrodes is a promising approach to address the rampant growth of dangerous lithium morphologies (dendritic and dead Li0) and low Coulombic efficiency that plague development of lithium metal batteries, but how Li+ transport behavior in the SEI is coupled with mechanical properties remains unknown. We demonstrate here a facile and scalable solution-processed approach to form a Li3N-rich SEI with a phase-pure crystalline structure that minimizes the diffusion energy barrier of Li+ across the SEI. Compared with a polycrystalline Li3N SEI obtained from conventional practice, the phase-pure/single crystalline Li3N-rich SEI constitutes an interphase of high mechanical strength and low Li+ diffusion barrier. We elucidate the correlation among Li+ transference number, diffusion behavior, concentration gradient, and the stability of the lithium metal electrode by integrating phase field simulations with experiments. We demonstrate improved reversibility and charge/discharge cycling behaviors for both symmetric cells and full lithium-metal batteries constructed with this Li3N-rich SEI. These studies may cast new insight into the design and engineering of an ideal artificial SEI for stable and high-performance lithium metal batteries.
Strain-insensitive viscoelastic perovskite film for intrinsically stretchable neuromorphic vision-adaptive transistors
Authors: Wang Chengyu , Bian Yangshuang , Liu Kai , Qin Mingcong , Zhang Fan , Zhu Mingliang , Shi Wenkang , Shao Mingchao , Shang Shengcong , Hong Jiaxin , Zhu Zhiheng , Zhao Zhiyuan , Liu Yunqi , Guo Yunlong
Published: April 2024

Stretchable neuromorphic optoelectronics present tantalizing opportunities for intelligent vision applications that necessitate high spatial resolution and multimodal interaction. Existing neuromorphic devices are either stretchable but not reconcilable with multifunctionality, or discrete but with low-end neurological function and limited flexibility. Herein, we propose a defect-tunable viscoelastic perovskite film that is assembled into strain-insensitive quasi-continuous microsphere morphologies for intrinsically stretchable neuromorphic vision-adaptive transistors. The resulting device achieves trichromatic photoadaptation and a rapid adaptive speed (<150 s) beyond human eyes (3 ~ 30 min) even under 100% mechanical strain. When acted as an artificial synapse, the device can operate at an ultra-low energy consumption (15 aJ) (far below the human brain of 1 ~ 10 fJ) with a high paired-pulse facilitation index of 270% (one of the best figures of merit in stretchable synaptic phototransistors). Furthermore, adaptive optical imaging is achieved by the strain-insensitive perovskite films, accelerating the implementation of next-generation neuromorphic vision systems.
Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies
Authors: Hou Yingying , Chen Min , Bian Yuan , Hu Yuan , Chuan Junlan , Zhong Lei , Zhu Yuxuan , Tong Rongsheng
Published: April 2024

Immunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.
CDK4/6 inhibition sensitizes MEK inhibition by inhibiting cell cycle and proliferation in pancreatic ductal adenocarcinoma
Authors: Cheng Ke , Zhou Zijian , Chen Qiangxing , Chen Zixin , Cai Yu , Cai He , Wu Shangdi , Gao Pan , Cai Yunqiang , Zhou Jin , Wang Xin , Wu Zhong , Peng Bing
Published: April 2024

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.
The impact of environmental regulation on green investment efficiency of thermal power enterprises in China-based on a three-stage exogenous variable model
Authors: Ren Fang-rong , Wu Tao-feng , Ren Yang-jun , Liu Xiao-yan , Yuan Xiaomei
Published: April 2024

Due to the increased frequency of extreme weather events and the implementation of the China’s dual-carbon target, thermal power companies have been under pressure to construct green infrastructure and to actively pursue low-carbon transformation in response to stricter environmental regulations. This research thus selects 30 listed thermal power enterprises in China as study objects and assesses their green investment efficiency in the low-carbon transition process using three-stage DEA evaluation model with environmental regulation as an exogenous variable. Based on this, a benchmark regression model is used to corroborate the relationship between environmental regulation and green investment. Simultaneously, we carry out analysis to compare the correlation between thermal power firms’ green investment efficiency and their focus on green investments. The results show in terms of total efficiency that environmental regulation significantly improves the total efficiency of 80% of thermal power enterprises compared to the absence of this exogenous variable. With the addition of environmental regulation, firms’ total efficiency declines gradually in general from 2018 to 2022, with the mean value of efficiency falling by 0.068. In terms of stage-specific efficiency, the efficiency of the green investment stage of the majority of firms is between 0.3 and 0.6, which is much lower than that of the operational stage and the market performance stage. In terms of sub-indicator efficiency, both green investment efficiency and social donation efficiency among thermal power enterprises show obvious polarization, with 30% of them having an efficiency of 1 and 30% less than 0.1. In terms of green investment focus, thermal power unit renovation has a more obvious role in boosting the green investment efficiency of thermal power enterprises than do wind power and photovoltaic projects. Therefore, both governmental departments and thermal power enterprises need to take active measures in order to achieve green transformation from the perspective of green investment efficiency. Through the segmentation of important projects of green investment, this paper provides a reasonable investment direction reference for the sustainable transformation of China’s thermal power industry. It also provides a rich and novel theoretical basis for the Chinese government to further improve the relevant environmental protection laws and regulations of thermal power industry.
Blood groups and Rhesus status as potential predictors of outcomes in patients with cardiac resynchronisation therapy
Authors: Papageorgiou Nikolaos , Sohrabi Catrin , Bakogiannis Constantinos , Tsarouchas Anastasios , Kukendrarajah Kishore , Matiti Luso , Srinivasan Neil T. , Ahsan Syed , Sporton Simon , Schilling Richard J. , Hunter Ross J. , Muthumala Amal , Creta Antonio , Chow Anthony W. , Providencia Rui
Published: April 2024

Cardiac resynchronisation therapy (CRT) improves prognosis in patients with heart failure (HF) however the role of ABO blood groups and Rhesus factor are poorly understood. We hypothesise that blood groups may influence clinical and survival outcomes in HF patients undergoing CRT. A total of 499 patients with HF who fulfilled the criteria for CRT implantation were included. Primary outcome of all-cause mortality and/or heart transplant/left ventricular assist device was assessed over a median follow-up of 4.6 years (IQR 2.3–7.5). Online repositories were searched to provide biological context to the identified associations. Patients were divided into blood (O, A, B, and AB) and Rhesus factor (Rh-positive and Rh-negative) groups. Mean patient age was 66.4 ± 12.8 years with a left ventricular ejection fraction of 29 ± 11%. There were no baseline differences in age, gender, and cardioprotective medication. In a Cox proportional hazard multivariate model, only Rh-negative blood group was associated with a significant survival benefit (HR 0.68 [0.47–0.98], p = 0.040). No association was observed for the ABO blood group (HR 0.97 [0.76–1.23], p = 0.778). No significant interaction was observed with prevention, disease aetiology, and presence of defibrillator. Rhesus-related genes were associated with erythrocyte and platelet function, and cholesterol and glycated haemoglobin levels. Four drugs under development targeting RHD were identified (Rozrolimupab, Roledumab, Atorolimumab, and Morolimumab). Rhesus blood type was associated with better survival in HF patients with CRT. Further research into Rhesus-associated pathways and related drugs, namely whether there is a cardiac signal, is required.