bluuebunny/crossref_metadata_2025 huggingface dataset:
Power and Personal Experience in Online Anonymous Communities: A Corpus-Driven Exploration
Authors: Busso Lucia
Published: June 2024

The paper presents an innovative corpus study on Personal Experience as a pragmatic-discursive resource to express power in anonymous online interactions. Specifically, we explore a corpus-driven methodology to extract lexico grammatical features typical of Personal Experience in representative samples (around 160,000 words) of 3 online fora. The method is rooted in Part of Speech and semantic domain keyness (Rayson in Int J Corpus Linguist 13(4):519–549, 2008), which we combine in Corpus Language Queries to extract statistically relevant patterns in the data. Results show that the 3 datasets share a “core” set of key lexico-grammatical features. Furthermore, our findings align with the scientific literature exploring personal experiences and narratives in many different genres. This strongly supports the idea that our inductive protocol can be reliably used to break down the discursive textual function of Personal Experience into lower-level, scalable features. In other words, we suggest that our method can be used to extract “form” (i.e. lexical, grammatical, and syntactical units) from “function” (i.e. pragmatic and discursive annotations). Findings are discussed in the context of language and power in online interactions and in the context of building automatic feature detectors for the analysis of larger cross-genre corpora.
Enhancing mechanical properties of aluminium 6063 with crab shell particle reinforcement
Authors: Owa Adebayo Felix , Olubambi Peter Apata
Published: June 2024

The versatility and beneficial properties of aluminium 6063 make it an excellent material for various applications, but limited in engineering production where strength is a major material selection factor. The utilization of natural resources in material science has gained prominence due to the quest for sustainable and innovative materials. This work explores the development and characterization of an aluminium matrix composite reinforced with crab shell particles (CSPs). The CSPs are produced via the milling process for 72 h and the CSPs are incorporated in varying percentages (0–20 wt%) into the aluminium matrix using a stir casting technique, the mechanical properties (tensile strength, compressive strength, % elongation, and impact energy) of the composites are determined using an Instron universal testing machine (UTM) and a Charpy impact testing machine, respectively. A scanning electron microscope (SEM) is used to examine the microstructure of the composite fracture surfaces and Gywddion 2.65 software is used to view the SEM images of the fracture surfaces in three dimensions (3D). The results revealed that tensile strength, compressive strength, % elongation, and impact energy are enhanced by adding varying percentages of CSPs on the aluminium 6063 composites.
Young Adult Mental Health Problem Incidence Varies by Specific Combinations of Adverse Childhood Experiences
Authors: Agrawal Juhee , Lei Yvonne , Shah Vivek , Bui Anthony L. , Halfon Neal , Schickedanz Adam
Published: June 2024

Adverse childhood experiences (ACEs) have been shown to impact mental health. Risk associated with ACEs is commonly estimated based on counts from the conventional ACE types, but ACEs may not all carry the same health risk, either individually or in combination. Evidence is needed to understand the health impact of different ACE types and combinations of ACE types. We aimed to assess variation in risk of mental illness diagnosis and severe psychological distress in young adulthood based on differences in exposure to individual ACEs and combinations of ACEs, which can improve precision of ACE-based risk assessment. We used data from six waves of the Transition to Adulthood Supplement (2007–2017; n = 1832 young adults ages 18–28) of the Panel Study of Income Dynamics. We used logistic regression with cluster-robust variation estimation to test associations between each ACE, pairwise combinations of ACEs, and outcomes including new or existing mental illness diagnoses and severe psychological distress. Individual ACEs associated with greatest risk for new or existing mental illness diagnoses and severe psychological distress were parental mental illness and sexual abuse. Combinations of ACEs associated with greatest risk were parental mental illness-plus-sexual abuse and parental mental illness-plus-emotional neglect. ACEs associated with the lowest risk were parental substance use, physical abuse, and household violence. In this nationally representative longitudinal study of mental health outcomes in young adults, different individual and combinations of ACEs were associated with varying levels of mental health risk. This carries implications for risk assessment and ACE intervention prioritization.
Clinical and Imaging Characteristics of Herlyn-Werner-Wunderlich Syndrome: a Comprehensive Analysis
Authors: Qi Jiani , Zhou Ping , Peng Hong , Deng Jin , Shao Yang , Ye Lingjuan , Luo Shengjuan
Published: June 2024

Purpose

To describe the clinical and imaging characteristics of Herlyn-Werner-Wunderlich syndrome (HWWS).

Methods

This study presented an observational case series involving consecutive patients diagnosed with HWWS, whose medical records were retrospectively reviewed. From June 2012 to December 2022, there were a total of 85 patients with HWWS enrolled in our study. We obtained the medical history, including demographic characteristics, clinical presentation, treatment, complications, and radiologic examinations performed. Patients > 18 years of age (n = 58) were recontacted.

Result

In our analysis, 27 patients were categorised as having complete obstruction, and 58 were categorised as having incomplete obstruction. The mean age at the onset of symptoms and diagnosis of complete obstruction was significantly younger than incomplete obstruction (P < 0.05). For complete obstruction, the median time between menarche and the onset of symptoms was 2.1 years, while for incomplete obstruction, it was 5.3 years. There was a significantly lower incidence of intermittent mucopurulent discharge, irregular vaginal haemorrhage, and occasional examination findings of complete obstruction than incomplete obstruction (P < 0.05). Complete obstruction was significantly associated with dysmenorrhea and pelvic endometriosis compared with incomplete obstruction (P < 0.05).

Conclusions

There are distinct clinical differences between patients with complete obstruction of the hemivagina and those with incomplete obstruction. HWWS can manifest as various combinations of uterine anomalies, communications anomalies, and renal anomalies. Early recognition and treatment can avoid complications and preserve fertility.

Keyswords

Herlyn-Werner-Wunderlich syndrome (HWWS); complete obstruction; incomplete obstruction; obstructed hemivagina; congenital malformation.
Initial Professional Education for Youth and Community Workers: Exploring Academic’s Experiences
Authors: Norris Pat
Published: June 2024

This paper reflects on a small-scale piece of research into the experience of academics involved in the initial professional education of youth and community workers in England during the period 2015–2016, when multiple factors were affecting degree-qualifying youth and community worker education. Interviews with six academics identify the influences of funding issues, changing contexts for fieldwork settings, varied perceptions of professional youth work to ongoing pressures within higher education which inform their experience. This research draws on Bourdieu’s thinking tools of habitus and illusio as a theoretical lens to explore academics’ ongoing commitment to professional youth and community worker education. The actions and messages from the research participants offer an insight into the varied situations academics are navigating at this point in time, and resonate with a contemporary, post-pandemic context. The paper concludes with areas for further research into the ongoing development of initial professional youth and community worker education.
Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs
Authors: Lee Boyoung , Kwon Yeo-Jung , Shin Sangyun , Kwon Tae-Uk , Park Hyemin , Lee Hyein , Kwak Ji-Heung , Chun Young-Jin
Published: June 2024

MicroRNAs (miRNAs), molecules comprising 18–22 nucleotides, regulate expression of genes post-transcriptionally at the 3′ untranslated region of target mRNAs. However, the biological roles and mechanisms of action of miRNAs in breast cancer remain unelucidated. Thus, in this study, we aimed to investigate the functions and possible mechanisms of action of miRNAs in breast cancer to suppress carcinogenesis. Using miRNA databases, we selected miR-34a and miR-605-5p to downregulate MDM4 and MDM2, respectively, because these ubiquitin E3 ligases degrade p53 and promote carcinogenesis. Results showed that miR-34a and miR-605-5p suppressed MDM4 and MDM2 expression, respectively. Moreover, they reduced the expression of yes‑associated protein 1 (YAP1), a well-known oncogene involved in Hippo signaling, but upregulated the mRNA and protein expression of yippee-like 3 (YPEL3). To elucidate whether these miRNAs promote cellular senescence and death through YPEL3 upregulation, we examined their effects on cellular proliferation, SA-β-gal activity, and mitochondrial activity in human breast cancer MCF-7 cells. Given their upregulating effect on YPEL3 expression, miR-34a and miR-605-5p increased the number of β-galactosidase-positive cells and depolarized live cells (by 10%–12%). These data suggest that miR-34a and miR-605-5p promote cellular senescence and cell death. Thus, they may act as tumor suppressors by inducing Hippo signaling and may serve as novel therapeutic agents in breast cancer treatment.
Multi-domain fusion for cargo UAV fault diagnosis knowledge graph construction
Authors: Xiao Ao , Yan Wei , Zhang Xumei , Liu Ying , Zhang Hua , Liu Qi
Published: June 2024

The fault diagnosis of cargo UAVs (Unmanned Aerial Vehicles) is crucial to ensure the safety of logistics distribution. In the context of smart logistics, the new trend of utilizing knowledge graph (KG) for fault diagnosis is gradually emerging, bringing new opportunities to improve the efficiency and accuracy of fault diagnosis in the era of Industry 4.0. The operating environment of cargo UAVs is complex, and their faults are typically closely related to it. However, the available data only considers faults and maintenance data, making it difficult to diagnose faults accurately. Moreover, the existing KG suffers from the problem of confusing entity boundaries during the extraction process, which leads to lower extraction efficiency. Therefore, a fault diagnosis knowledge graph (FDKG) for cargo UAVs constructed based on multi-domain fusion and incorporating an attention mechanism is proposed. Firstly, the multi-domain ontology modeling is realized based on the multi-domain fault diagnosis concept analysis expression model and multi-dimensional similarity calculation method for cargo UAVs. Secondly, a multi-head attention mechanism is added to the BERT-BILSTM-CRF network model for entity extraction, relationship extraction is performed through ERNIE, and the extracted triples are stored in the Neo4j graph database. Finally, the DJI cargo UAV failure is taken as an example for validation, and the results show that the new model based on multi-domain fusion data is better than the traditional model, and the precision rate, recall rate, and F1 value can reach 87.52%, 90.47%, and 88.97%, respectively.
Synthesis of silver nanoparticles as an antimicrobial mediator
Authors: Khaldoun Khadija , Khizar Sumera , Saidi-Besbes Salima , Zine Nadia , Errachid Abdelhamid , Elaissari Abdelhamid
Published: June 2024

Silver nanoparticles (AgNPs) become a topic of great research on account of their exemplary properties (optical, electrical, and antimicrobial properties). They have been executed as an exceptional antimicrobial agent having ability to combat microorganism’s in vivo and in vitro causing infections. The antibacterial activity of AgNPs covers Gram-positive and Gram-negative bacteria, as well as multidrug resistant (MDR) strains. AgNPs display manifold and immediate mechanisms of activity and in incorporation with antimicrobial agents as antibiotics or organic compounds, it exhibit synergistic impact against pathogens bacteria. The properties of AgNPs make them appropriate for their usage in healthcare and medical products where they might treat infections or inhibit them competently. A range of approaches to synthesize AgNPs are stated in literature; including physical, biological, and chemical techniques, with a growing need to establish eco-friendly processes. With the imperative need for novel and effective antimicrobial agents, this review intends to establish aspects affecting antimicrobial impacts of AgNPs, as well as to descript the benefits of employing AgNPs as new antimicrobial in different life science applications. This review summarizes synthesis of AgNPs and remarkable implementation of AgNPs dealing with their antimicrobic properties in the field of textile, food industry, agriculture, water treatment, and most importantly in health care sector. Additionally fundamental mechanism by which they implement their antimicrobic activity will also be addressed.

Graphical abstract
Design and application of B-containing hard coatings for high-speed dry cutting against Ti-alloys- A review
Authors: Fang Wei , Tao Langlang , Zhang Benchi , Huang Ju , Cai Fei , Gyawali Gobinda , Zhang Shihong
Published: June 2024

Titanium alloys have been extensively applied due to their outstanding features, including high specific strength and corrosion resistance. However, the machining of these alloys presents challenges, leading to significant tool wear and reduced tool lifetime, ascribed to the difficult-to-machine features of Ti alloys. In the context of pursuing environmental sustainability and enhanced productivity, high-speed dry-cutting technology coupled with high-quality tool coatings are prospective. This paper comprehensively explores wear patterns and recent advancements in tool coatings for high-speed dry cutting of Ti-alloys. Key coating properties such as resistance to abrasion, adhesion, oxidation, fatigue, hot hardness, and self-adaptability are briefly introduced. Design strategies for enhancing micro-hardness, toughness, and adhesion, including nanocomposite, multilayer, and gradient architectures, are also discussed. Furthermore, the paper highlights several Boron (B) doped hard coatings as promising candidates for high-speed dry cutting against Ti-alloys, exploring the impact of B on microstructure, hardness, thermal stability, oxidation resistance, and lubrication. In summary, this work provides a systematic overview of novel B-doped tool coatings applied in high-speed dry cutting against Ti-alloys.
Vitamins B9 and B12 in children with attention deficit hyperactivity disorder (ADHD)
Authors: Razavinia Fatemeh , Ebrahimiyan Atefeh , Faal Siahkal Shahla , Ghazinezhad Neda , Abedi Parvin
Published: June 2024

Abstract: Background: Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder that begins before age 12. Given the role of B group vitamins in cell metabolism, synthesis of nucleotides, and neurotransmitters, the present study systematically investigated the plasma levels of vitamins B9 and B12 in children with ADHD. Methods: We searched electronic databases including Web of Science, MEDLINE, EMBASE, Scopus, Iran MEDEX, Cochran database, and SID from conception to June 2023. Full-text case-control or cross-sectional studies were included in this study. Participants in the case group were children with ADHD aged 6–12 years. Review Manager Software (RevMan 5.4) was used for statistical analyses. Standardized mean differences (SMD) with 95% CIs were used to determine the differences between the two groups. Results: Six studies were included in the present meta-analysis. They included 982 children, of whom, 204 were girls and 744 were boys. The mean age of the children was 8.86±2.03 years. The level of vitamin B9 was significantly different between children with and without ADHD [SMD –0.80, 95% CI (–1.55, –0.04)]. Vitamin B12 was significantly lower in children with ADHD [SMD –0.29, 95% CI (–0.42, –0.16)]. However, due to high heterogeneity (I2 = 93%), sensitivity analysis was used, I2 fell to 21%, and significant difference was observed between the two groups [SMD –0.19, 95% CI (–0.34, −0.04)]. Conclusion: The results of this systematic review showed that the level of vitamins B9 and B12 in children with ADHD was significantly lower than that in healthy children.
Depth‐Dependent Anisotropy Along Northwest Segment of the North Anatolian Fault Zone: Evidence for Paleo‐Tectonic Structures Contributing to Overall Complexity
Authors: Keleş Derya , Eken Tuna , Licciardi Andrea , Frederiksen Andrew W. , Taymaz Tuncay
Published: June 2024

The North Anatolian Fault Zone (NAFZ) is a prominent tectonic structure with a significant impact on the observed active deformation in Türkiye. Detailed knowledge of the seismic anisotropy in the crust and mantle along this nascent shear deformation zone provides insights into the kinematics associated with past and present tectonic events. We employed teleseismic earthquakes observed by the Dense Array North Anatolia seismic network to map 3‐ D variations in crustal and mantle anisotropy in/around the NW segment of the NAFZ. To achieve this, we first performed a harmonic decomposition analysis of P‐receiver functions. The results were then used as a priori information to conduct an anisotropic receiver function inversion with the Neighborhood Algorithm that enabled imaging of the actual orientation and geometry of anisotropic structures. SKS splitting measurements are further used to make a comparison between the anisotropic behavior of crustal and mantle structures. Crustal anisotropy parameters estimated in our analyses/models well identify the signature of deformation caused by accumulated strain in the earthquake cycle through the strike of shallow cutting faults in the brittle crust beneath the NAFZ. Diffuse intense anisotropic energy at lower crustal depths was attributed to lattice preferred orientation of crystals or partially molten lenses elongated along the shear direction. Strong harmonic energy variations beneath the northern part of the Istanbul Zone likely reflect imprints of LPO‐originated frozen fabric at shallow depths (0–20 km) associated with the palaeotectonic Odessa Shelf, Intra‐Pontide Suture Zones or remnants of the Tethys Ocean.
The 2019 Marine Heatwave at Ocean Station Papa: A Multi‐Disciplinary Assessment of Ocean Conditions and Impacts on Marine Ecosystems
Authors: Kohlman Catherine , Cronin Meghan F. , Dziak Robert , Mellinger David K. , Sutton Adrienne , Galbraith Moira , Robert Marie , Thomson Jim , Zhang Dongxiao , Thompson LuAnne
Published: June 2024

In the past decade, two large marine heatwaves (MHWs) formed in the northeast Pacific near Ocean Station Papa (OSP), one of the oldest oceanic time series stations. Physical, biogeochemical, and biological parameters observed at OSP from 2013 to 2020 are used to assess ocean response and potential impacts on marine life from the 2019 northeast Pacific MHW. The 2019 MHW reached peak surface and subsurface temperature anomalies in the summertime and had both coastal, impacting fisheries, and offshore consequences that could potentially affect multiple trophic levels in the Gulf of Alaska. In the Gulf of Alaska, the 2019 MHW was preceded by calm and stratified upper ocean conditions, which preconditioned the enhanced surface warming in late spring and early summer. The MHW coincided with lower dissolved inorganic carbon and higher pH of surface waters relative to the 2013–2020 period. A spike in the summertime chlorophyll followed by a decrease in surface macronutrients suggests increased productivity in the well‐lit stratified upper ocean during summer 2019. More blue whale calls were recorded at OSP in 2019 compared to the prior year. This study shows how the utility of long‐term, continuous oceanographic data sets and analysis with an interdisciplinary lens is necessary to understand the potential impact of MHWs on marine ecosystems.
Exploring Climate‐Disease Connections in Geopolitical Versus Ecological Regions: The Case of West Nile Virus in the United States
Authors: Moser S. Kane , Spencer Julie A. , Barnard Martha , Hyman James M. , Manore Carrie A. , Gorris Morgan E.
Published: June 2024

Many infectious disease forecasting models in the United States (US) are built with data partitioned into geopolitical regions centered on human activity as opposed to regions defined by natural ecosystems; although useful for data collection and intervention, this has the potential to mask biological relationships between the environment and disease. We explored this concept by analyzing the correlations between climate and West Nile virus (WNV) case data aggregated to geopolitical and ecological regions. We compared correlations between minimum, maximum, and mean annual temperature; precipitation; and annual WNV neuroinvasive disease (WNND) case data from 2005 to 2019 when partitioned into (a) climate regions defined by the National Oceanic and Atmospheric Administration (NOAA) and (b) Level I ecoregions defined by the Environmental Protection Agency (EPA). We found that correlations between climate and WNND in NOAA climate regions and EPA ecoregions were often contradictory in both direction and magnitude, with EPA ecoregions more often supporting previously established biological hypotheses and environmental dynamics underlying vector‐borne disease transmission. Using ecological regions to examine the relationships between climate and disease cases can enhance the predictive power of forecasts at various scales, motivating a conceptual shift in large‐scale analyses from geopolitical frameworks to more ecologically meaningful regions.
USP21-mediated G3BP1 stabilization accelerates proliferation and metastasis of esophageal squamous cell carcinoma via activating Wnt/β-Catenin signaling
Authors: Guo Jiazhong , Zhao Yunpeng , Sui Huacong , Liu Lei , Liu Fanrong , Yang Lingxiao , Gao Fengyuan , Wang Jinfu , Zhu Yilin , Li Lingbing , Song Xiangqing , Li Peng , Tian Zhongxian , Li Peichao , Zhao Xiaogang
Published: June 2024

Lacking effective therapeutic targets heavily restricts the improvement of clinical prognosis for patients diagnosed with esophageal squamous cell carcinoma (ESCC). Ubiquitin Specific Peptidase 21 (USP21) is dysregulated in plenty of human cancers, however, its potential function and relevant molecular mechanisms in ESCC malignant progression as well as its value in clinical translation remain largely unknown. Here, in vitro and in vivo experiments revealed that aberrant upregulation of USP21 accelerated the proliferation and metastasis of ESCC in a deubiquitinase-dependent manner. Mechanistically, we found that USP21 binds to, deubiquitinates, and stabilizes the G3BP Stress Granule Assembly Factor 1 (G3BP1) protein, which is required for USP21-mediated ESCC progression. Further molecular studies demonstrated that the USP21/G3BP1 axis played a tumor-promoting role in ESCC progression by activating the Wnt/β-Catenin signaling pathway. Additionally, disulfiram (DSF), an inhibitor against USP21 deubiquitylation activity, markedly abolished the USP21-mediated stability of G3BP1 protein and significantly displayed an anti-tumor effect on USP21-driving ESCC progression. Finally, the regulatory axis of USP21/G3BP1 was demonstrated to be aberrantly activated in ESCC tumor tissues and closely associated with advanced clinical stages and unfavorable prognoses, which provides a promising therapeutic strategy targeting USP21/G3BP1 axis for ESCC patients.
Language and sensory characteristics are reflected in voice-evoked responses in low birth weight children
Authors: Yoshimura Yuko , Mitani Yusuke , Ikeda Takashi , Tanaka Sanae , Suda Momoka , Yaoi Ken , Hasegawa Chiaki , An Kyung-min , Iwasaki Sumie , Kumazaki Hirokazu , Saito Daisuke N. , Ohta Hidenobu , Ando Akiko , Cho Kazutoshi , Kikuchi Mitsuru , Wada Taizo
Published: June 2024

Background

Children born with very low birth weight (VLBW) are at higher risk for cognitive impairment, including language deficits and sensorimotor difficulties. Voice-evoked response (P1m), which has been suggested as a language development biomarker in young children, remains unexplored for its efficacy in VLBW children. Furthermore, the relation between P1m and sensory difficulties in VLBW children remains unclear.

Methods

40 children with VLBW were recruited at 5-to-6 years old (26 male, 14 female, mean age of months ± SD, 80.0 ± 4.9). We measured their voice-evoked brain response using child-customized magnetoencephalography (MEG) and examined the relation between P1m and language conceptual inference ability and sensory characteristics.

Results

The final sample comprised 36 children (23 boys, 13 girls; ages 61–86 months; gestational ages 24–36 weeks). As a result of multiple regression analysis, voice-evoked P1m in the left hemisphere was correlated significantly with language ability (β = 0.414 P = 0.015) and sensory hypersensitivity (β = 0.471 P = 0.005).

Conclusion

Our findings indicate that the relation between P1m and language conceptual inference ability observed in term children in earlier studies is replicated in VLBW children, and suggests P1m intensity as a biomarker of sensory sensitivity characteristics.

Impact

We investigated brain functions related to language development and sensory problems in very low birth-weight children.

In very low birth weight children at early school age, brain responses to human voices are associated with language conceptual inference ability and sensory hypersensitivity.

These findings promote a physiological understanding of both language development and sensory characteristics in very low birth weight children.
Development of a differential treatment selection model for depression on consolidated and transformed clinical trial datasets
Authors: Perlman Kelly , Mehltretter Joseph , Benrimoh David , Armstrong Caitrin , Fratila Robert , Popescu Christina , Tunteng Jingla-Fri , Williams Jerome , Rollins Colleen , Golden Grace , Turecki Gustavo
Published: June 2024

Major depressive disorder (MDD) is the leading cause of disability worldwide, yet treatment selection still proceeds via “trial and error”. Given the varied presentation of MDD and heterogeneity of treatment response, the use of machine learning to understand complex, non-linear relationships in data may be key for treatment personalization. Well-organized, structured data from clinical trials with standardized outcome measures is useful for training machine learning models; however, combining data across trials poses numerous challenges. There is also persistent concern that machine learning models can propagate harmful biases. We have created a methodology for organizing and preprocessing depression clinical trial data such that transformed variables harmonized across disparate datasets can be used as input for feature selection. Using Bayesian optimization, we identified an optimal multi-layer dense neural network that used data from 21 clinical and sociodemographic features as input in order to perform differential treatment benefit prediction. With this combined dataset of 5032 individuals and 6 drugs, we created a differential treatment benefit prediction model. Our model generalized well to the held-out test set and produced similar accuracy metrics in the test and validation set with an AUC of 0.7 when predicting binary remission. To address the potential for bias propagation, we used a bias testing performance metric to evaluate the model for harmful biases related to ethnicity, age, or sex. We present a full pipeline from data preprocessing to model validation that was employed to create the first differential treatment benefit prediction model for MDD containing 6 treatment options.
MT1G induces lipid droplet accumulation through modulation of H3K14 trimethylation accelerating clear cell renal cell carcinoma progression
Authors: Wang Sen , Wang Kexin , Yue Dong , Yang Xiaxia , Pan Xiaozao , Kong Feifei , Zhao Rou , Bie Qingli , Tian Dongxing , Zhu Shuqing , He Baoyu , Bin Zhang
Published: June 2024

Background

Lipid droplet formation is a prominent histological feature in clear cell renal cell carcinoma (ccRCC), but the significance and mechanisms underlying lipid droplet accumulation remain unclear.

Methods

Expression and clinical significance of MT1G in ccRCC were analyzed by using TCGA data, GEO data and scRNASeq data. MT1G overexpression or knockdown ccRCC cell lines were constructed and in situ ccRCC model, lung metastasis assay, metabolomics and lipid droplets staining were performed to explore the role of MT1G on lipid droplet accumulation in ccRCC.

Results

Initially, we observed low MT1G expression in ccRCC tissues, whereas high MT1G expression correlated with advanced disease stage and poorer prognosis. Elevated MT1G expression promoted ccRCC growth and metastasis both in vitro and in vivo. Mechanistically, MT1G significantly suppressed acylcarnitine levels and downstream tricarboxylic acid (TCA) cycle activity, resulting in increased fatty acid and lipid accumulation without affecting cholesterol metabolism. Notably, MT1G inhibited H3K14 trimethylation (H3K14me3) modification. Under these conditions, MT1G-mediated H3K14me3 was recruited to the CPT1B promoter through direct interaction with specific promoter regions, leading to reduced CPT1B transcription and translation.

Conclusions

Our study unveils a novel mechanism of lipid droplet accumulation in ccRCC, where MT1G inhibits CPT1B expression through modulation of H3K14 trimethylation, consequently enhancing lipid droplet accumulation and promoting ccRCC progression.
Regulator of G protein signaling 16 restrains apoptosis in colorectal cancer through disrupting TRAF6-TAB2-TAK1-JNK/p38 MAPK signaling
Authors: Shen Hao , Yuan Jie , Tong Dafeng , Chen Bingchen , Yu Enda , Chen Guanglei , Peng Cheng , Chang Wenjun , E Jifu , Cao Fuao
Published: June 2024

Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.
Multiomics integration-based immunological characterizations of adamantinomatous craniopharyngioma in relation to keratinization
Authors: Xu Chunming , Wu Jie , Ye Jiye , Si Yuancheng , Zhang Jinshi , Wu Bowen , Pan Laisheng , Fu Jun , Ren Quan , Xie Shenhao , Tang Bin , Xiao Yingqun , Hong Tao
Published: June 2024

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.
Mathematical biases in the calculation of the Living Planet Index lead to overestimation of vertebrate population decline
Authors: Toszogyova Anna , Smyčka Jan , Storch David
Published: June 2024

The Living Planet Index (LPI) measures the average change in population size of vertebrate species over recent decades and has been repeatedly used to assess the changing state of nature. The LPI indicates that vertebrate populations have decreased by almost 70% over the last 50 years. This is in striking contrast with current studies based on the same population time series data that show that increasing and decreasing populations are balanced on average. Here, we examine the methodological pipeline of calculating the LPI to search for the source of this discrepancy. We find that the calculation of the LPI is biased by several mathematical issues which impose an imbalance between detected increasing and decreasing trends and overestimate population declines. Rather than indicating that vertebrate populations do not substantially change, our findings imply that we need better measures for providing a balanced picture of current biodiversity changes. We also show some modifications to improve the reliability of the LPI.
ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma
Authors: Laverty Daniel J. , Gupta Shiv K. , Bradshaw Gary A. , Hunter Alexander S. , Carlson Brett L. , Calmo Nery Matias , Chen Jiajia , Tian Shulan , Sarkaria Jann N. , Nagel Zachary D.
Published: June 2024

Determining the balance between DNA double strand break repair (DSBR) pathways is essential for understanding treatment response in cancer. We report a method for simultaneously measuring non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ). Using this method, we show that patient-derived glioblastoma (GBM) samples with acquired temozolomide (TMZ) resistance display elevated HR and MMEJ activity, suggesting that these pathways contribute to treatment resistance. We screen clinically relevant small molecules for DSBR inhibition with the aim of identifying improved GBM combination therapy regimens. We identify the ATM kinase inhibitor, AZD1390, as a potent dual HR/MMEJ inhibitor that suppresses radiation-induced phosphorylation of DSBR proteins, blocks DSB end resection, and enhances the cytotoxic effects of TMZ in treatment-naïve and treatment-resistant GBMs with TP53 mutation. We further show that a combination of G2/M checkpoint deficiency and reliance upon ATM-dependent DSBR renders TP53 mutant GBMs hypersensitive to TMZ/AZD1390 and radiation/AZD1390 combinations. This report identifies ATM-dependent HR and MMEJ as targetable resistance mechanisms in TP53-mutant GBM and establishes an approach for simultaneously measuring multiple DSBR pathways in treatment selection and oncology research.
The maternal drug exposure birth cohort (DEBC) in China
Authors: Li Lu , Wang Ke , Wang Meixian , Tao Jing , Li Xiaohong , Liu Zhen , Li Nana , Qiu Xiaoxia , Wei Hongwei , Lin Yuan , He Yuan , Deng Ying , Kang Hong , Li Yuting , Yu Ping , Wang Yanping , Zhu Jun , Liu Hanmin
Published: June 2024

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.
Scalable multifunctional MOFs-textiles via diazonium chemistry
Authors: Li Wulong , Yu Zhen , Zhang Yaoxin , Lv Cun , He Xiaoxiang , Wang Shuai , Wang Zhixun , He Bing , Yuan Shixing , Xin Jiwu , Liu Yanting , Zhou Tianzhu , Li Zhanxiong , Tan Swee Ching , Wei Lei
Published: June 2024

Cellulose fiber-based textiles are ubiquitous in daily life for their processability, biodegradability, and outstanding flexibility. Integrating cellulose textiles with functional coating materials can unlock their potential functionalities to engage diverse applications. Metal-organic frameworks (MOFs) are ideal candidate materials for such integration, thanks to their unique merits, such as large specific surface area, tunable pore size, and species diversity. However, achieving scalable fabrication of MOFs-textiles with high mechanical durability remains challenging. Here, we report a facile and scalable strategy for direct MOF growth on cotton fibers grafted via the diazonium chemistry. The as-prepared ZIF-67-Cotton textile (ZIF-67-CT) exhibits excellent ultraviolet (UV) resistance and organic contamination degradation via the peroxymonosulfate activation. The ZIF-67-CT is also used to encapsulate essential oils such as carvacrol to enable antibacterial activity against E. coli and S. aureus. Additionally, by directly tethering a hydrophobic molecular layer onto the MOF-coated surface, superhydrophobic ZIF-67-CT is achieved with excellent self-cleaning, antifouling, and oil-water separation performances. More importantly, the reported strategy is generic and applicable to other MOFs and cellulose fiber-based materials, and various large-scale multi-functional MOFs-textiles can be successfully manufactured, resulting in vast applications in wastewater purification, fragrance industry, and outdoor gears.
In-situ direct seawater electrolysis using floating platform in ocean with uncontrollable wave motion
Authors: Liu Tao , Zhao Zhiyu , Tang Wenbin , Chen Yi , Lan Cheng , Zhu Liangyu , Jiang Wenchuan , Wu Yifan , Wang Yunpeng , Yang Zezhou , Yang Dongsheng , Wang Qijun , Luo Lunbo , Liu Taisheng , Xie Heping
Published: June 2024

Direct hydrogen production from inexhaustible seawater using abundant offshore wind power offers a promising pathway for achieving a sustainable energy industry and fuel economy. Various direct seawater electrolysis methods have been demonstrated to be effective at the laboratory scale. However, larger-scale in situ demonstrations that are completely free of corrosion and side reactions in fluctuating oceans are lacking. Here, fluctuating conditions of the ocean were considered for the first time, and seawater electrolysis in wave motion environment was achieved. We present the successful scaling of a floating seawater electrolysis system that employed wind power in Xinghua Bay and the integration of a 1.2 Nm3 h−1-scale pilot system. Stable electrolysis operation was achieved for over 240 h with an electrolytic energy consumption of 5 kWh Nm−3 H2 and a high purity (>99.9%) of hydrogen under fluctuating ocean conditions (0~0.9 m wave height, 0~15 m s−1 wind speed), which is comparable to that during onshore water electrolysis. The concentration of impurity ions in the electrolyte was low and stable over a long period of time under complex and changing scenarios. We identified the technological challenges and performances of the key system components and examined the future outlook for this emerging technology.
Global patterns of organic carbon transfer and accumulation across the land–ocean continuum constrained by radiocarbon data
Authors: Wang Chenglong , Qiu Yifei , Hao Zhe , Wang Junjie , Zhang Chuchu , Middelburg Jack J. , Wang Yaping , Zou Xinqing
Published: June 2024

Radiocarbon (Δ14C) serves as an effective tracer for identifying the origin and cycling of carbon in aquatic ecosystems. Global patterns of organic carbon (OC) Δ14C values in riverine particles and coastal sediments are essential for understanding the contemporary carbon cycle, but are poorly constrained due to under-sampling. This hinders our understanding of OC transfer and accumulation across the land–ocean continuum worldwide. Here, using machine learning approaches and >3,800 observations, we construct a high-spatial resolution global atlas of Δ14C values in river–ocean continuums and show that Δ14C values of river particles and corresponding coastal sediments can be similar or different. Specifically, four characteristic OC transfer and accumulation modes are recognized: the old–young mode for systems with low river and high coastal sediment Δ14C values; the young–old and old–old modes for coastal systems with old OC accumulation receiving riverine particles with high and low Δ14C values, respectively; and the young–young mode with young OC for both riverine and coastal deposited particles. Distinguishing these modes and their spatial patterns is critical to furthering our understanding of the global carbon system. Specifically, among coastal areas with high OC contents worldwide, old–old systems are largely neutral to slightly negative to contemporary atmospheric carbon dioxide (CO2) removal, whereas young–old and old–young systems represent CO2 sources and sinks, respectively. These spatial patterns of OC content and isotope composition constrain the local potential for blue carbon solutions.
Deciphering spatial domains from spatial multi-omics with SpatialGlue
Authors: Long Yahui , Ang Kok Siong , Sethi Raman , Liao Sha , Heng Yang , van Olst Lynn , Ye Shuchen , Zhong Chengwei , Xu Hang , Zhang Di , Kwok Immanuel , Husna Nazihah , Jian Min , Ng Lai Guan , Chen Ao , Gascoigne Nicholas R. J. , Gate David , Fan Rong , Xu Xun , Chen Jinmiao
Published: June 2024

Advances in spatial omics technologies now allow multiple types of data to be acquired from the same tissue slice. To realize the full potential of such data, we need spatially informed methods for data integration. Here, we introduce SpatialGlue, a graph neural network model with a dual-attention mechanism that deciphers spatial domains by intra-omics integration of spatial location and omics measurement followed by cross-omics integration. We demonstrated SpatialGlue on data acquired from different tissue types using different technologies, including spatial epigenome–transcriptome and transcriptome–proteome modalities. Compared to other methods, SpatialGlue captured more anatomical details and more accurately resolved spatial domains such as the cortex layers of the brain. Our method also identified cell types like spleen macrophage subsets located at three different zones that were not available in the original data annotations. SpatialGlue scales well with data size and can be used to integrate three modalities. Our spatial multi-omics analysis tool combines the information from complementary omics modalities to obtain a holistic view of cellular and tissue properties.
Prospects and limitations of cumate-inducible lentivirus as a tool for investigating VEGF-A-mediated pathology in diabetic retinopathy
Authors: Lelyte Inesa , Rao Vidhya R. , Kalesnykas Giedrius , Ragauskas Symantas , Kaja Simon , Ahmed Zubair
Published: June 2024

Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading to visual impairment. However, animal models accurately reflecting these pathologies are lacking. Vascular endothelial growth factor A (VEGF-A) is an important factor in the development of micro- and macro-vascular pathology in DR. In this study, we evaluated the feasibility of using a cumate-inducible lentivirus (LV) mediated expression of vegf-a to understand DR pathology in vitro and in vivo. Retinal pigment epithelial cells (ARPE-19) were transduced with cumate-inducible LV expressing vegf-a, with subsequent analysis of vegf-a expression and its impact on cell proliferation, viability, motility, and permeability. Cumate tolerability in adult Wistar rat eyes was assessed as an initial step towards a potential DR animal model development, by administering cumate via intravitreal injections (IVT) and evaluating consequent effects by spectral domain optical coherence tomography (SD-OCT), flash electroretinography (fERG), ophthalmic examination (OE), and immunohistochemistry. Transduction of ARPE-19 cells with cumate-inducible LV resulted in ~ 2.5-fold increase in vegf-a mRNA and ~ threefold increase in VEGF-A protein secretion. Transduced cells displayed enhanced cell proliferation, viability, permeability, and migration in tube-like structures. However, IVT cumate injections led to apparent retinal toxicity, manifesting as retinal layer abnormalities, haemorrhage, vitreous opacities, and significant reductions in a- and b-wave amplitudes, along with increased microglial activation and reactive gliosis. In summary, while cumate-inducible LV-mediated vegf-a expression is valuable for in vitro mechanistic studies in cellular drug discovery, its use is not a feasible approach to model DR in in vivo studies due to cumate-induced retinal toxicity.
Identifying key morphometrics to post-storm beach recovery through explainable AI
Authors: Thilakarathne Salika , Suzuki Takayuki , Mäll Martin , Banno Masayuki
Published: June 2024

In the context of ongoing discussions about climate change, the focus on beach resilience has gained significant attention in contemporary studies. However, a comprehensive understanding of beach resilience, particularly in the short term, remains limited. This study utilizes a dataset of 104 storm events in Hasaki beach, located on the East coast of Japan, to investigate the 10-day beach recovery. The study considers four types of distinct beach profile patterns based on sandbar formations. Employing XGBoost and the SHAP explanation method, the influence of morphometric indicators on beach resilience were explored. Resilient beach profiles are anticipated to exhibit rapid recovery following erosional storm events. The results reveal that morphometrics play a crucial role in determining the short-term, 10-day, recovery of beaches, with specific morphometric features demonstrating pronounced effects based on profile patterns. The study contributes to the current knowledge of post-storm beach recovery and provides insights that could inform discussions on beach resilience.