bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary intake of pistachios or mixed nuts results in higher systemic antioxidant capacity with minimal effects on bone in adolescent male rats
Authors: Wickman Brooke E. , Clayton Zachary S. , Rochester Eric , Kern Mark , Hong Mee Young , Liu Changqi , Hooshmand Shirin
Published: January 2023

Nutrition is a key determinant of bone health and attainment of peak bone mass. Excess oxidative stress induces bone loss while increasing antioxidant capacity promotes protective effects on bone. Nuts are rich in antioxidants; therefore, we tested the hypothesis that compared to a control diet high in fat (40 % energy) and cholesterol, diets containing isocaloric amounts of pistachios (8·1 % g/g) or mixed nuts (7·5 % g/g) for 8 weeks would result in greater bone health in male adolescent (3 weeks; a state of continued skeletal growth) Sprague-Dawley rats. We found no difference in bone mechanical properties among groups. Tibial apparent density was ~5 % higher in the pistachio and mixed nuts groupsv. control (P< 0·05) with no clear difference detected for the femur. Expressions of genes known to impact bone turnover and serum bone turnover biomarkers were unaffected by either diet relative to control. Serum antioxidant capacity was ~2-fold higher in the pistachio and mixed nuts groups compared with control (P< 0·05) but were similar between groups. Therefore, pistachios and mixed nuts may increase tibial density, in part, due to increasing antioxidant capacity. Longer dietary interventions may be necessary to elicit detectable changes in other bones (e.g. femur) and to detect potential mechanisms for the possible bone protective effects of nuts.
Asia Faces a Growing Threat From Intraseasonal Compound Weather Whiplash
Authors: Fang Beijing , Lu Mengqian
Published: January 2023

The sudden swings between drought/heat and pluvial could cause adverse impacts far surpassing the sum of their individual effect. We propose a concept of intraseasonal “compound whiplash event” (CWE) to investigate sudden swings between wet and the compounding warm‐dry events and their changes under climate change. We find that global warming would likely escalate the compound whiplash frequency to two to three and half times (two to three times) by the end of the 21st century under the business‐as‐usual scenario (mitigated scenario). The growing threat of CWE not only stems from the increasing occurrence but also from its intensified severity and extended spatial coverage. Among all sub‐regions, East Asian summer monsoon (EASM) region would expect the largest intensification. The resulting population exposure would soar two‐to‐three‐fold over Asia. Populous regions such as North India and EASM region might face a much worse situation than the western China where population is sparse and projected to decline. Moreover, the seasonality of swings with opposite directions would further split as a response to the skewed Asian monsoon annual cycle, leading to more frequent heat‐drought to pluvial swings in spring, and more opposite‐direction swings in autumn, disrupting cultivation and water management convention.
The Unlocking Process Leading to the 2016 Central Italy Seismic Sequence
Authors: Sugan M. , Campanella S. , Chiaraluce L. , Michele M. , Vuan A.
Published: January 2023

Approximately 23,000 well‐located earthquakes from 2009 to 2016 are used as templates to recover seismic activity preceding the 2016 Central Italy seismic sequence. The resulting spatiotemporal pattern is analyzed by additional ∼91,000 newly detected events. In the 8 years before the sequence onset, seismicity (ML ≤ 3.7) develops at the hangingwall of the 2016 normal faults and along a sub‐horizontal shear zone, bounding the active extensional system at depth. This activity, mainly organized in foreshock‐mainshock and swarm‐like clusters, migrates toward the nucleation area of the first Mw 6.0 mainshock of the sequence (24th of August in Amatrice). We propose an unlocking process based on variable temporal clustering of the seismicity, including repeaters, identifying fault portions with different degrees of coupling. Such a progressive localization of the seismic activity at the fault edges induces a weakening of the locked patch of the Amatrice mainshock.
Electron‐Scale Front of Magnetic Pile‐Up Region in Reconnection Exhaust
Authors: Chen Z. Z. , Liu C. M. , Yu J. , Wang T. Y. , Wang J. , Cui J. , Cao J. B.
Published: January 2023

The magnetic pile‐up region and its front, which plays a crucial role in electron energization during magnetic reconnection, has been widely studied at fluid and ion scales. However, there have been few studies on electron‐scale front of magnetic pile‐up regions so far. Here, we present detailed observations of electron‐scale front in a tailward reconnection exhaust. With a thickness of ∼5.5 de (electron inertial length), the front propagated along its normal direction, mainly along the reconnection outflow direction. At this front, the strong energy conversion observed was mainly driven by the perpendicular electron current. The front can lead to adiabatic electron heating and acceleration. The front hosts an intense and highly structured electric field, reaching up to ∼120 mV/m and predominantly attributed to the electron convection term. Electrostatic waves with frequencies higher than the electron gyrofrequency and parallel normal angles (WRT background magnetic field) were detected adjacent to the front. Our study can provide insight into the roles of fronts and electron‐scale physics in magnetic reconnection.
Influence of Mesospheric Gravity Wave Drag on the Formation of Winter Helium Bulge in the Thermosphere
Authors: Ren Dexin , Lei Jiuhou , Liu Han‐Li , Wang Wenbin , Yue Jia , Liu Huixin
Published: January 2023

In this study, we focused on the influences of mesospheric gravity wave drag on the winter helium bulge in the thermosphere. The related physical mechanisms are investigated based on the three‐dimensional physics‐based Thermosphere‐Ionosphere‐Mesosphere Electrodynamic General Circulation Model. The simulation results suggested that the mesospheric gravity wave drag can contribute to the high amplitude of winter helium bulge due to the intensified summer‐to‐winter circulation in the thermosphere. It was found that the meridional pressure gradient force, which dominates the generation of thermospheric large‐scale circulation, shows an increase when the effect of mesospheric gravity wave drag is considered. The change in thermospheric pressure force is attributed to the mesospheric gravity wave drag related winter‐to‐summer flow in the lower thermosphere. This intensified summer‐to‐winter circulation in the thermosphere leads to the decrease and increase of helium concentration in summer and winter, respectively, which thus contributes to the thermospheric winter helium bulge under the effects of mesospheric gravity wave drag.
Regional Sources and Seasonal Variability of Rainwater Dissolved Organic and Inorganic Nitrogen at a Mid‐Atlantic, USA Coastal Site
Authors: Czarnecki J. I. , Levia D. F. , Scudlark J. R. , Ouyang T. , Wozniak A. S.
Published: January 2023

Changes in anthropogenic activities have altered the speciation and concentration of inorganic reactive nitrogen (Nr) delivered to coastal and oceanic waters with precipitation. Less is known about rainwater dissolved organic nitrogen (DON) despite its quantitative importance (>20% of Nr) and potential contributions to primary and secondary production. We document decreases in rainwater nitrogen and carbon amounts between 1994 and 2019 in Delaware, USA with the major reduction observed for nitrate (64%) reflecting emissions technology improvements. [DON] in 2019 was 55% that of 1994, though only 2 years of data are available precluding any assessment of trends. Season, airmass back trajectory (AMBT), rainfall amount, and meteorology influenced Nr amounts in 2018–2019 rain. [DON], which peaked in Summer, had different seasonal patterns than inorganic Nr and dissolved organic carbon, suggesting a biological source. Marine AMBT events showed the lowest Nr abundances. AMBTs from the southwest had the highest concentrations of Nr and DOC partially due to low rainfall amounts. Characterization of the oxidized fraction of DON revealed abundant highly unsaturated aliphatic and peptide‐like formulas suggesting a combination of secondary organic, biomass burning, and biological sources. The large changes in Nr and DOC loads emphasize the dynamic nature of atmosphere to land/water fluxes due to the influence of anthropogenic processes with potential implications for coastal and oceanic water quality and ecology. Models of atmospheric deposition to watersheds and the ocean should be frequently reevaluated with current data to accurately assess inputs from changing atmospheric sources.
Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure
Authors: Hollestein Viola , Poelmans Geert , Forde Natalie J. , Beckmann Christian F. , Ecker Christine , Mann Caroline , Schäfer Tim , Moessnang Carolin , Baumeister Sarah , Banaschewski Tobias , Bourgeron Thomas , Loth Eva , Dell’Acqua Flavio , Murphy Declan G. M. , Puts Nicolaas A. , Tillmann Julian , Charman Tony , Jones Emily J. H. , Mason Luke , Ambrosino Sara , Holt Rosemary , Bölte Sven , Buitelaar Jan K. , Naaijen Jilly
Published: January 2023

The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods—combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6–30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.
USP14 promotes colorectal cancer progression by targeting JNK for stabilization
Authors: Du Xue-Hua , Ke Shao-Bo , Liang Xin-Yi , Gao Jie , Xie Xiao-Xiao , Qi Lin-Zhi , Liu Xue-Yi , Xu Guo-Yuan , Zhang Xiao-Dong , Du Run-Lei , Li Shang-Ze
Published: January 2023

MAPK/JNK signaling is pivotal in carcinogenesis. However, ubiquitin-mediated homeostasis of JNK remains to be verified. Here, with results from RNA sequencing (RNA-seq) and luciferase reporter pathway identification, we show that USP14 orchestrates MAPK/JNK signaling and identify USP14 as a deubiquitinase that interacts and stabilizes JNK. USP14 is elevated in colorectal cancer patients and is positively associated with JNK protein and downstream gene expression. USP14 ablation reduces cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by downregulating MAPK/JNK pathway activation. Moreover, USP14 expression is induced by TNF-α, forming a feedback loop with JNK and leading to tumor amplification. Our study suggests that elevated expression of USP14 promotes MAPK/JNK signaling by stabilizing JNK, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased USP14 expression.
Phosphorylation of UHRF2 affects malignant phenotypes of HCC and HBV replication by blocking DHX9 ubiquitylation
Authors: Wu Kejia , Zhang Yiqi , Liu Yuxin , Li Qingxiu , Chen Yong , Chen Juan , Duan Changzhu
Published: January 2023

Hepatitis B virus (HBV) infection is one of main contributors to poor prognosis and rapid progression of hepatocellular cancer (HCC). We previously identified the important role of the phosphorylation of ubiquitin-like with PHD and ring finger domains (UHRF2) in HBV-associated HCC. In this study we identify upregulated UHRF2 protein levels in HBV-associated HCC cells and tissues. UHRF2 overexpression promotes the viability, proliferation, migration and invasiveness of HBV-positive HCC cell lines, and enhances HBV DNA replication. To obtain a comprehensive understanding of the interaction networks of UHRF2 and their underlying mechanism, this study suggests that UHRF2 facilitates the ubiquitin-proteasome-mediated proteolysis of DExD/H (Asp-Glu-Ala-His) -box helicase enzyme 9 (DHX9). However, phosphorylation of UHRF2 by HBx at S643 inhibits E3 ubiquitin ligase activity of UHRF2 and improves DHX9 protein stability. Furthermore, results suggest that HBx promotes phosphorylation of UHRF2 by the ETS1-CDK2 axis through the downregulation of miR-222-3p in HBV-associated HCC specimens and cells. Our findings suggest that HBx-induced phosphorylation of UHRF2 S643 acts as a “switch” in HBV-associated HCC oncogenesis, activating the positive feedback between phosphorylated UHRF2 and HBV, provide evidence that UHRF2 is a new regulator and a potential prognostic indicator of poor prognosis for HBV-associated HCC.
Integrative genetic analysis illuminates ALS heritability and identifies risk genes
Authors: Megat Salim , Mora Natalia , Sanogo Jason , Roman Olga , Catanese Alberto , Alami Najwa Ouali , Freischmidt Axel , Mingaj Xhuljana , De Calbiac Hortense , Muratet François , Dirrig-Grosch Sylvie , Dieterle Stéphane , Van Bakel Nick , Müller Kathrin , Sieverding Kirsten , Weishaupt Jochen , Andersen Peter Munch , Weber Markus , Neuwirth Christoph , Margelisch Markus , Sommacal Andreas , Van Eijk Kristel R. , Veldink Jan H. ,   Project Mine Als Sequencing Consortium, Lautrette Géraldine , Couratier Philippe , Camuzat Agnès , Le Ber Isabelle , Grassano Maurizio , Chio Adriano , Boeckers Tobias , Ludolph Albert C. , Roselli Francesco , Yilmazer-Hanke Deniz , Millecamps Stéphanie , Kabashi Edor , Storkebaum Erik , Sellier Chantal , Dupuis Luc
Published: January 2023

Amyotrophic lateral sclerosis (ALS) has substantial heritability, in part shared with fronto-temporal dementia (FTD). We show that ALS heritability is enriched in splicing variants and in binding sites of 6 RNA-binding proteins including TDP-43 and FUS. A transcriptome wide association study (TWAS) identified 6 loci associated with ALS, including inNUP50encoding for the nucleopore basket protein NUP50. Independently, rare variants inNUP50were associated with ALS risk (P = 3.71.10−03; odds ratio = 3.29; 95%CI, 1.37 to 7.87) in a cohort of 9,390 ALS/FTD patients and 4,594 controls. Cells from one patient carrying aNUP50frameshift mutation displayed a decreased level of NUP50. Loss of NUP50 leads to death of cultured neurons, and motor defects inDrosophilaand zebrafish. Thus, our study identifies alterations in splicing in neurons as critical in ALS and provides genetic evidence linking nuclear pore defects to ALS.
A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene
Authors: Gao Yuandi , Guitton-Sert Laure , Dessapt Julien , Coulombe Yan , Rodrigue Amélie , Milano Larissa , Blondeau Andréanne , Larsen Nicolai Balle , Duxin Julien P. , Hussein Samer , Fradet-Turcotte Amélie , Masson Jean-Yves
Published: January 2023

Fanconi Anemia (FA) is a rare, genome instability-associated disease characterized by a deficiency in repairing DNA crosslinks, which are known to perturb several cellular processes, including DNA transcription, replication, and repair. Formaldehyde, a by-product of metabolism, is thought to drive FA by generating DNA interstrand crosslinks (ICLs) and DNA-protein crosslinks (DPCs). However, the impact of formaldehyde on global cellular pathways has not been investigated thoroughly. Herein, using a pangenomic CRISPR-Cas9 screen, we identify EXO1 as a critical regulator of formaldehyde-induced DNA lesions. We show that EXO1 knockout cell lines exhibit formaldehyde sensitivity leading to the accumulation of replicative stress, DNA double-strand breaks, and quadriradial chromosomes, a typical feature of FA. After formaldehyde exposure, EXO1 is recruited to chromatin, protects DNA replication forks from degradation, and functions in parallel with the FA pathway to promote cell survival. In vitro, EXO1-mediated exonuclease activity is proficient in removing DPCs. Collectively, we show that EXO1 limits replication stress and DNA damage to counteract formaldehyde-induced genome instability.
Acid enhanced zipping effect to densify MWCNT packing for multifunctional MWCNT films with ultra-high electrical conductivity
Authors: Wang Hong , Sun Xu , Wang Yizhuo , Li Kuncai , Wang Jing , Dai Xu , Chen Bin , Chong Daotong , Zhang Liuyang , Yan Junjie
Published: January 2023

The outstanding electrical and mechanical properties remain elusive on macroscopic carbon nanotube (CNT) films because of the difficult material process, which limits their wide practical applications. Herein, we report high-performance multifunctional MWCNT films that possess the specific electrical conductivity of metals as well as high strength. These MWCNT films were synthesized by a floating chemical vapor deposition method, purified at high temperature and treated with concentrated HCl, and then densified due to the developed chlorosulfonic acid-enhanced zipping effect. These large scalable films exhibit high electromagnetic interference shielding efficiency, high thermoelectric power factor, and high ampacity because of the densely packed crystalline structure of MWCNTs, which are promising for practical applications.
Population differentiated copy number variation between Eurasian wild boar and domesticated pig populations
Authors: Jang Jisung , Kim Bongsang , Jhang So Yun , Ahn Byeongyong , Kang Mingue , Park Chankyu , Cho Eun Seok , Kim Young-Sin , Park Woncheoul , Kim Heebal
Published: January 2023

Sus scrofa is a globally distributed livestock species that still maintains two different ways of life: wild and domesticated. Herein, we detected copy number variation (CNV) of 328 animals using short read alignment on Sscrofa11.1. We compared CNV among five groups of porcine populations: Asian domesticated (AD), European domesticated (ED), Asian wild (AW), European wild (EW), and Near Eastern wild (NEW). In total, 21,673 genes were identified on 154,872 copy number variation region (CNVR). Differences in gene copy numbers between populations were measured by considering the variance-based value $${V}_{ST}$$

V

ST

and the one-way ANOVA test followed by Scheffe test. As a result, 111 genes were suggested as copy number variable genes. Abnormally gained copy number on EEA1 in all populations was suggested the presence of minor CNV in the reference genome assembly, Sscrofa11.1. Copy number variable genes were related to meat quality, immune response, and reproduction traits. Hierarchical clustering of all individuals and mean pairwise $${V}_{ST}$$

V

ST

in breed level were visualized genetic relationship of 328 individuals and 56 populations separately. Our findings have shown how the complex history of pig evolution appears in genome-wide CNV of various populations with different regions and lifestyles.
Neuronal glutathione loss leads to neurodegeneration involving gasdermin activation
Authors: Hashimoto Shoko , Matsuba Yukio , Takahashi Mika , Kamano Naoko , Watamura Naoto , Sasaguri Hiroki , Takado Yuhei , Yoshihara Yoshihiro , Saito Takashi , Saido Takaomi C.
Published: January 2023

Accumulating evidence suggests that glutathione loss is closely associated with the progression of neurodegenerative disorders. Here, we found that the neuronal conditional-knockout (KO) of glutamyl-cysteine-ligase catalytic-subunit (GCLC), a rate-limiting enzyme for glutathione synthesis, induced brain atrophy accompanied by neuronal loss and neuroinflammation. GCLC-KO mice showed activation of C1q, which triggers engulfment of neurons by microglia, and disease-associated-microglia (DAM), suggesting that activation of microglia is linked to the neuronal loss. Furthermore, gasdermins, which regulate inflammatory form of cell death, were upregulated in the brains of GCLC-KO mice, suggesting the contribution of pyroptosis to neuronal cell death in these animals. In particular, GSDME-deficiency significantly attenuated the hippocampal atrophy and changed levels of DAM markers in GCLC-KO mice. Finally, we found that the expression of GCLC was decreased around amyloid plaques in AppNL-G-F AD model mice. AppNL-G-F mouse also exhibited inflammatory events similar to GCLC-KO mouse. We propose a mechanism by which a vicious cycle of oxidative stress and neuroinflammation enhances neurodegenerative processes. Furthermore, GCLC-KO mouse will serve as a useful tool to investigate the molecular mechanisms underlying neurodegeneration and in the development of new treatment strategies to address neurodegenerative diseases.
Fluid–structure interaction simulation of visceral perfusion and impact of different cannulation methods on aortic dissection
Authors: Lee Gyu-Han , Heo Woon , Lee Youngjin , Kim Tae-Hoon , Huh Hyungkyu , Song Suk-Won , Ha Hojin
Published: January 2023

Hemodynamics in aortic dissection (AD) is closely associated with the risk of aortic aneurysm, rupture, and malperfusion. Altered blood flow in patients with AD can lead to severe complications such as visceral malperfusion. In this study, we aimed to investigate the effect of cannulation flow on hemodynamics in AD using a fluid–structure interaction simulation. We developed a specific-idealized AD model that included an intimal tear in the descending thoracic aorta, a re-entry tear in the left iliac artery, and nine branches. Two different cannulation methods were tested: (1) axillary cannulation (AC) only through the brachiocephalic trunk and (2) combined axillary and femoral cannulation (AFC) through the brachiocephalic trunk and the right common iliac artery. AC was found to result in the development of a pressure difference between the true lumen and false lumen, owing to the difference in the flow rate through each lumen. This pressure difference collapsed the true lumen, disturbing blood flow to the celiac and superior mesenteric arteries. However, in AFC, the pressure levels between the two lumens were similar, and no collapse occurred. Moreover, the visceral flow was higher than that in AC. Lastly, the stiffness of the intimal flap affected the true lumen's collapse.
Membrane vesicles released by Lacticaseibacillus casei BL23 inhibit the biofilm formation of Salmonella Enteritidis
Authors: da Silva Barreira David , Laurent Julie , Lourenço Jessica , Novion Ducassou Julia , Couté Yohann , Guzzo Jean , Rieu Aurélie
Published: January 2023

Biofilms represent a major concern in the food industry and healthcare. The use of probiotic bacteria and their derivatives as an alternative to conventional treatments to fight biofilm development is a promising option that has provided convincing results in the last decades. Recently, membrane vesicles (MVs) produced by probiotics have generated considerable interest due to the diversity of roles they have been associated with. However, the antimicrobial activity of probiotic MVs remains to be studied. In this work, we showed that membrane vesicles produced by Lacticaseibacillus casei BL23 (LC-MVs) exhibited strong antibiofilm activity against Salmonella enterica serovar Enteritidis (S. Enteritidis) without affecting bacterial growth. Furthermore, we found that LC-MVs affected the early stages of S. Enteritidis biofilm development and prevented attachment of bacteria to polystyrene surfaces. Importantly, LC-MVs did not impact the biomass of already established biofilms. We also demonstrated that the antibiofilm activity depended on the proteins associated with the LC-MV fraction. Finally, two peptidoglycan hydrolases (PGHs) were found to be associated with the antibiofilm activity of LC-MVs. Overall, this work allowed to identify the antibiofilm properties of LC-MVs and paved the way for the use of probiotic MVs against the development of negative biofilms.
Human osteoarthritis knee joint synovial fluids cleave and activate Proteinase-Activated Receptor (PAR) mediated signaling
Authors: Chandrabalan Arundhasa , Firth Andrew , Litchfield Robert B. , Appleton C. Thomas , Getgood Alan , Ramachandran Rithwik
Published: January 2023

Osteoarthritis (OA) is the most prevalent joint disorder with increasing worldwide incidence. Mechanistic insights into OA pathophysiology are evolving and there are currently no disease-modifying OA drugs. An increase in protease activity is linked to progressive degradation of the cartilage in OA. Proteases also trigger inflammation through a family of G protein-coupled receptors (GPCRs) called the Proteinase-Activated Receptors (PARs). PAR signaling can trigger pro-inflammatory responses and targeting PARs is proposed as a therapeutic approach in OA. Several enzymes can cleave the PAR N-terminus, but the endogenous protease activators of PARs in OA remain unclear. Here we characterized PAR activating enzymes in knee joint synovial fluids from OA patients and healthy donors using genetically encoded PAR biosensor expressing cells. Calcium signaling assays were performed to examine receptor activation. The class and type of enzymes cleaving the PARs was further characterized using protease inhibitors and fluorogenic substrates. We find that PAR1, PAR2 and PAR4 activating enzymes are present in knee joint synovial fluids from healthy controls and OA patients. Compared to healthy controls, PAR1 activating enzymes are elevated in OA synovial fluids while PAR4 activating enzyme levels are decreased. Using enzyme class and type selective inhibitors and fluorogenic substrates we find that multiple PAR activating enzymes are present in OA joint fluids and identify serine proteinases (thrombin and trypsin-like) and matrix metalloproteinases as the major classes of PAR activating enzymes in the OA synovial fluids. Synovial fluid driven increase in calcium signaling was significantly reduced in cells treated with PAR1 and PAR2 antagonists, but not in PAR4 antagonist treated cells. OA associated elevation of PAR1 cleavage suggests that targeting this receptor may be beneficial in the treatment of OA.
Intense vortical-field generation using coherent superposition of multiple vortex beams
Authors: Guo Xinju , Zhang Xiaomei , Xu Dirui , Chen Weixin , Guo Yi , Lan Ke , Shen Baifei
Published: January 2023

Coherent beam combining technology applied to multiple vortex beams is a promising method to generate high-power vortex beams. We utilize the coherent combination of multiple Laguerre-Gaussian beams at the waist plane and propose theoretically a practical generation system for a high-power beam carrying orbital angular momentum by considering oblique incidence. The results demonstrate that the orbital angular momentum distribution of the combined field is similar to that of a single Laguerre-Gaussian beam within the Rayleigh length. Moreover, the combined field has relativistic intensity local spots that exhibit stable spatial propagation. The proposed system may potentially be applied to intense vortical fields, large scale nuclear fusion device, such as suppressing stimulated Raman scattering and filamentation when a laser beam propagates in plasma.
Efficient dynamic channel assignment through laser chaos: a multiuser parallel processing learning algorithm
Authors: Chen Zengjing , Wang Lu , Xing Chengzhi
Published: January 2023

As laser chaos has been proven to be a robust tool to solve the multi-armed bandit (MAB) problem, this study investigates the problem of multiuser dynamic channel assignment using laser chaos in cognitive radio networks with K-orthogonal channels and M secondary users. A novel dynamic channel assignment algorithm with laser chaos series for multiple users, named parallel processing learning with laser chaos (PPL-LC) algorithm, is proposed to efficiently address two main objectives: stable channel assignment and fuzzy stable channel assignment. The latter objective accounts for the realistic scenario where users have fuzzy preferences and do not necessarily pursue the best preference. The PPL-LC algorithm uses the randomness properties of laser chaos to learn the assignment of channels to multiple users without any limitations on the number of channels, which has not been considered in existing laser chaos algorithms. Moreover, the PPL-LC is equipped with parallel processing channel selections, resulting in higher throughput and stronger adaptability with environmental changes over time than comparison algorithms, such as distributed stable strategy learning and coordinated stable marriage MAB algorithms. Finally, numerical examples are presented to demonstrate the performance of the PPL-LC algorithm.
Alpine-ice record of bismuth pollution implies a major role of military use during World War II
Authors: Legrand Michel , McConnell Joseph R. , Bergametti Gilles , Preunkert Susanne , Chellman Nathan , Desboeufs Karine , Lestel Laurence , Plach Andreas , Stohl Andreas
Published: January 2023

Military conflicts result in local environmental damage, but documenting regional and larger scale impacts such as heavy metal pollution has proven elusive. Anthropogenic emissions of bismuth (Bi) include coal burning and various commodity productions but no emission estimates over the past century exist. Here we used Bi measurements in ice cores from the French Alps to show evidence of regional-scale Bi pollution concurrent with the Spanish Civil War and World War II. Tracers of the main sources of Bi emissions measured in the same ice—coal-burning, steel- and aluminum-industry, alloy and other metal processing—indicate a major, previously undocumented additional emissions source that we attribute to military activities between 1935 and 1945 Common Era (CE) in western Europe. These include the use of bismuth for low-melting point alloys for shells, thin-walled aluminum alloy aircraft oil, and munitions.
Deep learning can yield clinically useful right ventricular segmentations faster than fully manual analysis
Authors: Åkesson Julius , Ostenfeld Ellen , Carlsson Marcus , Arheden Håkan , Heiberg Einar
Published: January 2023

Right ventricular (RV) volumes are commonly obtained through time-consuming manual delineations of cardiac magnetic resonance (CMR) images. Deep learning-based methods can generate RV delineations, but few studies have assessed their ability to accelerate clinical practice. Therefore, we aimed to develop a clinical pipeline for deep learning-based RV delineations and validate its ability to reduce the manual delineation time. Quality-controlled delineations in short-axis CMR scans from 1114 subjects were used for development. Time reduction was assessed by two observers using 50 additional clinical scans. Automated delineations were subjectively rated as (A) sufficient for clinical use, or as needing (B) minor or (C) major corrections. Times were measured for manual corrections of delineations rated as B or C, and for fully manual delineations on all 50 scans. Fifty-eight % of automated delineations were rated as A, 42% as B, and none as C. The average time was 6 min for a fully manual delineation, 2 s for an automated delineation, and 2 min for a minor correction, yielding a time reduction of 87%. The deep learning-based pipeline could substantially reduce the time needed to manually obtain clinically applicable delineations, indicating ability to yield right ventricular assessments faster than fully manual analysis in clinical practice. However, these results may not generalize to clinics using other RV delineation guidelines.
A data driven approach to mineral chemistry unveils magmatic processes associated with long-lasting, low-intensity volcanic activity
Authors: Costa Simone , Caricchi Luca , Pistolesi Marco , Gioncada Anna , Masotta Matteo , Bonadonna Costanza , Rosi Mauro
Published: January 2023

The most frequent volcanic eruptions are of low-intensity and small magnitude. They produce abundant ash-sized (< 2 mm) clasts, which are too small to establish quantitative links between magmatic processes and eruptive dynamics using classic approaches. This inhibits our ability to study the past behaviour of frequently erupting volcanoes, essential to predict their future activity and mitigate their impact. The Palizzi unit (10–13th century, Vulcano, Italy) includes a prototype sequence of ash deposits resulting from prolonged Vulcanian eruptions punctuated by those of two larger sub-Plinian events. We apply Hierarchical Clustering to chemical analyses of clinopyroxene collected along the stratigraphy to decipher magma dynamics during this eruptive period. We identify periods of magma input and we link deep magmatic processes to eruptive dynamics, also showing that our approach can be used to connect magma and eruptive dynamics in any volcanic sequence. This is essential to track the processes occurring during frequent eruptions and to identify the build-up to larger explosive events.
The characteristics and impact of small and medium forest enterprises on sustainable forest management in Ghana
Authors: Anane Stephen , Kombiok Emmanuel , Afrifa Alexander Baffour
Published: January 2023

Small and Medium Forest Enterprises are considered promoters of local development and growth due to their contributions to over 50% of forest-based employment in some countries like Brazil, Uganda, and India. Despite the many potentials of these enterprises, their operations go unchecked, which poses a serious threat to the sustainability of tropical forests. This study highlights the characteristics of SMFEs and the impact of SMFEs on sustainable forest management in Ghana from a survey of 80 randomly sampled enterprises in seven communities in the Amenfi West Municipality in Ghana. Data was gathered using structured questionnaires and key informant interviews and analyzed with statistical tools in SPSS version 25. The findings show that 71.25% of the SMFEs are not registered with the appropriate authorities like the Registrar General’s department and the Municipal Assemblies. In addition, 55 (68.8%) of these enterprises have a direct dependency on the forest for raw materials with 21.8% of this number claiming to have obtained the needed permits/licenses to harvest the raw materials they need from the forests. For 91.25% of the enterprises, factors such as resource availability and profits drive their activities and 8.75% are driven by access to labor and job creation. The analysis showed that belonging to an association is a significant determinant of business registration at p = 0.001. Forest policies must seek to promote sustainable management of forest resources by enforcing registration and permit laws. SMFEs must be consistently monitored and supervised to ensure that their activities are guided by policy and their compliance rewarded through capacity building and government support.
A proteome scale study reveals how plastic surfaces and agitation promote protein aggregation
Authors: Schvartz Marion , Saudrais Florent , Devineau Stéphanie , Aude Jean-Christophe , Chédin Stéphane , Henry Céline , Millán-Oropeza Aarón , Perrault Thomas , Pieri Laura , Pin Serge , Boulard Yves , Brotons Guillaume , Renault Jean-Philippe
Published: January 2023

Protein aggregation in biotherapeutics can reduce their activity and effectiveness. It may also promote immune reactions responsible for severe adverse effects. The impact of plastic materials on protein destabilization is not totally understood. Here, we propose to deconvolve the effects of material surface, air/liquid interface, and agitation to decipher their respective role in protein destabilization and aggregation. We analyzed the effect of polypropylene, TEFLON, glass and LOBIND surfaces on the stability of purified proteins (bovine serum albumin, hemoglobin and α-synuclein) and on a cell extract composed of 6000 soluble proteins during agitation (P = 0.1–1.2 W/kg). Proteomic analysis revealed that chaperonins, intrinsically disordered proteins and ribosomes were more sensitive to the combined effects of material surfaces and agitation while small metabolic oligomers could be protected in the same conditions. Protein loss observations coupled to Raman microscopy, dynamic light scattering and proteomic allowed us to propose a mechanistic model of protein destabilization by plastics. Our results suggest that protein loss is not primarily due to the nucleation of small aggregates in solution, but to the destabilization of proteins exposed to material surfaces and their subsequent aggregation at the sheared air/liquid interface, an effect that cannot be prevented by using LOBIND tubes. A guidance can be established on how to minimize these adverse effects. Remove one of the components of this combined stress - material, air (even partially), or agitation - and proteins will be preserved.
Outcome predictors in anterior and posterior ischemic strokes: a study based on the Iranian SITS registry
Authors: Jalali Nazanin , Sadeghi Hokmabadi Elyar , Ghoreishi Abdoreza , Sariaslan Payam , Rafie Shahram , Borhani-Haghighi Afshin , Moghadam Ahmadi Amir , Azin Hossein , Vakilian Alireza , Khalili Parvin , Farhoudi Mehdi
Published: January 2023

Ischemic stroke is the major form of stroke with two separate vascular territories. Many risk factors are related to stroke outcomes in both territories. The present descriptive research was carried out on the basis of data obtained from the Safe Implementation of Treatments in Stroke (SITS) registry on Iranian intravenous thrombolysis ischemic stroke cases. Vascular territory involved in each case and three-month excellent outcome, functional independence, mortality rate, and brain hemorrhage occurrence were determined. Univariable and multivariable logistics regression analyses were utilized in order to investigate association of ischemic stroke outcomes with the vascular territory involved and other related factors. Among 1566 patients 95.4% was anterior circulation stroke patients and 4.6% was posterior circulation stroke cases. There is no significant association between vascular territory with mortality (OR of PCS vs ACS: 0.74, 95% CI 0.37–1.46), excellent functional outcome (OR 0.72, 95% CI 0.44–1.19), functional outcome (OR 0.86, 95% CI 0.52–1.42) and local hemorrhage (OR 0.98, 95% CI 0.30–3.21). Among major risk factors, age, diabetes, NIHSS score and admission duration, increased significantly odds of three-month mortality, excellent outcome, and functional independence in the multivariate analysis. The highest of odds was in NIHSS score with a dose–response association. The vascular territory was not an outcome predictor in ischemic strokes. The most important predictor was baseline NIHSS.
Substrate stiffness controls proinflammatory responses in human gingival fibroblasts
Authors: Tiskratok Watcharaphol , Yamada Masahiro , Watanabe Jun , Kartikasari Nadia , Kimura Tsuyoshi , Egusa Hiroshi
Published: January 2023

Soft gingiva is often compromised in gingival health; however, the underlying biological mechanisms remain unknown. Extracellular matrix (ECM) stiffness is involved in the progression of various fibroblast-related inflammatory disorders via cellular mechanotransduction. Gingival stiffness might regulate cellular mechanotransduction-mediated proinflammatory responses in gingival fibroblasts. This in vitro study aims to investigate the effects of substrate stiffness on proinflammatory responses in human gingival fibroblasts (hGFs). The hGFs isolated from two healthy donors cultured on type I collagen-coated polydimethylsiloxane substrates with different stiffnesses, representing soft (5 kPa) or hard (25 kPa) gingiva. Expression levels of proinflammatory mediators, prostaglandin E2 or interleukin-1β, in hGFs were significantly higher with the soft substrate than with the hard substrate, even without and with lipopolysaccharide (LPS) to induce inflammation. Expression levels of gingival ECM and collagen cross-linking agents in hGFs were downregulated more with the soft substrate than with the hard substrate through 14 days of culture. The soft substrate suppressed the expression of mechanotransduction-related transcriptional factors and activated the expression of inflammation-related factors, whereas the hard substrate demonstrated the opposite effects. Soft substrate induced proinflammatory responses and inhibition of ECM synthesis in hGFs by inactivating cellular mechanotransduction. This supports the importance of ECM stiffness in gingival health.
Moving suicide prevention upstream by understanding the effect of flourishing on suicidal ideation in midlife: an instrumental variable approach
Authors: Xiao Yunyu , Brown Timothy T.
Published: January 2023

Prior research has examined the association between flourishing and suicidal ideation, but it is unknown whether this association is causal. Understanding the causality between flourishing and suicidal ideation is important for clinicians and policymakers to determine the value of innovative suicide prevention programs by improving flourishing in at-risk groups. Using a linked nationwide longitudinal sample of 1619 middle-aged adults (mean age 53, 53% female, 88% White) from the National Survey of Midlife Development in the United States (MIDUS), this retrospective cohort study aims to assess the causal relationship between flourishing and suicidal ideation among middle-aged adults in the US. Flourishing is a theory-informed 13-scale index covering three domains: emotional, psychological, and social well-being. Suicidal ideation was self-reported in a follow-up interview conducted after measuring flourishing. We estimated instrumental variable models to examine the potential causal relationship between flourishing and suicidal ideation. High-level flourishing (binary) was reported by 486 (30.0%) individuals, and was associated with an 18.6% reduction in any suicidal ideation (binary) (95% CI, − 29.3– − 8.0). Using alternative measures, a one standard deviation increase in flourishing (z-score) was associated with a 0.518 (95% CI, 0.069, 0.968) standard deviation decrease in suicidal ideation (z-score). Our results suggest that prevention programs that increase flourishing in midlife should result in meaningful reductions in suicide risk. Strengthening population-level collaboration between policymakers, clinical practitioners, and non-medical partners to promote flourishing can support our collective ability to reduce suicide risks across social, economic, and other structural circumstances.
Depolymerization of robust polyetheretherketone to regenerate monomer units using sulfur reagents
Authors: Minami Yasunori , Matsuyama Nao , Takeichi Yasuo , Watanabe Ryota , Mathew Siby , Nakajima Yumiko
Published: January 2023

Super engineering plastics, high-performance thermoplastic resins such as polyetheretherketone, and polyphenylene sulfide have been utilized in industries, owing to their high thermal stability and mechanical strength. However, their robustness hinders their depolymerization to produce monomers and low-weight molecules. Presently, chemical recycling for most super engineering plastics remains relatively unexplored. Herein, we report the depolymerization of insoluble polyetheretherketone using sulfur nucleophiles via carbon–oxygen bond cleavages to form benzophenone dithiolate and hydroquinone. Treatment with organic halides converted only the former products to afford various dithiofunctionalized benzophenones. The depolymerization proceeded as a solid–liquid reaction in the initial phase. Therefore, this method was not affected by the shape of polyetheretherketone, e.g., pellets or films. Moreover, this depolymerization method was applicable to carbon- or glass fiber-enforced polyetheretherketone material. The depolymerized product, dithiofunctionalized benzophenones, could be converted into diiodobenzophenone, which was applicable to the polymerization.
Hyperfine-structure-resolved laser spectroscopy of many-electron highly charged ions
Authors: Kimura Naoki , Priti  , Kono Yasutaka , Pipatpakorn Pativate , Soutome Keigo , Numadate Naoki , Kuma Susumu , Azuma Toshiyuki , Nakamura Nobuyuki
Published: January 2023

Hyperfine structures of highly charged ions (HCIs) are favourable spectroscopic targets for exploring fundamental physics along with nuclear properties. Recent proposals of HCI atomic clocks highlight their importance, especially for many-electron HCIs, and they have been theoretically investigated by refining atomic-structure calculations. However, developments in hyperfine spectroscopy of many-electron HCIs have not proceeded due to experimental difficulty. Here, we demonstrate hyperfine-structure-resolved laser spectroscopy of HCIs in an electron beam ion trap plasma, employing the magnetic-dipole transition in the 4d95s state of 127I7+. Ion-state manipulation by controlled electron collisions in the well-defined laboratory plasma enables laser-induced fluorescence spectroscopy of trapped HCIs. The observed spectrum of evaporatively cooled ions under low magnetic fields shows characteristic features reflecting the hyperfine structures. The present demonstration using combined optical and plasma approaches provides a benchmark for state-of-the-art atomic calculations of hyperfine structures in many-electron HCIs, and offers possibilities for a variety of unexploited experiments.
Proteomic analysis of milk fat globule membranes from small-sized milk fat globules and their function in promoting lipid droplet fusion in bovine mammary epithelial cells
Authors: Han Liqiang , Huang Qixue , Yang JingNa , Lu Wenyan , Hu Mingyue , Yang Yanbin , Zhu Heshui , Pang Kun , Yang Guoyu
Published: January 2023

In mammary epithelial cells, milk fat is synthesized as lipid droplets and secreted in the form of globules.
Low-density lipoprotein: a versatile nanoscale platform for targeted delivery
Authors: Dai Luyao , Li Shuaijun , Hao Qian , Zhou Ruina , Zhou Hui , Lei Wenxi , Kang Huafeng , Wu Hao , Li Yuanpei , Ma Xiaobin
Published: January 2023

This review introduces low-density lipoprotein (LDL) delivery systems, summarizes the research status and progress in targeted diagnosis and therapy, and looks forward to the clinical application of LDL as an effective delivery vehicle.
Guest differentiation and fingerprinting based on the conformational diversity of a dynamic corannulene-based cage
Authors: Shao Chengyuan , Zhao Yani , Han Senkai , Huang Fu , Guo Weijie , Jiang Hua , Wang Ying
Published: January 2023

The differentiation of chemical species those are structurally similar is very challenging. Herein, a new strategy based on the conformational diversity of hosts is proposed for guest differentiating and fingerprinting rapidly and efficiently.
Preparation and self-assembly of ionic (PNIPAM-co-VIM) microgels and their adsorption property for phosphate ions
Authors: Yang Jianping , Huang Bei , Lv Zhengxiang , Cao Zheng
Published: January 2023

The ionic P(NIPAM-co-VIM) microgels were prepared by a two-step method, and used as functional coating on Quartz Crystal Microbalance (QCM) sensor for the detection of trace phosphate ions in water.
Modelling PIP4K2A inhibitory activity of 1,7-naphthyridine analogues using machine learning and molecular docking studies
Authors: Ibrahim Muktar Musa , Uzairu Adamu , Ibrahim Muhammad Tukur , Umar Abdullahi Bello
Published: January 2023

PIP4K2A is a type II lipid kinase that catalyzed the rate-limiting step of the conversion of phosphatidylinositol-5-phosphate (PI5P) into phosphatidylinositol 4,5-bisphosphate (PI4,5P2).