bluuebunny/crossref_metadata_2025_split huggingface dataset:
O‐GlcNAcylation promotes malignancy and cisplatin resistance of lung cancer by stabilising NRF2
Authors: Zhang Yihan , Sun Changning , Ma Leina , Xiao Guokai , Gu Yuchao , Yu Wengong 
Published: October 2024

AbstractBackgroundThe transcription factor NRF2 plays a significant role in regulating genes that protect cells from oxidative damage. O‐GlcNAc modification, a type of posttranslational modification, is crucial for cellular response to stress. Although the involvement of both NRF2 and O‐GlcNAc in maintaining cellular redox balance and promoting cancer malignancy has been demonstrated, the potential mechanisms remain elusive.MethodsThe immunoblotting, luciferase reporter, ROS assay, co‐immunoprecipitation, and immunofluorescence was used to detect the effects of global cellular O‐GlcNAcylation on NRF2. Mass spectrometry was utilised to map the O‐GlcNAcylation sites on NRF2, which was validated by site‐specific mutagenesis and O‐GlcNAc enzymatic labelling. Human lung cancer samples were employed to verify the association between O‐GlcNAc and NRF2. Subsequently, the impact of NRF2 O‐GlcNAcylation in lung cancer malignancy and cisplatin resistance were evaluated in vitro and in vivo.ResultsNRF2 is O‐GlcNAcylated at Ser103 residue, which hinders its binding to KEAP1 and thus enhances its stability, nuclear localisation, and transcription activity. Oxidative stress and cisplatin can elevate the phosphorylation of OGT at Thr444 through the activation of AMPK kinase, leading to enhanced binding of OGT to NRF2 and subsequent elevation of NRF2 O‐GlcNAcylation. Both in cellular and xenograft mouse models, O‐GlcNAcylation of NRF2 at Ser103 promotes the malignancy of lung cancer. In human lung cancer tissue samples, there was a significant increase in global O‐GlcNAcylation, and elevated levels of NRF2 and its O‐GlcNAcylation compared to paired adjacent normal tissues. Chemotherapy promotes NRF2 O‐GlcNAcylation, which in turn decreases cellular ROS levels and drives lung cancer cell survival.ConclusionOur findings indicate that OGT O‐GlcNAcylates NRF2 at Ser103, and this modification plays a role in cellular antioxidant, lung cancer malignancy, and cisplatin resistance.
Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation
Authors: Du Xue , Xu Jun , Mei Fuqi , Shen Jiangyun , Zhou Bincheng , Zhu Zhenhu , Li Zhongding , Su Xian , Li Jianmin , Schlüter Dirk , Ruan Jing , Wang Xu 
Published: October 2024

AbstractBackgroundInflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD.MethodsTo study the function of OTUB2 in IBD, we generated Otub2–/– mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods.ResultsOTUB2 was highly expressed in colon‐infiltrating macrophages in both humans with IBD and mice with DSS‐induced experimental colitis. Colitis was significantly aggravated in Otub2–/– mice and bone marrow chimeric mice receiving Otub2–/– bone marrow. OTUB2‐deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48‐linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis.ConclusionThis study identified OTUB2 as a novel regulator of intestinal inflammation.
ATF3‐mediated transactivation of CXCL14 in HSCs during liver fibrosis
Authors: Li Xinmiao , Lin Lifan , Li Yifei , Zhang Weizhi , Lang Zhichao , Zheng Jianjian 
Published: October 2024

ABSTRACTBackground and aimsMyofibroblasts, the primary producers of extracellular matrix, primarily originate from hepatic stellate cells (HSCs), and their activation plays a pivotal role in liver fibrosis. This study aimed to investigate the function of CXC motif ligand 14 (CXCL14) in the progression of liver fibrosis.Approach and resultsCXCL14 knockdown significantly reduced the extent of liver fibrosis. Using Ingenuity pathway analysis and qRT‐PCR, activating transcription factor 3 (ATF3) was identified as a key upstream regulator of CXCL14 expression. Mechanistically, ATF3 was shown to bind to the CXCL14 promoter, promoting its transactivation by TGF‐β in HSCs. Notably, both global CXCL14 deletion (CXCL14−/−) and HSC/myofibroblast‐specific CXCL14 knockdown significantly attenuated liver fibrosis in mice. RNA‐seq comparisons between CXCL14−/− and WT mice highlighted Jak2 as the most significantly downregulated gene, implicating its role in the antifibrotic effects of CXCL14 suppression on HSC inactivation. Moreover, Jak2 overexpression reversed the inhibition of liver fibrosis caused by CXCL14 knockdown in vivo.ConclusionsThese findings unveil a novel ATF3/CXCL14/Jak2 signalling axis in liver fibrosis, presenting potential therapeutic targets for the disease.
A High‐Performance 3D Eight‐Port THz‐MIMO Antenna System Verified With Machine Learning for Enhanced Wireless Communication Systems
Authors: Al‐Bawri Samir Salem , Abdulkawi Wazie M. , Sheta Abdel‐Fattah A. , Moniruzzaman Md. 
Published: October 2024

ABSTRACTThis article proposes an eight‐port octagonal‐shaped multiple‐input multiple‐output (MIMO) wideband 3D antenna system for terahertz (THz) applications. The 3D configuration of the proposed THz‐MIMO antenna is placed on a 55‐μm‐thick polyimide substrate. A modified butterfly‐shaped radiating patch and full ground plane make up the single antenna element. Every antenna element spans a wide impedance bandwidth for THz spectrums from 0.9‐ to 1.68‐THz frequency band, a frequency operating range with the highest radiation efficiency of 98% and is printed in a compact size of 130 × 110 μm2 (0.00004 × 0.00005 , with respect to the lowest operating frequency). The THz‐MIMO antenna system with eight ports is composed of both symmetric and nonsymmetric array arrangements. For configurations that are symmetric or nonsymmetric, the estimated MIMO performance parameters, envelope correlation coefficient (ECC) < 0.01 within allowable bounds, diversity gain (DG) exceeding 9.99 dB, total active reflection coefficient (TARC) < −10 dB, and channel capacity loss (CCL) below 0.2 bits/s/Hz, and the exhibited gain is above 7.5 dBi. Furthermore, another approach, such as supervised regression machine learning (ML), is used to forecast antenna gain. The variance score, mean square error (MSE), root mean square error (RMSE), R square, mean squared logarithmic error (MSLE), mean absolute error (MAE), and so forth are used to gauge how well ML models perform. The accuracy of ridge regression gain prediction is approximately 98%, with errors of less than unity, which is better than the other ML models. The suggested THz‐MIMO antenna system is appropriate for the wireless communication networks operating in the sixth generation.
Sm(Ⅲ), Gd(Ⅲ), and Eu(Ⅲ) complexes with 8‐hydroxyquinoline derivatives as potential anticancer agents via inhibiting cell proliferation, blocking cell cycle, and inducing apoptosis in NCI‐H460 cells
Authors: Yang Kun , Li Huan‐Qing , Hu Mei‐Qi , Ma Meng‐Xue , Gu Yun‐Qiong , Yang Qi‐Yuan , Iqbal Choudhary Muhammad , Liang Hong , Chen Zhen‐Feng 
Published: October 2024

AbstractFour lanthanide complexes with 8‐hydroxyquinoline‐2‐aldehyde‐2‐hydrazinopyridine (H‐L1), 8‐hydroxyquinoline‐2‐aldehyde‐2‐hydrazimidazole (H‐L2): [Sm(L1)2][Sm(L1)(NO3)3]·CHCl3·2CH3OH (1), [Gd(L1)2][Gd(L1)(NO3)3]·CHCl3·2CH3OH (2), [Sm(L2)(NO3)2]2·CH3OH (3), and [Eu(L2)(NO3)2]2·CH3OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI‐H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI‐H460 cells in G1 phase and induced mitochondria‐mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca2+ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis‐related proteins and activated the caspase‐3/9 in NCI‐H460 cells. Therefore, complex 1 is a potential anticancer agent.
Hypoxia regulate developmental coronary angiogenesis potentially through VEGF‐R2‐ and SOX17‐mediated signaling
Authors: Vitali Halie E. , Kuschel Bryce , Sherpa Chhiring , Jones Brendan W. , Jacob Nisha , Madiha Syeda A. , Elliott Sam , Dziennik Eddie , Kreun Lily , Conatser Cora , Bhetwal Bhupal P. , Sharma Bikram 
Published: October 2024

AbstractBackgroundThe development of coronary vessels in embryonic mouse heart involves various progenitor populations, including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is known to regulate coronary growth from the SV, whereas VEGF‐A/VEGF‐R2 signaling controls growth from the endocardium. Previous studies suggest hypoxia might regulate coronary growth, but its specific downstream pathways are unclear. In this study, we further investigated the role of hypoxia and have identified SOX17‐ and VEGF‐R2‐mediated signaling as the potential downstream pathways in its regulation of developmental coronary angiogenesis.ResultsHIF‐1α stabilization by knocking out von Hippel Lindau (VHL) protein in the myocardium (cKO) disrupted normal coronary angiogenesis in embryonic mouse hearts, resembling patterns of accelerated coronary growth. VEGF‐R2 expression was increased in coronary endothelial cells under hypoxia in vitro and in VHL cKO hearts in vivo. Similarly, SOX17 expression was increased in the VHL cKO hearts, while its knockout in the endocardium disrupted normal coronary growth.ConclusionThese findings provide further evidence that hypoxia regulates developmental coronary growth potentially through VEGF‐R2 and SOX17 pathways, shedding light on mechanisms of coronary vessel development.
Structural and functional differences of gut microbiota in Pomacea canaliculata from different geographical locations and habitats
Authors: Fang Miao , Yu Fandong , Shu Lu , Wei Hui , Mu Xidong , Wang Xuejie , Xu Meng , Gu Dangen 
Published: October 2024

AbstractGut microbiota is related to host fitness, and influenced by geographical locations and habitats. Pomacea canaliculata is a malignant invasive alien snail that threatens agricultural production and ecosystem functions worldwide. Clarifying the general rules of the gut microbial community structure and function of the snails in different geographical locations and habitats is of great significance for understanding their invasion at different spatial scales. This study used high‐throughput sequencing technology to compare and analyze the differences in community structure and function of gut microbiota in P. canaliculata from five geographical locations (Liuzhou, Yulin, Nanning, Wuzhou, and Hezhou) and three different habitats (pond, paddy field, and ditch) in Guangxi Province. The results showed that intestinal microbial alpha diversity of P. canaliculata was higher in Liuzhou, Yulin, lower in Nanning, Wuzhou, Hezhou, and higher in ponds compared with paddy fields and ditches. The dominant phyla of gut microbiota in snails were Firmicutes, Cyanobacteria, Proteobacteria, Fusobacteriota, Bacteroidota, and the dominant genus was Lactococcus. The community structure of gut microbiota in snails varied significantly across different geographical locations and habitats, and the phyla Firmicutes, Cyanobacteria had significantly higher relative abundance in snails collected from Nanning and Yulin, respectively. Moreover, the relative abundance of gut functional microbiota associated with human disease in P. canaliculata was significantly affected by geographical locations and habitats, and with the highest abundance in ponds. However, the relative abundance of functional microbiota related to metabolism, genetic information processing, organizational system, environmental information processing, and cellular processes were only significantly affected by geographical locations. Collectively, geographical locations and habitats had significantly different effects on the community structure and function of gut microbiota in P. canaliculata, and the greater differences were caused by geographical locations rather than by habitats.
Revealing suitable habitats for Juniperus procera and Olea europaea tree species in the remnant dry Afromontane forests of Ethiopia: Insights from ensemble species distribution modeling approach
Authors: Zenebe Gebreyohannes , Zenebe Amanuel , Birhane Emiru , Girma Atkilt , Shiferaw Henok 
Published: October 2024

AbstractHuman activities and climate change pose a significant threat to the dry Afromontane forests in Ethiopia, which are essential for millions of people both economically and ecologically. In Ethiopia, trees are planted elsewhere even if they are not likely to be well suited to the area. This study aims to identify the suitable habitat for the most exploited Juniperus procera (J. procera) and Olea europaea (O. europaea) tree species in northern Ethiopia. As inputs, least correlated temperature, moisture, soil, and topographic variables were selected through a stepwise procedure. The study evaluated five individual and ensemble models using the area under the curve (AUC) and true skill statistic (TSS) values. The ensemble model outperformed with mean AUC of 0.95 and TSS of 0.78 for J. procera, while securing the second position for O. europaea with an AUC of 0.88 and TSS of 0.71. Climatic factors emerged as the most influential, followed by soil and topography. Suitable areas for both species were found when Isothermality (Bio3) values range from 52% to 62%, temperature seasonality (Bio4) of 16–29°C. Moreover, well drained soils with soil texture not heavier than sandy clay, and soil organic carbon ranging from 5 to 42 g kg−1 were found suitable. The optimal suitable altitude for J. procera and O. europaea was determined to be 2200–2600 and 2100–2500 m.a.s.l., respectively. The suitable areas for J. procera and O. europaea were estimated to be 3130 and 3946 km2, respectively. Furthermore, potential plantation areas were identified beyond Desa'a and Hugumbirda Grat‐Kahsu protected forests, covering 2721 km2 (86.9%) for J. procera and 3576 km2 (90.6%) for O. europaea. These findings hold significance for the conservation and sustainable management of these valuable tree species in northern Ethiopia. We recommend implementing a similar approach for other locally restricted dry Afromontane tree species with wider potential distribution.
Gender‐specific risks for incident cancer in patients with different heart failure phenotypes
Authors: Chen Qin‐Fen , Katsouras Christos S. , Liu Chenyang , Shi Jingjing , Luan Xiaoqian , Ni Chao , Yao Hongxia , Lu Yingdan , Lin Wei‐Hong , Zhou Xiao‐Dong 
Published: October 2024

AbstractBackgroundThere is conflicting evidence regarding whether heart failure (HF) increases the risk of developing cancer.ObjectiveThis study aimed to assess the association between HF and incident cancer, considering gender differences and HF phenotypes.MethodsThis retrospective study was conducted on data of adult individuals, free of cancer at baseline, from the First Affiliated Hospital of Wenzhou Medical University between January 2009 and February 2023. The patients with HF were categorized as HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). The primary outcome was incident cancer, including obesity‐related, tobacco‐related, lung, colorectal and breast cancers.ResultsOf 33 033 individuals enrolled, 16 722 were diagnosed with HF, including 10 086 (60.3%) with HFpEF and 6636 (39.7%) with HFrEF. During a median follow‐up period of 4.6 years (inter‐quartile range: 2.6–7.3), incident cancer was diagnosed in 10.5% (1707 patients) of the non‐HF group and 15.1% (2533 individuals) of the HF group. After adjusting for potential confounding factors, patients with HF had a 58% increased risk of cancer than those without HF [adjusted hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.48–1.69, P < 0.001]. This risk was consistent across genders (female: adjusted HR 1.95, 95% CI 1.74–2.18, P < 0.001; male: adjusted HR 1.41, 95% CI 1.30–1.54, P < 0.001) and HF phenotypes (HFpEF: adjusted HR 1.69, 95% CI 1.57–1.81, P < 0.001; HFrEF: adjusted HR 1.32, 95% CI 1.20–1.46, P < 0.001).ConclusionsBoth HFpEF and HFrEF are associated with an increased risk of incident cancer. This correlation maintains its validity across genders.
Analysis of epilepsy‐associated variants in HCN3 – Functional implications and clinical observations
Authors: Zhao Peiwei , Xiong Hongbo , Kuang Gunagtao , Sun Chen , Zhang Xiankai , Huang Yufeng , Luo Sukun , Zhang Lei , Jiang Jun , He Xuelian 
Published: October 2024

AbstractObjectiveThis case study investigates the role of hyperpolarization‐activated, cyclic nucleotide‐gated (HCN) ion channels, which are integral membrane proteins crucial for regulating neuronal excitability. HCN channels are composed of four subunits (HCN1‐4), with HCN1, HCN2, and HCN4 previously linked to epilepsy. However, the role of the HCN3 in epileptogenesis remains underexplored.MethodsWe recruited a cohort of 298 epilepsy patients to screen for genetic variants in the HCN3 (NM_020897.3) using Sanger sequencing. We identified rare variants and conducted functional assays to evaluate their pathogenicity.ResultsWe identified three rare heterozygous variants in HCN3: c.1370G > A (R457H), c.1982G > A (R661Q), and c.1982G > A(P630L). In vitro functional analyses demonstrated that these variants affected the expression level of HCN3 protein without altering its membrane localization. Whole‐cell voltage‐clamp experiments showed that two variants (R457H and R661Q) significantly reduced current density in cells, while P630L has no effect on ion channel current.SignificanceOur findings suggest that the identified HCN3 genetic variants disrupt HCN ion channel function, highlighting HCN3 as a novel candidate gene involved in epileptic disorders. This expands the genetic landscape of epilepsy and provides new insights into its molecular underpinnings.Plain Language SummaryEpilepsy is a brain disease that can be caused by mutations in specific genes. We found three rare variants in HCN3 gene in 298 patients with epilepsy, and two of the three mutations could be pathogenic and cause epilepsy and another one is single‐nucleotide polymorphism, which could have no effect and no contribution to the development of epilepsy.
The greenhouse gas footprint of liquefied natural gas (LNG) exported from the United States
Authors: Howarth Robert W. 
Published: October 2024

AbstractLiquefied natural gas (LNG) exports from the United States have risen dramatically since the LNG‐export ban was lifted in 2016, and the United States is now the world's largest exporter. This LNG is produced largely from shale gas. Production of shale gas, as well as liquefaction to make LNG and LNG transport by tanker, is energy‐intensive, which contributes significantly to the LNG greenhouse gas footprint. The production and transport of shale gas emits a substantial amount of methane as well, and liquefaction and tanker transport of LNG can further increase methane emissions. Consequently, carbon dioxide (CO2) from end‐use combustion of LNG contributes only 34% of the total LNG greenhouse gas footprint, when CO2 and methane are compared over 20 years global warming potential (GWP20) following emission. Upstream and midstream methane emissions are the largest contributors to the LNG footprint (38% of total LNG emissions, based on GWP20). Adding CO2 emissions from the energy used to produce LNG, total upstream and midstream emissions make up on average 47% of the total greenhouse gas footprint of LNG. Other significant emissions are the liquefaction process (8.8% of the total, on average, using GWP20) and tanker transport (5.5% of the total, on average, using GWP20). Emissions from tankers vary from 3.9% to 8.1% depending upon the type of tanker. Surprisingly, the most modern tankers propelled by two‐ and four‐stroke engines have higher total greenhouse gas emissions than steam‐powered tankers, despite their greater fuel efficiency and lower CO2 emissions, due to methane slippage in their exhaust. Overall, the greenhouse gas footprint for LNG as a fuel source is 33% greater than that for coal when analyzed using GWP20 (160 g CO2‐equivalent/MJ vs. 120 g CO2‐equivalent/MJ). Even considered on the time frame of 100 years after emission (GWP100), which severely understates the climatic damage of methane, the LNG footprint equals or exceeds that of coal.
A meta‐analysis of cognitive flexibility in aging: Perspective from functional network and lateralization
Authors: Xia Haishuo , Hou Yongqing , Li Qing , Chen Antao 
Published: October 2024

AbstractCognitive flexibility, the ability to switch between mental processes to generate appropriate behavioral responses, is reduced with typical aging. Previous studies have found that age‐related declines in cognitive flexibility are often accompanied by variations in the activation of multiple regions. However, no meta‐analyses have examined the relationship between cognitive flexibility in aging and age‐related variations in activation within large‐scale networks. Here, we conducted a meta‐analysis employing multilevel kernel density analysis to identify regions with different activity patterns between age groups, and determined how these regions fall into functional networks. We also employed lateralization analysis to explore the spatial distribution of regions exhibiting group differences in activation. The permutation tests based on Monte Carlo simulation were used to determine the significance of the activation and lateralization results. The results showed that cognitive flexibility in aging was associated with both decreased and increased activation in several functional networks. Compared to young adults, older adults exhibited increased activation in the default mode, dorsal attention, ventral attention, and somatomotor networks, while displayed decreased activation in the visual network. Moreover, we found a global‐level left lateralization for regions with decreased activation, but no lateralization for regions with higher activation in older adults. At the network level, the regions with decreased activation were left‐lateralized, while the regions with increased activation showed varying lateralization patterns within different networks. To sum up, we found that networks that support various mental functions contribute to age‐related variations in cognitive flexibility. Additionally, the aging brain exhibited network‐dependent activation and lateralization patterns in response to tasks involving cognitive flexibility. We highlighted that the comprehensive meta‐analysis in this study offered new insights into understanding cognitive flexibility in aging from a network perspective.