bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants
Authors: Straumann Isabelle , Avedisian Isidora , Klaiber Aaron , Varghese Nimmy , Eckert Anne , Rudin Deborah , Luethi Dino , Liechti Matthias E. 
Published: August 2024

Abstract
Racemic 3,4-methylenedioxymethamphetamine (MDMA) acutely increases mood, feelings of empathy, trust, and closeness to others and is investigated to assist psychotherapy. Preclinical research indicates that S-MDMA releases monoamines and oxytocin more potently than R-MDMA, whereas R-MDMA more potently stimulates serotonin 5-hydroxytryptamine-2A receptors. S-MDMA may have more stimulant properties, and R-MDMA may be more psychedelic-like. However, acute effects of S- and R-MDMA have not been examined in a controlled human study. We used a double-blind, randomized, placebo-controlled, crossover design to compare acute effects of MDMA (125 mg), S-MDMA (125 mg), R-MDMA (125 mg and 250 mg), and placebo in 24 healthy participants. Outcome measures included subjective, autonomic, and adverse effects, pharmacokinetics, and plasma oxytocin, prolactin, and cortisol concentrations. S-MDMA (125 mg) induced greater subjective effects (“stimulation,” “drug high,” “happy,” “open”) and higher increases in blood pressure than R-MDMA (both 125 and 250 mg) and MDMA (125 mg). Unexpectedly, R-MDMA did not produce more psychedelic-like effects than S-MDMA. S-MDMA increased plasma prolactin more than MDMA, and S-MDMA increased plasma cortisol and oxytocin more than MDMA and R-MDMA. The plasma elimination half-life of S-MDMA was 4.1 h after administration. The half-life of R-MDMA was 12 and 14 h after the administration of 125 and 250 mg, respectively. Half-lives for S-MDMA and R-MDMA were 5.1 h and 11 h, respectively, after racemic MDMA administration. Concentrations of the CYP2D6-formed MDMA-metabolite 4-hydroxy-3-methoxymethamphetamine were lower after R-MDMA administration compared with S-MDMA administration. The pharmacokinetic findings are consistent with the R-MDMA-mediated inhibition of CYP2D6. Stronger stimulant-like effects of S-MDMA in the present study may reflect the higher potency of S-MDMA rather than qualitative differences between S-MDMA and R-MDMA. Equivalent acute effects of S-MDMA, MDMA, and R-MDMA can be expected at doses of 100, 125, and 300 mg, respectively, and need to be investigated.
Trial registration: ClinicalTrials.gov identifier: NCT05277636
Dietary iron intake predicts all-cause and cardiovascular mortality in patients with diabetes
Authors: Yang Chenchen , Hu Tingting , Li Chenglin , Gong Aifeng 
Published: August 2024

Abstract
Background
Limited data exists on the link between dietary iron intake and mortality in diabetes. Our investigation aimed to explore how dietary iron intake correlates with overall and cause-specific mortality in diabetic individuals.

Methods
This analysis encompassed 5970 participants with diabetes from the National Health and Nutrition Examination Survey spanning 1999 to 2014. Baseline data were collected through surveys and examinations, with mortality status tracked via National Death Index records until December 31, 2015. Cox proportional hazard models were utilized to calculate hazard ratios (HR) and 95% confidence intervals (CI) for mortality from various causes, including cardiovascular disease (CVD) and cancer.

Results
The average iron intake among the cohort was 14.1 ± 7.4 mg daily, with an average participant age of 61.3 and 3059 (51.3%) male adults. Over 41,425 person-years of follow-up, 1497 deaths were recorded. Following adjustments for multiple variables, an iron intake between 11.1 and 14.4 mg was associated with the lowest risk of all-cause mortality (HR 0.83 [0.70, 0.99], P < 0.05) compared to the reference group (<8.3 mg). Analysis of dose-response curves revealed an L-shaped pattern in men and a J-shaped pattern in women concerning the relationship between iron intake and all-cause mortality.

Conclusions
Our findings suggest a nonlinear association between dietary iron intake and all-cause mortality in individuals with diabetes. Specifically, higher iron intake may increase all-cause mortality risk in men, while potentially exert a protective effect in women.
UCK2 promotes intrahepatic cholangiocarcinoma progression and desensitizes cisplatin treatment by PI3K/AKT/mTOR/autophagic axis
Authors: Wu Xiwen , Chen Da , Li Muqi , Liang Gehao , Ye Huizhen 
Published: August 2024

AbstractIntrahepatic cholangiocarcinoma (iCCA) is a highly aggressive tumor with extremely poor prognosis due to the low resection rate, high recurrence rate and drug resistance. Uridine-cytidine kinase 2 (UCK2) is proved to promote progression and drug resistance of various carcinomas by regulating pyrimidine metabolism. However, the role of UCK2 in progression and drug resistance of iCCA was largely unclear. Gene expression matrices were obtained from public database and were verified by qRT-PCR using tumor sample from Sun Yat-sen University Cancer Center. Knockdown and overexpression of UCK2 were used to evaluate the effects of UCK2 on carcinogenesis and cisplatin response in iCCA. CCK8-kit assays and plate clone formation assays were performed to detect the effect of UCK2 on proliferative activity of tumor cells. Western blotting was performed to investigate protein level of UCK2 and the relevant biomarkers of PI3K/AKT/mTOR/autophagic axis. Cell migration and invasion were assessed by using wound-healing and transwell assays. UCK2 expression was detected elevated in iCCA tissues compared with adjacent normal tissues. Biologically, overexpression of UCK2 can promote proliferation of iCCA cells, and desensitizes iCCA to cisplatin in both in vivo and in vitro models. Mechanistically, UCK2 promote iCCA progression and cisplatin resistance through inhibition of autophagy by activating the PI3K/AKT/mTOR signaling pathway. Clinically, higher UCK2 expression in iCCA tumor was associated with aggressive tumor features, poorer survival and lower sensitivity of chemotherapy. UCK2 promotes iCCA progression and desensitizes cisplatin treatment by regulating PI3K/AKT/mTOR/autophagic axis. UCK2 exhibited potential as a biomarker in predicting prognosis and drug sensitivity of iCCA patients.
Long wavelength near-infrared and red light-driven consecutive photo-induced electron transfer for highly effective photoredox catalysis
Authors: Zeng Le , Huang Ling , Huang Zhi , Mani Tomoyasu , Huang Kai , Duan Chunying , Han Gang 
Published: August 2024

AbstractConsecutive photoinduced electron transfer (conPET) processes accumulate the energies of two photons to overcome the thermodynamic limit of traditional photoredox catalysis. However, the excitation wavelength of conPET systems mainly focused on short wavelength visible light, leading to photodamage and incompatibility with large-scale reactions. Herein, we report on conPET systems triggered by near-infrared (NIR) and red light. Specifically, a blue-absorbing conPET photocatalyst, perylene diimide (PDI) is sensitized by a palladium-based photosensitizer to triplet excited state (3PDI*), which generates PDI radical anion (PDI•–) over 100-fold faster than that in the conventional conPET. Accordingly, photoreduction with superior reaction rate and penetration depth, as well as reduced photodamage is detected. More importantly, our work offers comprehensive design rules for the triplet-mediated conPET strategy, whose versatility is confirmed by metal-free dye pairs and NIR-active PtTNP/PDI. Notably, our work achieves NIR-driven atom transfer radical polymerization using an inert aromatic halide as the initiator.
Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure
Authors: Lisowski Pawel , Lickfett Selene , Rybak-Wolf Agnieszka , Menacho Carmen , Le Stephanie , Pentimalli Tancredi Massimo , Notopoulou Sofia , Dykstra Werner , Oehler Daniel , López-Calcerrada Sandra , Mlody Barbara , Otto Maximilian , Wu Haijia , Richter Yasmin , Roth Philipp , Anand Ruchika , Kulka Linda A. M. , Meierhofer David , Glazar Petar , Legnini Ivano , Telugu Narasimha Swamy , Hahn Tobias , Neuendorf Nancy , Miller Duncan C. , Böddrich Annett , Polzin Amin , Mayatepek Ertan , Diecke Sebastian , Olzscha Heidi , Kirstein Janine , Ugalde Cristina , Petrakis Spyros , Cambridge Sidney , Rajewsky Nikolaus , Kühn Ralf , Wanker Erich E. , Priller Josef , Metzger Jakob J. , Prigione Alessandro 
Published: August 2024

AbstractExpansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.
Relating sex-bias in human cortical and hippocampal microstructure to sex hormones
Authors: Küchenhoff Svenja , Bayrak Şeyma , Zsido Rachel G. , Saberi Amin , Bernhardt Boris C. , Weis Susanne , Schaare H. Lina , Sacher Julia , Eickhoff Simon , Valk Sofie L. 
Published: August 2024

AbstractDetermining sex-bias in brain structure is of great societal interest to improve diagnostics and treatment of brain-related disorders. So far, studies on sex-bias in brain structure predominantly focus on macro-scale measures, and often ignore factors determining this bias. Here we study sex-bias in cortical and hippocampal microstructure in relation to sex hormones. Investigating quantitative intracortical profiling in-vivo using the T1w/T2w ratio in 1093 healthy females and males of the cross-sectional Human Connectome Project young adult sample, we find that regional cortical and hippocampal microstructure differs between males and females and that the effect size of this sex-bias varies depending on self-reported hormonal status in females. Microstructural sex-bias and expression of sex hormone genes, based on an independent post-mortem sample, are spatially coupled. Lastly, sex-bias is most pronounced in paralimbic areas, with low laminar complexity, which are predicted to be most plastic based on their cytoarchitectural properties. Albeit correlative, our study underscores the importance of incorporating sex hormone variables into the investigation of brain structure and plasticity.
Crossmodal sensory neurons based on high-performance flexible memristors for human-machine in-sensor computing system
Authors: Li Zhiyuan , Li Zhongshao , Tang Wei , Yao Jiaping , Dou Zhipeng , Gong Junjie , Li Yongfei , Zhang Beining , Dong Yunxiao , Xia Jian , Sun Lin , Jiang Peng , Cao Xun , Yang Rui , Miao Xiangshui , Yang Ronggui 
Published: August 2024

AbstractConstructing crossmodal in-sensor processing system based on high-performance flexible devices is of great significance for the development of wearable human-machine interfaces. A bio-inspired crossmodal in-sensor computing system can perform real-time energy-efficient processing of multimodal signals, alleviating data conversion and transmission between different modules in conventional chips. Here, we report a bio-inspired crossmodal spiking sensory neuron (CSSN) based on a flexible VO2 memristor, and demonstrate a crossmodal in-sensor encoding and computing system for wearable human-machine interfaces. We demonstrate excellent performance in the VO2 memristor including endurance (>1012), uniformity (0.72% for cycle-to-cycle variations and 3.73% for device-to-device variations), speed (<30 ns), and flexibility (bendable to a curvature radius of 1 mm). A flexible hardware processing system is implemented based on the CSSN, which can directly perceive and encode pressure and temperature bimodal information into spikes, and then enables the real-time haptic-feedback for human-machine interaction. We successfully construct a crossmodal in-sensor spiking reservoir computing system via the CSSNs, which can achieve dynamic objects identification with a high accuracy of 98.1% and real-time signal feedback. This work provides a feasible approach for constructing flexible bio-inspired crossmodal in-sensor computing systems for wearable human-machine interfaces.
Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence
Authors: Went Sam C. , Picton David M. , Morgan Richard D. , Nelson Andrew , Brady Aisling , Mariano Giuseppina , Dryden David T. F. , Smith Darren L. , Wenner Nicolas , Hinton Jay C. D. , Blower Tim R. 
Published: August 2024

AbstractBacteria have evolved a broad range of systems that provide defence against their viral predators, bacteriophages. Bacteriophage Exclusion (BREX) systems recognise and methylate 6 bp non-palindromic motifs within the host genome, and prevent replication of non-methylated phage DNA that encodes these same motifs. How BREX recognises cognate motifs has not been fully understood. In this study we characterise BREX from pathogenic Salmonella and present X-ray crystallographic structures of the conserved BREX protein, PglX. The PglX N-terminal domain encodes the methyltransferase, whereas the C-terminal domain is for motif recognition. We also present the structure of PglX bound to the phage-derived DNA mimic, Ocr, an inhibitor of BREX activity. Our analyses propose modes for DNA-binding by PglX and indicate that both methyltransferase activity and defence require larger BREX complexes. Through rational engineering of PglX we broaden both the range of phages targeted, and the host motif sequences that are methylated by BREX. Our data demonstrate that PglX is used to recognise specific DNA sequences for BREX activity, contributing to motif recognition for both phage defence and host methylation.
Identifying the multiple drivers of cactus diversification
Authors: Thompson Jamie B. , Hernández-Hernández Tania , Keeling Georgia , Vásquez-Cruz Marilyn , Priest Nicholas K. 
Published: August 2024

AbstractOur understanding of the complexity of forces at play in the rise of major angiosperm lineages remains incomplete. The diversity and heterogeneous distribution of most angiosperm lineages is so extraordinary that it confounds our ability to identify simple drivers of diversification. Using machine learning in combination with phylogenetic modelling, we show that five separate abiotic and biotic variables significantly contribute to the diversification of Cactaceae. We reconstruct a comprehensive phylogeny, build a dataset of 39 abiotic and biotic variables, and predict the variables of central importance, while accounting for potential interactions between those variables. We use state-dependent diversification models to confirm that five abiotic and biotic variables shape diversification in the cactus family. Of highest importance are diurnal air temperature range, soil sand content and plant size, with lesser importance identified in isothermality and geographic range size. Interestingly, each of the estimated optimal conditions for abiotic variables were intermediate, indicating that cactus diversification is promoted by moderate, not extreme, climates. Our results reveal the potential primary drivers of cactus diversification, and the need to account for the complexity underlying the evolution of angiosperm lineages.
Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice
Authors: Sarrazin David H. , Gardner Wilf , Marchese Carole , Balzinger Martin , Ramanathan Chockalingam , Schott Marion , Rozov Stanislav , Veleanu Maxime , Vestring Stefan , Normann Claus , Rantamäki Tomi , Antoine Benedicte , Barrot Michel , Challet Etienne , Bourgin Patrice , Serchov Tsvetan 
Published: August 2024

AbstractDepression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant ketamine. Selective Bmal1KO in CaMK2a excitatory neurons revealed that the functional mPFC clock is an essential factor for the development of a depression-like phenotype and ketamine effects. Per2 silencing in mPFC produced antidepressant-like effects, while REV-ERB agonism enhanced the depression-like phenotype and suppressed ketamine action. Pharmacological potentiation of clock positive modulator ROR elicited antidepressant-like effects, upregulating plasticity protein Homer1a, synaptic AMPA receptors expression and plasticity-related slow wave activity specifically in the mPFC. Our data demonstrate a critical role for mPFC molecular clock in regulating depression-like behavior and the therapeutic potential of clock pharmacological manipulations influencing glutamatergic-dependent plasticity.
Telomeric repeats in the commercial SB-1 vaccine facilitate viral integration and contribute to vaccine efficacy
Authors: You Yu , Kheimar Ahmed M. , Vychodil Tereza , Kossak Lisa , Sabsabi Mohammad A. , Conradie Andelé M. , Reddy Sanjay M. , Bertzbach Luca D. , Kaufer Benedikt B. 
Published: August 2024

AbstractMarek’s disease virus (MDV) integrates its genome into the telomeres of host chromosomes and causes fatal lymphomas in chickens. This integration is facilitated by telomeric repeat sequences (TMRs) at the ends of the viral genome, and is crucial for MDV-induced lymphomagenesis. The SB-1 vaccine virus is commonly used in commercial bivalent vaccines against MDV and also contains TMRs at its ends. Here, we demonstrate that SB-1 efficiently integrates its genome into the chromosomes of latently infected T cells. Deletion of the TMRs from the SB-1 genome did not affect virus replication, but severely impaired virus integration and genome maintenance in latently infected T cells and in chickens. Strikingly, the reduced integration and maintenance of latent SB-1 significantly impaired vaccine protection. Taken together, our data revealed that the TMRs facilitate SB-1 integration and that integration and/or maintenance of the latent viral genome is critical for vaccine protection.
Transcriptional responses and secondary metabolites variation of tomato plant in response to tobacco mosaic virus infestation
Authors: Rabie Mona , Aseel Dalia G. , Younes Hosny A. , Behiry Said I. , Abdelkhalek Ahmed 
Published: August 2024

AbstractThe present study focused on the impact of infection with the tobacco mosaic virus (TMV). Specifically, changes in phytochemicals and gene activity related to pathogenesis-related and phenylpropanoid pathway genes in tomato plants (Solanum lycopersicum L.) during a period of 2–14 days post-inoculation (dpi). According to TEM investigation and coat protein sequence analysis, the purified TMV Egyptian AM isolate (PP133743) has a rod-shaped structure with a diameter of around 110 nm. The RT-qPCR analysis revealed that PR-1 showed an initial increase after TMV infection, as seen in the time-course analysis. In contrast, PR-2 was consistently elevated throughout the infection, suggesting a stronger reaction to the virus and suppressing PAL expression at 6 to 14 dpi. The expression levels of HQT and CHS transcripts exhibited alternating patterns of up-regulation and down-regulation at different time intervals. The HPLC and GC–MS analysis of control- and TMV-infected tomato extracts revealed that different phenolic, flavonoid, and fatty acid compounds were increased (such as naringenin, rutin, flavone, ferulic acid, and pyrogallol) or significantly decreased (such as salicylic acid and chlorogenic acid) after TMV infection. The ability of TMV to inhibit most polyphenolic compounds could potentially accelerate the viral life cycle. Consequently, focusing on enhancing the levels of such suppressed compounds may be critical for developing plant viral infection management strategies.
Early and late gut microbiota signatures of stroke in high salt-fed stroke-prone spontaneously hypertensive rats
Authors: Bencivenni Silvia , Roggiani Sara , Zannoni Augusta , Conti Gabriele , Fabbrini Marco , Cotugno Maria , Stanzione Rosita , Pietrangelo Donatella , Litterio Margherita , Forte Maurizio , Busceti Carla Letizia , Fornai Francesco , Volpe Massimo , Turroni Silvia , Brigidi Patrizia , Forni Monica , Rubattu Speranza , D’Amico Federica 
Published: August 2024

AbstractThe high salt-fed stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable tool to study the mechanisms underlying stroke pathogenesis. Salt intake modifies the gut microbiota (GM) in rats and humans and alterations of the GM have previously been associated with increased stroke occurrence. We aimed to characterize the GM profile in SHRSPs fed a high-salt stroke-permissive diet (Japanese diet, JD), compared to the closely related stroke-resistant control (SHRSR), to identify possible changes associated with stroke occurrence. SHRSPs and SHRSRs were fed a regular diet or JD for 4 weeks (short-term, ST) or a maximum of 10 weeks (long-term, LT). Stroke occurred in SHRSPs on JD-LT, preceded by proteinuria and diarrhoea. The GM of JD-fed SHRSPs underwent early and late compositional changes compared to SHRSRs. An overrepresentation of Streptococcaceae and an underrepresentation of Lachnospiraceae were observed in SHRSPs JD-ST, while in SHRSPs JD-LT short-chain fatty acid producers, e.g. Lachnobacterium and Faecalibacterium, decreased and pathobionts such as Coriobacteriaceae and Desulfovibrio increased. Occludin gene expression behaved differently in SHRSPs and SHRSRs. Calprotectin levels were unchanged. In conclusion, the altered GM in JD-fed SHRSPs may be detrimental to gut homeostasis and contribute to stroke occurrence.