bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrochemical carbon–carbon coupling with enhanced activity and racemate stereoselectivity by microenvironment regulation
Authors: Kong Kejian , Li An-Zhen , Wang Ye , Shi Qiujin , Li Jing , Ji Kaiyue , Duan Haohong
Published: October 2023

Enzymes are characteristic of catalytic efficiency and specificity by maneuvering multiple components in concert at a confined nanoscale space. However, achieving such a configuration in artificial catalysts remains challenging. Herein, we report a microenvironment regulation strategy by modifying carbon paper with hexadecyltrimethylammonium cations, delivering electrochemical carbon–carbon coupling of benzaldehyde with enhanced activity and racemate stereoselectivity. The modified electrode–electrolyte interface creates an optimal microenvironment for electrocatalysis—it engenders dipolar interaction with the reaction intermediate, giving a 2.2-fold higher reaction rate (from 0.13 to 0.28 mmol h−1 cm−2); Moreover, it repels interfacial water and modulates the conformational specificity of reaction intermediate by facilitating intermolecular hydrogen bonding, affording 2.5-fold higher diastereomeric ratio of racemate to mesomer (from 0.73 to 1.82). We expect that the microenvironment regulation strategy will lead to the advanced design of electrode–electrolyte interface for enhanced activity and (stereo)selectivity that mimics enzymes.
Stress-induced red nucleus attenuation induces anxiety-like behavior and lymph node CCL5 secretion
Authors: Shi Dong-Dong , Zhang Ying-Dan , Zhang Sen , Liao Bing-Bing , Chu Min-Yi , Su Shanshan , Zhuo Kaiming , Hu Hao , Zhang Chen , Wang Zhen
Published: October 2023

Previous studies have speculated that brain activity directly controls immune responses in lymphoid organs. However, the upstream brain regions that control lymphoid organs and how they interface with lymphoid organs to produce stress-induced anxiety-like behavior remain elusive. Using stressed human participants and rat models, we show that CCL5 levels are increased in stressed individuals compared to controls. Stress-inducible CCL5 is mainly produced from cervical lymph nodes (CLN). Retrograde tracing from CLN identifies glutamatergic neurons in the red nucleus (RN), the activities of which are tightly correlated with CCL5 levels and anxiety-like behavior in male rats. Ablation or chemogenetic inhibition of RN glutamatergic neurons increases anxiety levels and CCL5 expression in the serum and CLNs, whereas pharmacogenetic activation of these neurons reduces anxiety levels and CCL5 synthesis after restraint stress exposure. Chemogenetic inhibition of the projection from primary motor cortex to RN elicits anxiety-like behavior and CCL5 synthesis. This brain-lymph node axis provides insights into lymph node tissue as a stress-responsive endocrine organ.
PhysiBoSS 2.0: a sustainable integration of stochastic Boolean and agent-based modelling frameworks
Authors: Ponce-de-Leon Miguel , Montagud Arnau , Noël Vincent , Meert Annika , Pradas Gerard , Barillot Emmanuel , Calzone Laurence , Valencia Alfonso
Published: October 2023

In systems biology, mathematical models and simulations play a crucial role in understanding complex biological systems. Different modelling frameworks are employed depending on the nature and scales of the system under study. For instance, signalling and regulatory networks can be simulated using Boolean modelling, whereas multicellular systems can be studied using agent-based modelling. Herein, we present PhysiBoSS 2.0, a hybrid agent-based modelling framework that allows simulating signalling and regulatory networks within individual cell agents. PhysiBoSS 2.0 is a redesign and reimplementation of PhysiBoSS 1.0 and was conceived as an add-on that expands the PhysiCell functionalities by enabling the simulation of intracellular cell signalling using MaBoSS while keeping a decoupled, maintainable and model-agnostic design. PhysiBoSS 2.0 also expands the set of functionalities offered to the users, including custom models and cell specifications, mechanistic submodels of substrate internalisation and detailed control over simulation parameters. Together with PhysiBoSS 2.0, we introduce PCTK, a Python package developed for handling and processing simulation outputs, and generating summary plots and 3D renders. PhysiBoSS 2.0 allows studying the interplay between the microenvironment, the signalling pathways that control cellular processes and population dynamics, suitable for modelling cancer. We show different approaches for integrating Boolean networks into multi-scale simulations using strategies to study the drug effects and synergies in models of cancer cell lines and validate them using experimental data. PhysiBoSS 2.0 is open-source and publicly available on GitHub with several repositories of accompanying interoperable tools.
Climate change exacerbates nutrient disparities from seafood
Authors: Cheung William W. L. , Maire Eva , Oyinlola Muhammed A. , Robinson James P. W. , Graham Nicholas A. J. , Lam Vicky W. Y. , MacNeil M. Aaron , Hicks Christina C.
Published: October 2023

Seafood is an important source of bioavailable micronutrients supporting human health, yet it is unclear how micronutrient production has changed in the past or how climate change will influence its availability. Here combining reconstructed fisheries databases and predictive models, we assess nutrient availability from fisheries and mariculture in the past and project their futures under climate change. Since the 1990s, availabilities of iron, calcium and omega-3 from seafood for direct human consumption have increased but stagnated for protein. Under climate change, nutrient availability is projected to decrease disproportionately in tropical low-income countries that are already highly dependent on seafood-derived nutrients. At 4 oC of warming, nutrient availability is projected to decline by ~30% by 2100 in low income countries, while at 1.5–2.0 oC warming, decreases are projected to be ~10%. We demonstrate the importance of effective mitigation to support nutritional security of vulnerable nations and global health equity.
The molecular basis of drug selectivity for α5 subunit-containing GABAA receptors
Authors: Kasaragod Vikram Babu , Malinauskas Tomas , Wahid Ayla A. , Lengyel Judith , Knoflach Frederic , Hardwick Steven W. , Jones Charlotte F. , Chen Wan-Na , Lucas Xavier , El Omari Kamel , Chirgadze Dimitri Y. , Aricescu A. Radu , Cecere Giuseppe , Hernandez Maria-Clemencia , Miller Paul S.
Published: October 2023

α5 subunit-containing γ-aminobutyric acid type A (GABAA) receptors represent a promising drug target for neurological and neuropsychiatric disorders. Altered expression and function contributes to neurodevelopmental disorders such as Dup15q and Angelman syndromes, developmental epilepsy and autism. Effective drug action without side effects is dependent on both α5-subtype selectivity and the strength of the positive or negative allosteric modulation (PAM or NAM). Here we solve structures of drugs bound to the α5 subunit. These define the molecular basis of binding and α5 selectivity of the β-carboline, methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), type II benzodiazepine NAMs, and a series of isoxazole NAMs and PAMs. For the isoxazole series, each molecule appears as an ‘upper’ and ‘lower’ moiety in the pocket. Structural data and radioligand binding data reveal a positional displacement of the upper moiety containing the isoxazole between the NAMs and PAMs. Using a hybrid molecule we directly measure the functional contribution of the upper moiety to NAM versus PAM activity. Overall, these structures provide a framework by which to understand distinct modulator binding modes and their basis of α5-subtype selectivity, appreciate structure–activity relationships, and empower future structure-based drug design campaigns.
A novel approach for predicting upstream regulators (PURE) that affect gene expression
Authors: Nguyen Tuan-Minh , Craig Douglas B. , Tran Duc , Nguyen Tin , Draghici Sorin
Published: October 2023

External factors such as exposure to a chemical, drug, or toxicant (CDT), or conversely, the lack of certain chemicals can cause many diseases. The ability to identify such causal CDTs based on changes in the gene expression profile is extremely important in many studies. Furthermore, the ability to correctly infer CDTs that can revert the gene expression changes induced by a given disease phenotype is a crucial step in drug repurposing. We present an approach for Predicting Upstream REgulators (PURE) designed to tackle this challenge. PURE can correctly infer a CDT from the measured expression changes in a given phenotype, as well as correctly identify drugs that could revert disease-induced gene expression changes. We compared the proposed approach with four classical approaches as well as with the causal analysis used in Ingenuity Pathway Analysis (IPA) on 16 data sets (1 rat, 5 mouse, and 10 human data sets), involving 8 chemicals or drugs. We assessed the results based on the ability to correctly identify the CDT as indicated by its rank. We also considered the number of false positives, i.e. CDTs other than the correct CDT that were reported to be significant by each method. The proposed approach performed best in 11 out of the 16 experiments, reporting the correct CDT at the very top 7 times. IPA was the second best, reporting the correct CDT at the top 5 times, but was unable to identify the correct CDT at all in 5 out of the 16 experiments. The validation results showed that our approach, PURE, outperformed some of the most popular methods in the field. PURE could effectively infer the true CDTs responsible for the observed gene expression changes and could also be useful in drug repurposing applications.
Identifying target areas for risk-based surveillance and control of transboundary animal diseases: a seasonal analysis of slaughter and live-trade cattle movements in Uganda
Authors: González-Gordon Lina , Porphyre Thibaud , Muwonge Adrian , Nantima Noelina , Ademun Rose , Ochwo Sylvester , Mwiine Norbert Frank , Boden Lisa , Muhanguzi Dennis , Bronsvoort Barend Mark de C.
Published: October 2023

Animal movements are a major driver for the spread of Transboundary Animal Diseases (TADs). These movements link populations that would otherwise be isolated and hence create opportunities for susceptible and infected individuals to meet. We used social network analysis to describe the seasonal network structure of cattle movements in Uganda and unravel critical network features that identify districts or sub-regions for targeted risk-based surveillance and intervention. We constructed weighted, directed networks based on 2019 between-district cattle movements using official livestock mobility data; the purpose of the movement (‘slaughter’ vs. ‘live trade’) was used to subset the network and capture the risks more reliably. Our results show that cattle trade can result in local and long-distance disease spread in Uganda. Seasonal variability appears to impact the structure of the network, with high heterogeneity of node and edge activity identified throughout the seasons. These observations mean that the structure of the live trade network can be exploited to target influential district hubs within the cattle corridor and peripheral areas in the south and west, which would result in rapid network fragmentation, reducing the contact structure-related trade risks. Similar exploitable features were observed for the slaughter network, where cattle traffic serves mainly slaughter hubs close to urban centres along the cattle corridor. Critically, analyses that target the complex livestock supply value chain offer a unique framework for understanding and quantifying risks for TADs such as Foot-and-Mouth disease in a land-locked country like Uganda. These findings can be used to inform the development of risk-based surveillance strategies and decision making on resource allocation. For instance, vaccine deployment, biosecurity enforcement and capacity building for stakeholders at the local community and across animal health services with the potential to limit the socio-economic impact of outbreaks, or indeed reduce their frequency.
Cytotoxicity, mutagenicity and genotoxicity of electronic cigarettes emission aerosols compared to cigarette smoke: the REPLICA project
Authors: Emma Rosalia , Fuochi Virginia , Distefano Alfio , Partsinevelos Konstantinos , Rust Sonja , Zadjali Fahad , Al Tobi Mohammed , Zadjali Razan , Alharthi Zaina , Pulvirenti Roberta , Furneri Pio Maria , Polosa Riccardo , Sun Ang , Caruso Massimo , Li Volti Giovanni ,   the Replica Project Group, Li Volti Giovanni , Caruso Massimo , Emma Rosalia , Giordano Antonio , Sun Ang , Volarevic Vladislav , Lesmana Ronny , Poulas Konstantinos , Distefano Alfio , Partsinevelos Konstantinos , Pulvirenti Roberta , Costa Aurora , Arsenijevic Aleksandar , Barliana Melisa I. , Mesiakaris Konstantinos , Albalushi Najwa , Giardina Chiara , Furnari Salvatore
Published: October 2023

Concerns have recently increased that the integrity of some scientific research is questionable due to the inability to reproduce the claimed results of some experiments and thereby confirm that the original researcher's conclusions were justified. This phenomenon has been described as 'reproducibility crisis' and affects various fields from medicine to basic applied sciences. In this context, the REPLICA project aims to replicate previously conducted in vitro studies on the toxicity of cigarette smoke and e-cigarette aerosol, sometimes adding experiments or conditions where necessary, in order to verify the robustness and replicability of the data. In this work the REPLICA Team replicated biological and toxicological assessment published by Rudd and colleagues in 2020. As in the original paper, we performed Neutral Red Uptake (NRU) assay for the evaluation of cytotoxicity, Ames test for the evaluation of mutagenesis and In Vitro Micronuclei (IVMN) assay for the evaluation of genotoxicity on cells treated with cigarette smoke or e-cigarette aerosol. The results showed high cytotoxicity, mutagenicity and genotoxicity induced by cigarette smoke, but slight or no cytotoxic, mutagenic and genotoxic effects induced by the e-cigarette aerosol. Although the two studies presented some methodological differences, the findings supported those previously presented by Rudd and colleagues.
Observation of momentum-dependent charge density wave gap in a layered antiferromagnet $${\textrm{Gd}}{\textrm{Te}}_{3}$$
Authors: Regmi Sabin , Bin Elius Iftakhar , Sakhya Anup Pradhan , Jeff Dylan , Sprague Milo , Mondal Mazharul Islam , Jarrett Damani , Valadez Nathan , Agosto Alexis , Romanova Tetiana , Chu Jiun-Haw , Khondaker Saiful I. , Ptok Andrzej , Kaczorowski Dariusz , Neupane Madhab
Published: October 2023

Charge density wave (CDW) ordering has been an important topic of study for a long time owing to its connection with other exotic phases such as superconductivity and magnetism. The $$R{\textrm{Te}}_{3}$$

R

Te
3

(R = rare-earth elements) family of materials provides a fertile ground to study the dynamics of CDW in van der Waals layered materials, and the presence of magnetism in these materials allows to explore the interplay among CDW and long range magnetic ordering. Here, we have carried out a high-resolution angle-resolved photoemission spectroscopy (ARPES) study of a CDW material $${\textrm{Gd}}{\textrm{Te}}_{3}$$

Gd

Te
3

, which is antiferromagnetic below $$\sim \mathrm {12~K}$$

∼

12

K

, along with thermodynamic, electrical transport, magnetic, and Raman measurements. Our ARPES data show a two-fold symmetric Fermi surface with both gapped and ungapped regions indicative of the partial nesting. The gap is momentum dependent, maximum along $${\overline{\Gamma }}-\mathrm{\overline{Z}}$$

Γ
¯

-

Z
¯

and gradually decreases going towards $${\overline{\Gamma }}-\mathrm{\overline{X}}$$

Γ
¯

-

X
¯

. Our study provides a platform to study the dynamics of CDW and its interaction with other physical orders in two- and three-dimensions.
Psychometric investigation of the gamification Hexad user types scale with Brazilian Portuguese adolescents speakers
Authors: Santos Ana Cláudia Guimarães , Muramatsu Pedro Kenzo , Oliveira Wilk , Joaquim Sivaldo , Hamari Juho , Isotani Seiji
Published: October 2023

Gamification has been applied in different fields over the last years, impacting the development of technologies, services, and products towards a more game-like world. Albeit its success, some results indicated personal differences influencing the success of its application, leading to the creation of user models (e.g., Hexad), a way to represent user profiles in gamified environments. Even though a great effort has been made to create and discuss instruments to represent these user models, many of them lack investigation into their psychometric properties. At the same time, although gamification can be particularly interesting in engaging adolescents, few attempts analyzed instruments considering this population. Addressing this lack, in this study, we evaluated the psychometric properties of the gamification Hexad scale in Brazilian Portuguese considering a sample ($$N = 110$$

N
=
110

) of adolescents aged between 13 and 16 years old. Through a quantitative study (i.e., confirmatory factor analysis and correlation), we analyzed the psychometric properties of the scale and the correlations between user types when using data collected from adolescents. Results demonstrated that the current version of the scale needs improvements to better assess the user types of the Brazilian adolescent population, especially regarding the Disruptor user type. Also, the user types presented fewer correlations when compared with the adult sample. At the same time that the results of this study can be used in the academy and industry as a source of measurement of user types from Brazilian adolescents, it also opens several possibilities for new studies in personalized gamification considering this population.
High-resolution geoelectrical characterization and monitoring of natural fluids emission systems to understand possible gas leakages from geological carbon storage reservoirs
Authors: Salone Rosanna , De Paola Claudio , Carbonari Rolando , Rufino Francesco , Avino Rosario , Caliro Stefano , Cuoco Emilio , Santi Alessandro , Di Maio Rosa
Published: October 2023

Gas leakage from deep geologic storage formations to the Earth’s surface is one of the main hazards in geological carbon sequestration and storage. Permeable sediment covers together with natural pathways, such as faults and/or fracture systems, are the main factors controlling surface leakages. Therefore, the characterization of natural systems, where large amounts of natural gases are released, can be helpful for understanding the effects of potential gas leaks from carbon dioxide storage systems. In this framework, we propose a combined use of high-resolution geoelectrical investigations (i.e. resistivity tomography and self-potential surveys) for reconstructing shallow buried fracture networks in the caprock and detecting preferential gas migration pathways before it enters the atmosphere. Such methodologies appear to be among the most suitable for the research purposes because of the strong dependence of the electrical properties of water-bearing permeable rock, or unconsolidated materials, on many factors relevant to CO2storage (i.e. porosity, fracturing, water saturation, etc.). The effectiveness of the suggested geoelectrical approach is tested in an area of natural gas degassing (mainly CH4) located in the active fault zone of the Bolle della Malvizza (Southern Apennines,Italy), which could represent a natural analogue of gas storage sites due to the significant thicknesses (hundreds of meters) of impermeable rock (caprock) that is generally required to prevent carbon dioxide stored at depth from rising to the surface. The obtained 3D geophysical model, validated by the good correlation with geochemical data acquired in the study area and the available geological information, provided a structural and physical characterization of the investigated subsurface volume. Moreover, the time variations of the observed geophysical parameters allowed the identification of possible migration pathways of fluids to the surface.
A large-scale comparison of human-written versus ChatGPT-generated essays
Authors: Herbold Steffen , Hautli-Janisz Annette , Heuer Ute , Kikteva Zlata , Trautsch Alexander
Published: October 2023

ChatGPT and similar generative AI models have attracted hundreds of millions of users and have become part of the public discourse. Many believe that such models will disrupt society and lead to significant changes in the education system and information generation. So far, this belief is based on either colloquial evidence or benchmarks from the owners of the models—both lack scientific rigor. We systematically assess the quality of AI-generated content through a large-scale study comparing human-written versus ChatGPT-generated argumentative student essays. We use essays that were rated by a large number of human experts (teachers). We augment the analysis by considering a set of linguistic characteristics of the generated essays. Our results demonstrate that ChatGPT generates essays that are rated higher regarding quality than human-written essays. The writing style of the AI models exhibits linguistic characteristics that are different from those of the human-written essays. Since the technology is readily available, we believe that educators must act immediately. We must re-invent homework and develop teaching concepts that utilize these AI models in the same way as math utilizes the calculator: teach the general concepts first and then use AI tools to free up time for other learning objectives.
Prediction method for the truck's fault time in open-pit mines based on exponential smoothing neural network
Authors: Liu Wei , Sun Jiayang , Huang Jinbiao , Liu Guangwei , Bai Runcai
Published: October 2023

The transport truck is one of the important equipment for open-pit mines, and predicting the truck's fault time is of great significance in improving the economic benefits of open-pit mines. In this paper, we discuss the reason for the large prediction error of the exponential smoothing method. Then, we propose a novel nonlinear exponential smoothing method (ESNN) for predicting the truck's fault time, and demonstrate the equivalence between our approach and the neural network structure. Finally, based on the augmented Lagrange function, the solving method of ESNN is proposed. We conduct experiments on real-world datasets and our results demonstrate the effectiveness of ESNN in comparison to existing state-of-the-art methods. Our approach makes it easier for maintenance personnel to predict fault situations in advance and provides a basis for enterprises to develop preventive maintenance plans.
Novel 3-phenylquinazolin-2,4(1H,3H)-diones as dual VEGFR-2/c-Met-TK inhibitors: design, synthesis, and biological evaluation
Authors: Hassan Abdelfattah , Mosallam Ahmed M. , Ibrahim Amal O. A. , Badr Mohamed , Abdelmonsef Aboubakr H.
Published: October 2023

Multitarget anticancer drugs are more superior than single target drugs regarding patient compliance, drug adverse effects, drug-drug interactions, drug resistance as well as pharmaceutical industry economics. Dysregulation of both VEGFR-2 and c-Met tyrosine kinases (TKs) could result in development and progression of different human cancers. Herein, we reported a novel series of 3-phenylquinazolin-2,4(1H,3H)-diones with thiourea moiety as dual VEGFR-2/c-Met TKs. Compared to sorafenib, cabozantinib went behind VEGFR-2 inhibition to target c-Met TK. The dual VEGFR-2/c-Met inhibitory activity of cabozantinib is due to a longer HB domain than that of sorafenib. Based on pharmacophore of cabozantinib analogues, we designed new dual VEGFR-2/c-Met TKs. We synthesized the target compounds via a new single pot three-component reaction. The cytotoxic activity of synthesized compounds was conducted against HCT-116 colorectal cancer cell line. Compounds 3c and 3e exhibited the highest cytotoxic activity against HCT-116 cell line (IC50 1.184 and 3.403 µM, respectively). The in vitro enzyme inhibitory activity was carried out against both VEGFR-2 and c-Met TKs. Compound 3e has the highest inhibitory activity against both VEGFR-2/c-Met (IC50 = 83 and 48 nM, respectively). Docking studies showed that α-oxo moiety in quinazoline ring formed hydrogen bond HB with Met1160 residue in the adenine region of c-Met TK.
Primary breast tumor induced extracellular matrix remodeling in premetastatic lungs
Authors: Cai Ruoqing , Tressler Caitlin M. , Cheng Menglin , Sonkar Kanchan , Tan Zheqiong , Paidi Santosh Kumar , Ayyappan Vinay , Barman Ishan , Glunde Kristine
Published: October 2023

The premetastatic niche hypothesis proposes an active priming of the metastatic site by factors secreted from the primary tumor prior to the arrival of the first cancer cells. We investigated several extracellular matrix (ECM) structural proteins, ECM degrading enzymes, and ECM processing proteins involved in the ECM remodeling of the premetastatic niche. Our in vitro model consisted of lung fibroblasts, which were exposed to factors secreted by nonmalignant breast epithelial cells, nonmetastatic breast cancer cells, or metastatic breast cancer cells. We assessed ECM remodeling in vivo in premetastatic lungs of female mice growing orthotopic primary breast tumor xenografts, as compared to lungs of control mice without tumors. Premetastatic lungs contained significantly upregulated Collagen (Col) Col4A5, matrix metalloproteinases (MMPs) MMP9 and MMP14, and decreased levels of MMP13 and lysyl oxidase (LOX) as compared to control lungs. These in vivo findings were consistent with several of our in vitro cell culture findings, which showed elevated Col14A1, Col4A5, glypican-1 (GPC1) and decreased Col5A1 and Col15A1 for ECM structural proteins, increased MMP2, MMP3, and MMP14 for ECM degrading enzymes, and decreased LOX, LOXL2, and prolyl 4-hydroxylase alpha-1 (P4HA1) for ECM processing proteins in lung fibroblasts conditioned with metastatic breast cancer cell media as compared to control. Taken together, our data show that premetastatic priming of lungs by primary breast tumors resulted in significant ECM remodeling which could facilitate metastasis by increasing interstitial fibrillar collagens and ECM stiffness (Col14A1), disruptions of basement membranes (Col4A5), and formation of leaky blood vessels (MMP2, MMP3, MMP9, and MMP14) to promote metastasis.
Circulating DNA and frequency of colorectal cancer brain metastases in a presumed high-risk group
Authors: Callesen Louise Bach , Boysen Anders Kindberg , Andersen Rikke Fredslund , Dalby Rikke Beese , Spindler Karen-Lise Garm
Published: October 2023

This explorative prospective observational pilot study investigated if suggested risk factors, rectal cancer and lung metastases, could add to a relevant detection rate of asymptomatic brain metastases (BM) from colorectal cancer (CRC). Secondary, prognostic biological aspects were investigated by translational analysis of plasma samples. The study enrolled patients with rectal cancer and lung metastases. At inclusion, patients underwent a standard MRI scan of the brain. Cell-free DNA (cfDNA) level was measured by a direct fluorescence assay (DFA), and circulating tumor DNA (ctDNA) by ddPCR. BM was detected in one of twenty-nine included patients. Patients had higher cfDNA levels than healthy subjects (p < 0.01). Patients with the primary tumor in situ had higher cfDNA levels than those with resected primary tumor (p < 0.01). Patients with liver involvement had higher cfDNA levels (p = 0.12) and circulating tumor DNA levels (p = 0.01) than those without liver involvement. In conclusion, the modest incidence of BM does not justify routine MRI of the brain in this selected population. cfDNA by DFA could be a valuable tool when planning treatment and follow-up for CRC patients. Future studies should focus on identifying further characteristics and biomarkers associated with a high risk of BM, enhancing the possibility for early intervention.
Alzheimer’s disease: new insight in assessing of amyloid plaques morphologies using multifractal geometry based on Naive Bayes optimized by random forest algorithm
Authors: Amin Elshaimaa , Elgammal Yasmina M. , Zahran M. A. , Abdelsalam Mohamed M.
Published: October 2023

Alzheimer’s disease (AD) is a physical illness, which damages a person’s brain; it is the most common cause of dementia. AD can be characterized by the formation of amyloid-beta (Aβ) deposits. They exhibit diverse morphologies that range from diffuse to dense-core plaques. Most of the histological images cannot be described precisely by traditional geometry or methods. Therefore, this study aims to employ multifractal geometry in assessing and classifying amyloid plaque morphologies. The classification process is based on extracting the most descriptive features related to the amyloid-beta (Aβ) deposits using the Naive Bayes classifier. To eliminate the less important features, the Random Forest algorithm has been used. The proposed methodology has achieved an accuracy of 99%, sensitivity of 100%, and specificity of 98.5%. This study employed a new dataset that had not been widely used before.
Experimental investigation and modelling of the mechanical properties of palm oil fuel ash concrete using Scheffe’s method
Authors: Akeke Godwin Adie , Inem Philip-Edidiong Udo , Alaneme George Uwadiegwu , Nyah Efiok Etim
Published: October 2023

This study explores the enhancement of mechanical properties in concrete blended with palm oil fuel ash (POFA) through Scheffe's optimization. The utilization of POFA as supplementary cementitious material in concrete has gained attention for its potential environmental benefits. Utilizing a (5,2) simplex-lattice design, a systematic approach is employed for optimizing mixture proportions based on response parameters. The laboratory tests to evaluate concrete's mechanical behavior were conducted using the computed mixture ratios from the design experimental points after 28 days of hydration. The results showed maximum flexural strength at 8.84 N/mm2and compressive strength at 31.16 N/mm2, achieved with a mix of 0.65:0.54:2.3:3.96:0.35 for cement, water, coarse aggregate, fine aggregate, and POFA. Additionally, maximum splitting tensile strength reached 8.84 N/mm2with a mix of 0.62:0.55:2.09:3.86:0.38 for the same components. Conversely, the minimum flexural, splitting tensile and compressive strength within the experimental factor space was 4.25, 2.08 and 19.82 N/mm2respectively. The results obtained indicated a satisfactory mechanical strength performance at POFA replacement of 35 percent in the concrete mixture. The developed mathematical model was statistically validated using analysis of variance (ANOVA) at a 95% confidence interval which showed satisfactory prediction performance. The findings from this study provide valuable insights into optimizing POFA-blended concrete for enhanced mechanical performance, offering potential sustainable solutions for the construction industry.
Clinical usefulness of urinary biomarkers for early prediction of acute kidney injury in patients undergoing transaortic valve implantation
Authors: Obata Yumi , Kamijo-Ikemori Atsuko , Shimmi Sachi , Inoue Soichiro
Published: October 2023

This study aimed to reveal the clinical usefulness of urinary biomarkers for the early prediction of AKI onset after transcatheter aortic valve implantation (TAVI) (n = 173). In this study, 22 (12.7%) patients had AKI, of which 21 had mild AKI and 1 had moderate AKI. Higher levels of urinary liver-type fatty acid binding protein (L-FABP), [tissue inhibitor of metalloproteinases-2] × [insulin-like growth factor-binding protein 7], clusterin and urinary albumin before, after and 4 h after TAVI were associated with AKI onset. However, the time point of higher urinary N-acetyl-β-d-glucosaminidase levels related to AKI onset was only before TAVI. No significant differences were found in the area under the receiver-operator characteristic curves (AUC) for predicting AKI onset between urinary biomarkers before TAVI. After TAVI, the AUC (0.81) of urinary albumin was significantly higher than those of any other urinary biomarkers. The sensitivity (0.86) in urinary albumin after TAVI and specificity (0.98) in urinary L-FABP before TAVI were the highest among urinary biomarkers. In conclusion, urinary biomarkers may be clinically useful for early differentiation of patients with a higher or lower risk for AKI onset or early prediction of post-TAVI onset of AKI.
Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma
Authors: Wu Qinjuan , Li Xin , Long Menghong , Xie Xianfeng , Liu Qing
Published: October 2023

Histone lysine lactylation (Kla) plays a vital role in the tumorigenesis of hepatocellular carcinoma (HCC). Hence, we focused on Kla-specific genes to select novel therapeutic targets. Differentially expressed Kla-specific genes (DEKlaGs) were identified from TCGA with the cut-off criteria |log2(FlodChange (FC))| > 2, p-value < 0.05, following investigating the prognostic value. The correlation between lactate accumulation and prognostic DEKlaGs expression was further investigated. On the other hand, we explored the roles of Kla activation in the immune microenvironment, immunotherapy, and drug resistance. We conducted gene set enrichment analysis (GSEA) to predict the pathways influenced by Kla. The predictive power of Cox model was further identified in ICGC and GEO databases. A total of 129 DEKlaGs were identified, and 32 molecules might be potential prognostic biomarkers. A Cox model including ARHGEF37, MTFR2, NR6A1, NT5DC2, OSBP2, RNASEH2A, SFN, and UNC119B was constructed, which suggested unfavorable overall survival in high-risk score group, and risk score could serve as an indicator for large tumor size, poor pathological grade and advanced stage. NR6A1, OSBP2 and UNC119B could inhibit NK cell as well as TIL cell infiltration, and impair Type-I and II IFN responses in HCC, thereby contributing to unsatisfactory prognosis and immunotherapy resistance. OSBP2 and UNC119B were identified to be related to chemotherapy resistance. GSEA showed that WNT, MTOR, MAPK and NOTCH signaling pathways were activated, indicating that these pathways might play a crucial role during the Kla process. On the other hand, we showed that NR6A1 and OSBP2 were overexpressed in GEO. OSBP2 and UNC119B contributed to poor survival and advanced stage in ICGC. In summary, histone Kla was related to HCC prognosis and might serve as an independent biomarker. NR6A1, OSBP2 and UNC119B were associated with the prognosis, immunotherapy, and chemotherapy resistance, suggesting that NR6A1, OSBP2 and UNC119B might be novel candidate therapeutic targets for HCC.
Discovering golden ratio in the world’s first five-agent network in ancient China
Authors: Yang Ciann-Dong
Published: October 2023

The world’s first five-agent network, also called Wuxing network in ancient China, had been fully established in the second century BC. Surprisingly, the key to cracking the operation of Wuxing network is the golden ratio, the world’s most astonishing number originating from ancient Greece. Wuxing network is composed of five agents located on the vertices of a pentagon such that adjacent agents cooperate with each other, while spaced-apart agents oppose each other. Although it was proposed more than 2000 years ago, it is still an unparalleled network operation protocol. This article reveals the role of the golden ratio in the balance and stability of Wuxing network, and demonstrates how to detect the golden ratio experimentally in Wuxing electronic circuits and in Wuxing formation flight of drones.
Synthesis and physicochemical characterization of carbon quantum dots produced from folic acid
Authors: Fawaz Walaa , Hasian Jameela , Alghoraibi Ibrahim
Published: October 2023

The rising interest in carbon dots (c-dots) is driven by their remarkable potential in the field of biomedical applications. This is due to their distinctive and adjustable photoluminescence characteristics, outstanding physicochemical properties, excellent photostability, and biocompatibility. Herein, carbon dots were successfully produced via the heat synthesis method and characterization for physical and chemical properties using UV–Vis spectrophotometer, photoluminescence spectroscopy, Fourier Transform Infrared and Raman spectroscopy, Energy-dispersive X-ray analysis, and quantum yield. The resulting carbon dots exhibited a distinct blue fluorescence upon exposure to ultraviolet radiation with a 366 nm wavelength. The photoluminescence spectrum of carbon dots displayed a fluorescence peak around 470 nm when excited with a 325 nm wavelength. The synthesized carbon dots demonstrated thermal stability and maintained photoluminescence intensity under different pH conditions, including neutral and alkaline mediums, and good salt resistance ability. Raman spectroscopy confirmed the presence of structural defects within the carbon dots, which are associated with the presence of hybrid groups on their surface. Fourier-transform infrared analysis detected various carbon-bonded, nitrogen-bonded, and oxygen-bonded units. The quantum yield was around 8.9%. These findings from our experiments indicate that the manufactured carbon dots possess substantial promise for a wide range of applications within the biotechnology field.
Achieving quantitative reproducibility in label-free multisite DIA experiments through multirun alignment
Authors: Gupta Shubham , Sing Justin C. , Röst Hannes L.
Published: October 2023

DIA is a mainstream method for quantitative proteomics, but consistent quantification across multiple LC-MS/MS instruments remains a bottleneck in parallelizing data acquisition. One reason for this inconsistency and missing quantification is the retention time shift which current software does not adequately address for runs from multiple sites. We present multirun chromatogram alignment strategies to map peaks across columns, including the traditional reference-based Star method, and two novel approaches: MST and Progressive alignment. These reference-free strategies produce a quantitatively accurate data-matrix, even from heterogeneous multi-column studies. Progressive alignment also generates merged chromatograms from all runs which has not been previously achieved for LC-MS/MS data. First, we demonstrate the effectiveness of multirun alignment strategies on a gold-standard annotated dataset, resulting in a threefold reduction in quantitation error-rate compared to non-aligned DIA results. Subsequently, on a multi-species dataset that DIAlignR effectively controls the quantitative error rate, improves precision in protein measurements, and exhibits conservative peak alignment. We next show that the MST alignment reduces cross-site CV by 50% for highly abundant proteins when applied to a dataset from 11 different LC-MS/MS setups. Finally, the reanalysis of 949 plasma runs with multirun alignment revealed a more than 50% increase in insulin resistance (IR) and respiratory viral infection (RVI) proteins, identifying 11 and 13 proteins respectively, compared to prior analysis without it. The three strategies are implemented in our DIAlignR workflow (>2.3) and can be combined with linear, non-linear, or hybrid pairwise alignment.
PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy
Authors: Dou Xuefeng , Fu Qiang , Long Qilai , Liu Shuning , Zou Yejun , Fu Da , Xu Qixia , Jiang Zhirui , Ren Xiaohui , Zhang Guilong , Wei Xiaoling , Li Qingfeng , Campisi Judith , Zhao Yuzheng , Sun Yu
Published: October 2023

Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. Senescent cells display a PDK4-dependent increase in aerobic glycolysis and enhanced lactate production but maintain mitochondrial respiration and redox activity, thus adopting a special form of metabolic reprogramming. Medium from PDK4+ stromal cells promotes the malignancy of recipient cancer cells in vitro, whereas inhibition of PDK4 causes tumor regression in vivo. We find that lactate promotes reactive oxygen species production via NOX1 to drive the senescence-associated secretory phenotype, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype. In preclinical trials, PDK4 inhibition alleviates physical dysfunction and prevents age-associated frailty. Together, our study confirms the hypercatabolic nature of senescent cells and reveals a metabolic link between cellular senescence, lactate production, and possibly, age-related pathologies, including but not limited to cancer.
Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia
Authors: Bruedigam Claudia , Porter Amy H. , Song Axia , Vroeg in de Wei Gerjanne , Stoll Thomas , Straube Jasmin , Cooper Leanne , Cheng Guidan , Kahl Vivian F. S. , Sobinoff Alexander P. , Ling Victoria Y. , Jebaraj Billy Michael Chelliah , Janardhanan Yashaswini , Haldar Rohit , Bray Laura J. , Bullinger Lars , Heidel Florian H. , Kennedy Glen A. , Hill Michelle M. , Pickett Hilda A. , Abdel-Wahab Omar , Hartel Gunter , Lane Steven W.
Published: October 2023

Telomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transcriptomics and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized phase II-like preclinical trial in patient-derived xenografts, imetelstat effectively diminishes AML burden and preferentially targets subgroups containing mutant NRAS and oxidative stress-associated gene expression signatures. Unbiased, genome-wide CRISPR/Cas9 editing identifies ferroptosis regulators as key mediators of imetelstat efficacy. Imetelstat promotes the formation of polyunsaturated fatty acid-containing phospholipids, causing excessive levels of lipid peroxidation and oxidative stress. Pharmacological inhibition of ferroptosis diminishes imetelstat efficacy. We leverage these mechanistic insights to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing substantial disease control in AML.
Assessment of collagen content in fish skin – development of a flow analysis method for hydroxyproline determination
Authors: Melo Maria M. P. , Mesquita Raquel B. R. , Coscueta Ezequiel R. , Pintado Manuela E. , Rangel António O. S. S.
Published: October 2023

Flow injection method for the quantification of hydroxyproline to corelate with collagen content in blue shark skin.
Water vapour induced structural flexibility in a square lattice coordination network
Authors: Koupepidou Kyriaki , Bezrukov Andrey A. , Castell Dominic C. , Sensharma Debobroto , Mukherjee Soumya , Zaworotko Michael J.
Published: October 2023

Herein, we introduce a new square lattice topology coordination network, sql-(1,3-bib)(ndc)-Ni, with three types of connection and detail its gas and vapour induced phase transformations.
A phosphate tolerant Pt-based oxygen reduction catalyst enabled by synergistic modulation of alloying and surface modification
Authors: Long Daojun , Xie Zhenyang , Wang Minjian , Chen Siguo , Wei Zidong
Published: October 2023

The oxygen reduction reaction activity and phosphate tolerance of Pt were improved by the alloying effect of Co and by surface modification of MoOx, respectively.
Rotational spectra and semi-experimental structures of furonitrile and its water cluster
Authors: Melosso Mattia , Alessandrini Silvia , Spada Lorenzo , Melli Alessio , Wang Xiujuan , Zheng Yang , Duan Chunguo , Li Jiayi , Du Weiping , Gou Qian , Bizzocchi Luca , Dore Luca , Barone Vincenzo , Puzzarini Cristina
Published: October 2023

Rotational spectroscopy together with quantum chemistry led to the spectroscopic and structural characterization of 2- and 3-furonitrile. Rotational spectra of four different intermolecular water adducts have also been investigated.
Revealing the mechanism of damage to the carbonate ester in PADC polymeric nuclear track detector using low-energy electron stimulated desorption
Authors: Kusumoto Tamon , Fromm Michel , Cloutier Pierre , Bass Andrew D , Sanche Léon , Kodaira Satoshi
Published: October 2023

We investigate the mechanism of damage to the carbonate ester chemical functions in Poly allyl diglycol carbonate induced by low-energy electrons of <50 eV, which are major components of the initial secondary products of ionizing radiation.
Low temperature NH3 regeneration of a sulfur poisoned Pt/Al2O3 monolith catalyst
Authors: Fang Chenhao , Harold Michael P.
Published: October 2023

Sulfur poisoning is a ubiquitous challenge in diesel emission control.
Bulky, electron-rich, renewable: analogues of Beller's phosphine for cross-couplings
Authors: van der Westhuizen Danielle , Castro Abril C. , Hazari Nilay , Gevorgyan Ashot
Published: October 2023

We have harnessed biomass-derived molecules to create sustainable phosphine ligands for catalysis. These renewable ligands exhibit high activity in Pd-catalyzed cross-couplings, opening new avenues for the late-stage modification of pharmaceuticals.
Synthesis and structural features of indium(iii) furan-2-thiocarboxylates showing efficient catalytic activity toward multicomponent reactions via Knoevenagel condensation
Authors: Kumar Krishna , Kumar Sahani Raj , Garai Somenath , Bhattacharya Subrato
Published: October 2023

Furan-2-thiocarboxylate complexes of In(iii) were synthesized. Partial Hydrolysis of a complex led to the first In(iii) complex with a hydrosulfide ligand. A thioester was obtained serendipitously. Complexes were used as catalysts for Knoevenagel and Knoevenagel initiated MCRs.
Zn/N/S Co-doped hierarchical porous carbon as a high-efficiency oxygen reduction catalyst in Zn–air batteries
Authors: Liu Mincong , Zhang Jing , Ye Guohua , Peng Yan , Guan Shiyou
Published: October 2023

Zn/N/S co doped hierarchical porous carbon exhibits excellent performance as an oxygen reduction catalyst for zinc air batteries.
Photochemical conversion of nitrate to ammonium ions by a newly developed photo-reductive titanium dioxide catalyst: implications on nitrogen recovery
Authors: Sanchez Andrew , Ye Zuyang , Yin Yadong , Liu Haizhou
Published: October 2023

Global nitrate contamination in source water poses a threat to both natural ecosystems and public health. Application of diethylene glycol (DEG) ligand-doped titanium dioxide nanoparticles serves to photo-reductively convert nitrate to ammonium.
Development of sodium alginate–aloe vera hydrogel films enriched with organic fibers: study of the physical, mechanical, and barrier properties for food-packaging applications
Authors: Hadi Alina , Nawab Anjum , Alam Feroz , Naqvi Sara
Published: October 2023

Hydrogels from a botanical origin can be beneficially utilized in the development of edible and biodegradable food-packaging films.
Association between whole-grain consumption and carotid atherosclerosis: the Tianjin chronic low-grade systemic inflammation and health (TCLSIH) cohort study
Authors: Meng Ge , Yao Jiping , Li Jiaoyang , Gu Yeqing , Wu Hongmei , Zhang Qing , Liu Li , Wang Xuena , Zhang Juanjuan , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Niu Kaijun
Published: October 2023

Whole-grain contains beneficial nutrients that play a role in preventing chronic diseases. The study demonstrate that whole-grain consumption had no significant association with the risk of carotid atherosclerosis in an adult Chinese population.