bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccarin Ameliorates Doxorubicin-Induced Cardiotoxicity via Inhibition of p38 MAPK Mediated Mitochondrial Dysfunction
Authors: Shi Xin , Cao Yang , Wang Hongyu , Zhao Qi , Yan Cong , Li Shengzhu , Jing Ling
Published: June 2024

Doxorubicin is a frequently used chemotherapeutic agent for treating various malignancies. However, it leads to severe cardiotoxic side effects, such as heart failure, and elevates the risk of sudden cardiac death among cancer patients. While oxidative stress has been identified as the primary cause of doxorubicin-induced cardiotoxicity, therapeutic antioxidant approaches have yielded unsatisfactory outcomes. The aim of this study is to explore the therapeutic potential of vaccarin, an active flavonoid glycoside extracted from traditional Chinese herbal agent Semen Vaccariae, in doxorubicin-induced cardiotoxicity. We observed that vaccarin significantly ameliorates doxorubicin-induced heart dysfunction in mouse model and suppresses oxidative stress mediated cell apoptosis via specifically inhibiting the activation of p38 MAPK pathway. In vitro, we observed that vaccarin alleviates doxorubicin-induced mitochondrial membrane depolarization and ROS generation in H9c2 cell, but the p38 MAPK agonist anisomycin reverses these effects. Our findings provide a promising natural antioxidant to protect against DOX-induced cardiotoxicity.

Graphic Abstract
PG I and PG II show unique value in diagnosing postoperative biochemical recurrence in patients with gastric cancer after total gastrectomy
Authors: Zhang Jiuru , Liu Jiameng , Dong Liyang , Wang Xi , Mao Xueqian , Mao Yufei , Mao Chaoming
Published: June 2024

Objective

To investigate the potential of group I pepsinogen (PG I) and group II pepsinogen (PG II) as diagnostic markers for recurrence in gastric cancer (GC) patients post-total gastrectomy.

Methods

Ninety-six patients who underwent total gastrectomy for GC between June 2022 and June 2023 were included in this study. Clinical data, serum samples, and ascites samples were collected. Patients were categorized based on recurrence status at the time of sample collection and the primary tumor site. PG I and PG II levels were determined using a chemiluminescent immunoassay, and their clinical utility following total gastrectomy for GC was evaluated via receiver operating characteristic (ROC) curve analysis.

Results

This study included 96 GC patients who underwent total gastrectomy, 55 of whom experienced postoperative recurrence (57.29%). The levels of serum PG I (27.86 (27.04, 30.97) vs. 26.05 (24.16, 27.09) ng/mL; P < 0.0001) and PG II (1.95 (1.23, 3.05) vs. 0.63 (0.47, 0.90) ng/mL; P < 0.0001) were significantly greater in the recurrent group compared to the non-recurrent group. The secretion of PG I and/or PG II by metastatic cancer cells correlated with the primary lesion site. When the cut-off value for serum PG I was 26.93 ng/mL, the area under the curve (AUC) for PG I was 0.77. When the cut-off value for serum PG II was 0.96 ng/mL, the AUC reached 0.90. The combined AUC was 0.97.

Conclusion

These findings suggest that serum PG I and PG II are valuable biomarkers for identifying GC patients with biochemical recurrence post-total gastrectomy.
Prediction of prognosis in glioblastoma with radiomics features extracted by synthetic MRI images using cycle-consistent GAN
Authors: Yoshimura Hisanori , Kawahara Daisuke , Saito Akito , Ozawa Shuichi , Nagata Yasushi
Published: June 2024

To propose a style transfer model for multi-contrast magnetic resonance imaging (MRI) images with a cycle-consistent generative adversarial network (CycleGAN) and evaluate the image quality and prognosis prediction performance for glioblastoma (GBM) patients from the extracted radiomics features. Style transfer models of T1 weighted MRI image (T1w) to T2 weighted MRI image (T2w) and T2w to T1w with CycleGAN were constructed using the BraTS dataset. The style transfer model was validated with the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) dataset. Moreover, imaging features were extracted from real and synthesized images. These features were transformed to rad-scores by the least absolute shrinkage and selection operator (LASSO)-Cox regression. The prognosis performance was estimated by the Kaplan–Meier method. For the accuracy of the image quality of the real and synthesized MRI images, the MI, RMSE, PSNR, and SSIM were 0.991 ± 2.10 $$\times {10}^{-4}$$

×

10

-
4

, 2.79 ± 0.16, 40.16 ± 0.38, and 0.995 ± 2.11 $$\times {10}^{-4}$$

×

10

-
4

, for T2w, and .992 ± 2.63 $$\times {10}^{-4}$$

×

10

-
4

, 2.49 ± 6.89 $$\times {10}^{-2}$$

×

10

-
2

, 40.51 ± 0.22, and 0.993 ± 3.40 $$\times {10}^{-4}$$

×

10

-
4

for T1w, respectively. The survival time had a significant difference between good and poor prognosis groups for both real and synthesized T2w (p < 0.05). However, the survival time had no significant difference between good and poor prognosis groups for both real and synthesized T1w. On the other hand, there was no significant difference between the real and synthesized T2w in both good and poor prognoses. The results of T1w were similar in the point that there was no significant difference between the real and synthesized T1w. It was found that the synthesized image could be used for prognosis prediction. The proposed prognostic model using CycleGAN could reduce the cost and time of image scanning, leading to a promotion to build the patient’s outcome prediction with multi-contrast images.
Heavy metals and microbial assessment of air conditioning condensate water in Jeddah city-Saudi Arabia: concept of sustainable water resources
Authors: AlGhamdi Shareefa A. , Alromi Deemah , Jambi Ebtihaj , Alzughaibi Torki , Al-Ansari Ahmed
Published: June 2024

The demand for water is rising worldwide, especially in Saudi Arabia, where the existing water sources are barely sufficient to meet the present requirements. Condensates from air-conditioning units can be invested as an economical and supportive source of available water resources, which can be considered within global water supply accounts. The aim of the present study is to examine the possibility of recovering condensate water from air conditioner (AC) systems by determining the quantity and quality of AC water generated by either split or window AC systems. The results showed that split air conditioner systems were more effective than window-type air conditioners in generating condensate water in terms of quantity and quality. There was a significant correlation between the humidity and water content. The results indicate that the annual amount of water generated was 8,725 L for window AC and 20,614 L for split AC. The recorded levels of all elements in the water samples obtained from both the window and split air conditioning units, including pH, TDS, EC, PO4-3, Cl-, SO4-2, COD, and heavy metals, were found to be within the acceptable thresholds set for both drinking water and irrigation purposes. Bacteria were only present in three water samples from the window AC, and all were non-pathogenic. Utilizing air conditioner condensate as a strategic measure can address the issue of water scarcity in Saudi Arabia’s agricultural and industrial sectors. The findings of this study are extremely relevant and opportune, especially given the growing concerns about water scarcity and the need to conserve resources. By demonstrating that the HVAC water condensate is clean and safe for consumption, this study adds to our understanding of how we can make better use of available resources.
The Root Extraction Problem in Braid Group-Based Cryptography
Authors: Cumplido María , Kahrobaei Delaram , Noce Marialaura
Published: June 2024

The root extraction problem in braid groups is the following: given a braid $$\beta \in \mathcal {B}_n$$

β
∈

B
n

and a number $$k\in \mathbb {N}$$

k
∈
N

, find $$\alpha \in \mathcal {B}_n$$

α
∈

B
n

such that $$\alpha ^k=\beta $$

α
k

=
β

. In the last decades, several cryptosystems based on the root extraction problem, including authentication schemes and digital signatures, have been proposed. In this survey paper, we describe these cryptosystems built around braid groups. Then we explain that, in general, these authentication schemes and digital signatures are not secure, and we present for each of them a possible attack.
Transdisciplinary perspectives on ‘the narrative’ and ‘the analytical’ for critical literacy
Authors: Humphrey Sally , Stosic Dragana , Barrington Therese , Brake Nicki , Pagano Rebecca
Published: June 2024

This paper reports on the design of a multimodal metalanguage developed by teacher education researchers to support pre-service teachers’ understandings of critical literacy and critical health literacies in a changing communication landscape. The design of metalanguage constitutes the first stage of an ongoing transdisciplinary project, Multiliteracies Across Teaching Areas (MATA), which aims to design and implement cohesive disciplinary multiliteracies pedagogies across teaching areas of an initial teacher education (ITE) programme. The focus on metalanguage design is motivated by concerns shared by critical literacy scholars and scholars in health literacy to balance deconstruction of texts with actionable response through the ‘deep moral grammar of narrative’ Kindenberg and Freebody (Australian Journal of Language and Literacy, 44(2), 90-99, 2021). Such concerns also align with recent World Health Organisation calls for the use of solution-oriented literacies to empower communities. These sociocultural understandings of critical literacy and Kindenberg and Freebody’s (Australian Journal of Language and Literacy, 44(2), 90-99, 2021) call to balance ‘the analytical’ and the narrative’ in critical literacy practice provide the starting point for designing metalanguage for transdisciplinary research in Health and Physical Education (HPE) and English. We firstly review relevant models of the critical informing both subject areas to establish synergous understandings and then analyse expectations of critical practice in descriptions and elaborations of the HPE and English curricula. We provide an overview of the semiotic resources available for transdisciplinary conversations within the English curriculum with clarifying ‘bridging’ terminology informed by social semiotic descriptions. Through close analysis of four representative texts selected for critical literacy practice by English and HPE teacher educators in the MATA project, we demonstrate how such metalanguage was shared to build understandings of both critical analysis and actionable response. Along with analytical features to build and analyse issues according to disciplinary criteria, we show how stories are used to build rapport with their diverse audiences and to motivate their peers to take positive health action.
The genetic orchestra of salicylic acid in plant resilience to climate change induced abiotic stress: critical review
Authors: Elsisi Mohamed , Elshiekh Moaz , Sabry Nourine , Aziz Mark , attia Kotb , Islam Faisal , Chen Jian , Abdelrahman Mohamed
Published: June 2024

Climate change, driven by human activities and natural processes, has led to critical alterations in varying patterns during cropping seasons and is a vital threat to global food security. The climate change impose several abiotic stresses on crop production systems. These abiotic stresses include extreme temperatures, drought, and salinity, which expose agricultural fields to more vulnerable conditions and lead to substantial crop yield and quality losses. Plant hormones, especially salicylic acid (SA), has crucial roles for plant resiliency under unfavorable environments. This review explores the genetics and molecular mechanisms underlying SA's role in mitigating abiotic stress-induced damage in plants. It also explores the SA biosynthesis pathways, and highlights the regulation of their products under several abiotic stresses. Various roles and possible modes of action of SA in mitigating abiotic stresses are discussed, along with unraveling the genetic mechanisms and genes involved in responses under stress conditions. Additionally, this review investigates molecular pathways and mechanisms through which SA exerts its protective effects, such as redox signaling, cross-talks with other plant hormones, and mitogen-activated protein kinase pathways. Moreover, the review discusses potentials of using genetic engineering approaches, such as CRISPR technology, for deciphering the roles of SA in enhancing plant resilience to climate change related abiotic stresses. This comprehensive analysis bridges the gap between genetics of SA role in response to climate change related stressors. Overall goal is to highlight SA's significance in safeguarding plants and by offering insights of SA hormone for sustainable agriculture under challenging environmental conditions.
Determinants of urban agriculture market participation decision and intensity in eastern Ethiopia
Authors: Nigus Gebregziabher , Ketema Mengistu , Haji Jema , Sileshi Million
Published: June 2024

Small-scale urban farmers' active involvement in the urban agriculture (UA) output market is one strategy to ease an urban food shortage while sustaining their livelihoods and income. Enhancing market participation and intensity requires identifying the factors that affect UA market participation. Thus, the study aimed to determine the factors influencing UA market participation decisions and intensity in Eastern Ethiopia. Using a semi-structured questionnaire, the study utilized primary data collected from 270 randomly selected urban farmers. The Double Hurdle (DH) Model was used to determine the factors influencing urban farmers' participation and intensity in the UA output market. According to the first stage DH Model results, age, education, occupation, family size, farming experience, UA-related training, dependency ratio, and market information, all had a significant impact on the decision to participate in the UA output market. The second stage DH Model of Truncated regression indicated that the intensity of UA output market participation decision was significantly affected by the education, land size, UA-related training, and market information are all important factors determine the intensity of UA output market participation. Improving the ability to use the land for UA purposes, awareness creation through short-term training, and improving information access are important recommendations to enhance UA output market participation and intensity of participation.
Fuzzy Evaluation and Benchmarking Framework for Robust Machine Learning Model in Real-Time Autism Triage Applications
Authors: Shayea Ghadeer Ghazi , Zabil Mohd Hazli Mohammed , Albahri A. S. , Joudar Shahad Sabbar , Hamid Rula A. , Albahri O. S. , Alamoodi A. H. , Zahid Idrees A. , Sharaf Iman Mohamad
Published: June 2024

In the context of autism spectrum disorder (ASD) triage, the robustness of machine learning (ML) models is a paramount concern. Ensuring the robustness of ML models faces issues such as model selection, criterion importance, trade-offs, and conflicts in the evaluation and benchmarking of ML models. Furthermore, the development of ML models must contend with two real-time scenarios: normal tests and adversarial attack cases. This study addresses this challenge by integrating three key phases that bridge the domains of machine learning and fuzzy multicriteria decision-making (MCDM). First, the utilized dataset comprises authentic information, encompassing 19 medical and sociodemographic features from 1296 autistic patients who received autism diagnoses via the intelligent triage method. These patients were categorized into one of three triage labels: urgent, moderate, or minor. We employ principal component analysis (PCA) and two algorithms to fuse a large number of dataset features. Second, this fused dataset forms the basis for rigorously testing eight ML models, considering normal and adversarial attack scenarios, and evaluating classifier performance using nine metrics. The third phase developed a robust decision-making framework that encompasses the creation of a decision matrix (DM) and the development of the 2-tuple linguistic Fermatean fuzzy decision by opinion score method (2TLFFDOSM) for benchmarking multiple-ML models from normal and adversarial perspectives, accomplished through individual and external group aggregation of ranks. Our findings highlight the effectiveness of PCA algorithms, yielding 12 principal components with acceptable variance. In the external ranking, logistic regression (LR) emerged as the top-performing ML model in terms of the 2TLFFDOSM score (1.3370). A comparative analysis with five benchmark studies demonstrated the superior performance of our framework across all six checklist comparison points.
Questioning Leadership
Authors: Harvey Michael
Published: June 2024

This Element posits that questions are the heart of leadership. Leaders ask hard questions that spark creative solutions and new understandings. Asking by itself isn't enough - leaders must also help find answers and turn them into effective action. But the leader's work begins with questions. This Element surveys the main traditions of leadership thought; considers the nature of the group and its questions; explores how culture and bureaucracy serve to provide stable answers to the group's questions; and explores how leaders offers disruptive answers, especially in times of change and crisis. It uses the lens of questions to consider two parallel American lives, President Abraham Lincoln and General Robert E. Lee.
Natural Variability Can Mask Forced Permafrost Response to Stratospheric Aerosol Injection in the ARISE‐SAI‐1.5 Simulations
Authors: Morrison A. L. , Barnes E. A. , Hurrell J. W.
Published: June 2024

Stratospheric aerosol injection (SAI) has been proposed as a potential method for mitigating risks and impacts associated with anthropogenic climate change. One such risk is widespread permafrost thaw and associated carbon release. While permafrost has been shown to stabilize under different SAI scenarios, natural variability may mask this forced response and make it difficult to detect if and when SAI is stabilizing permafrost. Here we use the 10‐member ensemble from the ARISE‐SAI‐1.5 simulations to assess the spread in projected active layer depth and permafrost temperature across boreal permafrost soils and specifically in four peatland and Yedoma regions. The forced response in active layer depth and permafrost temperature quickly diverges between an SAI and non‐SAI world, but individual ensemble members overlap for several years following SAI deployment. We find that, due to projected permafrost variability, it may take more than a decade of SAI deployment to detect the effects of SAI on permafrost temperature and almost 30 years to detect its effects on active layer depth. Not only does natural variability make it more difficult to detect SAI's influence, it could also affect the likelihood of reaching a permafrost tipping point. In some realizations, SAI fails to prevent a local tipping point that is also reached in a non‐SAI world. Our results underscore the importance of accounting for natural variability in assessments of SAI's potential influence on the climate system.
Occurrence of Equatorial Plasma Bubbles (EPBs) Over the Indian Region on 15 January 2022 and Their Plausible Connection to the Tonga Volcano Eruption
Authors: Barad Rajesh Kumar , Sripathi S. , Banola S. , Vijaykumar K.
Published: June 2024

This study focuses on the causes for the generation of equatorial plasma bubbles (EPBs) over the Indian subcontinent and their correlation with atmospheric‐ionospheric disturbances resulting from the eruption of the Tonga volcano on 15 January 2022. Concurrent ionosonde observations obtained from Tirunelveli (8.67°N, 77.81°E) and Prayagraj (25.41°N, 81.93°E) show the presence of spread‐F traces in ionograms. Notably, the EPBs are also accompanied by plasma blobs (PBs), with their pronounced occurrence during midnight at Prayagraj and Tirunelveli. Analysis of in situ electron density observations obtained from the Swarm B and C satellites reveals substantial plasma density depletions associated with EPBs. An intriguing observation is the intensification of Pre‐Reversal Enhancement (PRE) immediately preceding the onset of spread‐F at Tirunelveli due to enhanced eastward F region zonal winds by Tonga Volcano, as seen in the satellite observations. Furthermore, the isofrequency analysis from Tirunelveli shows the presence of gravity wave‐like oscillations in the equatorial F‐region over India. The investigation of Total Electron Content (TEC) obtained from a Pseudo Random Number (PRN)‐14 over Indian longitudes suggests the presence of two dominant modes of Traveling Ionospheric Disturbances (TIDs) with speeds ∼452 m/s and ∼406 m/s having periods in the range of ∼65–75 min. These observations reaffirm that volcano triggered atmospheric/ionospheric disturbances can propagate long distances for several hours and can provide necessary seeding conditions for the generation of EPBs.
Oven Design for In‐Situ Thermal Extraction of Volatiles From Lunar Regolith
Authors: Ruan Renhao , Yang Wei , Hao Jialong , Guo Guangjun
Published: June 2024

Extracting volatiles from lunar regolith for analysis or utilization is one of the most important aspects of future lunar exploration. However, the low thermal conductivity of lunar regolith poses a challenge. Here, we conduct simulations to analyze the heat and mass transfer processes within the sample inside the oven. We identify three main factors affecting oven heat‐up rate: water ice content (WIC) in the regolith, oven diameter, and power supply. Taking these factors into account, we devise an oven design and apply it to three case studies: (a) assessing water ice and isotopic composition in Permanently Shadowed Regions, akin to Chang'e‐7 mini‐fly probe missions; (b) measuring noble gases, as Chang'e‐7 and Luna‐27 landers; and (c) large‐scale in‐situ resources utilization (ISRU). The simulation results indicate that water ice can be extracted using sufficiently high heating power without issues. However, the complete extraction of noble gases is challenging and may require alternative heating methods. For ISRU purposes, large ovens can be subdivided into smaller ones by adding internal structures, for example, honeycomb, to improve the heat‐up rate by at least 1.5 times. Additionally, we find that the oven can serve as a scientific payload for WIC measurement using the heating curve. A flowchart of this new WIC measurement method is provided, offering an alternative method to mass spectrometry or spectroscopy measurements.
Eccentricity Paces Late Pleistocene Glaciations
Authors: Blackburn T. , Kodama S. , Piccione G.
Published: June 2024

Late Pleistocene glacial terminations are caused by rising atmospheric CO2 occurring in response to atmospheric and ocean circulation changes induced by increased discharge from Northern Hemisphere ice sheets. While climate records place glacial terminations coincident with decreasing orbital precession, it remains unclear why a specific precession minimum causes a termination. We compare the orbital and ice volume configuration at each precession minima over the last million years to demonstrate that eccentricity, through its control on precession amplitude, period and coherence with obliquity, along with ice sheet size, determine whether a given precession minimum will cause a termination. We also demonstrate how eccentricity controls obliquity maxima and precession minima coherence, varying the duration of glaciations. Glaciations lasting ∼100 thousand years are controlled by Earth's eccentricity cycle of the same period, while the shortest (20–40 ka) and longest (155 ka) occupy the maxima and minimums of the 400 thousand year eccentricity cycle.
Elasticity of Single‐Crystal Clinohumite at High Pressures and Temperatures: Implication for the H2O and F Circulation in the Earth's Mantle
Authors: Li Luo , Zhang Qingchun , Yu Yingxin , Sun Ningyu , Mao Zhu , Li Wancai , Li Xinyang , Wang Sha , Ye Yu
Published: June 2024

In this study, we have determined the single‐crystal elasticity of clinohumite [Mg8.85Ti0.19Si3.93O16(OH1.11F0.89)] using Brillouin measurement up to 21 GPa at 300 K and 1 bar at 750 K, respectively. The elasticity of clinohumite was determined to be KS0 = 126.2(3) GPa, G0 = 79.7(2) GPa with pressure derivatives KS′ = 4.2(1), G′ = 1.3(1), pressure derivatives ∂KS/∂T = −0.024(1) GPa/K, and ∂G/∂T = −0.011(1) GPa/K). We comprehensively examined the effects of varying H2O, fluorine content and thermal states, on the velocity and density structures of the subducted harzburgite layer. Assuming a typical H2O content of 2 wt.% within harzburgite, our modeling has shown that hydrous harzburgite with clinohumite as the decomposition product of serpentine along a hot slab geotherm even has the VP and VS 0.4–0.8(6)% greater than it dry counterpart at 250–380 km depth. Yet in the top transition zone, the addition of H2O and F can effectively lower the sound velocities and density. The F‐bearing hydrous harzburgite has the VP and VS 1.1(5)–1.3(3)% lower than its dry counterpart, and only 0.6(5)% and 2.3(5)% greater than the pyrolitic mantle. Along cold slab geotherm, phase A will replace clinohumite as the dominant hydrous phase in the harzburgite, the VP and VS are 4.8(5)–5.3(3)% and 5.9(5)–6.0(3)% greater than the pyrolitic mantle in the upper mantle. In the top transition zone, the difference is approximately 3% in VP and 5% in VS. Our results provide crucial experimental evidence for future assessments of the seismic signals of subducted slabs with different hydrous minerals and thermal states.
Telling Tales of Water Journeys With Isotopic Tracers
Authors: Koren Gerbrand
Published: June 2024

Determining the sources of water inside plants using its isotopic composition is a long‐standing research challenge in ecohydrology. A better understanding of water sources can help improve models and ultimately contribute to more accurate forecasts of water availability, food production, carbon sequestration or ecosystem status. Over the years, several methods have been developed and applied to water source partitioning, and Gai et al. (2023, https://doi.org/10.1029/2022wr033849) provide a systematic assessment of the uncertainty of different isotopic tracers (2H, 3H, 17O, 18O) and mixing models (IsoSource, SIAR, MixSIR, MixSIAR) for an apple tree orchard on the Loess Plateau in north‐central China. For that study area, the combination of 2H and 18O with the MixSIAR mixing model is recommended. Importantly, the systematic assessment provides a framework that can be applied to select a suitable combination of tracers and mixing models for different ecosystems and climate zones. This commentary aims to provide a wider context for a selection of key results from Gai et al. (2023, https://doi.org/10.1029/2022wr033849) and highlight potential future research directions.
Synergistic immunochemotherapy targeted SAMD4B-APOA2-PD-L1 axis potentiates antitumor immunity in hepatocellular carcinoma
Authors: Qi Feng , Zhang Jian , Li Jia , Li Donghe , Gao Na , Qi Zhuoran , Kong Xiuyan , Yu Zhijie , Fang Yuan , Cui Wenguo , Xia Jinglin
Published: June 2024

Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new therapeutic schemes, but most of which are not satisfactory. Single-cell RNA sequencing was performed in PDX mouse models with or without TCC therapy. 2-’O-Methylation modification and multiplex immunofluorescence staining were used to explore the function and mechanism of SAMD4B in the immune context of HCC. Here, we propose for the first time a synergistic immunochemotherapy that exerts a potent antitumour effect for patients with advanced hepatocellular carcinoma (HCC) in clinical practice based on three common antitumour drugs and found that HCC patients with new synergistic immunochemotherapy had better three-year overall survival (p = 0.004) and significantly higher survival ratio (increased by 2.3 times) than the control group. We further reveal the immunoregulatory mechanism of synergistic immunochemotherapy through 2’-O-Methylation modification mediated by SAMD4B, a tumour suppressor gene. Mechanistically, SAMD4B, increased by the reduced mutations of upstream genes NOTCH1 and NOTCH2, affected the instability of APOA2 mRNA by 2-’O-Methylation modification of the C-terminus. The decreased APOA2 further attenuated programmed death ligand 1 (PD-L1) level with a direct interaction pattern. The high-SAMD4B tumour tissues contained fewer native CD29+CD8+ T cells, which improved immune microenvironment to achieve the effect of antitumour effect. Overall, we developed a potent synergistic immunochemotherapy strategy that exerts an efficient anti-HCC effect inducing SAMD4B-APOA2-PD-L1 axis to inhibit tumour immune evasion.
TGF-β1 facilitates gallbladder carcinoma metastasis by regulating FOXA1 translation efficiency through m6A modification
Authors: Wu Zhenheng , Ke Qiming , Jiang Lei , Hong Haijie , Pan Wei , Chen Wen , Abudukeremu Xiahenazi , She Feifei , Chen Yanling
Published: June 2024

TGF-β1 plays a pivotal role in the metastatic cascade of malignant neoplasms. N6-methyladenosine (m6A) stands as one of the most abundant modifications on the mRNA transcriptome. However, in the metastasis of gallbladder carcinoma (GBC), the effect of TGF-β1 with mRNA m6A modification, especially the effect of mRNA translation efficiency associated with m6A modification, remains poorly elucidated. Here we demonstrated a negative correlation between FOXA1 and TGF-β1 expression in GBC. Overexpression of FOXA1 inhibited TGF-β1-induced migration and epithelial-mesenchymal transition (EMT) in GBC cells. Mechanistically, we confirmed that TGF-β1 suppressed the translation efficiency of FOXA1 mRNA through polysome profiling analysis. Importantly, both in vivo and in vitro experiments showed that TGF-β1 promoted m6A modification on the coding sequence (CDS) region of FOXA1 mRNA, which was responsible for the inhibition of FOXA1 mRNA translation by TGF-β1. We demonstrated through MeRIP and RIP assays, dual-luciferase reporter assays and site-directed mutagenesis that ALKBH5 promoted FOXA1 protein expression by inhibiting m6A modification on the CDS region of FOXA1 mRNA. Moreover, TGF-β1 inhibited the binding capacity of ALKBH5 to the FOXA1 CDS region. Lastly, our study confirmed that overexpression of FOXA1 suppressed lung metastasis and EMT in a nude mice lung metastasis model. In summary, our research findings underscore the role of TGF-β1 in regulating TGF-β1/FOXA1-induced GBC EMT and metastasis by inhibiting FOXA1 translation efficiency through m6A modification.
Dysregulation of SNX1-retromer axis in pharmacogenetic models of Parkinson’s disease
Authors: Yoshida Shun , Hasegawa Takafumi , Nakamura Takaaki , Sato Kazuki , Sugeno Naoto , Ishiyama Shun , Sekiguchi Kiyotoshi , Tobita Muneshige , Takeda Atsushi , Aoki Masashi
Published: June 2024

Since the identification of vacuolar protein sorting (VPS) 35, as a causative molecule for familial Parkinson’s disease (PD), retromer-mediated endosomal machinery has been a rising factor in the pathogenesis of the disease. The retromer complex cooperates with sorting nexin (SNX) dimer and DNAJC13, another causal molecule in PD, to transport cargoes from endosomes to the trans-Golgi network, and is also involved in mitochondrial dynamics and autophagy. Retromer dysfunction may induce neuronal death leading to PD via several biological cascades, including misfolded, insoluble α-synuclein (aS) accumulation and mitochondrial dysfunction; however, the detailed mechanisms remain poorly understood. In this study, we showed that the stagnation of retromer-mediated retrograde transport consistently occurs in different PD-mimetic conditions, i.e., overexpression of PD-linked mutant DNAJC13, excess aS induction, or toxin-induced mitochondrial dysfunction. Mechanistically, DNAJC13 was found to be involved in clathrin-dependent retromer transport as a functional modulator of SNX1 together with heat shock cognate 70 kDa protein (Hsc70), which was controlled by the binding and dissociation of DNAJC13 and SNX1 in an Hsc70 activity-dependent manner. In addition, excess amount of aS decreased the interaction between SNX1 and VPS35, the core component of retromer. Furthermore, R33, a pharmacological retromer chaperone, reduced insoluble aS and mitigated rotenone-induced neuronal apoptosis. These findings suggest that retrograde transport regulated by SNX1-retromer may be profoundly involved in the pathogenesis of PD and is a potential target for disease-modifying therapy for the disease.
Differential cortical layer engagement during seizure initiation and spread in humans
Authors: Bourdillon Pierre , Ren Liankun , Halgren Mila , Paulk Angelique C. , Salami Pariya , Ulbert István , Fabó Dániel , King Jean-Rémi , Sjoberg Kane M. , Eskandar Emad N. , Madsen Joseph R. , Halgren Eric , Cash Sydney S.
Published: June 2024

Despite decades of research, we still do not understand how spontaneous human seizures start and spread – especially at the level of neuronal microcircuits. In this study, we used laminar arrays of micro-electrodes to simultaneously record the local field potentials and multi-unit neural activities across the six layers of the neocortex during focal seizures in humans. We found that, within the ictal onset zone, the discharges generated during a seizure consisted of current sinks and sources only within the infra-granular and granular layers. Outside of the seizure onset zone, ictal discharges reflected current flow in the supra-granular layers. Interestingly, these patterns of current flow evolved during the course of the seizure – especially outside the seizure onset zone where superficial sinks and sources extended into the deeper layers. Based on these observations, a framework describing cortical-cortical dynamics of seizures is proposed with implications for seizure localization, surgical targeting, and neuromodulation techniques to block the generation and propagation of seizures.
Conceptualizing soil fauna effects on labile and stabilized soil organic matter
Authors: Angst Gerrit , Potapov Anton , Joly François-Xavier , Angst Šárka , Frouz Jan , Ganault Pierre , Eisenhauer Nico
Published: June 2024

Fauna is highly abundant and diverse in soils worldwide, but surprisingly little is known about how it affects soil organic matter stabilization. Here, we review how the ecological strategies of a multitude of soil faunal taxa can affect the formation and persistence of labile (particulate organic matter, POM) and stabilized soil organic matter (mineral-associated organic matter, MAOM). We propose three major mechanisms - transformation, translocation, and grazing on microorganisms - by which soil fauna alters factors deemed essential in the formation of POM and MAOM, including the quantity and decomposability of organic matter, soil mineralogy, and the abundance, location, and composition of the microbial community. Determining the relevance of these mechanisms to POM and MAOM formation in cross-disciplinary studies that cover individual taxa and more complex faunal communities, and employ physical fractionation, isotopic, and microbiological approaches is essential to advance concepts, models, and policies focused on soil organic matter and effectively manage soils as carbon sinks, nutrient stores, and providers of food.
Highly accurate carbohydrate-binding site prediction with DeepGlycanSite
Authors: He Xinheng , Zhao Lifen , Tian Yinping , Li Rui , Chu Qinyu , Gu Zhiyong , Zheng Mingyue , Wang Yusong , Li Shaoning , Jiang Hualiang , Jiang Yi , Wen Liuqing , Wang Dingyan , Cheng Xi
Published: June 2024

As the most abundant organic substances in nature, carbohydrates are essential for life. Understanding how carbohydrates regulate proteins in the physiological and pathological processes presents opportunities to address crucial biological problems and develop new therapeutics. However, the diversity and complexity of carbohydrates pose a challenge in experimentally identifying the sites where carbohydrates bind to and act on proteins. Here, we introduce a deep learning model, DeepGlycanSite, capable of accurately predicting carbohydrate-binding sites on a given protein structure. Incorporating geometric and evolutionary features of proteins into a deep equivariant graph neural network with the transformer architecture, DeepGlycanSite remarkably outperforms previous state-of-the-art methods and effectively predicts binding sites for diverse carbohydrates. Integrating with a mutagenesis study, DeepGlycanSite reveals the guanosine-5’-diphosphate-sugar-recognition site of an important G-protein coupled receptor. These findings demonstrate DeepGlycanSite is invaluable for carbohydrate-binding site prediction and could provide insights into molecular mechanisms underlying carbohydrate-regulation of therapeutically important proteins.
Embodied CO2 emissions of equity portfolios for Chinese asset managers
Authors: Wang Jinglei , Zhang Zengkai , Chen Danbo , Guan Dabo
Published: June 2024

The 2015 Paris Agreement has set out the climate change target of limiting global warming to 1.5 °C, which poses a serious challenge to countries to reduce emissions. As the world’s largest carbon emitter, promoting the realization of the “dual-carbon” goal is the key to realizing China’s green transformation and high-quality development. Chinese asset managers play active roles in the capital market as an important channel of asset allocation. Currently, the vast majority of Chinese asset managers hold high percentages of high-carbon industries in their portfolios, and lack quantitative data of their carbon footprints embodied in equity investments, which faces huge carbon-related risks. Therefore, it’s an urgent need to comprehensively and scientifically measure financed emissions of Chinese asset managers, which is of great significance for asset managers’ carbon risk management and sustainable investment. This paper develops a detailed inventory of carbon emissions for equity portfolios managed by Chinese asset managers from 2010 to 2020, which stands as a pivotal reference for in-depth analysis of emission characteristics.
An experienced racial-ethnic diversity dataset in the United States using human mobility data
Authors: Xu Wenfei , Wang Zhuojun , Attia Nada , Attia Youssef , Zhang Yucheng , Zong Haotian
Published: June 2024

Despite the importance of measuring racial-ethnic segregation and diversity in the United States, current measurements are largely based on the Census and, thus, only reflect segregation and diversity as understood through residential location. This leaves out the social contexts experienced throughout the course of the day during work, leisure, errands, and other activities. The National Experienced Racial-ethnic Diversity (NERD) dataset provides estimates of diversity for the entire United States at the census tract level based on the range of place and times when people have the opportunity to come into contact with one another. Using anonymized and opted-in mobile phone location data to determine co-locations of people and their demographic backgrounds, these measurements of diversity in potential social interactions are estimated at 38.2 m × 19.1 m scale and 15-minute timeframe for a representative year and aggregated to the Census tract level for purposes of data privacy. As well, we detail some of the characteristics and limitations of the data for potential use in national, comparative studies.
Association of intensity and dominance of CEOs’ smiles with corporate performance
Authors: Fujiwara Ken , Plusquellec Pierrich
Published: June 2024

This study investigated whether the facial expressions of chief executive officers (CEOs) are associated with corporate performance. A photograph of the CEO or president of each company that appeared on the Fortune Global 500 list for 2018 was taken from the company’s official website. The smile intensity and action unit activation in each face were calculated using a pre-trained machine learning algorithm, FACET. The results revealed a positive association between smile intensity and company profit, even when controlling for the company’s geographic location (Western culture versus others) and the CEO’s gender. Furthermore, when the type of smile was examined with the activation of each action unit, this significant positive association was identified in the dominant smile but not in the reward and affiliative smiles. Relationships among the leader’s smile intensity, group strategy, and group performance are discussed.
Mechanical evaluation of soil and artisanal bricks for quality masonry product management, Limpopo South Africa
Authors: Akintola George Oluwole , Amponsah-Dacosta Francis , Mhlongo Sphiwe Emmanuel , Matsiketa Khensani Eullen
Published: June 2024

The selection of raw materials to produce quality artisanal bricks is imperative for sustainable building in rural regions. Artisanal brick-making process often employs traditional kiln to fire brick because it is an affordable, and applicable technology in the rural region. However, there are noticeable cracks, increasing among buildings constructed with artisanal bricks from the rural region in South Africa. In response, this study aims to evaluate the soil and artisanal brick specimens to understand the suitability of the raw materials and quality of products in the study area. A total of twenty soil samples and twenty-seven artisanal burnt bricks were collected from three different artisanal brick-making sites designated as Site A, B, and C. In all samples, the geotechnical tests revealed a sandy loam soil type with a predominance of chlorite clay minerals and non-clay minerals. Furthermore, the sand-size particles depict a relatively higher proportion compared to clay-size particles. Besides, Atterberg’s limit test plotted above the A-line of the plasticity chart indicates an inorganic clay of low plasticity with a low to medium compressibility property. Based on the empirical workability and mechanical tests, most of the studied soils are suitable for optimum and acceptable extrusion bricks and suitable for an on-site single-story construction based on SANS 227:2007 standards.
Joint stereo 3D object detection and implicit surface reconstruction
Authors: Li Shichao , Huang Xijie , Liu Zechun , Cheng Kwang-Ting
Published: June 2024

We present a new learning-based framework S-3D-RCNN that can recover accurate object orientation in SO(3) and simultaneously predict implicit rigid shapes from stereo RGB images. For orientation estimation, in contrast to previous studies that map local appearance to observation angles, we propose a progressive approach by extracting meaningful Intermediate Geometrical Representations (IGRs). This approach features a deep model that transforms perceived intensities from one or two views to object part coordinates to achieve direct egocentric object orientation estimation in the camera coordinate system. To further achieve finer description inside 3D bounding boxes, we investigate the implicit shape estimation problem from stereo images. We model visible object surfaces by designing a point-based representation, augmenting IGRs to explicitly address the unseen surface hallucination problem. Extensive experiments validate the effectiveness of the proposed IGRs, and S-3D-RCNN achieves superior 3D scene understanding performance. We also designed new metrics on the KITTI benchmark for our evaluation of implicit shape estimation.
Enhancing soil amendment for salt stress using pretreated rice straw and cellulolytic fungi
Authors: Ma Yen Nhi , Mongkolthanaruk Wiyada , Riddech Nuntavun
Published: June 2024

Rice straw breakdown is sluggish, which makes agricultural waste management difficult, however pretreatment procedures and cellulolytic fungi can address this issue. Through ITS sequencing, Chaetomium globosum C1, Aspergillus sp. F2, and Ascomycota sp. SM2 were identified from diverse sources. Ascomycota sp. SM2 exhibited the highest carboxymethyl cellulase (CMCase) activity (0.86 IU/mL) and filter-paper cellulase (FPase) activity (1.054 FPU/mL), while Aspergillus sp. F2 showed the highest CMCase activity (0.185 IU/mL) after various pretreatments of rice straw. These fungi thrived across a wide pH range, with Ascomycota sp. SM2 from pH 4 to 9, Aspergillus sp. F2, and Chaetomium globosum C1 thriving in alkaline conditions (pH 9). FTIR spectroscopy revealed significant structural changes in rice straw after enzymatic hydrolysis and solid-state fermentation, indicating lignin, cellulose, and hemicellulose degradation. Soil amendments with pretreated rice straw, cow manure, biochar, and these fungi increased root growth and soil nutrient availability, even under severe salt stress (up to 9.3 dS/m). The study emphasizes the need for a better understanding of Ascomycota sp. degradation capabilities and proposes that using cellulolytic fungus and pretreatment rice straw into soil amendments could mitigate salt-related difficulties and improve nutrient availability in salty soils.
The associations of leukocyte telomere length and intermediary cardiovascular phenotype with adverse cardiovascular outcomes in the white population
Authors: Chung Ho-Gi , Yang Pil-Sung , Cho Seunghoon , Jang Eunsun , Kim Daehoon , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Sung Jung-Hoon , Pak Hui-Nam , Lee Moon-Hyoung , Joung Boyoung
Published: June 2024

The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2–12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72–0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84–0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74–0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.