bluuebunny/crossref_metadata_2025 huggingface dataset:
A universal metabolite repair enzyme removes a strong inhibitor of the TCA cycle
Authors: Zmuda Anthony J. , Kang Xiaojun , Wissbroecker Katie B. , Freund Saxhaug Katrina , Costa Kyle C. , Hegeman Adrian D. , Niehaus Thomas D.
Published: January 2024

A prevalent side-reaction of succinate dehydrogenase oxidizes malate to enol-oxaloacetate (OAA), a metabolically inactive form of OAA that is a strong inhibitor of succinate dehydrogenase. We purified from cow heart mitochondria an enzyme (OAT1) with OAA tautomerase (OAT) activity that converts enol-OAA to the physiological keto-OAA form, and determined that it belongs to the highly conserved and previously uncharacterized Fumarylacetoacetate_hydrolase_domain-containing protein family. From all three domains of life, heterologously expressed proteins were shown to have strong OAT activity, and ablating the OAT1 homolog caused significant growth defects. In Escherichia coli, expression of succinate dehydrogenase was necessary for OAT1-associated growth defects to occur, and ablating OAT1 caused a significant increase in acetate and other metabolites associated with anaerobic respiration. OAT1 increased the succinate dehydrogenase reaction rate by 35% in in vitro assays with physiological concentrations of both succinate and malate. Our results suggest that OAT1 is a universal metabolite repair enzyme that is required to maximize aerobic respiration efficiency by preventing succinate dehydrogenase inhibition.
FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress
Authors: Tischler Jessica D. , Tsuchida Hiroshi , Bosire Rosevalentine , Oda Tommy T. , Park Ana , Adeyemi Richard O.
Published: January 2024

Homologous recombination (HR) plays critical roles in repairing lesions that arise during DNA replication and is thus essential for viability. RAD51 plays important roles during replication and HR, however, how RAD51 is regulated downstream of nucleofilament formation and how the varied RAD51 functions are regulated is not clear. We have investigated the protein c1orf112/FLIP that previously scored in genome-wide screens for mediators of DNA inter-strand crosslink (ICL) repair. Upon ICL agent exposure, FLIP loss leads to marked cell death, elevated chromosomal instability, increased micronuclei formation, altered cell cycle progression and increased DNA damage signaling. FLIP is recruited to damage foci and forms a complex with FIGNL1. Both proteins have epistatic roles in ICL repair, forming a stable complex. Mechanistically, FLIP loss leads to increased RAD51 amounts and foci on chromatin both with or without exogenous DNA damage, defective replication fork progression and reduced HR competency. We posit that FLIP is essential for limiting RAD51 levels on chromatin in the absence of damage and for RAD51 dissociation from nucleofilaments to properly complete HR. Failure to do so leads to replication slowing and inability to complete repair.
A nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota
Authors: Liu Tao , Chai Shuang , Li Mingyang , Chen Xu , Xie Yutao , Zhao Zehui , Xie Jingjing , Yu Yunpeng , Gao Feng , Zhu Feng , Yang Lihua
Published: January 2024

Infection by Helicobacter pylori, a prevalent global pathogen, currently requires antibiotic-based treatments, which often lead to antimicrobial resistance and gut microbiota dysbiosis. Here, we develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, in conjunction with localized ultrasound exposure of a dosage permissible for ultrasound medical devices. This study reveals dual functionality of Ver-PLGA@Lecithin. It effectively neutralizes vacuolating cytotoxin A, a key virulence factor secreted by H. pylori, even in the absence of ultrasound. When coupled with ultrasound exposure, it inactivates H. pylori by generating reactive oxygen species, offering a potential solution to overcome antimicrobial resistance. In female mouse models bearing H. pylori infection, this sonodynamic therapy performs comparably to the standard triple therapy in reducing gastric infection. Significantly, unlike the antibiotic treatments, the sonodynamic therapy does not negatively disrupt gut microbiota, with the only major impact being upregulation of Lactobacillus, which is a bacterium widely used in yogurt products and probiotics. This study presents a promising alternative to the current antibiotic-based therapies for H. pylori infection, offering a reduced risk of antimicrobial resistance and minimal disturbance to the gut microbiota.
Structural and biochemical insights into the mechanism of the Gabija bacterial immunity system
Authors: Huo Yanwu , Kong Lingfei , Zhang Ye , Xiao Min , Du Kang , Xu Sunyuntao , Yan Xiaoxue , Ma Jun , Wei Taotao
Published: January 2024

The Gabija system is a newly discovered bacterial immune system that consists of GajA and GajB. Here we report the cryo-EM structure of the Gabija complex from Bacillus cereus VD045 at 3.6 Å, which provides the direct evidence of interactions between GajA and GajB. The Gabija complex is an octameric ring structure with four GajA and four GajB. GajA is an OLD nucleases family protein, while GajB belongs to the SF1 helicases. The Gabija complex has sequence-specific DNA nuclease activity and prefers circular rather than linear DNA as substrate, its activity is more sensitive to concentrations change of nucleotides compared to GajA alone. Our data suggest a mechanism of Gabija immunity: the nuclease activity of Gabija complex is inhibited under physiological conditions, while it is activated by depletion of NTP and dNTP upon the replication and transcription of invading phages and cleave the circular DNA to prevent phage DNA replication.
Efficient conversion of propane in a microchannel reactor at ambient conditions
Authors: Li Chunsong , Zhang Haochen , Liu Wenxuan , Sheng Lin , Cheng Mu-Jeng , Xu Bingjun , Luo Guangsheng , Lu Qi
Published: January 2024

The oxidative dehydrogenation of propane, primarily sourced from shale gas, holds promise in meeting the surging global demand for propylene. However, this process necessitates high operating temperatures, which amplifies safety concerns in its application due to the use of mixed propane and oxygen. Moreover, these elevated temperatures may heighten the risk of overoxidation, leading to carbon dioxide formation. Here we introduce a microchannel reaction system designed for the oxidative dehydrogenation of propane within an aqueous environment, enabling highly selective and active propylene production at room temperature and ambient pressure with mitigated safety risks. A propylene selectivity of over 92% and production rate of 19.57 mmol mCu−2 h−1 are simultaneously achieved. This exceptional performance stems from the in situ creation of a highly active, oxygen-containing Cu catalytic surface for propane activation, and the enhanced propane transfer via an enlarged gas-liquid interfacial area and a reduced diffusion path by establishing a gas-liquid Taylor flow using a custom-made T-junction microdevice. This microchannel reaction system offers an appealing approach to accelerate gas-liquid-solid reactions limited by the solubility of gaseous reactant.
A genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice
Authors: Greiss Ferdinand , Lardon Nicolas , Schütz Leonie , Barak Yoav , Daube Shirley S. , Weinhold Elmar , Noireaux Vincent , Bar-Ziv Roy
Published: January 2024

Realizing genetic circuits on single DNA molecules as self-encoded dissipative nanodevices is a major step toward miniaturization of autonomous biological systems. A circuit operating on a single DNA implies that genetically encoded proteins localize during coupled transcription-translation to DNA, but a single-molecule measurement demonstrating this has remained a challenge. Here, we use a genetically encoded fluorescent reporter system with improved temporal resolution and observe the synthesis of individual proteins tethered to a DNA molecule by transient complexes of RNA polymerase, messenger RNA, and ribosome. Against expectations in dilute cell-free conditions where equilibrium considerations favor dispersion, these nascent proteins linger long enough to regulate cascaded reactions on the same DNA. We rationally design a pulsatile genetic circuit by encoding an activator and repressor in feedback on the same DNA molecule. Driven by the local synthesis of only several proteins per hour and gene, the circuit dynamics exhibit enhanced variability between individual DNA molecules, and fluctuations with a broad power spectrum. Our results demonstrate that co-expressional localization, as a nonequilibrium process, facilitates single-DNA genetic circuits as dissipative nanodevices, with implications for nanobiotechnology applications and artificial cell design.
Transgenic expression of cif genes from Wolbachia strain wAlbB recapitulates cytoplasmic incompatibility in Aedes aegypti
Authors: McNamara Cameron J. , Ant Thomas H. , Harvey-Samuel Tim , White-Cooper Helen , Martinez Julien , Alphey Luke , Sinkins Steven P.
Published: January 2024

The endosymbiotic bacteria Wolbachia can invade insect populations by modifying host reproduction through cytoplasmic incompatibility (CI), an effect that results in embryonic lethality when Wolbachia-carrying males mate with Wolbachia-free females. Here we describe a transgenic system for recreating CI in the major arbovirus vector Aedes aegypti using CI factor (cif) genes from wAlbB, a Wolbachia strain currently being deployed to reduce dengue transmission. CI-like sterility is induced when cifA and cifB are co-expressed in testes; this sterility is rescued by maternal cifA expression, thereby reproducing the pattern of Wolbachia-induced CI. Expression of cifB alone is associated with extensive DNA damage and disrupted spermatogenesis. The strength of rescue by maternal cifA expression is dependent on the comparative levels of cifA/cifB expression in males. These findings are consistent with CifB acting as a toxin and CifA as an antitoxin, with CifA attenuating CifB toxicity in both the male germline and in developing embryos. These findings provide important insights into the interactions between cif genes and their mechanism of activity and provide a foundation for the building of a cif gene-based drive system in Ae. aegypti.
Ultrafast Bragg coherent diffraction imaging of epitaxial thin films using deep complex-valued neural networks
Authors: Yu Xi , Wu Longlong , Lin Yuewei , Diao Jiecheng , Liu Jialun , Hallmann Jörg , Boesenberg Ulrike , Lu Wei , Möller Johannes , Scholz Markus , Zozulya Alexey , Madsen Anders , Assefa Tadesse , Bozin Emil S. , Cao Yue , You Hoydoo , Sheyfer Dina , Rosenkranz Stephan , Marks Samuel D. , Evans Paul G. , Keen David A. , He Xi , Božović Ivan , Dean Mark P. M. , Yoo Shinjae , Robinson Ian K.
Published: January 2024

Domain wall structures form spontaneously due to epitaxial misfit during thin film growth. Imaging the dynamics of domains and domain walls at ultrafast timescales can provide fundamental clues to features that impact electrical transport in electronic devices. Recently, deep learning based methods showed promising phase retrieval (PR) performance, allowing intensity-only measurements to be transformed into snapshot real space images. While the Fourier imaging model involves complex-valued quantities, most existing deep learning based methods solve the PR problem with real-valued based models, where the connection between amplitude and phase is ignored. To this end, we involve complex numbers operation in the neural network to preserve the amplitude and phase connection. Therefore, we employ the complex-valued neural network for solving the PR problem and evaluate it on Bragg coherent diffraction data streams collected from an epitaxial La2-xSrxCuO4 (LSCO) thin film using an X-ray Free Electron Laser (XFEL). Our proposed complex-valued neural network based approach outperforms the traditional real-valued neural network methods in both supervised and unsupervised learning manner. Phase domains are also observed from the LSCO thin film at an ultrafast timescale using the complex-valued neural network.
Soft, full Wheatstone bridge 3D pressure sensors for cardiovascular monitoring
Authors: Park Yoonseok , Luan Haiwen , Kwon Kyeongha , Chung Ted S. , Oh Seyong , Yoo Jae-Young , Chung Gooyoon , Kim Junha , Kim Suhyeon , Kwak Sung Soo , Choi Junhwan , Phan Hoang-Phuong , Yoo Seonggwang , Jeong Hyoyoung , Shin Jaeho , Won Sang Min , Yoon Hong-Joon , Jung Yei Hwan , Rogers John A.
Published: January 2024

Variations in parameters associated with the ambient environment can introduce noise in soft, body-worn sensors. For example, many piezoresistive pressure sensors exhibit a high degree of sensitivity to fluctuations in temperature, thereby requiring active compensation strategies. The research presented here addresses this challenge with a multilayered 3D microsystem design that integrates four piezoresistive sensors in a full-Wheatstone bridge configuration. An optimized layout of the sensors relative to the neutral mechanical plane leads to both an insensitivity to temperature and an increased sensitivity to pressure, relative to previously reported devices that rely on similar operating principles. Integrating this 3D pressure sensor into a soft, flexible electronics platform yields a system capable of real-time, wireless measurements from the surface of the skin. Placement above the radial and carotid arteries yields high-quality waveforms associated with pulsatile blood flow, with quantitative correlations to blood pressure. The results establish the materials and engineering aspects of a technology with broad potential in remote health monitoring.
Multidimensional well-being of US households at a fine spatial scale using fused household surveys
Authors: Ummel Kevin , Poblete-Cazenave Miguel , Akkiraju Karthik , Graetz Nick , Ashman Hero , Kingdon Cora , Herrera Tenorio Steven , Singhal Aaryaman Sunny , Cohen Daniel Aldana , Rao Narasimha D.
Published: January 2024

Social science often relies on surveys of households and individuals. Dozens of such surveys are regularly administered by the U.S. government. However, they field independent, unconnected samples with specialized questions, limiting research questions to those that can be answered by a single survey. The presented data comprise the fusion onto the American Community Survey (ACS) microdata of select donor variables from the Residential Energy Consumption Survey (RECS) of 2015, the National Household Travel Survey (NHTS) of 2017, the American Housing Survey (AHS) of 2019, and the Consumer Expenditure Survey - Interview (CEI) for the years 2015–2019. This results in an integrated microdataset of household attributes and well-being dimensions that can be analyzed to address research questions in ways that are not currently possible. The underlying statistical techniques, designed under the fusionACS project, are included in an open-sourceRpackage, fusionModel, that provides generic tools for the creation, analysis, and validation of fused microdata.
Clinical and immunological relevance of SLAMF6 expression in the tumor microenvironment of breast cancer and melanoma
Authors: Oba Takaaki , Long Mark D. , Ito Ken-ichi , Ito Fumito
Published: January 2024

Compelling evidence shows that the frequency of T cells in the tumor microenvironment correlates with prognosis as well as response to immunotherapy. However, considerable heterogeneity exists within tumor-infiltrating T cells, and significance of their genomic and transcriptomic landscape on clinical outcomes remains to be elucidated. Signaling lymphocyte activation molecule 6 (SLAMF6) is expressed on intra-tumoral progenitor-exhausted T cells, which exhibit the capacity to proliferate, self-renew and produce terminally-exhausted T cells in pre-clinical models and patients. Here, we investigated the impact of SLAMF6 expression on prognosis in two immunologically different tumor types using publicly available databases. Our findings demonstrate that high SLAMF6 expression is associated with better prognosis, expression of TCF7 (encoding T-cell factor 1), and increased gene signatures associated with conventional type 1 dendritic cells and effector function of T cells in melanoma and breast cancer. Single-cell profiling of breast cancer tumor microenvironment reveals SLAMF6 expression overlaps CD8 T cells with a T-effector signature, which includes subsets expressing TCF7, memory and effector-related genes, analogous to progenitor-exhausted T cells. These findings illustrate the significance of SLAMF6 in the tumor as a marker for better effector responses, and provide insights into the predictive and prognostic determinants for cancer patients.
A concentrated machine learning-based classification system for age-related macular degeneration (AMD) diagnosis using fundus images
Authors: Abd El-Khalek Aya A. , Balaha Hossam Magdy , Alghamdi Norah Saleh , Ghazal Mohammed , Khalil Abeer T. , Abo-Elsoud Mohy Eldin A. , El-Baz Ayman
Published: January 2024

The increase in eye disorders among older individuals has raised concerns, necessitating early detection through regular eye examinations. Age-related macular degeneration (AMD), a prevalent condition in individuals over 45, is a leading cause of vision impairment in the elderly. This paper presents a comprehensive computer-aided diagnosis (CAD) framework to categorize fundus images into geographic atrophy (GA), intermediate AMD, normal, and wet AMD categories. This is crucial for early detection and precise diagnosis of age-related macular degeneration (AMD), enabling timely intervention and personalized treatment strategies. We have developed a novel system that extracts both local and global appearance markers from fundus images. These markers are obtained from the entire retina and iso-regions aligned with the optical disc. Applying weighted majority voting on the best classifiers improves performance, resulting in an accuracy of 96.85%, sensitivity of 93.72%, specificity of 97.89%, precision of 93.86%, F1 of 93.72%, ROC of 95.85%, balanced accuracy of 95.81%, and weighted sum of 95.38%. This system not only achieves high accuracy but also provides a detailed assessment of the severity of each retinal region. This approach ensures that the final diagnosis aligns with the physician’s understanding of AMD, aiding them in ongoing treatment and follow-up for AMD patients.
A retrospective study of inpatients diagnosed with degloving skin and soft tissue injuries
Authors: Yu Shao-shuo , Zhu Zhe , Fang He , Jiang Yao-nan , Tang Chen-qi , Shi Ying , Gan Lan-xia , Tang Hong-tai , Wang Hai-bo , Sun Yu , Xia Zhao-fan
Published: January 2024

The overall picture of degloving skin and soft tissue injuries (DSTI) remains a blank space in China. Therefore, a retrospective study was designed to summarize the current situation of this injury. Patients diagnosed with DSTI hospitalized between 2013 and 2018 were identified from the Hospital Quality Monitoring System (HQMS) database, of whom demographics, injury characteristics, hospitalization and cost information were analyzed. A total of 62,709 patients were enrolled in this study. Male sex predominated, with a mean age of 43.01 ± 19.70 years. Peasants seemed to be the most vulnerable. East China and Hubei province had the most patients. The most and least frequently injured anatomic site were lower extremity and torso, respectively. Traffic-related accidents and summer accounted for the highest proportion in terms of injury mechanism and season. The operation rate of DSTI roughly showed a growing trend, and the average length of stay was 22.02 ± 29.73 days. At discharge, 0.93% of DSTI patients ended up in death. Medicine accounted mostly for hospitalization cost, while the proportion decreased year by year. More than half DSTI patients paid at their own charge. This study made a relatively detailed description of DSTI patients nationwide, and might provide enlightenments for better prevention and treatment.
Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury
Authors: Rossignol Guillaume , Muller Xavier , Brunet Thomas Alexandre , Bidault Valeska , Hervieu Valerie , Clement Yohann , Ayciriex Sophie , Mabrut Jean-Yves , Salvador Arnaud , Mohkam Kayvan
Published: January 2024

Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion. The BA pool in bile samples was analyzed with liquid chromatography coupled with tandem mass spectrometry. We identified 16 BA and observed significant changes in response to ischemia-reperfusion, which were associated with both protective and injury mechanisms. Second, HOPE-treated liver grafts exhibited a more protective BA phenotype, characterized by a more hydrophilic BA pool compared to SCS. Key BA, such as GlycoCholic Acid, were identified and were associated with a decreased transaminase release and improved lactate clearance during reperfusion. Partial Least Square-Discriminant Analysis revealed a distinct injury profile for the HOPE group. In conclusion, the BA pool changes with liver graft IRI, and preservation with HOPE results in a protective BA phenotype compared to SCS.
A Wilkinson power divider with harmonic suppression through low-pass filter for GSM and LTE applications
Authors: Mohammadi Nariman , Moloudian Gholamhosein , Roshani Saeed , Roshani Sobhan , Parandin Fariborz , Lalbakhsh Ali
Published: January 2024

Conventional Wilkinson power dividers (WPDs) perform satisfactorily near the intended operation frequency. Nonetheless, these WPDs demonstrate subpar performance in the stopband and necessitate a significant physical space. To enhance the existing level of advancement and in order to improve on the current state-of-the-art, a modified WPD is designed and fabricated, demonstrating a significant improvement in stopband and superior isolation between output ports. To improve the stopband and suppress unwanted harmonics, a low-pass filter (LPF) structure is placed in the both branches of the conventional WPD. The proposed modified WPD depicts a wide stopband bandwidth (fSB > 17.25 GHz) from 2.75 to over 20 GHz with an attenuation level of 20 dB, suppressing 2nd to 11th harmonics. According to measured results, the input return loss (|S11|), insertion loss (|S21|) and output isolation (|S32|) at f = 1.8 GHz are better than 33 dB, 3.2 dB and 21 dB, respectively. Indeed, the proposed modified WPD exhibits a magnitude imbalance of 0.00018, a phase imbalance of 1.25 degrees and a group delay of 0.5 ns. The proposed WPD depicts a compact size of 35 mm × 25 mm (0.38 λg × 0.27 λg), where λg is the guided wavelength at f = 1.8 GHz. There is a good agreement between the simulated and measured results. According to the obtained results, the proposed modified WPD shows a desirable performance for modern LTE and GSM communication applications.
Occurrence and temporal overlap of sympatric jungle cats and leopard cats in Parsa‒Koshi Complex, Nepal
Authors: Sharma Hari Prasad , Bhattarai Bishnu Prasad , Regmi Sandeep , Bhandari Shivish , Adhikari Dipendra , Aryal Bishnu , Tamang Krishna , Nepali Amrit , K. C. Sabin , Rawal Basudha , Parajuli Sagar , Baral Bashu Dev , Devkota Surya , Koirala Sabina , Belant Jerrold L. , Katuwal Hem Bahadur
Published: January 2024

Co-occurrence and spatial and temporal overlap of sympatric jungle and leopard cats are influenced by habitat preferences, and interspecific competition. Understanding these factors influence is crucial for developing effective conservation strategies. We conducted a camera survey in Parsa‒Koshi Complex (PKC), Nepal during December 2022–March 2023 to investigate factors influencing occupancy and spatial and temporal overlap between jungle cats (Felis chaus) and leopard cats (Prionailurus bengalensis). The mean detection probability (t = 0.664,p = 0.507) did not differ between jungle cats (p = 0.500 ± 0.289) and leopard cats (p = 0.501 ± 0.288); however, occupancy (t = 31.008,p < 0.001) was greater for jungle cats (ψ = 0.247 ± 0.020) than leopard cats (ψ = 0.178 ± 0.019). Jungle cats and leopard cats were positively associated with large predators, and jungle cats were positively associated with human presence and negatively associated with canopy cover. We observed high diel overlap between leopard cats and jungle cats (Dhat1 = 0.802, norm0CI: 0.720–0.884), with both species largely nocturnal. Co-existence of jungle cats and leopard cats in PKC appears to be facilitated by spatial segregation. These findings provide valuable insights into the complex ecological dynamics and interactions between sympatric jungle and leopard cats.
Boosting Solanum tuberosum resistance to Alternaria solani through green synthesized ferric oxide (Fe2O3) nanoparticles
Authors: Anwaar Sadaf , Ijaz Dur-e-Shahwar , Anwar Tauseef , Qureshi Huma , Nazish Moona , Alrefaei Abdulwahed Fahad , Almutairi Mikhlid H. , Alharbi Sultan N.
Published: January 2024

Potato (Solanum tuberosum) is the third crucial global crop facing threats from Alternaria solani, a necrotrophic fungal pathogen causing early blight disease. Beyond crop impact, it leads to substantial production reduction and economic losses worldwide. This study introduces a green synthesis method for producing Ferric Oxide nanoparticles (FNPs) using dried Guava (Psidium guajava) leaves. Guava leaf extract acts as a reducing agent, with iron (III) chloride hexahydrate (FeCl3·6H2O) as the oxidizing agent. This study employed various characterization techniques for Ferric Oxide nanoparticles (FNPs). Fourier Transform Infrared Spectroscopy (FTIR) revealed peaks at 877 cm−1, 1180 cm−1, 1630 cm−1, 1833 cm−1, 2344 cm−1, and 3614 cm−1, associated with Maghemite vibrations, polyphenol compounds, and amino acids. UV–Vis spectroscopy exhibited a characteristic absorbance peak at 252 nm for FNPs. Scanning Electron Microscope (SEM) images illustrated particle sizes of 29-41 nm, and Energy Dispersive Spectroscopy (EDS) indicated elemental composition. X-ray diffraction (XRD) confirmed crystalline FNPs with peaks at 26.78, 30.64, 36.06, 38.21, 43.64, 53.52, 57.42, 63.14 and 78.32. Disease resistance assays demonstrated FNPs’ effectiveness against A. solani, reducing disease incidence and severity. In the leaf detach assay, concentrations of 15, 10 and 5 mg/L showed a dose-dependent reduction in disease severity and incidence. The Greenhouse Assay confirmed FNPs’ concentration-dependent effect on disease incidence and severity. The study also explored FNPs’ potential as biocontrol agents showing no adverse effects on overall plant development. Additionally, the study highlighted the agronomic potential of FNPs in enhancing plant growth and development emphasizing their role as micronutrients in biofortification. The findings suggest the promising application of FNPs in plant protection and biofortification strategies.
Light pollution disrupts circadian clock gene expression in two mosquito vectors during their overwintering dormancy
Authors: Fyie Lydia R. , Westby Katie M. , Meuti Megan E.
Published: January 2024

Artificial light at night (ALAN) is an increasingly important form of environmental disturbance as it alters Light:Dark cycles that regulate daily and seasonal changes in physiology and phenology. The Northern house mosquito (Culex pipiens) and the tiger mosquito (Aedes albopictus) enter an overwintering dormancy known as diapause that is cued by short days. These two species differ in diapause strategy: Cx. pipiens diapause as adult females while Ae. albopictus enter a maternally-programmed, egg diapause. Previous studies found that ALAN inhibits diapause in both species, but the mechanism is unknown. As the circadian clock is implicated in the regulation of diapause in many insects, we examined whether exposure to ALAN altered the daily expression of core circadian cloc genes (cycle, Clock, period, timeless, cryptochrome 1, cryptochrome 2, and Par domain protein 1) in these two species when reared under short-day, diapause-inducing conditions. We found that exposure to ALAN altered the abundance of several clock genes in adult females of both species, but that clock gene rhythmicity was maintained for most genes. ALAN also had little effect on clock gene abundance in mature oocytes that were dissected from female Ae. albopictus that were reared under short day conditions. Our findings indicate that ALAN may inhibit diapause initiation through the circadian clock in two medically-important mosquitoes.
Determinants of household adoption of clean energy with its rural–urban disparities in Bangladesh
Authors: Haq Iqramul , Khan Maruf , Chakma Sharanon , Hossain Md. Ismail , Sarkar Shuvongkar , Rejvi Md. Rayhan Ali , Salauddin Md. , Sarker Md Mizanur Rahman
Published: January 2024

This study aims to investigate factors influencing the adoption of clean energy among households in Bangladesh, using Blinder-Oaxaca decomposition and extended probit regression model with data from the 2019 Bangladesh multiple indicator cluster survey. Small households, primarily Muslim and urban dwellers, who speak the Bengali language and are Internet and mobile users, were likelier to adopt cleaner fuels than their counterparts. On the contrary, households residing in the Barisal, Khulna, Rajshahi, and Rangpur divisions, belonging to poor and middle-class households, with household heads aged 15–64 and without formal education, were less likely to adopt cleaner fuels than their counterparts. The concentration curve revealed socioeconomic inequality in the adoption of clean energy, particularly favouring richer households in urban and rural areas. Further analysis using the Blinder-Oaxaca decomposition showed that urban residents showed a higher probability of adopting clean energy, with a significant difference of 0.508 compared to rural areas. Regarding the endowment effect, poor wealth quintile contributed the most, followed by the ownership of rented dwellings and the middle wealth quintile. The Bengali differential effect made the largest contribution to this aspect of the disparity, followed by the exposure of the Internet and the influence of the Dhaka and Chattogram divisions. The detailed analysis provides valuable insights for policymakers and practitioners on the issue of disparities in the adoption of clean energy between urban and rural areas in Bangladesh.
Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs
Authors: Abd El-Hafeez Tarek , Shams Mahmoud Y. , Elshaier Yaseen A. M. M. , Farghaly Heba Mamdouh , Hassanien Aboul Ella
Published: January 2024

Combination therapy is a fundamental strategy in cancer chemotherapy. It involves administering two or more anti-cancer agents to increase efficacy and overcome multidrug resistance compared to monotherapy. However, drug combinations can exhibit synergy, additivity, or antagonism. This study presents a machine learning framework to classify and predict cancer drug combinations. The framework utilizes several key steps including data collection and annotation from the O’Neil drug interaction dataset, data preprocessing, stratified splitting into training and test sets, construction and evaluation of classification models to categorize combinations as synergistic, additive, or antagonistic, application of regression models to predict combination sensitivity scores for enhanced predictions compared to prior work, and the last step is examination of drug features and mechanisms of action to understand synergy behaviors for optimal combinations. The models identified combination pairs most likely to synergize against different cancers. Kinase inhibitors combined with mTOR inhibitors, DNA damage-inducing drugs or HDAC inhibitors showed benefit, particularly for ovarian, melanoma, prostate, lung and colorectal carcinomas. Analysis highlighted Gemcitabine, MK-8776 and AZD1775 as frequently synergizing across cancer types. This machine learning framework provides a valuable approach to uncover more effective multi-drug regimens.
Cycle threshold of SARS-CoV-2 RT-PCR as a driver of retesting
Authors: Markewitz Robert , Dargvainiene Justina , Junker Ralf , Wandinger Klaus-Peter
Published: January 2024

SARS-CoV-2 RT-PCR is a critical and, at times, limited resource. Frequent Retesting of patients may strain testing infrastructure unduly. Recommendations that include cycle threshold (Ct) cutoffs may incentivize early retesting when the Ct value is reported. We aimed to investigate patterns of retesting in association with initial Ct-values. We performed a retrospective analysis of RT-PCR results (including Ct-values) for patients from whom ≥ 2 samples were collected within 14 days, the first of which had to be positive. We calculated absolute and baseline-corrected kinetics of Ct-values over time, as well as the median initial Ct-values in dependence of the timing of the first retesting and the time until RT-PCR negativity for SARS-CoV-2. Retesting after an initial positive SARS-CoV-2 RT-PCR was most commonly performed on day 7, with patients being retested as early as day 1. The majority of patients retested within 14 days remained SARS-CoV-2 positive in the RT-PCR. Baseline-corrected Ct-values showed a quasi-linear increase over 14 days since the initial positive result. Both the timing until the first retesting and until RT-PCR negativity were inversely correlated with the initial Ct-value. The timing of retesting after a positive SARS-CoV-2 RT-PCR appears to be significantly influenced by the initial Ct-value. Although it can be assumed that Ct-values will increase steadily over time, strategies that rely on rigid Ct-cutoffs should be discussed critically, not only because of methodological caveats but also because of the strain on testing infrastructure caused by the incentive for early retesting that Ct-values apparently represent.
Europe faces up to tenfold increase in extreme fires in a warming climate
Authors: El Garroussi Siham , Di Giuseppe Francesca , Barnard Christopher , Wetterhall Fredrik
Published: January 2024

This study quantifies how changes in temperature and precipitation would influence the intensity and duration of extreme fires across Europe. The analysis explores the impact of a range of climate change projections on fire events compared to a baseline of fire danger, using a 30-year ERA5 reanalysis. The results show that areas in southern Europe could experience a tenfold increase in the probability of catastrophic fires occurring in any given year under a moderate CMIP6 scenario. If global temperatures reach the +2 °C threshold, central and northern Europe will also become more susceptible to wildfires during droughts. The increased probability of fire extremes in a warming climate, in combination with an average one-week extension of the fire season across most countries, would put extra strain on Europe’s ability to cope in the forthcoming decades.
The pseudochiral Fermi surface of α-RuI3
Authors: Louat Alex , Watson Matthew D. , Kim Timur K. , Ni Danrui , Cava Robert J. , Cacho Cephise
Published: January 2024

In continuation of research into RuCl3 and RuBr3 as potential quantum spin liquids, a phase with unique magnetic order characterised by long-range quantum entanglement and fractionalised excitations, the compound RuI3 has been recently synthesised. Here, we show RuI3 is a moderately correlated metal with two bands crossing the Fermi level, implying the absence of any quantum spin liquids phase. We find that the Fermi surface as measured or calculated for a 2D (kx, ky) slice at any kz lacks mirror symmetry, i.e. is pseudochiral. We link this phenomenon to the ABC stacking in the R$$\bar{3}$$

3

¯

space group of α-RuI3, which is achiral but lacks any mirror or glide symmetries. We further provide a formal framework for understanding when such a pseudochiral electronic structure may be observed.
Enhancing polarization transfer from nitrogen-vacancy centers to external nuclear spins via dangling bond mediators
Authors: Espinós Hilario , Munuera-Javaloy Carlos , Panadero Iván , Acedo Pablo , Puebla Ricardo , Casanova Jorge , Torrontegui Erik
Published: January 2024

The use of nitrogen-vacancy (NV) centers in diamond as a non-invasive platform for hyperpolarizing nuclear spins in molecular samples is a promising area of research with the potential to enhance the sensitivity of nuclear magnetic resonance (NMR) experiments. Transferring NV polarization out of the diamond structure has been achieved on nanoscale targets using dynamical nuclear polarization methods, but extending this polarization transfer to relevant NMR volumes poses significant challenges. One major technical hurdle is the presence of paramagnetic defects in the diamond surface which interfere with polarization outflow. However, these defects can be harnessed as intermediaries for the interaction between NVs and nuclear spins. We present a method that benefits from existing microwave sequences, namely the PulsePol, to transfer polarization efficiently and robustly using dangling bonds or other localized electronic spins, with the potential to increase polarization rates under realistic conditions.
Impact of underlying liver disease on unresectable hepatocellular carcinoma treated with immune checkpoint inhibitors
Authors: Wu Y. Linda , Cappuyns Sarah , Loh Amanda , Sun Sean , Lewis Sara , Sung Max W. , Schwartz Myron , Llovet Josep M. , Cohen Deirdre J.
Published: January 2024

Background

Immune checkpoint inhibitors (ICIs) are standard therapy for unresectable HCC, but many patients do not respond. Non-viral HCC, particularly non-alcoholic steatohepatitis (NASH), have been implicated in ICI resistance.

Methods

We reviewed 288 patients with unresectable HCC who received ICI from 1/2017 to 12/2021. The overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between patients with viral HCC and non-viral HCC were compared using the full and Child Pugh (CP) class A only cohorts.

Results

In total, 206 patients (71.5%) had viral HCC (most HCV), and 82 patients had non-viral HCC. Non-viral HCC was associated with worse OS (HR 1.6, 95% CI: 1.1–2.1, P = 0.006) and PFS (HR 1.5, 95% CI: 1.2–2, P = 0.002) in univariate but not multivariate analyses. For the CP class A cohort, non-viral HCC was independently associated with worse OS (HR 1.8, 95% CI: 1.2–2.7, P = 0.005) and PFS (HR 1.9, 95% CI: 1.3–2.7, P < 0.001). Viral HCC and CP class A liver disease was associated with better ORR than non-viral HCC (38% vs. 16%, P = 0.001).

Conclusions

Following ICI treatment, non-viral HCC correlated with worse OS, PFS, and ORR than viral HCC, particularly in patients with preserved liver function.
The helicase domain of human Dicer prevents RNAi-independent activation of antiviral and inflammatory pathways
Authors: Baldaccini Morgane , Gaucherand Léa , Chane-Woon-Ming Béatrice , Messmer Mélanie , Gucciardi Floriane , Pfeffer Sébastien
Published: January 2024

In mammalian somatic cells, the relative contribution of RNAi and the type I interferon response during viral infection is unclear. The apparent inefficiency of antiviral RNAi might be due to self-limiting properties and mitigating co-factors of the key enzyme Dicer. In particular, the helicase domain of human Dicer appears to be an important restriction factor of its activity. Here, we study the involvement of several helicase-truncated mutants of human Dicer in the antiviral response. All deletion mutants display a PKR-dependent antiviral phenotype against certain viruses, and one of them, Dicer N1, acts in a completely RNAi-independent manner. Transcriptomic analyses show that many genes from the interferon and inflammatory response pathways are upregulated in Dicer N1 expressing cells. We show that some of these genes are controlled by NF-kB and that blocking this pathway abrogates the antiviral phenotype of Dicer N1. Our findings highlight the crosstalk between Dicer, PKR, and the NF-kB pathway, and suggest that human Dicer may have repurposed its helicase domain to prevent basal activation of antiviral and inflammatory pathways.
Optineurin provides a mitophagy contact site for TBK1 activation
Authors: Yamano Koji , Sawada Momoha , Kikuchi Reika , Nagataki Kafu , Kojima Waka , Endo Ryu , Kinefuchi Hiroki , Sugihara Atsushi , Fujino Tomoshige , Watanabe Aiko , Tanaka Keiji , Hayashi Gosuke , Murakami Hiroshi , Matsuda Noriyuki
Published: January 2024

Tank-binding kinase 1 (TBK1) is a Ser/Thr kinase that is involved in many intracellular processes, such as innate immunity, cell cycle, and apoptosis. TBK1 is also important for phosphorylating the autophagy adaptors that mediate the selective autophagic removal of damaged mitochondria. However, the mechanism by which PINK1-Parkin-mediated mitophagy activates TBK1 remains largely unknown. Here, we show that the autophagy adaptor optineurin (OPTN) provides a unique platform for TBK1 activation. Both the OPTN-ubiquitin and the OPTN-pre-autophagosomal structure (PAS) interaction axes facilitate assembly of the OPTN-TBK1 complex at a contact sites between damaged mitochondria and the autophagosome formation sites. At this assembly point, a positive feedback loop for TBK1 activation is initiated that accelerates hetero-autophosphorylation of the protein. Expression of monobodies engineered here to bind OPTN impaired OPTN accumulation at contact sites, as well as the subsequent activation of TBK1, thereby inhibiting mitochondrial degradation. Taken together, these data show that a positive and reciprocal relationship between OPTN and TBK1 initiates autophagosome biogenesis on damaged mitochondria.
Repurposing an endogenous degradation domain for antibody-mediated disposal of cell-surface proteins
Authors: Schmitt Janika , Poole Emma , Groves Ian , Owen David J , Graham Stephen C , Sinclair John , Kelly Bernard T
Published: January 2024

The exquisite specificity of antibodies can be harnessed to effect targeted degradation of membrane proteins. Here, we demonstrate targeted protein removal utilising a protein degradation domain derived from the endogenous human protein Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9). Recombinant antibodies genetically fused to this domain drive the degradation of membrane proteins that undergo constitutive internalisation and recycling, including the transferrin receptor and the human cytomegalovirus latency-associated protein US28. We term this approach PACTAC (PCSK9-Antibody Clearance-Targeting Chimeras).
Systematic identification of 20S proteasome substrates
Authors: Pepelnjak Monika , Rogawski Rivkah , Arkind Galina , Leushkin Yegor , Fainer Irit , Ben-Nissan Gili , Picotti Paola , Sharon Michal
Published: January 2024

For years, proteasomal degradation was predominantly attributed to the ubiquitin-26S proteasome pathway. However, it is now evident that the core 20S proteasome can independently target proteins for degradation. With approximately half of the cellular proteasomes comprising free 20S complexes, this degradation mechanism is not rare. Identifying 20S-specific substrates is challenging due to the dual-targeting of some proteins to either 20S or 26S proteasomes and the non-specificity of proteasome inhibitors. Consequently, knowledge of 20S proteasome substrates relies on limited hypothesis-driven studies. To comprehensively explore 20S proteasome substrates, we employed advanced mass spectrometry, along with biochemical and cellular analyses. This systematic approach revealed hundreds of 20S proteasome substrates, including proteins undergoing specific N- or C-terminal cleavage, possibly for regulation. Notably, these substrates were enriched in RNA- and DNA-binding proteins with intrinsically disordered regions, often found in the nucleus and stress granules. Under cellular stress, we observed reduced proteolytic activity in oxidized proteasomes, with oxidized protein substrates exhibiting higher structural disorder compared to unmodified proteins. Overall, our study illuminates the nature of 20S substrates, offering crucial insights into 20S proteasome biology.
A high sucrose detection threshold is associated with increased energy intake and improved post-prandial glucose response independent of the sweetness intensity of isocaloric sucrose solutions
Authors: Preinfalk Verena , Schweiger Kerstin , Hüller Leonie , Dunkel Andreas , Kimmeswenger Isabella , Deck Corinna M. , Rust Petra , Somoza Veronika , Krammer Gerhard E. , Ley Jakob P. , Lieder Barbara
Published: January 2024

Several studies proposed a role for the sweet taste receptor in energy intake and blood glucose regulation, but little is yet known about the impact of the individual sweet taste perception. Here, we found in a cross-over human intervention study with 29 male participants that modulating the sweetness of an isocaloric sucrose solution did not influence postprandial plasma concentrations of blood glucose and associated hormones over 120 min and 2 h post-load energy intake. Independent of the sweetness of the test solution, tests persons with a higher sucrose detection threshold had an average of 402 ± 78.8 kcal (39 ± 21%) higher energy intake and a higher glucose/insulin ratio, combined with a higher liking for sweet tasting food, than the test persons of the low threshold group. The body composition suggested a higher fat-free mass in the high threshold group that may have influenced energy intake and post-prandial glucose responses.
Stimuli-responsive Ti3C2Tx MXene-based hydrogels: preparation and applications
Authors: Gao Qi , He Ping-Ping , Wang Xiaowen , Du Xiaoxue , Guo Weiwei
Published: January 2024

MXene-based stimuli-responsive hydrogels have emerged as a new class of smart soft materials and have shown great potential in various applications such as sensing, biomedicine, actuators and energy-related applications.
Serum-based metabolomics reveals the mechanism of action of isorhynchophylline in the intervention of atherosclerosis in ApoE−/− mice
Authors: Wang Lihua , Li Haichao , Zhang Hao , Song Xiayinan , Jiang Haiqiang , Wang Danyang , Wang Yu
Published: January 2024

IRN intervened in AS by modulating glycerophospholipid metabolism, linoleic acid metabolism and alpha-linolenic acid metabolism.
Analysis of tryptophan metabolites and related compounds in human and murine tissue: development and validation of a quantitative and semi-quantitative method using high resolution mass spectrometry
Authors: Abujrais Sandy , Ubhayasekera S. J. Kumari A. , Bergquist Jonas
Published: January 2024

A validated HRMS method for measuring tryptophan metabolites and related compounds has been developed, with simple sample preparation, successfully applied in human and murine plasma, as well as murine white adipose tissue.
A low-temperature self-flux route to prepare hexagonal rare earth fluorides and manipulation of upconversion luminescence in rodlike NaYbF4:Tm3+/Fe3+ crystals
Authors: Huang Xinyang , Liao Min
Published: January 2024

The distorted lattice, ET between Tm3+ and Fe3+ and no ET between Yb3+ and Fe3+ make 89Yb1Tm10Fe crystals obtained in low-temperature self-flux system exhibit the strongest emission with its absolute UCQY of 0.46% and of 0.56% with and without the magnetic field of 15 kOe, respectively.
Ultrafast excited state relaxation dynamics of pyran-based D–π–A systems: solvent polarity controls the triplet state
Authors: Vineetha Pookalavan Karicherry , Govind Chinju , Karunakaran Venugopal , Manoj Narayanapillai
Published: January 2024

The excited state relaxation dynamics of V-shaped D–π–A systems, EAPBA and TPAPBA were investigated using steady-state and time-resolved spectroscopy along with theoretical optimization.
Nuclear quantum effects in gas-phase 2-fluoroethanol
Authors: Arandhara Mrinal , Ramesh Sai G.
Published: January 2024

Path integral simulations reveal the nuclear quantum effects in the dihedral space of 2-fluoroethanol.