bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocyte-specific NR5A2 deficiency induces pyroptosis and exacerbates non-alcoholic steatohepatitis by downregulating ALDH1B1 expression
Authors: Zhao Rong , Guo Zizhen , Lu Kaikai , Chen Qian , Riaz Farooq , Zhou Yimeng , Yang Luyun , Cheng Xiaona , Wu Litao , Cheng Kexin , Feng Lina , Liu Sitong , Wu Xiaodan , Zheng Minghua , Yin Chunyan , Li Dongmin 
Published: October 2024

AbstractNonalcoholic steatohepatitis (NASH) is a prevalent chronic disease, yet its exact mechanisms and effective treatments remain elusive. Nuclear receptor subfamily 5 group A member 2 (NR5A2), a transcription factor closely associated with cholesterol metabolism in the liver, has been hindered from comprehensive investigation due to the lethality of NR5A2 loss in cell lines and animal models. To elucidate the role of NR5A2 in NASH, we generated hepatocyte-specific knockout mice for Nr5a2 (Nr5a2HKO) and examined their liver morphology across different age groups under a regular diet. Furthermore, we established cell lines expressing haploid levels of NR5A2 and subsequently reintroduced various isoforms of NR5A2. In the liver of Nr5a2HKO mice, inflammation and fibrosis spontaneously emerged from an early age, independent of lipid accumulation. Pyroptosis occurred in NR5A2-deficient cell lines, and different isoforms of NR5A2 reversed this form of cell death. Our findings unveiled that inhibition of NR5A2 triggers pyroptosis, a proinflammatory mode of cell death primarily mediated by the activation of the NF-κB pathway induced by reactive oxygen species (ROS). As a transcriptionally regulated molecule of NR5A2, aldehyde dehydrogenase 1 family member B1 (ALDH1B1) participates in pyroptosis through modulation of ROS level. In conclusion, the diverse isoforms of NR5A2 exert hepatoprotective effects against NASH by maintaining a finely tuned balance of ROS, which is contingent upon the activity of ALDH1B1.
VASH2 enhances KIF3C-mediated EGFR-endosomal recycling to promote aggression and chemoresistance of lung squamous cell carcinoma by increasing tubulin detyrosination
Authors: Wang Jing , Liu Pengpeng , Zhang Rui , Xing Biyuan , Chen Guidong , Han Lei , Yu Jinpu 
Published: October 2024

AbstractLung squamous cell carcinoma (LUSC) is associated with high mortality and has few therapeutic options. Chemotherapy remains the main treatment for LUSC patients, but multi-drug resistance has become the dominant challenge in the failure of chemotherapy in various cancers. Therefore, the effective therapeutic strategy for LUSC patients is an urgent unmet need. Here, we found vasohibin-2 (VASH2) was a prognostic biomarker for LUSC patients, and VASH2 promoted the malignant biological behaviors of LUSC cells and chemoresistance by increasing the detyrosination of α-tubulin. The high level of detyrosinated-tubulin was negatively associated with patient prognosis. Blocking the tubulin carboxypeptidase (TCP) activity of VASH2 inhibited the xenograft tumor growth and improved the treatment efficacy of paclitaxel in vivo. Results revealed that VASH2-induced increase in tubulin detyrosination boosted the binding of kinesin family member 3C (KIF3C) to microtubules and enhanced KIF3C-dependent endosomal recycling of EGFR, leading to the prolonged activation of PI3K/Akt/mTOR signaling. This study demonstrated that VASH2 was not only a prognostic biomarker but also a promising therapeutic target in LUSC, which offers a novel insight that combination of chemotherapy and EpoY, a TCP inhibitor, may be a promising treatment strategy for LUSC patients.
The origin and maintenance of supergenes contributing to ecological adaptation in Atlantic herring
Authors: Jamsandekar Minal , Ferreira Mafalda S. , Pettersson Mats E. , Farrell Edward D. , Davis Brian W. , Andersson Leif 
Published: October 2024

AbstractChromosomal inversions are associated with local adaptation in many species. However, questions regarding how they are formed, maintained and impact various other evolutionary processes remain elusive. Here, using a large genomic dataset of long-read and short-read sequencing, we ask these questions in one of the most abundant vertebrates on Earth, the Atlantic herring. This species has four megabase-sized inversions associated with ecological adaptation that correlate with water temperature. The S and N inversion alleles at these four loci dominate in the southern and northern parts, respectively, of the species distribution in the North Atlantic Ocean. By determining breakpoint coordinates of the four inversions and the structural variations surrounding them, we hypothesize that these inversions are formed by ectopic recombination between duplicated sequences immediately outside of the inversions. We show that these are old inversions (>1 MY), albeit formed after the split between the Atlantic herring and its sister species, the Pacific herring. There is evidence for extensive gene flux between inversion alleles at all four loci. The large Ne of herring combined with the common occurrence of opposite homozygotes across the species distribution has allowed effective purifying selection to prevent the accumulation of genetic load and repeats within the inversions.
Efficient and stable inverted perovskite solar cells enabled by homogenized PCBM with enhanced electron transport
Authors: Gong Cheng , Li Haiyun , Xu Zhiyuan , Li Yuheng , Wang Huaxin , Zhuang Qixin , Wang Awen , Li Zhijun , Guo Zhihao , Zhang Cong , Wang Baiqian , Li Xiong , Zang Zhigang 
Published: October 2024

AbstractFullerene derivatives are extensively employed in inverted perovskite solar cells due to their excellent electron extraction capabilities. However, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) agglomerates easily in solution and exhibits a relatively low ionization barrier, increasing charge recombination losses and charge accumulation in the interface. Here, tetramethylthiuram disulfide (TMDS) is introduced into the PCBM solution to induce the formation of reducing sulfur radicals through UV light irradiation, allowing for n doping of the PCBM material. The resulting modified PCBM layer exhibits enhanced conductivity and electron mobility, significantly suppressing charge recombination. As a result, the resulting devices incorporating TMDS achieve a champion efficiency of 26.10% (certified 25.39%) and 24.06% at a larger area (1.0 cm2) with negligible hysteresis. More importantly, the optimized devices retain 95% and 90% of their initial efficiency after 1090 h under damp heat testing (85 °C and 85% relative humidity) and after 1271 h under maximum power point-tracking conditions, respectively.
Sensory experience steers representational drift in mouse visual cortex
Authors: Bauer Joel , Lewin Uwe , Herbert Elizabeth , Gjorgjieva Julijana , Schoonover Carl E. , Fink Andrew J. P. , Rose Tobias , Bonhoeffer Tobias , Hübener Mark 
Published: October 2024

AbstractRepresentational drift—the gradual continuous change of neuronal representations—has been observed across many brain areas. It is unclear whether drift is caused by synaptic plasticity elicited by sensory experience, or by the intrinsic volatility of synapses. Here, using chronic two-photon calcium imaging in primary visual cortex of female mice, we find that the preferred stimulus orientation of individual neurons slowly drifts over the course of weeks. By using cylinder lens goggles to limit visual experience to a narrow range of orientations, we show that the direction of drift, but not its magnitude, is biased by the statistics of visual input. A network model suggests that drift of preferred orientation largely results from synaptic volatility, which under normal visual conditions is counteracted by experience-driven Hebbian mechanisms, stabilizing preferred orientation. Under deprivation conditions these Hebbian mechanisms enable adaptation. Thus, Hebbian synaptic plasticity steers drift to match the statistics of the environment.
Socio-demographic and genetic risk factors for drug adherence and persistence across 5 common medication classes
Authors: Cordioli Mattia , Corbetta Andrea , Kariis Hanna Maria , Jukarainen Sakari , Vartiainen Pekka , Kiiskinen Tuomo , Ferro Matteo ,   FinnGen, Perola Markus , Ripatti Samuli , Ganna Andrea ,   Estonian Biobank Research Team, Metspalu Andres , Milani Lili , Esko Tõnu , Mägi Reedik , Nelis Mari , Hudjashov Georgi , Perola Markus , Niemi Mikko , Ripatti Samuli , Lehto Kelli , Milani Lili , Ganna Andrea 
Published: October 2024

AbstractLow drug adherence is a major obstacle to the benefits of pharmacotherapies and it is therefore important to identify factors associated with discontinuing or being poorly adherent to a prescribed treatment regimen. Using high-quality nationwide health registry data and genome-wide genotyping, we evaluate the impact of socio-demographic and genetic risk factors on adherence and persistence for 5 common medication classes that require long-term, regular therapy (N = 1,814,591 individuals from Finnish nationwide registries, 217,005 with genetic data from Finland and Estonia). Need for social assistance and immigration status show a notable negative effect on persistence and adherence across the examined medications (odd ratios between 0.48 and 0.82 for persistence and between 1.1% to 4.3% decrease in adherence) while demographic and health factors show comparably modest or inconsistent effects. A genome-wide scan does not identify genetic variants associated with the two phenotypes, while some pharmacogenes (i.e. CYP2C9 and SLCO1B1) are modestly associated with persistence, but not with adherence. We observe significant genetic correlations between medication adherence and participation in research studies. Overall, our findings suggest that socio-economically disadvantaged groups would benefit from targeted interventions to improve the dispensing and uptake of pharmacological treatments.
Training caretakers to clean community wells is a highly cost-effective way to reduce exposure to coliform bacteria
Authors: Habib Md. Ahasan , Cocciolo Serena , Raihan Md. Mir Abu , Bhattacharya Prosun , Tompsett Anna 
Published: October 2024

AbstractExisting strategies for improving global access to safe drinking water have met only limited success. We consider an unglamorous and often neglected dimension of drinking water infrastructure provision: cleaning. We randomly assigned caretakers of community wells to participate in a training workshop about how to clean wells. Thirteen to seventeen months later, wells with caretakers assigned to receive training have negligible rates of contamination with Escherichia coli (13 months: 2%; 17 months: 4%), while control wells have substantial rates of E. coli contamination (13 months: 14%; 17 months: 19%). Rates of contamination with any coliform bacteria are almost halved (13 months: control 55%, treated 30%; 17 months: control 77%, treated 46%). We estimate the cost of preventing exposure to coliform bacteria in drinking water to be US$0.89 per person and that, if scaled up, each US$2376 spent on the intervention could avoid the death of a child.
Hemozoin induces malaria via activation of DNA damage, p38 MAPK and neurodegenerative pathways in a human iPSC-derived neuronal model of cerebral malaria
Authors: Pranty Abida Islam , Szepanowski Leon-Phillip , Wruck Wasco , Karikari Akua Afriyie , Adjaye James 
Published: October 2024

AbstractMalaria caused by Plasmodium falciparum infection results in severe complications including cerebral malaria (CM), in which approximately 30% of patients end up with neurological sequelae. Sparse in vitro cell culture-based experimental models which recapitulate the molecular basis of CM in humans has impeded progress in our understanding of its etiology. This study employed healthy human induced pluripotent stem cells (iPSCs)-derived neuronal cultures stimulated with hemozoin (HMZ) - the malarial toxin as a model for CM. Secretome, qRT-PCR, Metascape, and KEGG pathway analyses were conducted to assess elevated proteins, genes, and pathways. Neuronal cultures treated with HMZ showed enhanced secretion of interferon-gamma (IFN-γ), interleukin (IL)1-beta (IL-1β), IL-8 and IL-16. Enrichment analysis revealed malaria, positive regulation of cytokine production and positive regulation of mitogen-activated protein kinase (MAPK) cascade which confirm inflammatory response to HMZ exposure. KEGG assessment revealed up-regulation of malaria, MAPK and neurodegenerative diseases-associated pathways which corroborates findings from previous studies. Additionally, HMZ induced DNA damage in neurons. This study has unveiled that exposure of neuronal cultures to HMZ, activates molecules and pathways similar to those observed in CM and neurodegenerative diseases. Furthermore, our model is an alternative to rodent experimental models of CM.
Photocatalytic generation of alkyl carbanions from aryl alkenes
Authors: Czyz Milena L. , Horngren Tyra H. , Kondopoulos Andrew J. , Franov Liam J. , Forni José A. , Pham Le Nhan , Coote Michelle L. , Polyzos Anastasios 
Published: October 2024

AbstractOrganometallic reagents are routinely used as fundamental building blocks in organic chemistry to rapidly diversify molecular fragments via carbanion intermediates. However, the catalytic generation of carbanion equivalents, particularly from sp3-hybridized alkyl scaffolds, remains an underdeveloped goal in chemical synthesis. Here we disclose an approach for the generation of alkyl carbanions via single-electron reduction of aryl alkenes, enabled by multi-photon photoredox catalysis. We demonstrate that photocatalytically induced alkyl carbanions engage in intermolecular C–C bond-forming reactions with carbonyl electrophiles. Central to this method is the controlled formation of an alkene distonic radical anion intermediate that undergoes nucleophilic addition, followed by a kinetically favoured reductive polar crossover to produce a second carbanion available for further diversification. The versatility of this protocol was illustrated by the development of four distinct intermolecular C–C bond-forming reactions with aromatic alkenes (hydroalkoxylation, hydroamidation, aminoalkylation and carboxyaminoalkylation) to generate a range of valuable and complex scaffolds.
Follicle-intrinsic and spatially distinct molecular programs drive follicle rupture and luteinization during ex vivo mammalian ovulation
Authors: Zaniker Emily J. , Zhang Jiyang , Russo Daniela , Huang Ruixu , Suritis Kristine , Drake Riley S. , Barlow-Smith Esther , Shalek Alex K. , Woodruff Teresa K. , Xiao Shuo , Goods Brittany A. , Duncan Francesca E. 
Published: October 2024

AbstractDuring ovulation, the apical wall of the preovulatory follicle breaks down to facilitate gamete release. In parallel, the residual follicle wall differentiates into a progesterone-producing corpus luteum. Disruption of ovulation, whether through contraceptive intervention or infertility, has implications for women’s health. In this study, we harness the power of an ex vivo ovulation model and machine-learning guided microdissection to identify differences between the ruptured and unruptured sides of the follicle wall. We demonstrate that the unruptured side exhibits clear markers of luteinization after ovulation while the ruptured side exhibits cell death signals. RNA-sequencing of individual follicle sides reveals 2099 differentially expressed genes (DEGs) between follicle sides without ovulation induction, and 1673 DEGs 12 h after induction of ovulation. Our model validates molecular patterns consistent with known ovulation biology even though this process occurs in the absence of the ovarian stroma, vasculature, and immune cells. We further identify previously unappreciated pathways including amino acid transport and Jag-Notch signaling on the ruptured side and glycolysis, metal ion processing, and IL-11 signaling on the unruptured side of the follicle. This study yields key insights into follicle-inherent, spatially-defined pathways that underlie follicle rupture, which may further understanding of ovulation physiology and advance women’s health.
Witnessing their mother’s acute and prolonged stress affects executive functioning in children
Authors: Lashani Eileen , Larsen Isabella G. , Kanske Philipp , Rosendahl Jenny , Blasberg Jost U. , Engert Veronika 
Published: October 2024

AbstractStress can detrimentally affect physical and mental health, especially during childhood. During this critical period, parental bonds can foster resilience or amplify stress. This study explored whether mothers’ everyday stress can act as a source of childhood stress, affecting children’s executive functioning. 76 healthy mother-child dyads participated, with mothers assigned to a stress-inducing or stress-free condition. Children observed their mothers and were subsequently tested for cognitive flexibility and working memory. Subjective stress, heart rate, and cortisol were measured repeatedly in mothers and children, alongside everyday stress perceptions. Linear mixed models showed that children’s acute stress response was associated with impaired cognitive flexibility. Maternal stress, both acute and past-month, was a better predictor of children’s cognitive performance than children’s own stress. Quadratic relationships indicated the highest error rates at very low and high maternal stress. We found no evidence that children’s working memory was impaired by their own or their mothers’ stress. Although expected covariations of acute or prolonged stress between mothers and children were not observed, an interaction between maternal past-month stress and acute stress condition provided insights into adaptive mechanisms in children. These findings underscore the significant impact of maternal stress on children’s executive functioning, illustrating how parental experiences shape children’s everyday outcomes.
Wide voltage gain isolated LCC resonant converters for LED driver applications
Authors: Askari Shirin , Molavi Navid , Farzanehfard Hosein 
Published: October 2024

AbstractThis article proposes an isolated high‐efficiency resonant LED driver with wide‐input voltage range. The proposed converter is developed by integrating LCC resonant converter and buck‐boost converter. In this topology, the LCC network provides many features including the integration of buck‐boost filter inductor and the transformer magnetizing inductance. In addition, the LCC network provides zero voltage switching (ZVS) operation of the main switches and zero current switching (ZCS) operation of the rectifier diodes over a wide variation of duty cycle operation. Also, load‐independent output current characteristic with improved efficiency is obtained at the resonant frequency operation which is well‐suited for LED applications. Other topology variations of the proposed converter generating step‐up and step‐down voltage gains are introduced for applications with different input voltage ranges. To validate the theoretical analysis and LED driver operation, a 50 W laboratory prototype of the proposed LED driver is implemented for the wide input voltage of 18–40 V to deliver 500 mA output current to a string of 1–30 LEDs, which corresponds to an output voltage range of 3.3–100 V.
Dynamic modelling and equilibrium manifold of multi‐converter systems: A study on grid‐forming and grid‐following converters in renewable energy power plants
Authors: Zhang Ziqian , Schuerhuber Robert , Fickert Lothar , Chen Guochu 
Published: October 2024

AbstractThis study explores the optimal balance between grid‐forming (GFM) and grid‐following (GFL) converter capacities within power stations to ensure stable operations. The investigation introduces a novel, generic modelling approach for analysing multiple converter systems in the wind and photovoltaic power plants. The method aims to elucidate the dynamic characteristics of the converters in power plants, particularly focusing on the continuity and existence of the equilibrium manifolds and their impact on system stability. Findings reveal a pronounced difference in the recovery capabilities of GFM and GFL following synchronization losses, highlighting an asymmetry in their abilities. Specifically, GFL converters exhibit more effectiveness in reinstating synchrony after synchronization losses caused by GFM. Conversely, GFM demonstrates a lesser capacity to recover from synchronization losses induced by GFL. Furthermore, analysis indicates that when the capacity ratio of GFL to the system's short‐circuit capacity significantly exceeds that of GFM (exceeding a 1:5 ratio), the system experiences an absence of a stable equilibrium point, thereby affecting the synchronization stability of GFM. These conclusions have been validated through joint controller hardware‐in‐the‐loop testing.
A cooperative approach for generation and lines expansion planning in microgrid‐based active distribution networks
Authors: Nemati Bizhan , Hosseini Seyed Mohammad Hassan , Siahkali Hassan 
Published: October 2024

AbstractWith the growth of the load in the electricity networks, sufficient investment in the generation and lines expansion should be made in order to provide the energy needed by consumers with the lowest possible investment and operation costs. This issue is especially important in distribution networks, which are faced with the uncertainties of renewable energy generation and the development of microgrids and related issues.In this article, the planning of generation and lines expansion has been modeled with the aim of minimizing the total costs of microgrids, based on the cooperative approach. For this purpose, a bi‐level model has been developed; on the upper level, microgrids make investment decisions with a cooperative approach, and a constrained stochastic formulation has been developed with considering operational uncertainties on the lower level. Also, in this article, in order to ensure the supply of critical loads in island conditions, the self‐sufficiency index is defined. Three case studies have been considered to ensure the effectiveness of the developed model. In case 1, each microgrid will be able to supply its load only by generating of its units and purchasing from the retail market. In case 2, the possibility of trading with other microgrids in a non‐cooperative approach will also be available to the microgrids operators, and in case 3, microgrids can exchange energy with other microgrids in a cooperative manner. The simulation results showed that due to the possibility of using nearby microgrid resources, the cost of microgrid load supply in case 2 was reduced by 4.84% compared to case 1. Also, this cost in case 3 was reduced by 5.23% and 0.38%, respectively, compared to cases 1 and 2, due to the use of a cooperative manner in microgrid load providing.