bluuebunny/crossref_metadata_2025 huggingface dataset:
Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles
Authors: Faulkes Chris G. , Eykyn Thomas R. , Miljkovic Jan Lj. , Gilbert James D. , Charles Rebecca L. , Prag Hiran A. , Patel Nikayla , Hart Daniel W. , Murphy Michael P. , Bennett Nigel C. , Aksentijevic Dunja
Published: March 2024

The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span.
Expected and unexpected effects after systemic inhibition of Hippo transcriptional output in cancer
Authors: Baroja Isabel , Kyriakidis Nikolaos C. , Halder Georg , Moya Iván M.
Published: March 2024

Hyperactivation of YAP/TAZ, the Hippo pathway downstream effectors, is common in human cancer. The requirement of YAP/TAZ for cancer cell survival in preclinical models, prompted the development of pharmacological inhibitors that suppress their transcriptional activity. However, systemic YAP/TAZ inhibition may sometimes have unpredictable patient outcomes, with limited or even adverse effects because YAP/TAZ action is not simply tumor promoting but also tumor suppressive in some cell types. Here, we review the role of the Hippo pathway in distinct tumor cell populations, discuss the impact of inhibiting Hippo output on tumor growth, and examine current developments in YAP/TAZ inhibitors.
Development and validation of an interpretable model integrating multimodal information for improving ovarian cancer diagnosis
Authors: Xiang Huiling , Xiao Yongjie , Li Fang , Li Chunyan , Liu Lixian , Deng Tingting , Yan Cuiju , Zhou Fengtao , Wang Xi , Ou Jinjing , Lin Qingguang , Hong Ruixia , Huang Lishu , Luo Luyang , Lin Huangjing , Lin Xi , Chen Hao
Published: March 2024

Ovarian cancer, a group of heterogeneous diseases, presents with extensive characteristics with the highest mortality among gynecological malignancies. Accurate and early diagnosis of ovarian cancer is of great significance. Here, we present OvcaFinder, an interpretable model constructed from ultrasound images-based deep learning (DL) predictions, Ovarian–Adnexal Reporting and Data System scores from radiologists, and routine clinical variables. OvcaFinder outperforms the clinical model and the DL model with area under the curves (AUCs) of 0.978, and 0.947 in the internal and external test datasets, respectively. OvcaFinder assistance led to improved AUCs of radiologists and inter-reader agreement. The average AUCs were improved from 0.927 to 0.977 and from 0.904 to 0.941, and the false positive rates were decreased by 13.4% and 8.3% in the internal and external test datasets, respectively. This highlights the potential of OvcaFinder to improve the diagnostic accuracy, and consistency of radiologists in identifying ovarian cancer.
Benchtop mesoSPIM: a next-generation open-source light-sheet microscope for cleared samples
Authors: Vladimirov Nikita , Voigt Fabian F. , Naert Thomas , Araujo Gabriela R. , Cai Ruiyao , Reuss Anna Maria , Zhao Shan , Schmid Patricia , Hildebrand Sven , Schaettin Martina , Groos Dominik , Mateos José María , Bethge Philipp , Yamamoto Taiyo , Aerne Valentino , Roebroeck Alard , Ertürk Ali , Aguzzi Adriano , Ziegler Urs , Stoeckli Esther , Baudis Laura , Lienkamp Soeren S. , Helmchen Fritjof
Published: March 2024

In 2015, we launched the mesoSPIM initiative, an open-source project for making light-sheet microscopy of large cleared tissues more accessible. Meanwhile, the demand for imaging larger samples at higher speed and resolution has increased, requiring major improvements in the capabilities of such microscopes. Here, we introduce the next-generation mesoSPIM (“Benchtop”) with a significantly increased field of view, improved resolution, higher throughput, more affordable cost, and simpler assembly compared to the original version. We develop an optical method for testing detection objectives that enables us to select objectives optimal for light-sheet imaging with large-sensor cameras. The improved mesoSPIM achieves high spatial resolution (1.5 µm laterally, 3.3 µm axially) across the entire field of view, magnification up to 20×, and supports sample sizes ranging from sub-mm up to several centimeters while being compatible with multiple clearing techniques. The microscope serves a broad range of applications in neuroscience, developmental biology, pathology, and even physics.
Decreasing exciton dissociation rates for reduced voltage losses in organic solar cells
Authors: Wu Hongbo , Lu Hao , Li Yungui , Zhou Xin , Zhou Guanqing , Pan Hailin , Wu Hanyu , Feng Xunda , Liu Feng , Vandewal Koen , Tress Wolfgang , Ma Zaifei , Bo Zhishan , Tang Zheng
Published: March 2024

Enhancing the device electroluminescence quantum efficiency (EQEEL) is a critical factor in mitigating non-radiative voltage losses (VNR) and further improving the performance of organic solar cells (OSCs). While the common understanding attributes EQEEL in OSCs to the dynamics of charge transfer (CT) states, persistent efforts to manipulate these decay dynamics have yielded limited results, with the EQEEL of high-efficiency OSCs typically remaining below 10−2%. This value is considerably lower than that observed in high efficiency inorganic photovoltaic devices. Here, we report that EQEEL is also influenced by the dissociation rate constant of singlet states (kDS). Importantly, in contrast to the traditional belief that advocates maximizing kDS for superior photovoltaic quantum efficiency (EQEPV), a controlled reduction in kDS is shown to enhance EQEEL without compromising EQEPV. Consequently, a promising experimental approach to address the VNR challenge is proposed, resulting in a significant improvement in the performance of OSCs.
Anomalous anti-Kasha excited-state luminescence from symmetry-breaking heterogeneous carbon bisnanohoops
Authors: Zhang Xinyu , Chen Cheng , Zhang Wen , Yin Nan , Yuan Bing , Zhuang Guilin , Wang Xiao-Ye , Du Pingwu
Published: March 2024

It is a long-standing scientific controversy to achieve anti-Kasha-type multiple emissions by tuning the structures at a molecular level. Although it is known that some conjugated structures have excitation-dependent multiple emissions, no all-benzenoid molecules have yet been reported, the emissions of which originate from different excited states. Herein, we report the design of two symmetry-breaking heterogeneous carbon bisnanohoops that in solution become multiple fluorescent emitters with unusual anti-Kasha characteristics. This phenomenon can be spectroscopically and theoretically explained and will find applications in a wide range of sensing and imaging technologies.
High-performance ferroelectric field-effect transistors with ultra-thin indium tin oxide channels for flexible and transparent electronics
Authors: Li Qingxuan , Wang Siwei , Li Zhenhai , Hu Xuemeng , Liu Yongkai , Yu Jiajie , Yang Yafen , Wang Tianyu , Meng Jialin , Sun Qingqing , Zhang David Wei , Chen Lin
Published: March 2024

With the development of wearable devices and hafnium-based ferroelectrics (FE), there is an increasing demand for high-performance flexible ferroelectric memories. However, developing ferroelectric memories that simultaneously exhibit good flexibility and significant performance has proven challenging. Here, we developed a high-performance flexible field-effect transistor (FeFET) device with a thermal budget of less than 400 °C by integrating Zr-doped HfO2 (HZO) and ultra-thin indium tin oxide (ITO). The proposed FeFET has a large memory window (MW) of 2.78 V, a high current on/off ratio (ION/IOFF) of over 108, and high endurance up to 2×107 cycles. In addition, the FeFETs under different bending conditions exhibit excellent neuromorphic properties. The device exhibits excellent bending reliability over 5×105 pulse cycles at a bending radius of 5 mm. The efficient integration of hafnium-based ferroelectric materials with promising ultrathin channel materials (ITO) offers unique opportunities to enable high-performance back-end-of-line (BEOL) compatible wearable FeFETs for edge intelligence applications.
Significant enhancement of proton conductivity in solid acid at the monolayer limit
Authors: Zhang Zhangcai , Liang Lixin , Feng Jianze , Hou Guangjin , Ren Wencai
Published: March 2024

Proton transport in nanofluidic channels is not only fundamentally important but also essential for energy applications. Although various strategies have been developed to improve the concentration of active protons in the nanochannels, it remains challenging to achieve a proton conductivity higher than that of Nafion, the benchmark for proton conductors. Here, taking H3Sb3P2O14 and HSbP2O8 as examples, we show that the interactions between protons and the layer frameworks in layered solid acid HnMnZ2O3n+5 are substantially reduced at the monolayer limit, which significantly increases the number of active protons and consequently improves the proton conductivities by ∼8 ‒ 66 times depending on the humidity. The membranes assembled by monolayer H3Sb3P2O14 and HSbP2O8 nanosheets exhibit in-plane proton conductivities of ~ 1.02 and 1.18 S cm−1 at 100% relative humidity and 90 °C, respectively, which are over 5 times higher than the conductivity of Nafion. This work provides a general strategy for facilitating proton transport, which will have broad implications in advancing both nanofluidic research and device applications from energy storage and conversion to neuromorphic computing.
Observation of naturally canalized phonon polaritons in LiV2O5 thin layers
Authors: F. Tresguerres-Mata Ana I. , Lanza Christian , Taboada-Gutiérrez Javier , Matson Joseph. R. , Álvarez-Pérez Gonzalo , Isobe Masahiko , Tarazaga Martín-Luengo Aitana , Duan Jiahua , Partel Stefan , Vélez María , Martín-Sánchez Javier , Nikitin Alexey Y. , Caldwell Joshua D. , Alonso-González Pablo
Published: March 2024

Polariton canalization is characterized by intrinsic collimation of energy flow along a single crystalline axis. This optical phenomenon has been experimentally demonstrated at the nanoscale by stacking and twisting van der Waals (vdW) layers of α-MoO3, by combining α-MoO3 and graphene, or by fabricating an h-BN metasurface. However, these material platforms have significant drawbacks, such as complex fabrication and high optical losses in the case of metasurfaces. Ideally, it would be possible to canalize polaritons “naturally” in a single pristine layer. Here, we theoretically predict and experimentally demonstrate naturally canalized phonon polaritons (PhPs) in a single thin layer of the vdW crystal LiV2O5. In addition to canalization, PhPs in LiV2O5 exhibit strong field confinement ($${{{{{{\boldsymbol{\lambda }}}}}}}_{{{{{{\bf{p}}}}}}} \sim \frac{{{{{{{\boldsymbol{\lambda }}}}}}}_{{{{{{\bf{0}}}}}}}}{{{{{{\bf{27}}}}}}}$$

λ

p

~

λ

0

27

), slow group velocity (0.0015c), and ultra-low losses (lifetimes of 2 ps). Our findings are promising for the implementation of low-loss optical nanodevices where strongly directional light propagation is needed, such as waveguides or optical routers.
Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI
Authors: Molina Jonathan J. , Kohler Kurt N. , Gager Christopher , Andersen Marissa J. , Wongso Ellsa , Lucas Elizabeth R. , Paik Andrew , Xu Wei , Donahue Deborah L. , Bergeron Karla , Klim Aleksandra , Caparon Michael G. , Hultgren Scott J. , Desai Alana , Ploplis Victoria A. , Flick Matthew J. , Castellino Francis J. , Flores-Mireles Ana L.
Published: March 2024

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.
Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases
Authors: Guo Zongxin , Orädd Fredrik , Bågenholm Viktoria , Grønberg Christina , Ma Jian Feng , Ott Peter , Wang Yong , Andersson Magnus , Pedersen Per Amstrup , Wang Kaituo , Gourdon Pontus
Published: March 2024

Copper transporting P-type (P1B-1-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P1B-1-ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P1B-1-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD−1, serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD−1, MBD−2, likely assists in copper delivery to the ATPase core. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, allowing for copper uptake, binding and release. As such, our findings unify previously conflicting data on the transport and regulation of P1B-1-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P1B-1-disorders and ongoing clinical trials.
Insights into the modulation of bacterial NADase activity by phage proteins
Authors: Yin Hang , Li Xuzichao , Wang Xiaoshen , Zhang Chendi , Gao Jiaqi , Yu Guimei , He Qiuqiu , Yang Jie , Liu Xiang , Wei Yong , Li Zhuang , Zhang Heng
Published: March 2024

The Silent Information Regulator 2 (SIR2) protein is widely implicated in antiviral response by depleting the cellular metabolite NAD+. The defense-associated sirtuin 2 (DSR2) effector, a SIR2 domain-containing protein, protects bacteria from phage infection by depleting NAD+, while an anti-DSR2 protein (DSR anti-defense 1, DSAD1) is employed by some phages to evade this host defense. The NADase activity of DSR2 is unleashed by recognizing the phage tail tube protein (TTP). However, the activation and inhibition mechanisms of DSR2 are unclear. Here, we determine the cryo-EM structures of DSR2 in multiple states. DSR2 is arranged as a dimer of dimers, which is facilitated by the tetramerization of SIR2 domains. Moreover, the DSR2 assembly is essential for activating the NADase function. The activator TTP binding would trigger the opening of the catalytic pocket and the decoupling of the N-terminal SIR2 domain from the C-terminal domain (CTD) of DSR2. Importantly, we further show that the activation mechanism is conserved among other SIR2-dependent anti-phage systems. Interestingly, the inhibitor DSAD1 mimics TTP to trap DSR2, thus occupying the TTP-binding pocket and inhibiting the NADase function. Together, our results provide molecular insights into the regulatory mechanism of SIR2-dependent NAD+ depletion in antiviral immunity.
Substrate metabolism in male astronauts onboard the International Space Station: the ENERGY study
Authors: Le Roux Elisa , Zahariev Alexandre , Chery Isabelle , Schoeller Dale A. , Bourdier Pierre , Maillet Alain , Thevenot Cecile , Garnotel Maël , Gauquelin-Koch Guillemette , Van Den Berghe Laurie , Blanc Stéphane , Simon Chantal , Bergouignan Audrey
Published: March 2024

Bedrest shifts fasting and postprandial fuel selection towards carbohydrate use over lipids, potentially affecting astronauts’ performance and health. We investigated whether this change occurs in astronauts after at least 3 months onboard the International Space Station (ISS). We further explored the associations with diet, physical activity (PA), and body composition. Before and during spaceflight, respiratory quotient (RQ), carbohydrate, and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 males (age = 45.7 [SD 7.7] years, BMI = 24.3 [2.1] kg m−²). Postprandial substrate use was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). Food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and PA by accelerometry and diary logs. Spaceflight increased fasting RQ (P = 0.01) and carbohydrate oxidation (P = 0.04) and decreased fasting lipid oxidation (P < 0.01). An increase in FQ (P < 0.001) indicated dietary modifications onboard the ISS. Spaceflight-induced RQ changes adjusted for ground RQ correlated with inflight FQ (P < 0.01). In postprandial conditions, nutrient oxidation and ΔRQ were unaffected on average. Lipid oxidation changes negatively correlated with FFM changes and inflight aerobic exercise and positively with FM changes. The opposite was observed for carbohydrate oxidation. ΔRQ changes were negatively and positively related to FM and FFM changes, respectively. In conclusion, fasting substrate oxidation shift observed during spaceflight may primarily result from dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight PA.
Structural insights into the mechanism of protein transport by the Type 9 Secretion System translocon
Authors: Lauber Frédéric , Deme Justin C. , Liu Xiaolong , Kjær Andreas , Miller Helen L. , Alcock Felicity , Lea Susan M. , Berks Ben C.
Published: March 2024

Secretion systems are protein export machines that enable bacteria to exploit their environment through the release of protein effectors. The Type 9 Secretion System (T9SS) is responsible for protein export across the outer membrane (OM) of bacteria of the phylum Bacteroidota. Here we trap the T9SS of Flavobacterium johnsoniae in the process of substrate transport by disrupting the T9SS motor complex. Cryo-EM analysis of purified substrate-bound T9SS translocons reveals an extended translocon structure in which the previously described translocon core is augmented by a periplasmic structure incorporating the proteins SprE, PorD and a homologue of the canonical periplasmic chaperone Skp. Substrate proteins bind to the extracellular loops of a carrier protein within the translocon pore. As transport intermediates accumulate on the translocon when energetic input is removed, we deduce that release of the substrate–carrier protein complex from the translocon is the energy-requiring step in T9SS transport.
A figure of merit for efficiency roll-off in TADF-based organic LEDs
Authors: Diesing S. , Zhang L. , Zysman-Colman E. , Samuel I. D. W.
Published: March 2024

Organic light-emitting diodes (OLEDs) are a revolutionary light-emitting display technology that has been successfully commercialized in mobile phones and televisions1,2. The injected charges form both singlet and triplet excitons, and for high efficiency it is important to enable triplets as well as singlets to emit light. At present, materials that harvest triplets by thermally activated delayed fluorescence (TADF) are a very active field of research as an alternative to phosphorescent emitters that usually use heavy metal atoms3,4. Although excellent progress has been made, in most TADF OLEDs there is a severe decrease of efficiency as the drive current is increased, known as efficiency roll-off. So far, much of the literature suggests that efficiency roll-off should be reduced by minimizing the energy difference between singlet and triplet excited states (ΔEST) to maximize the rate of conversion of triplets to singlets by means of reverse intersystem crossing (kRISC)5–20. We analyse the efficiency roll-off in a wide range of TADF OLEDs and find that neither of these parameters fully accounts for the reported efficiency roll-off. By considering the dynamic equilibrium between singlets and triplets in TADF materials, we propose a figure of merit for materials design to reduce efficiency roll-off and discuss its correlation with reported data of TADF OLEDs. Our new figure of merit will guide the design and development of TADF materials that can reduce efficiency roll-off. It will help improve the efficiency of TADF OLEDs at realistic display operating conditions and expand the use of TADF materials to applications that require high brightness, such as lighting, augmented reality and lasing.
High-fidelity spin qubit operation and algorithmic initialization above 1 K
Authors: Huang Jonathan Y. , Su Rocky Y. , Lim Wee Han , Feng MengKe , van Straaten Barnaby , Severin Brandon , Gilbert Will , Dumoulin Stuyck Nard , Tanttu Tuomo , Serrano Santiago , Cifuentes Jesus D. , Hansen Ingvild , Seedhouse Amanda E. , Vahapoglu Ensar , Leon Ross C. C. , Abrosimov Nikolay V. , Pohl Hans-Joachim , Thewalt Michael L. W. , Hudson Fay E. , Escott Christopher C. , Ares Natalia , Bartlett Stephen D. , Morello Andrea , Saraiva Andre , Laucht Arne , Dzurak Andrew S. , Yang Chih Hwan
Published: March 2024

The encoding of qubits in semiconductor spin carriers has been recognized as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale1–10. However, the operation of the large number of qubits required for advantageous quantum applications11–13 will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 K, at which the cooling power is orders of magnitude higher14–18. Here we tune up and operate spin qubits in silicon above 1 K, with fidelities in the range required for fault-tolerant operations at these temperatures19–21. We design an algorithmic initialization protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies and incorporate radiofrequency readout to achieve fidelities up to 99.34% for both readout and initialization. We also demonstrate single-qubit Clifford gate fidelities up to 99.85% and a two-qubit gate fidelity of 98.92%. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for the high-fidelity operation to be possible, surmounting a main obstacle in the pathway to scalable and fault-tolerant quantum computation.
The complex polyploid genome architecture of sugarcane
Authors: Healey A. L. , Garsmeur O. , Lovell J. T. , Shengquiang S. , Sreedasyam A. , Jenkins J. , Plott C. B. , Piperidis N. , Pompidor N. , Llaca V. , Metcalfe C. J. , Doležel J. , Cápal P. , Carlson J. W. , Hoarau J. Y. , Hervouet C. , Zini C. , Dievart A. , Lipzen A. , Williams M. , Boston L. B. , Webber J. , Keymanesh K. , Tejomurthula S. , Rajasekar S. , Suchecki R. , Furtado A. , May G. , Parakkal P. , Simmons B. A. , Barry K. , Henry R. J. , Grimwood J. , Aitken K. S. , Schmutz J. , D’Hont A.
Published: March 2024

Sugarcane, the world’s most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype (‘monoploid’) representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.
Multi-organ single-cell transcriptomics of immune cells uncovered organ-specific gene expression and functions
Authors: Tsagiopoulou Maria , Rashmi Sonal , Aguilar-Fernandez Sergio , Nieto Juan , Gut Ivo G.
Published: March 2024

Despite the wealth of publicly available single-cell datasets, our understanding of distinct resident immune cells and their unique features in diverse human organs remains limited. To address this, we compiled a meta-analysis dataset of 114,275 CD45+ immune cells sourced from 14 organs in healthy donors. While the transcriptome of immune cells remains relatively consistent across organs, our analysis has unveiled organ-specific gene expression differences (GTPX3 in kidney, DNTT and ACVR2B in thymus). These alterations are linked to different transcriptional factor activities and pathways including metabolism. TNF-α signaling through the NFkB pathway was found in several organs and immune compartments. The presence of distinct expression profiles for NFkB family genes and their target genes, including cytokines, underscores their pivotal role in cell positioning. Taken together, immune cells serve a dual role: safeguarding the organs and dynamically adjusting to the intricacies of the host organ environment, thereby actively contributing to its functionality and overall homeostasis.
Compound Matrix-Based Project Database (CMPD)
Authors: Kosztyán Zsolt T. , Novák Gergely L.
Published: March 2024

The impact of projects is vital, from business operations to research to the national economy. Therefore, management science and operation research have extensively studied project scheduling and resource allocation for over six decades. Project databases were proposed to test algorithms, including simulated or real, single or multiprojects, and single-mode or multi-mode projects. However, the dozens of project databases are extremely heterogeneous regarding the file structure and the features of the modeled projects. Furthermore, the efficiency and performance of project scheduling and resource allocation algorithms are susceptible to the characteristics of projects. Therefore, the proposed Compound Matrix-Based Project Database (CMPD) collects and consolidates the most frequently used project databases. The proposed Unified Matrix-Based Project-Planning Model (UMP) sparse matrix-based model enables the addition of new features to existing project structures, such as completion priorities, structural flexibility, and quality parameters, to broaden the scope of considered projects and to take account of flexible approaches, such as agile, extreme, and hybrid projects.
The evolutionary dynamics of how languages signal who does what to whom
Authors: Shcherbakova Olena , Blasi Damián E. , Gast Volker , Skirgård Hedvig , Gray Russell D. , Greenhill Simon J.
Published: March 2024

Languages vary in how they signal “who does what to whom”. Three main strategies to indicate the participant roles of “who” and “whom” are case, verbal indexing, and rigid word order. Languages that disambiguate these roles with case tend to have either verb-final or flexible word order. Most previous studies that found these patterns used limited language samples and overlooked the causal mechanisms that could jointly explain the association between all three features. Here we analyze grammatical data from a Grambank sample of 1705 languages with phylogenetic causal graph methods. Our results corroborate the claims that verb-final word order generally gives rise to case and, strikingly, establish that case tends to lead to the development of flexible word order. The combination of novel statistical methods and the Grambank database provides a model for the rigorous testing of causal claims about the factors that shape patterns of linguistic diversity.
Vitamin D3 deficiency and osteopenia in spastic paraplegia type 5 indicate impaired bone homeostasis
Authors: Ehnert Sabrina , Hauser Stefan , Hengel Holger , Höflinger Philip , Schüle Rebecca , Lindig Tobias , Baets Jonathan , Deconinck Tine , de Jonghe Peter , Histing Tina , Nüssler Andreas K. , Schöls Ludger , Rattay Tim W.
Published: March 2024

Hereditary spastic paraplegia type 5 (SPG5) is an autosomal recessively inherited movement disorder characterized by progressive spastic gait disturbance and afferent ataxia. SPG5 is caused by bi-allelic loss of function mutations in CYP7B1 resulting in accumulation of the oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol in serum and cerebrospinal fluid of SPG5 patients. An effect of 27- hydroxycholesterol via the estrogen and liver X receptors was previously shown on bone homeostasis. This study analyzed bone homeostasis and osteopenia in 14 SPG5 patients as a non-motor feature leading to a potential increased risk for bone fractures. T-Scores in CT bone density measurements were reduced, indicating osteopenia in SPG5 patients. Further, we analyzed various metabolites of bone homeostasis by ELISA in serum samples of these patients. We identified a lack of vitamin D3 metabolites (Calcidiol and Calcitriol), an increase in Sclerostin as a bone formation/mineralization inhibiting factor, and a decrease in cross-linked N-telopeptide of type I collagen (NTX), a marker indicating reduced bone resorption. As statin treatment has been found to lower oxysterol levels, we evaluated its effect in samples of the STOP-SPG5 trial and found atorvastatin to normalize the increased sclerostin levels. In summary, our study identified osteopenia as a non-motor feature in SPG5 and suggests the need for vitamin D3 substitution in SPG5 patients. Sclerostin may be considered a therapeutic target and biomarker in upcoming therapeutical trials in SPG5.
Cretaceous to early Paleogene sediment provenance transition from continental to magmatic arc systems in the Northwestern Pacific Region
Authors: Harisma Harisma , Niki Sota , Hirata Takafumi , Naruse Hajime
Published: March 2024

Unraveling the Paleo-Kuril Arc's origins is key to understanding northwest Pacific tectonics. The Paleo-Kuril Arc is viewed as an intraoceanic arc from trench subduction between the Izanagi and Pacific Plates. Alternatively, several studies suggest the Paleo-Kuril Arc as a continental magmatic arc, hypothesizing the existence of a mid-oceanic ridge and Paleogene subduction, placing the Paleo-Kuril Arc near the Okhotsk Block's southern edge. This study clarifies these hypotheses, previously clouded by limited geochronological data on deposits in the Paleo-Kuril Arc. We conducted U–Pb dating to examine the origins of detrital zircons from the Cretaceous–Paleogene Tokoro and Nemuro Belts of the Paleo-Kuril Arc. Cluster analysis, merging new and existing data, identified two unique detrital zircon age clusters. The abundance of Precambrian zircons in Cretaceous–Paleocene Paleo-Kuril Arc sandstones (Type 1 Cluster) suggests a continental magmatic origin, supporting the ridge subduction model. However, an early Eocene shift to a consistent local volcanic source (Type 2 Cluster) highlights a significant provenance change. This geochronological evidence, indicating a separation from continental sources, calls for further research to decode the simultaneous development of sediment sources in different geological belts, potentially tied to the ridge subduction event.
Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines
Authors: Marallano Valerie J. , Ughetta Mary E. , Tejero Rut , Nanda Sidhanta , Ramalingam Rohana , Stalbow Lauren , Sattiraju Anirudh , Huang Yong , Ramakrishnan Aarthi , Shen Li , Wojcinski Alexandre , Kesari Santosh , Zou Hongyan , Tsankov Alexander M. , Friedel Roland H.
Published: March 2024

Glioblastoma (GBM) is the most common primary malignant cancer of the central nervous system. Insufficient oxygenation (hypoxia) has been linked to GBM invasion and aggression, leading to poor patient outcomes. Hypoxia induces gene expression for cellular adaptations. However, GBM is characterized by high intertumoral (molecular subtypes) and intratumoral heterogeneity (cell states), and it is not well understood to what extent hypoxia triggers patient-specific gene responses and cellular diversity in GBM. Here, we surveyed eight patient-derived GBM stem cell lines for invasion phenotypes in 3D culture, which identified two GBM lines showing increased invasiveness in response to hypoxia. RNA-seq analysis of the two patient GBM lines revealed a set of shared hypoxia response genes concerning glucose metabolism, angiogenesis, and autophagy, but also a large set of patient-specific hypoxia-induced genes featuring cell migration and anti-inflammation, highlighting intertumoral diversity of hypoxia responses in GBM. We further applied the Shared GBM Hypoxia gene signature to single cell RNA-seq datasets of glioma patients, which showed that hypoxic cells displayed a shift towards mesenchymal-like (MES) and astrocyte-like (AC) states. Interestingly, in response to hypoxia, tumor cells in IDH-mutant gliomas displayed a strong shift to the AC state, whereas tumor cells in IDH-wildtype gliomas mainly shifted to the MES state. This distinct hypoxia response of IDH-mutant gliomas may contribute to its more favorable prognosis. Our transcriptomic studies provide a basis for future approaches to better understand the diversity of hypoxic niches in gliomas.
Application of natural orifice transluminal endoscopic surgery with ENDOCRAB system for stomach perforation model: ex vivo porcine study
Authors: Jeon Han Jo , Hwang Hyunjoon , Lee Dokwan , Kim Yoonjin , Lee Jae Min , Kim Eun Sun , Keum Bora , Jeen Yoon Tae , Lee Hong Sik , Chun Hoon Jai , Choi Hyuk Soon , Song Yongnam
Published: March 2024

Iatrogenic stomach perforation is a detrimental, irreversible, and fatal condition. Traditional surgery and endoscopic suturing clips and devices have been introduced to seal holes and prevent sepsis and disease progression. However, the development of endoscopic devices for perforations remains challenging, with no standard device available. This study investigates the superficial layer approximation strengths of the newly designed ENDOCRAB system for gastric wall defects. Thirty porcine stomachs were prepared ex vivo for the perforation model and distributed equally into three groups: ENDOCRAB system, Through-the-Scope Clip (TTSC), and hand suturing (HS). Both ENDOCRAB and TTSC achieved mucosal–submucosal layer apposition, whereas HS allowed a full-thickness layer. Their air leakage pressure and procedural duration were measured. The analysis of air-leakage pressure demonstrated comparable suture strength between ENDOCRAB (118.5 ± 41.7 mmHg) and HS (127.4 ± 30.2 mmHg, P = 0.812), but inferior strength with TTSC (73.6 ± 21.6 mmHg, P = 0.012). HS achieved the shortest procedural duration, whereas ENDOCRAB and TTSC showed no significant differences. The ENDOCRAB system showed significantly greater strength than the TTSC, was comparable to HS in strength, and required a procedural duration similar to that of the TTSC. Furthermore, long-term in vivo experiments and histological evaluations are essential.
Synergistic interaction between hyperlipidemia and obesity as a risk factor for stress urinary incontinence in Americans
Authors: Zhu Fangyi , Chen Mao , Xiao Ya , Huang Xiaoyu , Chen Liying , Hong Li
Published: March 2024

Urinary incontinence is a common disease among middle-aged and elderly women, which not only affects the physical and mental health of patients, but also brings a great medical burden to society. Obesity is a known risk factor for urinary incontinence and is the most common secondary cause of hyperlipidemia. Most obese patients also suffer from hyperlipidemia in the clinic. However, few studies have explored the role of hyperlipidemia in women with urinary incontinence. Using data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES), we aimed to evaluated the independent associations of high body mass index and hyperlipidemia with urinary incontinence in Americans by conducting a weighted multivariate logistic regression model. Additive interactions were also assessed using the relative excess risk due to interaction (RERI), attributed proportion of interaction (AP) and synergy index (S). This study demonstrated that hyperlipidemia was associated with a higher risk of stress urinary incontinence among women with obesity (OR = 1.52, 95% CI = 1.03–2.25), and there was a significant synergistic effect of hyperlipidemia and obesity on stress urinary incontinence(adjusted RERI: 3.75, 95% CI 0.30–7.20; adjusted AP: 0.67, 95% CI 0.54–0.80; adjusted S: 5.49, 95% CI 4.15–7.27). Moreover, fasting serum triglyceride lipids were the most relevant blood lipid indicator for the risk of stress urinary incontinence, especially among obese women younger than 50 years old, which contributes to the development of more refined lipid control protocols for patients with urinary incontinence in different age groups.
Monolayer culture alters EGFR inhibitor response through abrogation of microRNA-mediated feedback regulation
Authors: Florio Angela , Johnson Sarah , Salvatori Rebecca , Vasmatzis George
Published: March 2024

Ex vivo drug screening is a potentially powerful tool for the future of cancer care, but the accuracy of results is contingent on the culture model. Both monolayer (2D) and spheroid (3D) culture systems offer advantages, but given the differences in mechanical environment, we hypothesized that that the suitability of one system over another would be critical for screening drugs with mechanical targets in mechanical tissues. HCC827 lung adenocarcinoma cells were challenged with EGFR tyrosine kinase inhibitors in monolayer and spheroid culture. RNA sequencing was performed on cells in both conditions to assess culture-induced transcriptional changes that could account for differences in drug response and differences in EGFR expression detected by immunostain. A microRNA microarray was performed to assess culture-induced differences in regulation of microRNA, and the impact of miR-146a-5p on drug response was verified by inhibition. Results were confirmed in human lung adenocarcinoma tissue. HCC827 spheroids were resistant to erlotinib and gefitinib, but significantly more sensitive in 2D culture. RNA-seq and immunostaining show a discrepancy in EGFR transcript and protein expression between the two conditions, which we attribute to miR-146a-5p. This microRNA targets EGFR and is differentially expressed between 2D and 3D culture. Inhibition of miR-146a-5p significantly increased erlotinib cytotoxicity, but validation in patient-derived spheroids suggests that the effect may be mutation-specific. Analysis of RNA-seq data suggests that cells in 2D culture become highly dependent on EGFR signaling to drive proliferation and cell spreading, resulting in a misleading level of sensitivity to EGFR TKIs, while the same cells in spheroid culture retain microRNA-driven EGFR feedback regulation that leaves them less vulnerable to EGFR inhibition. These findings underscore the need for close scrutiny of culture-induced effects on drug target regulation in model design for ex vivo drug screening.
Gaussian Aquila optimizer based dual convolutional neural networks for identification and grading of osteoarthritis using knee joint images
Authors: Subha B. , Jeyakumar Vijay , Deepa S. N.
Published: March 2024

Degenerative musculoskeletal disease known as Osteoarthritis (OA) causes serious pain and abnormalities for humans and on detecting at an early stage, timely treatment shall be initiated to the patients at the earliest to overcome this pain. In this research study, X-ray images are captured from the humans and the proposed Gaussian Aquila Optimizer based Dual Convolutional Neural Networks is employed for detecting and classifying the osteoarthritis patients. The new Gaussian Aquila Optimizer (GAO) is devised to include Gaussian mutation at the exploitation stage of Aquila optimizer, which results in attaining the best global optimal value. Novel Dual Convolutional Neural Network (DCNN) is devised to balance the convolutional layers in each convolutional model and the weight and bias parameters of the new DCNN model are optimized using the developed GAO. The novelty of the proposed work lies in evolving a new optimizer, Gaussian Aquila Optimizer for parameter optimization of the devised DCNN model and the new DCNN model is structured to minimize the computational burden incurred in spite of it possessing dual layers but with minimal number of layers. The knee dataset comprises of total 2283 knee images, out of which 1267 are normal knee images and 1016 are the osteoarthritis images with an image of 512 × 512-pixel width and height respectively. The proposed novel GAO-DCNN system attains the classification results of 98.25% of sensitivity, 98.93% of specificity and 98.77% of classification accuracy for abnormal knee case–knee joint images. Experimental simulation results carried out confirms the superiority of the developed hybrid GAO-DCNN over the existing deep learning neural models form previous literature studies.
Experimental investigation on utilization of Sesbania grandiflora residues through thermochemical conversion process for the production of value added chemicals and biofuels
Authors: Janardhana Kedri , Sowmya Dhanalakshmi C. , Thilagham K. T. , Chinnaiyan Santhosh Kumar , Jai Shanker Pillai H. P. , Sathish T. , Ağbulut Ümit , Palani Kumaran , De Poures Melvin Victor
Published: March 2024

All the countries in the world are now searching for renewable, environmentally friendly alternative fuels due to the shortage and environmental problems related with the usage of conventional fuels. The cultivation of cereal and noncereal crops through agricultural activities produces waste biomasses, which are being evaluated as renewable and viable fossil fuel substitutes. The thermochemical properties and thermal degradation behavior of Sesbania grandiflora residues were investigated for this work. A fluidized bed reactor was used for fast pyrolysis in order to produce pyrolysis oil, char and gas. Investigations were done to analyze the effect of operating parameters such as temperature (350–550 °C), particle size (0.5–2.0 mm), sweeping gas flow rate (1.5–2.25 m3/h). The maximum of pyrolysis oil (44.7 wt%), was obtained at 425 °C for 1.5 mm particle size at the sweep gas flow rate of 2.0 m3/h. Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry methods were used to examine the composition of the pyrolysis oil. The pyrolysis oil is rich with aliphatic, aromatic, phenolic, and some acidic chemicals. The physical characteristics of pyrolysis oil showed higher heating value of 19.76 MJ/kg. The char and gaseous components were also analyzed to find its suitability as a fuel.
RETRACTED ARTICLE: Flawless polyaniline coating for preservation and corrosion protection of ancient steel spearheads: an archaeological study from military museum, Al-Qala, Egypt
Authors: Megahed Mohamed M. , Elashery Noha H. , Saleh Saleh M. , El-Shamy Ashraf M.
Published: March 2024

The purpose of this research was to examine the viability of applying a flawless polyaniline coating on steel spearheads to preserve them and protect them from corrosion. The spearpoints, thought to be archaeologically significant, were acquired from the Military Museum in Al-Qala, Egypt. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy were used to characterize the spearheads chemical composition and microstructure (EDX). The spearheads were determined to be constructed of steel and to have a coating of ferric oxide and other corrosion products on their exteriors. After that, a flawless polyaniline coating was electrochemically deposited onto the spearpoints in a way that was both quick and cheap. Many types of corrosion tests, such as electrochemical impedance spectroscopy and potentiodynamic polarization (PDP) readings, were used to determine the coating’s effectiveness. The steel spearheads’ findings revealed a significant improvement in their resistance to corrosion after being coated with flawless polyaniline. The coating served as a barrier, blocking out water and other corrosive substances and slowing the buildup of corrosion byproducts on the spearpoints. In conclusion, our research shows that a flawless polyaniline coating may be an effective anti-corrosion treatment for ancient steel artifacts. The approach is straightforward, cheap, and readily scalable for massive conservation efforts.
Wiring surface loss of a superconducting transmon qubit
Authors: Smirnov Nikita S. , Krivko Elizaveta A. , Solovyova Anastasiya A. , Ivanov Anton I. , Rodionov Ilya A.
Published: March 2024

Quantum processors using superconducting qubits suffer from dielectric loss leading to noise and dissipation. Qubits are usually designed as large capacitor pads connected to a non-linear Josephson junction (or SQUID) by a superconducting thin metal wiring. Here, we report on finite-element simulation and experimental results confirming that more than 50% of surface loss in transmon qubits can originate from Josephson junctions wiring and can limit qubit relaxation time. We experimentally extracted dielectric loss tangents of qubit elements and showed that dominant surface loss of wiring can occur for real qubits designs. Finally, we experimentally demonstrate up to 20% improvement in qubit quality factor by wiring design optimization.