bluuebunny/crossref_metadata_2025 huggingface dataset:
Bei Risiken und Nebenwirkungen fragen Sie Ihre… Patientinnen und Patienten
Authors: Büchele Natascha , Mier Daniela , Rockstroh Brigitte , Viehl Kathrin , Schiller Sabine , Haupt Magdalena , Weitbrecht Maja , Gegenfurtner Carolin , Volkland Katharina , Odenwald Michael
Published: March 2023

Zusammenfassung: Theoretischer Hintergrund: Das Verständnis der Antipsychotika-Adhärenz ist lückenhaft, obwohl sie ein Grundpfeiler der Schizophrenie-Behandlung darstellt. Die spezifische Erfassung der Wahrnehmung von Risiken bei Einnahme sowie Absetzen von Antipsychotika könnte zur Erklärung der Adhärenz beitragen. Fragestellung: Explorative Studie zur Entwicklung und ersten Evaluierung des Fragebogens zur Risikowahrnehmung von Antipsychotika (FRA). Methode: Basierend auf theoretischen Überlegungen wurde ein Itempool für die Risikowahrnehmung des Absetzens und Einnehmens von Antipsychotika generiert. Eingeschlossen wurden ambulante und stationäre F2-Patient_innen. Stichprobe 1 ( N = 120) diente zur Itemselektion und explorativen Faktorenanalyse (faktorielle Validität). Anhand Online-Stichprobe 2 ( N = 39) wurde die diskriminante und konvergente Validität analysiert. Ergebnisse: Die explorative Faktorenanalyse ergab die theoretisch erwartete zweifaktorielle Struktur. Die Korrelationen des FRA zu Adhärenzmaßen und spezifischen Medikamentenfragebögen unterstützten die konvergente und diskriminante Validität. Schlussfolgerungen: Der FRA als Erhebungsinstrument der Wahrnehmung von Antipsychotika-Risiken könnte das Verständnis von Antipsychotika-Adhärenz und von Behandlungsansätzen verbessern. Prospektive konfirmatorische Studien müssen durchgeführt werden.
Quantifying the Safe Operating Space for Land‐System SDG Achievement via Machine Learning and Scenario Discovery
Authors: Khan Md Shakil , Moallemi Enayat A. , Nazari Asef , Thiruvady Dhananjay , Bryan Brett A.
Published: March 2023

We developed a machine learning based surrogate model to identify sustainability pathways through rapid scenario generation and defined the safe operating space for achieving them via scenario discovery. We trained a surrogate model to replicate the Land‐Use Trade‐Offs integrated model of the Australian land system. Latin hypercube sampling was used to create many scenarios exploring the impact of uncertainties in key drivers including future socio‐economic development, climate change mitigation, and agricultural productivity at a granular level. Economic and environmental impacts were evaluated against nationally downscaled SDG targets. Scenario discovery revealed new pathways to achieving five SDG targets for 2050 which required crop yield increases above 1.78 times, a carbon price above 100 AU$ tCO2−1, a >9% biodiversity levy on carbon plantings, and carefully regulated land‐use policy. Machine learning based surrogate modeling teamed with scenario discovery revealed the policy and scenario settings required for a more sustainable future for the Australian land sector.
Variability in Projected North American Mean and Extreme Temperature and Precipitation Trends for the 21st Century: Model‐To‐Model Differences Versus Internal Variability
Authors: Kelleher Mitchell K. , Grise Kevin M. , Schmidt Daniel F.
Published: March 2023

While climate change is expected to alter mean and extreme temperature and precipitation over the 21st century, regional changes in these fields remain difficult to project. For a given future emissions scenario, the uncertainty in future projections can be attributed to either model‐to‐model differences, which can presumably be reduced if models are improved, or internal variability, which cannot be constrained to a single outcome but can be used to quantify a range of plausible outcomes. This study examines the range of possible trends in North American mean and extreme temperature and precipitation across phase 6 of the Coupled Model Intercomparison Project models under the SSP3‐7.0 emissions scenario. While model‐to‐model differences primarily govern the spread in mean and extreme temperature trends across these model simulations, the spread in mean and extreme precipitation trends is dominated by internal variability in many regions. A storylines approach—a type of regression‐based analysis—is used to identify key dynamical drivers that explain the variance in future trends across model simulations. The dynamical drivers considered include trends in global mean surface temperature (GMST) and four common modes of climate variability. Combinations of these drivers can reinforce each other to create high‐impact storylines. For example, model simulations with large positive GMST and El Niño‐Southern Oscillation trends are associated with a large reduction in the annual maximum number of consecutive dry days in the American Southwest. However, limiting these storylines to only models with climate sensitivities consistent with observational constraints reduces the likelihood of a large reduction of consecutive dry days in this region.
Projecting the Changes in Multifaceted Characteristics of Heatwave Events Across China
Authors: Wei Jia , Wang Weiguang , Wang Guoqing , Cao Mingzhu , Yang Liyan , Zhang Shulin , Fu Jianyu , Xing Wanqiu
Published: March 2023

Understanding future variations and trends of heatwave events has critical implications for the ecosystem and human health. However, the diverse metrics of heatwave affect the comparable assessment of heatwave evolution at regional scales. The inadequate consideration of the enhanced warming trend and local antecedent heat conditions at different climate zones undermines the comprehensive understanding of future heatwave changes. Here, we systematically assess variations and trends in duration, frequency, and intensity of heatwave events in China from 1961 to 2100, using historical observations and climate model simulations from Coupled Model Intercomparison Project Phase 6. The increased rates and trends in the duration and frequency are more evident than those in intensity and severe heatwave days. Regionally, the northern and western regions are projected to suffer longer and more frequent consecutive heatwaves, while southern regions are likely at greater risk of severe heatwave days. A comparison among four scenarios shows that the future heatwave characteristics projected by the high forcing Shared Socioeconomic Pathway (SSP5‐8.5) exhibit substantial intensification than those in other three experiments, imposing intractable dangers to numerous organisms and ecosystems. Under the SSP1‐2.6, the acceleration of all heatwave characteristics is projected to slow down in all regions after 2040. In addition to maximum temperature, temperature advections are projected to contribute to heatwave intensification in western regions. Our results provide a comprehensive assessment of future variations and trends in heatwave events. The comparable future changes across unevenly developed regions are necessary for improving regional adaptive capacity to extreme heat risk.
Crustal Lg Attenuation Beneath the Iranian Plateau: Implications for Cenozoic Magmatism Related to Slab Subduction, Slab Break‐Off, and Mantle Flow
Authors: Yang Geng , Chen Ling , Zhao Lian‐Feng , Xie Xiao‐Bi , Yao Zhen‐Xing
Published: March 2023

Cenozoic magmatism is present across the Iranian Plateau but, despite playing an important role in the geodynamic evolution of the young plateau, remains poorly understood. In this study, the crustal thermal structure beneath the Iranian Plateau is investigated by high‐resolution Lg‐wave attenuation tomography using a newly compiled data set, which consists of records from three recent temporary seismic arrays (for a total of 197 stations) and previous regional networks. Strong Lg attenuation is mainly observed beneath the Zagros orogenic belt, Urumieh‐Dokhtar magmatic arc (UDMA), Makran magmatic arc, Lut magmatic zone, and Alborz reararc magmatic belt, which covers not only tectonic boundary belts but also the active internal zones of the Iranian Plateau. Combining deep seismological observations and geochemical data, the strong crustal attenuation characteristics beneath the northwestern and southeastern UDMA suggest that Miocene–Quaternary magmatism was activated by slab detachment‐induced upwelling after the cessation of oceanic subduction. Western Makran is characterized by strong Lg attenuation with a NE trend. The age of the Paleogene–Quaternary Makran volcanism decreases toward the NE and is likely related to the change in subduction dip. Diffuse magmatism and strong crustal attenuation are present in the northern Lut Block rather than the entire Lut–Afghan collision zone, which is likely associated with the accumulation of mantle magmas driven by the potential northward asthenospheric flow. In northern Iran, a strong attenuation anomaly spans the entire E‒W Alborz magma belt, suggesting that partial crustal melting and mantle thermal sources may exist in this region.
Convective Impact on the Global Lower Stratospheric Water Vapor Budget
Authors: Ueyama Rei , Schoeberl Mark , Jensen Eric , Pfister Leonhard , Park Mijeong , Ryoo Ju‐Mee
Published: March 2023

Water vapor in the stratosphere is primarily controlled by temperatures in the tropical upper troposphere and lower stratosphere. However, the direct impact of deep convection on the global lower stratospheric water vapor budget is still an actively debated issue. Two complementary modeling approaches are used to investigate the convective impact in boreal winter and summer. Convective influence is diagnosed by tracing trajectories through convective cloud top altitude fields derived from global rainfall and brightness temperature data. Backward trajectory model simulations coupled with a detailed treatment of cloud microphysical processes indicate that convection moistens the global lower stratosphere by approximately 0.3 ppmv in boreal winter and summer 2010. The diurnal peak in convection is responsible for about half of the total convective moistening during winter and nearly all of the convective moistening during summer. Deep convective clouds overshooting the tropopause have relatively minor effect on global lower stratospheric water vapor. A forward trajectory model coupled with a simplified cloud module is used to estimate the relative magnitude of the interannual variability of the convective impact. Combining the results from the two models, we find that the convective impact on the global lower stratospheric water vapor during 2006–2016 is approximately 0.3 ppmv with year‐to‐year variations of up to 0.1 ppmv. An important mechanism of convective hydration of the lower stratosphere is via the detrainment of saturated air and ice into the tropical uppermost troposphere and the subsequent upward transport of some of these moist air parcels across relatively warm and subsaturated tropopause.
The Contribution of Local and Remote Transpiration, Ground Evaporation, and Canopy Evaporation to Precipitation Across North America
Authors: Harrington Tyler S. , Nusbaumer Jesse , Skinner Christopher B.
Published: March 2023

Land surface evapotranspiration (ET) is a major source of moisture for the global hydrologic cycle. Though the influence of the land surface is well documented, moisture tracking analyses aimed at quantifying the contribution of the land surface to precipitation have often relied on offline tracking approaches that require simplifying assumptions and can bias results. Additionally, the contribution of the ET components (transpiration (T), canopy evaporation (C), and ground evaporation (E)) individually to precipitation is not well understood, inhibiting our understanding of moisture teleconnections in both the current and future climate. Here, we use the Community Earth System Model version 1.2 with online numerical water tracers to examine the contribution of local and remote land surface ET, including the contribution from each individual ET component, to precipitation across North America. Much of northern and northeastern North America receives up to 80% of summertime precipitation from land surface ET, and over 50% of that moisture originates from transpiration alone. Local moisture recycling constitutes an essential source of precipitation across much of the southern and western regions of North America, suggesting precipitation across the region is sensitive to local land surface conditions, including soil moisture and vegetation state. The reliance on locally recycled moisture is far less pronounced across northern and eastern North America, where remotely sourced moisture, particularly from transpiration, dominates precipitation contributions. The results highlight regions that are especially sensitive to land cover and hydrologic changes in local and upwind areas, providing key insights for drought prediction and water resource management.
Trend and Interannual Variations of Reactive Nitrogen Deposition in China During 2008–2017 and the Roles of Anthropogenic Emissions and Meteorological Conditions
Authors: Ma Mingrui , Zheng Bo , Xu Wen , Cao Jiachen , Zhou Kaiyue , Zhao Yu
Published: March 2023

Abundant emissions have made China as one of the hotpots of atmospheric reactive nitrogen (Nr) deposition over the world. Here we conducted multi‐year simulation and explored the trend and interannual variations (IAVs) of China's Nr deposition for different forms (wet and dry) and species (oxidized and reduced nitrogen, OXN and RDN) during 2008–2017. Sensitivity analysis scenarios were applied to evaluate the roles of anthropogenic emissions and meteorological conditions on the changing deposition. The annual mean Nr deposition was simulated at 15.7 ± 0.9 kg N ha−1 yr−1 for China. Attributed mainly to the changing OXN, the trend in Nr deposition over the 10‐year period showed an inverted “V” pattern, reflecting the benefit of nation actions on NOX emissions controls. The standard deviation ellipse analysis suggested a clear interannual shift of spatial distribution of Nr deposition to the southwest during 2013–2017. Based on the mean absolute deviation (MAD) and absolute percent departure from the mean obtained in different simulation scenarios, the IAVs of Nr deposition were found to be driven mainly by the changing meteorological conditions, and the correlation coefficient between MADs of Nr deposition and precipitation reached 0.47. Relative to meteorological factor, the changing emissions could explain 61%–83% of 10‐year trend of Nr deposition for the concerned regions, thus were identified as the main driver of the trend. The changing meteorological conditions played a more important role on shaping the IAVs of Nr deposition, with the relative contributions estimated at 60% for the concerned regions.
Quantifying an Overlooked Deciduous‐Needleleaf Carbon Sink at the Southern Margin of the Central‐Siberian Permafrost Zone
Authors: Liu Jialin , Cheng Fangyan , Commane Róisín , Zhu Yi , Ji Weiwen , Man Xiuling , Guan ChengHe , Munger J. William
Published: March 2023

With over 700 million km2 Siberia is the largest expanse of the northern boreal forest—deciduous‐needleleaf larch. Temperatures are increasing across this region, but the consequences to carbon balances are not well understood for larch forests. We present flux measurements from a larch forest near the southern edge of Central‐Siberia where permafrost degradation and ecosystem shifts are already observed. Results indicate net carbon exchanges are influenced by the seasonality of permafrost active layers, temperature and humidity, and soil water availability. During periods when surface soils are fully thawed, larch forest is a significant carbon sink. During the spring‐thaw and fall‐freeze transition, there is a weak signal of carbon uptake at mid‐day. Net carbon exchanges are near‐zero when the soil is fully frozen from the surface down to the permafrost. We fit an empirical ecosystem functional model to quantify the dependence of larch‐forest carbon balance on climatic drivers. The model provides a basis for ecosystem carbon budgets over time and space. Larch differs from boreal evergreens by having higher maximum productivity and lower respiration, leading to an increased carbon sink. Comparison to previous measurements from another northern larch site suggests climate change will result in an increased forest carbon sink if the southern larch subtype replaces the northern subtype. Observations of carbon fluxes in Siberian larch are still too sparse to adequately determine age dependence, inter‐annual variability, and spatial heterogeneity though they suggest that boreal larch accounts for a larger fraction of global carbon uptake than has been previously recognized.
On Dynamical Decomposition of Multiscale Oceanic Motions
Authors: Wang Chuanyin , Liu Zhiyu , Lin Hongyang
Published: March 2023

The ocean hosts a variety of fluid motions characterized by contrasting dynamical regimes and spatiotemporal scales. A practical decomposition of multiscale motions in realistic oceanic settings is crucial to advancing dynamical interpretation and prediction of oceanic processes, but remains a major challenge. To this end, methodology is developed in this study for decomposing multiscale oceanic motions based on their respective dynamical characteristics. Specifically, large‐scale currents and barotropic tides have the largest horizontal scales but contrasting frequencies; low‐mode internal gravity waves (IGWs) are well constrained by linear dispersion relations, whereas mesoscale flows are of relatively low frequency and with horizontal scales above the first baroclinic deformation radius; the intrinsic frequency of high‐mode IGWs (submesoscale flows) is above (well below) the inertial frequency. The validity and usefulness of the proposed methodology are demonstrated with a proof‐of‐concept application to simulated flows in the central basin of the South China Sea.
The Impact of Plant Oscillation on Dispersion in Emergent Aquatic Canopies
Authors: Sehat H. , Abdolahpour M. , Jamali M. , Ghisalberti M.
Published: March 2023

Flexible canopies bend and oscillate in both the in‐line and cross‐flow directions due to periodic forcing associated with vortex shedding. The resultant plant motion impacts the vegetation wake structure and, thus, the rate of lateral dispersion in these environments. Despite significant improvements in our understanding of dispersion in rigid canopies, a reliable framework to predict mixing in oscillating canopies is still lacking. This research demonstrates how plant oscillation can profoundly impact rates of lateral mixing in steady flows. The lateral dispersion coefficients were evaluated experimentally, using photographs of injected dye plumes within two types of emergent flexible model vegetation. Results revealed a significant increase in the rates of lateral dispersion (by up to 45%) due to the plant oscillation. A predictive model, based on a redefined vegetation density that incorporates the impact of plant oscillation, was developed that can accurately predict dispersion in emergent canopies. A quantitative prediction of dispersion in oscillating flexible vegetation is a significant step toward a more accurate description of material transport in aquatic environments.
Novel multivalent S100A8 inhibitory peptides attenuate tumor progression and metastasis by inhibiting the TLR4-dependent pathway
Authors: Deguchi Atsuko , Watanabe-Takahashi Miho , Mishima Taishi , Omori Tsutomu , Ohto Umeharu , Arashiki Nobuto , Nakamura Fumio , Nishikawa Kiyotaka , Maru Yoshiro
Published: March 2023

The tumor-elicited inflammation is closely related to tumor microenvironment during tumor progression. S100A8, an endogenous ligand of Toll-like receptor 4 (TLR4), is known as a key molecule in the tumor microenvironment and premetastatic niche formation. We firstly generated a novel multivalent S100A8 competitive inhibitory peptide (divalent peptide3A5) against TLR4/MD-2, using the alanine scanning. Divalent peptide3A5 suppressed S100A8-mediated interleukin-8 and vascular endothelial growth factor production in human colorectal tumor SW480 cells. Using SW480-transplanted xenograft models, divalent peptide3A5 suppressed tumor progression in a dose-dependent manner. We demonstrated that combination therapy with divalent peptide3A5 and bevacizumab synergistically suppressed tumor growth in SW480 xenograft models. Using syngeneic mouse models, we found that divalent peptide3A5 improved the efficacy of anti-programmed death (PD)1 antibody, and lung metastasis. In addition, by using multivalent peptide library screening based on peptide3A5, we then isolated two more candidates; divalent ILVIK, and tetravalent ILVIK. Of note, multivalent ILVIK, but not monovalent ILVIK showed competitive inhibitory activity against TLR4/MD-2 complex, and anti-tumoral activity in SW480 xenograft models. As most tumor cells including SW480 cells also express TLR4, S100A8 inhibitory peptides would target both the tumor microenvironment and tumor cells. Thus, multivalent S100A8 inhibitory peptides would provide new pharmaceutical options for aggressive cancers.
HIF1α-BNIP3-mediated mitophagy protects against renal fibrosis by decreasing ROS and inhibiting activation of the NLRP3 inflammasome
Authors: Li Jialin , Lin Qisheng , Shao Xinghua , Li Shu , Zhu Xuying , Wu Jingkui , Mou Shan , Gu Leyi , Wang Qin , Zhang Minfang , Zhang Kaiqi , Lu Jiayue , Ni Zhaohui
Published: March 2023

Chronic kidney disease affects approximately 14.3% of people worldwide. Tubulointerstitial fibrosis is the final stage of almost all progressive CKD. To date, the pathogenesis of renal fibrosis remains unclear, and there is a lack of effective treatments, leading to renal replacement therapy. Mitophagy is a type of selective autophagy that has been recognized as an important way to remove dysfunctional mitochondria and abrogate the excessive accumulation of mitochondrial-derived reactive oxygen species (ROS) to balance the function of cells. However, the role of mitophagy and its regulation in renal fibrosis need further examination. In this study, we showed that mitophagy was induced in renal tubular epithelial cells in renal fibrosis. After silencing BNIP3, mitophagy was abolished in vivo and in vitro, indicating the important effect of the BNIP3-dependent pathway on mitophagy. Furthermore, in unilateral ureteral obstruction (UUO) models and hypoxic conditions, the production of mitochondrial ROS, mitochondrial damage, activation of the NLRP3 inflammasome, and the levels of αSMA and TGFβ1 increased significantly following BNIP3 gene deletion or silencing. Following silencing BNIP3 and pretreatment with mitoTEMPO or MCC950, the protein levels of αSMA and TGFβ1 decreased significantly in HK-2 cells under hypoxic conditions. These findings demonstrated that HIF1α-BNIP3-mediated mitophagy played a protective role against hypoxia-induced renal epithelial cell injury and renal fibrosis by reducing mitochondrial ROS and inhibiting activation of the NLRP3 inflammasome.
CRISPR-induced DNA reorganization for multiplexed nucleic acid detection
Authors: Karlikow Margot , Amalfitano Evan , Yang Xiaolong , Doucet Jennifer , Chapman Abigail , Mousavi Peivand Sadat , Homme Paige , Sutyrina Polina , Chan Winston , Lemak Sofia , Yakunin Alexander F. , Dolezal Adam G. , Kelley Shana , Foster Leonard J. , Harpur Brock A. , Pardee Keith
Published: March 2023

Nucleic acid sensing powered by the sequence recognition of CRIPSR technologies has enabled major advancement toward rapid, accurate and deployable diagnostics. While exciting, there are still many challenges facing their practical implementation, such as the widespread need for a PAM sequence in the targeted nucleic acid, labile RNA inputs, and limited multiplexing. Here we report FACT (Functionalized Amplification CRISPR Tracing), a CRISPR-based nucleic acid barcoding technology compatible with Cas12a and Cas13a, enabling diagnostic outputs based on cis- and trans-cleavage from any sequence. Furthermore, we link the activation of CRISPR-Cas12a to the expression of proteins through a Reprogrammable PAIRing system (RePAIR). We then combine FACT and RePAIR to create FACTOR (FACT on RePAIR), a CRISPR-based diagnostic, that we use to detect infectious disease in an agricultural use case: honey bee viral infection. With high specificity and accuracy, we demonstrate the potential of FACTOR to be applied to the sensing of any nucleic acid of interest.
Seasonality of downward carbon export in the Pacific Southern Ocean revealed by multi-year robotic observations
Authors: Lacour Léo , Llort Joan , Briggs Nathan , Strutton Peter G. , Boyd Philip W.
Published: March 2023

At high latitudes, the biological carbon pump, which exports organic matter from the surface ocean to the interior, has been attributed to the gravitational sinking of particulate organic carbon. Conspicuous deficits in ocean carbon budgets challenge this as a sole particle export pathway. Recent model estimates revealed that particle injection pumps have a comparable downward flux of particulate organic carbon to the biological gravitational pump, but with different seasonality. To date, logistical constraints have prevented concomitant and extensive observations of these mechanisms. Here, using year-round robotic observations and recent advances in bio-optical signal analysis, we concurrently investigated the functioning of two particle injection pumps, the mixed layer and eddy subduction pumps, and the gravitational pump in Southern Ocean waters. By comparing three annual cycles in contrasting physical and biogeochemical environments, we show how physical forcing, phytoplankton phenology and particle characteristics influence the magnitude and seasonality of these export pathways, with implications for carbon sequestration efficiency over the annual cycle.
A melanopsin ganglion cell subtype forms a dorsal retinal mosaic projecting to the supraoptic nucleus
Authors: Berry Michael H. , Moldavan Michael , Garrett Tavita , Meadows Marc , Cravetchi Olga , White Elizabeth , Leffler Joseph , von Gersdorff Henrique , Wright Kevin M. , Allen Charles N. , Sivyer Benjamin
Published: March 2023

Visual input to the hypothalamus from intrinsically photosensitive retinal ganglion cells (ipRGCs) influences several functions including circadian entrainment, body temperature, and sleep. ipRGCs also project to nuclei such as the supraoptic nucleus (SON), which is involved in systemic fluid homeostasis, maternal behavior, social behaviors, and appetite. However, little is known about the SON-projecting ipRGCs or their relationship to well-characterized ipRGC subtypes. Using aGlyT2Cremouse line, we show a subtype of ipRGCs restricted to the dorsal retina that selectively projects to the SON. These ipRGCs tile a dorsal region of the retina, forming a substrate for encoding ground luminance. Optogenetic activation of their axons demonstrates they release the neurotransmitter glutamate in multiple regions, including the suprachiasmatic nucleus (SCN) and SON. Our results challenge the idea that ipRGC dendrites overlap to optimize photon capture and suggests non-image forming vision operates to sample local regions of the visual field to influence diverse behaviors.
Synergy of cations in high entropy oxide lithium ion battery anode
Authors: Wang Kai , Hua Weibo , Huang Xiaohui , Stenzel David , Wang Junbo , Ding Ziming , Cui Yanyan , Wang Qingsong , Ehrenberg Helmut , Breitung Ben , Kübel Christian , Mu Xiaoke
Published: March 2023

High entropy oxides (HEOs) with chemically disordered multi-cation structure attract intensive interest as negative electrode materials for battery applications. The outstanding electrochemical performance has been attributed to the high-entropy stabilization and the so-called ‘cocktail effect’. However, the configurational entropy of the HEO, which is thermodynamically only metastable at room-temperature, is insufficient to drive the structural reversibility during conversion-type battery reaction, and the ‘cocktail effect’ has not been explained thus far. This work unveils the multi-cations synergy of the HEO Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O at atomic and nanoscale during electrochemical reaction and explains the ‘cocktail effect’. The more electronegative elements form an electrochemically inert 3-dimensional metallic nano-network enabling electron transport. The electrochemical inactive cation stabilizes an oxide nanophase, which is semi-coherent with the metallic phase and accommodates Li+ ions. This self-assembled nanostructure enables stable cycling of micron-sized particles, which bypasses the need for nanoscale pre-modification required for conventional metal oxides in battery applications. This demonstrates elemental diversity is the key for optimizing multi-cation electrode materials.
The protective role of conjunctival goblet cell mucin sialylation
Authors: Matsuzawa Moe , Ando Tomoaki , Fukase Saaya , Kimura Meiko , Kume Yasuharu , Ide Takuma , Izawa Kumi , Kaitani Ayako , Hara Mutsuko , Nakamura Eri , Kamei Anna , Matsuda Akira , Nakano Nobuhiro , Maeda Keiko , Tada Norihiro , Ogawa Hideoki , Okumura Ko , Murakami Akira , Ebihara Nobuyuki , Kitaura Jiro
Published: March 2023

Gel-forming mucins secreted by conjunctival goblet cells have been implicated in the clearance of allergens, pathogens, and debris. However, their roles remain incompletely understood. Here we show that human and mouse conjunctival goblet cell mucins have Alcian blue-detectable sialic acids, but not sulfates in the steady state. Interestingly, Balb/c mouse strain lacks this sialylation due to a point mutation in a sialyltransferase gene, St6galnac1, which is responsible for sialyl-Tn synthesis. Introduction of intact St6galnac1 to Balb/c restores the sialylation of conjunctival goblet cell mucus. Sialylated mucus efficiently captures and encapsulates the allergen particles in an impenetrable layer, leading to the protection of mice from the development of allergic conjunctivitis. Expression of ST6GALNAC1 and sialyl-Tn is upregulated in humans under conditions with chronic stimuli. These results indicate that the sialylated glycans on the ocular mucins play an essential role in maintaining the conjunctival mucosa by protecting from the incoming foreign bodies such as allergen particles.
Wavelength engineerable porous organic polymer photosensitizers with protonation triggered ROS generation
Authors: Shin Jinwoo , Kang Dong Won , Lim Jong Hyeon , An Jong Min , Kim Youngseo , Kim Ji Hyeon , Ji Myung Sun , Park Sungnam , Kim Dokyoung , Lee Jin Yong , Kim Jong Seung , Hong Chang Seop
Published: March 2023

Engineering excitation wavelength of photosensitizers (PSs) for enhanced reactive oxygen species (ROS) generation has inspired new windows for opportunities, enabling investigation of previously impracticable biomedical and photocatalytic applications. However, controlling the wavelength corresponding to operating conditions remains challenging while maintaining high ROS generation. To address this challenge, we implement a wavelength-engineerable imidazolium-based porous organic photocatalytic ROS generation system (KUP system) via a cost-effective one-pot reaction. Remarkably, the optimal wavelength for maximum performance can be tuned by modifying the linker, generating ROS despite the absence of metal ions and covalently attached heavy atoms. We demonstrate that protonated polymerization exclusively enables photosensitization and closely interacts with oxygen related to the efficiency of photosensitizing. Furthermore, superior tumor eradication and biocompatibility of the KUP system were confirmed through bioassays. Overall, the results document an unprecedented polymerization method capable of engineering wavelength, providing a potential basis for designing nanoscale photosensitizers in various ROS-utilizing applications.
Telomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts
Authors: Adegunsoye Ayodeji , Newton Chad A. , Oldham Justin M. , Ley Brett , Lee Cathryn T. , Linderholm Angela L. , Chung Jonathan H. , Garcia Nicole , Zhang Da , Vij Rekha , Guzy Robert , Jablonski Renea , Bag Remzi , Voogt Rebecca S. , Ma Shwu-Fan , Sperling Anne I. , Raghu Ganesh , Martinez Fernando J. , Strek Mary E. , Wolters Paul J. , Garcia Christine Kim , Pierce Brandon L. , Noth Imre
Published: March 2023

Pulmonary fibrosis (PF) is characterized by profound scarring and poor survival. We investigated the association of leukocyte telomere length (LTL) with chronological age and mortality across racially diverse PF cohorts. LTL measurements among participants with PF stratified by race/ethnicity were assessed in relation to age and all-cause mortality, and compared to controls. Generalized linear models were used to evaluate the age-LTL relationship, Cox proportional hazards models were used for hazard ratio estimation, and the Cochran–Armitage test was used to assess quartiles of LTL. Standardized LTL shortened with increasing chronological age; this association in controls was strengthened in PF (R = −0.28; P < 0.0001). In PF, age- and sex-adjusted LTL below the median consistently predicted worse mortality across all racial groups (White, HR = 2.21, 95% CI = 1.79–2.72; Black, HR = 2.22, 95% CI = 1.05–4.66; Hispanic, HR = 3.40, 95% CI = 1.88–6.14; and Asian, HR = 2.11, 95% CI = 0.55–8.23). LTL associates uniformly with chronological age and is a biomarker predictive of mortality in PF across racial groups.
Insights into membrane association of the SMP domain of extended synaptotagmin
Authors: Wang Yunyun , Li Zhenni , Wang Xinyu , Zhao Ziyuan , Jiao Li , Liu Ruming , Wang Keying , Ma Rui , Yang Yang , Chen Guo , Wang Yong , Bian Xin
Published: March 2023

The Synaptotagmin-like Mitochondrial-lipid-binding Protein (SMP) domain is a newly identified lipid transfer module present in proteins that regulate lipid homeostasis at membrane contact sites (MCSs). However, how the SMP domain associates with the membrane to extract and unload lipids is unclear. Here, we performed in vitro DNA brick-assisted lipid transfer assays and in silico molecular dynamics simulations to investigate the molecular basis of the membrane association by the SMP domain of extended synaptotagmin (E-Syt), which tethers the tubular endoplasmic reticulum (ER) to the plasma membrane (PM). We demonstrate that the SMP domain uses its tip region to recognize the extremely curved subdomain of tubular ER and the acidic-lipid-enriched PM for highly efficient lipid transfer. Supporting these findings, disruption of these mechanisms results in a defect in autophagosome biogenesis contributed by E-Syt. Our results suggest a model that provides a coherent picture of the action of the SMP domain at MCSs.
Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease
Authors: Powell Nicholas R. , Liang Tiebing , Ipe Joseph , Cao Sha , Skaar Todd C. , Desta Zeruesenay , Qian Hui-Rong , Ebert Philip J. , Chen Yu , Thomas Melissa K. , Chalasani Naga
Published: March 2023

Polypharmacy is common in patients with nonalcoholic fatty liver disease (NAFLD) and previous reports suggest that NAFLD is associated with altered drug disposition. This study aims to determine if patients with NAFLD are at risk for altered drug response by characterizing changes in hepatic mRNA expression of genes mediating drug disposition (pharmacogenes) across the histological NAFLD severity spectrum. We utilize RNA-seq for 93 liver biopsies with histologically staged NAFLD Activity Score (NAS), fibrosis stage, and steatohepatitis (NASH). We identify 37 significant pharmacogene-NAFLD severity associations including CYP2C19 downregulation. We chose to validate CYP2C19 due to its actionability in drug prescribing. Meta-analysis of 16 independent studies demonstrate that CYP2C19 is significantly downregulated to 46% in NASH, to 58% in high NAS, and to 43% in severe fibrosis. Our data demonstrate the downregulation of CYP2C19 in NAFLD which supports developing personalized medicine approaches for drugs sensitive to metabolism by the CYP2C19 enzyme.
Blocking Dectin-1 prevents colorectal tumorigenesis by suppressing prostaglandin E2 production in myeloid-derived suppressor cells and enhancing IL-22 binding protein expression
Authors: Tang Ce , Sun Haiyang , Kadoki Motohiko , Han Wei , Ye Xiaoqi , Makusheva Yulia , Deng Jianping , Feng Bingbing , Qiu Ding , Tan Ying , Wang Xinying , Guo Zehao , Huang Chanyan , Peng Sui , Chen Minhu , Adachi Yoshiyuki , Ohno Naohito , Trombetta Sergio , Iwakura Yoichiro
Published: March 2023

Dectin-1 (gene Clec7a), a receptor for β-glucans, plays important roles in the host defense against fungi and immune homeostasis of the intestine. Although this molecule is also suggested to be involved in the regulation of tumorigenesis, the role in intestinal tumor development remains to be elucidated. In this study, we find that azoxymethane-dextran-sodium-sulfate-induced and ApcMin-induced intestinal tumorigenesis are suppressed in Clec7a−/− mice independently from commensal microbiota. Dectin-1 is preferentially expressed on myeloid-derived suppressor cells (MDSCs). In the Clec7a−/− mouse colon, the proportion of MDSCs and MDSC-derived prostaglandin E2 (PGE2) levels are reduced, while the expression of IL-22 binding protein (IL-22BP; gene Il22ra2) is upregulated. Dectin-1 signaling induces PGE2-synthesizing enzymes and PGE2 suppresses Il22ra2 expression in vitro and in vivo. Administration of short chain β-glucan laminarin, an antagonist of Dectin-1, suppresses the development of mouse colorectal tumors. Furthermore, in patients with colorectal cancer (CRC), the expression of CLEC7A is also observed in MDSCs and correlated with the death rate and tumor severity. Dectin-1 signaling upregulates PGE2-synthesizing enzyme expression and PGE2 suppresses IL22RA2 expression in human CRC-infiltrating cells. These observations indicate a role of the Dectin-1-PGE2-IL-22BP axis in regulating intestinal tumorigenesis, suggesting Dectin-1 as a potential target for CRC therapy.
Brain-wide and cell-specific transcriptomic insights into MRI-derived cortical morphology in macaque monkeys
Authors: Bo Tingting , Li Jie , Hu Ganlu , Zhang Ge , Wang Wei , Lv Qian , Zhao Shaoling , Ma Junjie , Qin Meng , Yao Xiaohui , Wang Meiyun , Wang Guang-Zhong , Wang Zheng
Published: March 2023

Integrative analyses of transcriptomic and neuroimaging data have generated a wealth of information about biological pathways underlying regional variability in imaging-derived brain phenotypes in humans, but rarely in nonhuman primates due to the lack of a comprehensive anatomically-defined atlas of brain transcriptomics. Here we generate complementary bulk RNA-sequencing dataset of 819 samples from 110 brain regions and single-nucleus RNA-sequencing dataset, and neuroimaging data from 162 cynomolgus macaques, to examine the link between brain-wide gene expression and regional variation in morphometry. We not only observe global/regional expression profiles of macaque brain comparable to human but unravel a dorsolateral-ventromedial gradient of gene assemblies within the primate frontal lobe. Furthermore, we identify a set of 971 protein-coding and 34 non-coding genes consistently associated with cortical thickness, specially enriched for neurons and oligodendrocytes. These data provide a unique resource to investigate nonhuman primate models of human diseases and probe cross-species evolutionary mechanisms.
Fabrication of phosphor in glass using waste glass for automotive lighting application
Authors: Choi Seung Hee , Kwon Seok Bin , Yoo Jung Hyeon , Na MinYoung , Kim Bo Young , Yoon HoShin , Park Seoung Hyok , Kinski Isabel , Kang Bong Kyun , Yoon Dae Ho , Song Young Hyun
Published: March 2023

With advancement of technology, requirements for light-emitting devices are increasing. Various types of packaging technologies have been suggested to improve the performance of light-emitting diode (LED). Among them, phosphor in glass (PiG) is attracting attention due to its manufactural facility and easily tunable characteristics. As PiG draws increasing attention, research on glass materials is also being actively conducted. However, studies about glass in the field of phosphor are mainly conducted on fabrication. Only a few studies about recycling have been reported. Thus, the objective of this study was to recycle waste glass discarded in other fields due to breakage and failure and use it to fabricate phosphor in glass. Cylindrical waste glass was pulverized into powder with an average size of 12 μm, mixed with a phosphor and sintered to be reborn as a phosphor in glass to broaden the recycling route for waste glass.
Practical overview of image classification with tensor-network quantum circuits
Authors: Guala Diego , Zhang Shaoming , Cruz Esther , Riofrío Carlos A. , Klepsch Johannes , Arrazola Juan Miguel
Published: March 2023

Circuit design for quantum machine learning remains a formidable challenge. Inspired by the applications of tensor networks across different fields and their novel presence in the classical machine learning context, one proposed method to design variational circuits is to base the circuit architecture on tensor networks. Here, we comprehensively describe tensor-network quantum circuits and how to implement them in simulations. This includes leveraging circuit cutting, a technique used to evaluate circuits with more qubits than those available on current quantum devices. We then illustrate the computational requirements and possible applications by simulating various tensor-network quantum circuits with PennyLane, an open-source python library for differential programming of quantum computers. Finally, we demonstrate how to apply these circuits to increasingly complex image processing tasks, completing this overview of a flexible method to design circuits that can be applied to industrially-relevant machine learning tasks.
Micro-CT-derived ventilation biomarkers for the longitudinal assessment of pathology and response to therapy in a mouse model of lung fibrosis
Authors: Pennati Francesca , Leo Ludovica , Ferrini Erica , Sverzellati Nicola , Bernardi Davide , Stellari Franco Fabio , Aliverti Andrea
Published: March 2023

Experimental in-vivo animal models are key tools to investigate the pathogenesis of lung disease and to discover new therapeutics. Histopathological and biochemical investigations of explanted lung tissue are currently considered the gold standard, but they provide space-localized information and are not amenable to longitudinal studies in individual animals. Here, we present an imaging procedure that uses micro-CT to extract morpho-functional indicators of lung pathology in a murine model of lung fibrosis. We quantified the decrease of lung ventilation and measured the antifibrotic effect of Nintedanib. A robust structure-function relationship was revealed by cumulative data correlating micro-CT with histomorphometric endpoints. The results highlight the potential of in-vivo micro-CT biomarkers as novel tools to monitor the progression of inflammatory and fibrotic lung disease and to shed light on the mechanism of action of candidate drugs. Our platform is also expected to streamline translation from preclinical studies to human patients.
Systematic analysis of prophage elements in actinobacterial genomes reveals a remarkable phylogenetic diversity
Authors: Sharma Vikas , Hünnefeld Max , Luthe Tom , Frunzke Julia
Published: March 2023

Actinobacteria represent one of the largest bacterial phyla harboring many species of high medical, biotechnological and ecological relevance. Prophage elements are major contributors to bacterial genome diversity and were shown to significantly shape bacterial fitness and host-microbe interactions. In this study, we performed a systematic analysis of prophage elements in 2406 complete actinobacterial genomes. Overall, 2106 prophage elements were predicted to be present in about 50% (1172/2406) of the analyzed datasets. Interestingly, these identified sequences compose a high prevalence of cryptic prophage elements, indicating genetic decay and domestication. Analysis of the sequence relationship of predicted prophages with known actinobacteriophage genomes revealed an exceptional high phylogenetic diversity of prophage elements. As a trend, we observed a higher prevalence of prophage elements in vicinity to the terminus. Analysis of the prophage-encoded gene functions revealed that prophage sequences significantly contribute to the bacterial antiviral immune system, but no biosynthetic gene clusters involved in the synthesis of known antiphage molecules were identified in prophage genomes. Overall, the current study highlights the remarkable diversity of prophages in actinobacterial genomes, with highly divergent prophages in actinobacterial genomes and thus provides an important basis for further investigation of phage-host interactions in this important bacterial phylum.
The broad scale impact of climate change on planning aerial wildlife surveys with drone-based thermal cameras
Authors: Camacho Annalysa M. , Perotto-Baldivieso Humberto L. , Tanner Evan P. , Montemayor Amanda L. , Gless Walter A. , Exum Jesse , Yamashita Thomas J. , Foley Aaron M. , DeYoung Randy W. , Nelson Shad D.
Published: March 2023

Helicopters used for aerial wildlife surveys are expensive, dangerous and time consuming. Drones and thermal infrared cameras can detect wildlife, though the ability to detect individuals is dependent on weather conditions. While we have a good understanding of local weather conditions, we do not have a broad-scale assessment of ambient temperature to plan drone wildlife surveys. Climate change will affect our ability to conduct thermal surveys in the future. Our objective was to determine optimal annual and daily time periods to conduct surveys. We present a case study in Texas, (United States of America [USA]) where we acquired and compared average monthly temperature data from 1990 to 2019, hourly temperature data from 2010 to 2019 and projected monthly temperature data from 2021 to 2040 to identify areas where surveys would detect a commonly studied ungulate (white-tailed deer [Odocoileus virginianus]) during sunny or cloudy conditions. Mean temperatures increased when comparing the 1990–2019 to 2010–2019 periods. Mean temperatures above the maximum ambient temperature in which white-tailed deer can be detected increased in 72, 10, 10, and 24 of the 254 Texas counties in June, July, August, and September, respectively. Future climate projections indicate that temperatures above the maximum ambient temperature in which white-tailed deer can be detected will increase in 32, 12, 15, and 47 counties in June, July, August, and September, respectively when comparing 2010–2019 with 2021–2040. This analysis can assist planning, and scheduling thermal drone wildlife surveys across the year and combined with daily data can be efficient to plan drone flights.