bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway
Authors: Zhou Xiqian , Zhao Junyong , Yan Tao , Ye Danrong , Wang Yuying , Zhou Bai’an , Liu Diya , Wang Xuehui , Zheng Wenfang , Zheng Bowen , Qian Fengyuan , Li Yating , Li Dengfeng , Fang Lin 
Published: April 2024

AbstractBreast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.
The Janus face of endogenous neuronal tPA: promoting self-protection and worsening the death of neighboring neurons
Authors: Prunotto Paul , Marie Pauline , Lebouvier Laurent , Hommet Yannick , Vivien Denis , Ali Carine 
Published: April 2024

AbstractRecombinant tissue-type plasminogen activator (r-tPA/Actilyse) stands as the prevailing pharmacological solution for treating ischemic stroke patients, of whom because their endogenous circulating tPA alone is not sufficient to rescue reperfusion and to promote favorable outcome. Beyond the tPA contributed by circulating endothelial cells and hepatocytes, neurons also express tPA, sparking debates regarding its impact on neuronal fate ranging from pro-survival to neurotoxic properties. In order to investigate the role of neuronal tPA during brain injuries, we developed models leading to its conditional deletion in neurons, employing AAV9-pPlat-GFP and AAV9-pPlat-Cre-GFP along with tPA floxed mice. These models were subjected to N-methyl-D-aspartate (NMDA)-induced excitotoxicity or thromboembolic ischemic stroke in mice. Initially, we established that our AAV9 constructs selectively transduce neurons, bypassing other brain cell types. Subsequently, we demonstrated that tPA-expressing neurons exhibit greater resistance against NMDA-induced excitotoxicity compared to tPA negative neurons. The targeted removal of tPA in neurons heightened the susceptibility of these neurons to cell death and prevented a paracrine neurotoxic effect on tPA non-expressing neurons. Under ischemic conditions, the self-neuroprotective influence of tPA encompassed both excitatory (GFP+/Tbr1+) and inhibitory (GFP+/GABA+) neurons. Our data indicate that endogenous neuronal tPA is a protective or deleterious factor against neuronal death in an excitotoxic/ischemic context, depending on whether it acts as an autocrine or a paracrine mediator.
Solvent-free selective hydrogenation of nitroaromatics to azoxy compounds over Co single atoms decorated on Nb2O5 nanomeshes
Authors: Li Zhijun , Lu Xiaowen , Guo Cong , Ji Siqi , Liu Hongxue , Guo Chunmin , Lu Xue , Wang Chao , Yan Wensheng , Liu Bingyu , Wu Wei , Horton J. Hugh , Xin Shixuan , Wang Yu 
Published: April 2024

AbstractThe solvent-free selective hydrogenation of nitroaromatics to azoxy compounds is highly important, yet challenging. Herein, we report an efficient strategy to construct individually dispersed Co atoms decorated on niobium pentaoxide nanomeshes with unique geometric and electronic properties. The use of this supported Co single atom catalysts in the selective hydrogenation of nitrobenzene to azoxybenzene results in high catalytic activity and selectivity, with 99% selectivity and 99% conversion within 0.5 h. Remarkably, it delivers an exceptionally high turnover frequency of 40377 h–1, which is amongst similar state-of-the-art catalysts. In addition, it demonstrates remarkable recyclability, reaction scalability, and wide substrate scope. Density functional theory calculations reveal that the catalytic activity and selectivity are significantly promoted by the unique electronic properties and strong electronic metal-support interaction in Co1/Nb2O5. The absence of precious metals, toxic solvents, and reagents makes this catalyst more appealing for synthesizing azoxy compounds from nitroaromatics. Our findings suggest the great potential of this strategy to access single atom catalysts with boosted activity and selectivity, thus offering blueprints for the design of nanomaterials for organocatalysis.
Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling
Authors: Sun Ting-Hsuan , Wang Chia-Chun , Liu Ting-Yuan , Lo Shih-Chang , Huang Yi-Xuan , Chien Shang-Yu , Chu Yu-De , Tsai Fuu-Jen , Hsu Kai-Cheng 
Published: April 2024

AbstractPolygenic scores estimate genetic susceptibility to diseases. We systematically calculated polygenic scores across 457 phenotypes using genotyping array data from China Medical University Hospital. Logistic regression models assessed polygenic scores’ ability to predict disease traits. The polygenic score model with the highest accuracy, based on maximal area under the receiver operating characteristic curve (AUC), is provided on the GeneAnaBase website of the hospital. Our findings indicate 49 phenotypes with AUC greater than 0.6, predominantly linked to endocrine and metabolic diseases. Notably, hyperplasia of the prostate exhibited the highest disease prediction ability (P value = 1.01 × 10−19, AUC = 0.874), highlighting the potential of these polygenic scores in preventive medicine and diagnosis. This study offers a comprehensive evaluation of polygenic scores performance across diverse human traits, identifying promising applications for precision medicine and personalized healthcare, thereby inspiring further research and development in this field.
Neurocomputational mechanisms involved in adaptation to fluctuating intentions of others
Authors: Philippe Rémi , Janet Rémi , Khalvati Koosha , Rao Rajesh P. N. , Lee Daeyeol , Dreher Jean-Claude 
Published: April 2024

AbstractHumans frequently interact with agents whose intentions can fluctuate between competition and cooperation over time. It is unclear how the brain adapts to fluctuating intentions of others when the nature of the interactions (to cooperate or compete) is not explicitly and truthfully signaled. Here, we use model-based fMRI and a task in which participants thought they were playing with another player. In fact, they played with an algorithm that alternated without signaling between cooperative and competitive strategies. We show that a neurocomputational mechanism with arbitration between competitive and cooperative experts outperforms other learning models in predicting choice behavior. At the brain level, the fMRI results show that the ventral striatum and ventromedial prefrontal cortex track the difference of reliability between these experts. When attributing competitive intentions, we find increased coupling between these regions and a network that distinguishes prediction errors related to competition and cooperation. These findings provide a neurocomputational account of how the brain arbitrates dynamically between cooperative and competitive intentions when making adaptive social decisions.
Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma
Authors: Liu Xiaodong , Zhang Ke , Kaya Neslihan A. , Jia Zhe , Wu Dafei , Chen Tingting , Liu Zhiyuan , Zhu Sinan , Hillmer Axel M. , Wuestefeld Torsten , Liu Jin , Chan Yun Shen , Hu Zheng , Ma Liang , Jiang Li , Zhai Weiwei 
Published: April 2024

AbstractSolid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a “spatially competing distribution” (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.
Quantum phase synchronization via exciton-vibrational energy dissipation sustains long-lived coherence in photosynthetic antennas
Authors: Zhu Ruidan , Li Wenjun , Zhen Zhanghe , Zou Jiading , Liao Guohong , Wang Jiayu , Wang Zhuan , Chen Hailong , Qin Song , Weng Yuxiang 
Published: April 2024

AbstractThe lifetime of electronic coherences found in photosynthetic antennas is known to be too short to match the energy transfer time, rendering the coherent energy transfer mechanism inactive. Exciton-vibrational coherence time in excitonic dimers which consist of two chromophores coupled by excitation transfer interaction, can however be much longer. Uncovering the mechanism for sustained coherences in a noisy biological environment is challenging, requiring the use of simpler model systems as proxies. Here, via two-dimensional electronic spectroscopy experiments, we present compelling evidence for longer exciton-vibrational coherence time in the allophycocyanin trimer, containing excitonic dimers, compared to isolated pigments. This is attributed to the quantum phase synchronization of the resonant vibrational collective modes of the dimer, where the anti-symmetric modes, coupled to excitonic states with fast dephasing, are dissipated. The decoupled symmetric counterparts are subject to slower energy dissipation. The resonant modes have a predicted nearly 50% reduction in the vibrational amplitudes, and almost zero amplitude in the corresponding dynamical Stokes shift spectrum compared to the isolated pigments. Our findings provide insights into the mechanisms for protecting coherences against the noisy environment.
Frustrated Lewis pair catalyst realizes efficient green diesel production
Authors: Li De-Chang , Pan Zhengyi , Tian Zhengbin , Zhang Qian , Deng Xiaohui , Jiang Heqing , Wang Guang-Hui 
Published: April 2024

AbstractHydrotreating renewable oils over sulfided metal catalysts is commercially applied to produce green diesel, but it requires a continuous sulfur replenishment to maintain catalyst activity, which inevitably results in sulfur contamination and increases production costs. We report a robust P-doped NiAl-oxide catalyst with frustrated Lewis pairs (i.e., P atom bonded with the O atom acts as an electron donor, while the spatially separated Ni atom acts as an electron acceptor) that allows efficient green diesel production without sulfur replenishment. The catalyst runs more than 500 h at a weight hourly space velocity (WHSV) of 28.3 h−1 without deactivation (methyl laurate as a model compound), and is able to completely convert a real feedstock of soybean oil to diesel-range hydrocarbons with selectivity >90% during 500 h of operation. This work is expected to open up a new avenue for designing non-sulfur catalysts that can make the green diesel production greener.
Dynamic interplay of microtubule and actomyosin forces drive tissue extension
Authors: Singh Amrita , Thale Sameedha , Leibner Tobias , Lamparter Lucas , Ricker Andrea , Nüsse Harald , Klingauf Jürgen , Galic Milos , Ohlberger Mario , Matis Maja 
Published: April 2024

AbstractIn order to shape a tissue, individual cell-based mechanical forces have to be integrated into a global force pattern. Over the last decades, the importance of actomyosin contractile arrays, which are the key constituents of various morphogenetic processes, has been established for many tissues. Recent studies have demonstrated that the microtubule cytoskeleton mediates folding and elongation of the epithelial sheet duringDrosophilamorphogenesis, placing microtubule mechanicson parwith actin-based processes. While these studies establish the importance of both cytoskeletal systems during cell and tissue rearrangements, a mechanistic understanding of their functional hierarchy is currently missing. Here, we dissect the individual roles of these two key generators of mechanical forces during epithelium elongation in the developingDrosophilawing. We show that wing extension, which entails columnar-to-cuboidal cell shape remodeling in a cell-autonomous manner, is driven by anisotropic cell expansion caused by the remodeling of the microtubule cytoskeleton from apico-basal to planarly polarized. Importantly, cell and tissue elongation is not associated with Myosin activity. Instead, Myosin II exhibits a homeostatic role, as actomyosin contraction balances polarized microtubule-based forces to determine the final cell shape. Using a reductionist model, we confirm that pairing microtubule and actomyosin-based forces is sufficient to recapitulate cell elongation and the final cell shape. These results support a hierarchical mechanism whereby microtubule-based forces in some epithelial systems prime actomyosin-generated forces.
Early deficits in an in vitro striatal microcircuit model carrying the Parkinson’s GBA-N370S mutation
Authors: Do Quyen B. , Noor Humaira , Marquez-Gomez Ricardo , Cramb Kaitlyn M. L. , Ng Bryan , Abbey Ajantha , Ibarra-Aizpurua Naroa , Caiazza Maria Claudia , Sharifi Parnaz , Lang Charmaine , Beccano-Kelly Dayne , Baleriola Jimena , Bengoa-Vergniory Nora , Wade-Martins Richard 
Published: April 2024

AbstractUnderstanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson’s disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chambered microfluidic platform and established a cortico-striato-nigral microcircuit partially recapitulating the striatal presynaptic landscape in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, cortical glutamatergic projections facilitated MSN synaptic activity, and dopaminergic transmission enhanced maturation of MSNs in vitro. Replacement of wild-type iPSC-derived dopamine neurons (iPSC-DaNs) in the striatal microcircuit with those carrying the PD-related GBA-N370S mutation led to a depolarisation of resting membrane potential and an increase in rheobase in iPSC-MSNs, as well as a reduction in both voltage-gated sodium and potassium currents. Such deficits were resolved in late microcircuit cultures, and could be reversed in younger cultures with antagonism of protein kinase A activity in iPSC-MSNs. Taken together, our results highlight the unique utility of modelling striatal neurons in a modular physiological circuit to reveal mechanistic insights into GBA1 mutations in PD.
Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis
Authors: Alvarez-Martinez Marisol , Cox Luke S. , Pearson Claire F. , Branchett William J. , Chakravarty Probir , Wu Xuemei , Slawinski Hubert , Al-Dibouni Alaa , Samelis Vasileios A. , Gabryšová Leona , Priestnall Simon L. , Suárez-Bonnet Alejandro , Mikolajczak Anna , Briscoe James , Powrie Fiona , O’Garra Anne 
Published: April 2024

AbstractIntestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4+ T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1fl/flMaffl/flCd4Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in TH1/NK/ILC1 effector genes in LPLs, while Prdm1fl/flCd4Cre and Maffl/flCd4Cre mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maffl/flCd4Cre mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell–myeloid–neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf, revealing potential mechanisms of human disease.
A novel on high voltage gain boost converter with cuckoo search optimization based MPPTController for solar PV system
Authors: Mariprasath T. , Basha C. H. Hussaian , Khan Baseem , Ali Ahmed 
Published: April 2024

AbstractTraditionally, isolated and non-isolated boost converters are used for solar photovoltaic systems (SPV). These converters have limitations such as low voltage gain, less voltage ripples, temperature dependence, high voltage stress across the switches, and being bulky in size. Besides, the solar PV system also has non-linear characteristics between I–V and P–V, and the energy yield potential is affected by partial shading phenomena. Therefore, maximum power point tracking (MPPT) is being added to the SPV system to get the maximum output power under steady and dynamic climate conditions. Although the conventional MPPT has drawbacks such as less accuracy in predicting the MPP under partial shading conditions, low tracking speed, and more ripples, Hence, the research proposes a stackable single switch boost converter (SSBC) with a Cuckoo search MPPT controller for the SPV system. The efficiency of the proposed circuit topology has been compared with conventional boost converters with various MPPTs. Subsequently, the accuracy of tracking true MPPT by CSO is compared with that of PSO and FPNA. The results show, that the CMPPT with CBC has produced more ripples, whereas the BMPPT with SSBC produces ripple-free power under steady conditions. It is also observed that SSBC with BMPPT produces more power than SSBC with TMPPT. The efficiency of SSBC with BMPPT is better than other combinations. Finally, a prototype model has been developed and verified.
Population structure and identification of genomic regions associated with productive traits in five Italian beef cattle breeds
Authors: Colombi Daniele , Rovelli Giacomo , Luigi-Sierra Maria Gracia , Ceccobelli Simone , Guan Dailu , Perini Francesco , Sbarra Fiorella , Quaglia Andrea , Sarti Francesca Maria , Pasquini Marina , Amills Marcel , Lasagna Emiliano 
Published: April 2024

AbstractItaly has a long history in beef production, with local breeds such as Marchigiana, Chianina, Romagnola, Maremmana, and Podolica which produce high-quality meat. Selection has improved meat production, precocity, growth ability and muscle development, but the genetic determinism of such traits is mostly unknown. Using 33K SNPs-data from young bulls (N = 4064) belonging to these five Italian breeds, we demonstrated that the Maremmana and Podolica rustic breeds are closely related, while the specialised Marchigiana, Chianina, and Romagnola breeds are more differentiated. A genome-wide association study for growth and muscle development traits (average daily gain during the performance test, weight at 1 year old, muscularity) was conducted in the five Italian breeds. Results indicated a region on chromosome 2, containing the myostatin gene (MSTN), which displayed significant genome-wide associations with muscularity in Marchigiana cattle, a breed in which the muscle hypertrophy phenotype is segregating. Moreover, a significant SNP on chromosome 14 was associated, in the Chianina breed, to muscularity. The identification of diverse genomic regions associated with conformation traits might increase our knowledge about the genomic basis of such traits in Italian beef cattle and, eventually, such information could be used to implement marker-assisted selection of young bulls tested in the performance test.
Molecular identification of Proteus mirabilis, Vibrio species leading to CRISPR-Cas9 modification of tcpA and UreC genes causing cholera and UTI
Authors: Naveed Muhammad , Tahir Fatima , Aziz Tariq , Waseem Muhammad , Makhdoom Syeda Izma , Ali Nouman , Alharbi Metab , Albekairi Thamer H. , Alasmari Abdullah F. 
Published: April 2024

AbstractHeavy metal accumulation increases rapidly in the environment due to anthropogenic activities and industrialization. The leather and surgical industry produces many contaminants containing heavy metals. Cadmium, a prominent contaminant, is linked to severe health risks, notably kidney and liver damage, especially among individuals exposed to contaminated wastewater. This study aims to leverage the natural cadmium resistance mechanisms in bacteria for bioaccumulation purposes. The industrial wastewater samples, characterized by an alarming cadmium concentration of 29.6 ppm, 52 ppm, and 76.4 ppm—far exceeding the recommended limit of 0.003 ppm—were subjected to screening for cadmium-resistant bacteria using cadmium-supplemented media with CdCl2. 16S rRNA characterization identified Vibrio cholerae and Proteus mirabilis as cadmium-resistant bacteria in the collected samples. Subsequently, the cadmium resistance-associated cadA gene was successfully amplified in Vibrio species and Proteus mirabilis, revealing a product size of 623 bp. Further analysis of the identified bacteria included the examination of virulent genes, specifically the tcpA gene (472 bp) associated with cholera and the UreC gene (317 bp) linked to urinary tract infections. To enhance the bioaccumulation of cadmium, the study proposes the potential suppression of virulent gene expression through in-silico gene-editing tools such as CRISPR-Cas9. A total of 27 gRNAs were generated for UreC, with five selected for expression. Similarly, 42 gRNA sequences were generated for tcpA, with eight chosen for expression analysis. The selected gRNAs were integrated into the lentiCRISPR v2 expression vector. This strategic approach aims to facilitate precise gene editing of disease-causing genes (tcpA and UreC) within the bacterial genome. In conclusion, this study underscores the potential utility of Vibrio species and Proteus mirabilis as effective candidates for the removal of cadmium from industrial wastewater, offering insights for future environmental remediation strategies.