bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supermarket Transaction Records In Dietary Evaluation: the STRIDE study: validation against self-reported dietary intake
Authors: Jenneson Victoria , Greenwood Darren C , Clarke Graham P , Rains Tim , Tempest Bethan , Shute Becky , Morris Michelle A 
Published: September 2023

AbstractObjective:Scalable methods are required for population dietary monitoring. The Supermarket Transaction Records In Dietary Evaluation (STRIDE) study compares dietary estimates from supermarket transactions with an online FFQ.Design:Participants were recruited in four waves, accounting for seasonal dietary variation. Purchases were collected for 1 year during and 1 year prior to the study. Bland–Altman agreement and limits of agreement (LoA) were calculated for energy, sugar, fat, saturated fat, protein and sodium (absolute and relative).Setting:This study was partnered with a large UK retailer.Participants:Totally, 1788 participants from four UK regions were recruited from the retailer’s loyalty card customer database, according to breadth and frequency of purchases. Six hundred and eighty-six participants were included for analysis.Results:The analysis sample were mostly female (72 %), with a mean age of 56 years (sd 13). The ratio of purchases to intakes varied depending on amounts purchased and consumed; purchases under-estimated intakes for smaller amounts on average, but over-estimated for larger amounts. For absolute measures, the LoA across households were wide, for example, for energy intake of 2000 kcal, purchases could under- or over-estimate intake by a factor of 5; values could be between 400 kcal and 10000 kcal. LoA for relative (energy-adjusted) estimates were smaller, for example, for 14 % of total energy from saturated fat, purchase estimates may be between 7 % and 27 %.Conclusions:Agreement between purchases and intake was highly variable, strongest for smaller loyal households and for relative values. For some customers, relative nutrient purchases are a reasonable proxy for dietary composition indicating utility in population-level dietary research.
Clinical and cognitive effects of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders: a systematic review and meta-analysis
Authors: Westwood Samuel J. , Conti Aldo Alberto , Tang Wanjie , Xue Shuang , Cortese Samuele , Rubia Katya 
Published: September 2023

AbstractThis pre-registered (CRD42022322038) systematic review and meta-analysis investigated clinical and cognitive outcomes of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders. PubMed, OVID, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and VIP database for Chinese technical periodicals were searched (until 16/03/2022) to identify trials investigating cognitive and clinical outcomes of eTNS in neurological or psychiatric disorders. The Cochrane Risk of Bias 2.0 tool assessed randomized controlled trials (RCTs), while the Risk of Bias of Non-Randomized Studies (ROBINS-I) assessed single-arm trials. Fifty-five peer-reviewed articles based on 48 (27 RCTs; 21 single-arm) trials were included, of which 12 trials were meta-analyzed (N participants = 1048; of which ~3% ADHD, ~3% Epilepsy, ~94% Migraine; age range: 10–49 years). The meta-analyses showed that migraine pain intensity (K trials = 4, N = 485; SMD = 1.03, 95% CI[0.84–1.23]) and quality of life (K = 2, N = 304; SMD = 1.88, 95% CI[1.22–2.53]) significantly improved with eTNS combined with anti-migraine medication. Dimensional measures of depression improved with eTNS across 3 different disorders (K = 3, N = 111; SMD = 0.45, 95% CI[0.01–0.88]). eTNS was well-tolerated, with a good adverse event profile across disorders. eTNS is potentially clinically relevant in other disorders, but well-blinded, adequately powered RCTs must replicate findings and support optimal dosage guidance.
Lysine methyltransferase SMYD2 inhibits antiviral innate immunity by promoting IRF3 dephosphorylation
Authors: Wu Jiacheng , Hu Ye , Song Jiaying , Xu Jia , Zhang Qian , Chai Yangyang , Wang Xin , Wang Bingjing , Zhao Yong , Cao Xuetao , Xu Xiaoqing 
Published: September 2023

AbstractsPhosphorylation of IRF3 is critical to induce type I interferon (IFN-I) production in antiviral innate response. Here we report that lysine methyltransferase SMYD2 inhibits the expressions of IFN-I and proinflammatory cytokines in macrophages upon viral infections. The Smyd2-deficient mice are more resistant to viral infection by producing more IFN-I and proinflammatory cytokines. Mechanistically, SMYD2 inhibits IRF3 phosphorylation in macrophages in response to viral infection independent of its methyltransferase activity. We found that SMYD2 interacts with the DNA-binding domain (DBD) and IRF association domain (IAD) domains of IRF3 by its insertion SET domain (SETi) and could recruit phosphatase PP1α to enhance its interaction with IRF3, which leads to decreased phosphorylation of IRF3 in the antiviral innate response. Our study identifies SMYD2 as a negative regulator of IFN-I production against virus infection. The new way of regulating IRF3 phosphorylation will provide insight into the understanding of IFN-I production in the innate response and possible intervention of the related immune disorders.
METTL16 controls Kaposi’s sarcoma-associated herpesvirus replication by regulating S-adenosylmethionine cycle
Authors: Zhang Xinquan , Meng Wen , Feng Jian , Gao Xinghong , Qin Chao , Feng Pinghui , Huang Yufei , Gao Shou-Jiang 
Published: September 2023

AbstractOncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) consists of latent and lytic replication phases, both of which are important for the development of KSHV-related cancers. As one of the most abundant RNA modifications, N6-methyladenosine (m6A) and its related complexes regulate KSHV life cycle. However, the role of METTL16, a newly discovered RNA methyltransferase, in KSHV life cycle remains unknown. In this study, we have identified a suppressive role of METTL16 in KSHV lytic replication. METTL16 knockdown increased while METTL16 overexpression reduced KSHV lytic replication. METTL16 binding to and writing of m6A on MAT2A transcript are essential for its splicing, maturation and expression. As a rate-limiting enzyme in the methionine-S-adenosylmethionine (SAM) cycle, MAT2A catalyzes the conversion of L-methionine to SAM required for the transmethylation of protein, DNA and RNA, transamination of polyamines, and transsulfuration of cystathionine. Consequently, knockdown or chemical inhibition of MAT2A reduced intracellular SAM level and enhanced KSHV lytic replication. In contrast, SAM treatment was sufficient to inhibit KSHV lytic replication and reverse the effect of the enhanced KSHV lytic program caused by METTL16 or MAT2A knockdown. Mechanistically, METTL16 or MAT2A knockdown increased while SAM treatment decreased the intracellular reactive oxygen species level by altering glutathione level, which is essential for efficient KSHV lytic replication. These findings demonstrate that METTL16 suppresses KSHV lytic replication by modulating the SAM cycle to maintain intracellular SAM level and redox homeostasis, thus illustrating the linkage of KSHV life cycle with specific m6A modifications, and cellular metabolic and oxidative conditions.
FNDC5 inhibits autophagy of bone marrow mesenchymal stem cells and promotes their survival after transplantation by downregulating Sp1
Authors: Wei Huan , Liu Shuaiye , Wang Tingting , Li Yanping , Liu Kangmei , Guo Qunying , Li Ling 
Published: September 2023

AbstractRegenerative therapy based on mesenchymal stem cells (MSCs) has great promise to achieve functional recovery in cerebral infarction patients. However, the survival rate of transplanted MSCs is extremely low because of destructive autophagy caused by the harsh ischemic microenvironment in cerebral infarct tissue. The mechanism by which fibronectin type III domain protein 5 (FNDC5) regulates autophagy of transplanted bone marrow-MSCs (BMSCs) following ischemic injury needs to be elucidated. In this study, we confirmed that FNDC5 promotes the survival of transplanted BMSCs in a rat cerebral infarction model. Furthermore, bioinformatic analysis and verification experiments revealed the transcription factor, Sp1, to be a key mediator of autophagy regulation by FNDC5. FNDC5 significantly inhibited BMSC autophagy by down-regulating Sp1 and the autophagy-related Sp1-target gene, ULK2. Transplanted BMSCs overexpressing FNDC5 (BMSCs-OE-FNDC5) promoted neurovascular proliferation and alleviated ischemic brain injury in cerebral infarct model rats. However, the increased survival and enhanced neuroprotective effect of transplanted BMSCs-OE-FNDC5 were reversed by simultaneous overexpression of Sp1. Our data indicate a role for FNDC5 in BMSC survival and reveal a novel mechanism of transcription regulation through Sp1 for the autophagy-related gene ULK2. Modulation of FNDC5 may promote survival capacity and improve the therapeutic effect of BMSCs in various tissues following ischemia.
Cryo-EM structures of human organic anion transporting polypeptide OATP1B1
Authors: Shan Ziyang , Yang Xuemei , Liu Huihui , Yuan Yafei , Xiao Yuan , Nan Jing , Zhang Wei , Song Wenqi , Wang Jufang , Wei Feiwen , Zhang Yanqing 
Published: September 2023

AbstractMembers of the solute carrier organic anion transporting polypeptide (OATPs) family function as transporters for a large variety of amphipathic organic anions including endogenous metabolites and clinical drugs, such as bile salts, steroids, thyroid hormones, statins, antibiotics, antivirals, and anticancer drugs. OATP1B1 plays a vital role in transporting such substances into the liver for hepatic clearance. FDA and EMA recommend conducting in vitro testing of drug–drug interactions (DDIs) involving OATP1B1. However, the structure and working mechanism of OATPs still remains elusive. In this study, we determined cryo-EM structures of human OATP1B1 bound with representative endogenous metabolites (bilirubin and estrone-3-sulfate), a clinical drug (simeprevir), and a fluorescent indicator (2′,7′-dichlorofluorescein), in both outward- and inward-open states. These structures reveal major and minor substrate binding pockets and conformational changes during transport. In combination with mutagenesis studies and molecular dynamics simulations, our work comprehensively elucidates the transport mechanism of OATP1B1 and provides the structural basis for DDI predictions involving OATP1B1, which will greatly promote our understanding of OATPs.
A pathogen-induced putative NAC transcription factor mediates leaf rust resistance in barley
Authors: Chen Chunhong , Jost Matthias , Outram Megan A. , Friendship Dorian , Chen Jian , Wang Aihua , Periyannan Sambasivam , Bartoš Jan , Holušová Kateřina , Doležel Jaroslav , Zhang Peng , Bhatt Dhara , Singh Davinder , Lagudah Evans , Park Robert F. , Dracatos Peter M. 
Published: September 2023

AbstractLeaf rust, caused by Puccinia hordei, is one of the most widespread and damaging foliar diseases affecting barley. The barley leaf rust resistance locus Rph7 has been shown to have unusually high sequence and haplotype divergence. In this study, we isolate the Rph7 gene using a fine mapping and RNA-Seq approach that is confirmed by mutational analysis and transgenic complementation. Rph7 is a pathogen-induced, non-canonical resistance gene encoding a protein that is distinct from other known plant disease resistance proteins in the Triticeae. Structural analysis using an AlphaFold2 protein model suggests that Rph7 encodes a putative NAC transcription factor with a zinc-finger BED domain with structural similarity to the N-terminal DNA-binding domain of the NAC transcription factor (ANAC019) from Arabidopsis. A global gene expression analysis suggests Rph7 mediates the activation and strength of the basal defence response. The isolation of Rph7 highlights the diversification of resistance mechanisms available for engineering disease control in crops.
Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling
Authors: Zhong Jing , He Xiaofang , Gao Xinxin , Liu Qiaohong , Zhao Yu , Hong Ying , Zhu Weize , Yan Juan , Li Yifan , Li Yan , Zheng Ningning , Bao Yiyang , Wang Hao , Ma Junli , Huang Wenjin , Liu Zekun , Lyu Yuanzhi , Ke Xisong , Jia Wei , Xie Cen , Hu Yiyang , Sheng Lili , Li Houkai 
Published: September 2023

AbstractNonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.
Prior information differentially affects discrimination decisions and subjective confidence reports
Authors: Constant Marika , Pereira Michael , Faivre Nathan , Filevich Elisa 
Published: September 2023

AbstractAccording to Bayesian models, both decisions and confidence are based on the same precision-weighted integration of prior expectations (“priors”) and incoming information (“likelihoods”). This assumes that priors are integrated optimally and equally in decisions and confidence, which has not been tested. In three experiments, we quantify how priors inform decisions and confidence. With a dual-decision task we create pairs of conditions that are matched in posterior information, but differ on whether the prior or likelihood is more informative. We find that priors are underweighted in discrimination decisions, but are less underweighted in confidence about those decisions, and this is not due to differences in processing time. The same patterns remain with exogenous probabilistic cues as priors. With a Bayesian model we quantify the weighting parameters for the prior at both levels, and find converging evidence that priors are more optimally used in explicit confidence, even when underused in decisions.
Cold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice
Authors: Xu Jinhong , Cui Le , Wang Jiaqi , Zheng Shasha , Zhang Huahua , Ke Shuo , Cao Xiaoqin , Shi Yanteng , Li Jing , Zen Ke , Vidal-Puig Antonio , Zhang Chen-Yu , Li Liang , Jiang Xiaohong 
Published: September 2023

AbstractDuring cold exposure, activated brown adipose tissue (BAT) takes up a large amount of circulating glucose to fuel non-shivering thermogenesis and defend against hypothermia. However, little is known about the endocrine function of BAT controlling glucose homoeostasis under this thermoregulatory challenge. Here, we show that in male mice, activated BAT-derived extracellular vesicles (BDEVs) reprogram systemic glucose metabolism by promoting hepatic gluconeogenesis during cold stress. Cold exposure facilitates the selective packaging of miR-378a-3p—one of the BAT-enriched miRNAs—into EVs and delivery into the liver. BAT-derived miR-378a-3p enhances gluconeogenesis by targeting p110α. miR-378 KO mice display reduced hepatic gluconeogenesis during cold exposure, while restoration of miR-378a-3p in iBAT induces the expression of gluconeogenic genes in the liver. These findings provide a mechanistic understanding of BDEV-miRNA as stress-induced batokine to coordinate systemic glucose homoeostasis. This miR-378a-3p-mediated interorgan communication highlights a novel endocrine function of BAT in preventing hypoglycemia during cold stress.
Regulating interfacial reaction through electrolyte chemistry enables gradient interphase for low-temperature zinc metal batteries
Authors: Wang Wei , Chen Shan , Liao Xuelong , Huang Rong , Wang Fengmei , Chen Jialei , Wang Yaxin , Wang Fei , Wang Huan 
Published: September 2023

AbstractIn situ formation of a stable interphase layer on zinc surface is an effective solution to suppress dendrite growth. However, the fast transport of bivalent Zn-ions within the solid interlayer remains very challenging. Herein, we engineer the SEI components and enable superior kinetics of Zn metal batteries under harsh conditions through regulating the sequence of interfacial chemical reaction. With the differences in chemical reactivity of trimethyl phosphate co-solvent and trifluoromethanesulfonate anions in the Zn2+-solvation shell, Zn3(PO4)2 and ZnF2 are successively generated on Zn metal surface to form a gradient ZnF2–Zn3(PO4)2 interphase. Mechanistic studies reveal the outer ZnF2 facilitates Zn2+ desolvation and inner Zn3(PO4)2 serves as channels for fast Zn2+ transport, contributing to long-term cycling at subzero temperatures. Impressively, the gradient SEI enables a high lifespan over 7000 hours in Zn symmetric cell and a capacity retention of 86.1% after 12000 cycles in Zn–KVOH full cell at –50 °C.
Polarized thermal emission from dust in a galaxy at redshift 2.6
Authors: Geach J. E. , Lopez-Rodriguez E. , Doherty M. J. , Chen Jianhang , Ivison R. J. , Bendo G. J. , Dye S. , Coppin K. E. K. 
Published: September 2023

AbstractMagnetic fields are fundamental to the evolution of galaxies, playing a key role in the astrophysics of the interstellar medium and star formation. Large-scale ordered magnetic fields have been mapped in the Milky Way and nearby galaxies1,2, but it is not known how early in the Universe such structures formed3. Here we report the detection of linearly polarized thermal emission from dust grains in a strongly lensed, intrinsically luminous galaxy that is forming stars at a rate more than 1,000 times that of the Milky Way at redshift 2.6, within 2.5 Gyr of the Big Bang4,5. The polarized emission arises from the alignment of dust grains with the local magnetic field6,7. The median polarization fraction is of the order of 1%, similar to nearby spiral galaxies8. Our observations support the presence of a 5-kiloparsec-scale ordered magnetic field with a strength of around 500 μG or lower, oriented parallel to the molecular gas disk. This confirms that such structures can be rapidly formed in galaxies, early in cosmic history.
Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vγ9Vδ2 T cells
Authors: Yuan Linjie , Ma Xianqiang , Yang Yunyun , Qu Yingying , Li Xin , Zhu Xiaoyu , Ma Weiwei , Duan Jianxin , Xue Jing , Yang Haoyu , Huang Jian-Wen , Yi Simin , Zhang Mengting , Cai Ningning , Zhang Lin , Ding Qingyang , Lai Kecheng , Liu Chang , Zhang Lilan , Liu Xinyi , Yao Yirong , Zhou Shuqi , Li Xian , Shen Panpan , Chang Qing , Malwal Satish R. , He Yuan , Li Wenqi , Chen Chunlai , Chen Chun-Chi , Oldfield Eric , Guo Rey-Ting , Zhang Yonghui 
Published: September 2023

AbstractIn both cancer and infections, diseased cells are presented to human Vγ9Vδ2 T cells through an ‘inside out’ signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A11–4. Here we show how—in both humans and alpaca—multiple pAgs function as ‘molecular glues’ to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1–BTN2A1 association, abolishing pAg-mediated Vγ9Vδ2 T cell activation. Analyses using structure-based molecular-dynamics simulations, 19F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor–mediated γδ T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human γδ T cell function.
Complete human day 14 post-implantation embryo models from naive ES cells
Authors: Oldak Bernardo , Wildschutz Emilie , Bondarenko Vladyslav , Comar Mehmet-Yunus , Zhao Cheng , Aguilera-Castrejon Alejandro , Tarazi Shadi , Viukov Sergey , Pham Thi Xuan Ai , Ashouokhi Shahd , Lokshtanov Dmitry , Roncato Francesco , Ariel Eitan , Rose Max , Livnat Nir , Shani Tom , Joubran Carine , Cohen Roni , Addadi Yoseph , Chemla Muriel , Kedmi Merav , Keren-Shaul Hadas , Pasque Vincent , Petropoulos Sophie , Lanner Fredrik , Novershtern Noa , Hanna Jacob H. 
Published: September 2023

AbstractThe ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation1. Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking1,2. Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs)3. Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions)4. Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13–14 days after fertilization (Carnegie stage 6a). These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior–posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development.