bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic profiles of archaea and bacteria within thermal and geochemical gradients of the Guaymas Basin deep subsurface
Authors: Mara Paraskevi , Geller-McGrath David , Edgcomb Virginia , Beaudoin David , Morono Yuki , Teske Andreas
Published: November 2023

Previous studies of microbial communities in subseafloor sediments reported that microbial abundance and diversity decrease with sediment depth and age, and microbes dominating at depth tend to be a subset of the local seafloor community. However, the existence of geographically widespread, subsurface-adapted specialists is also possible. Here, we use metagenomic and metatranscriptomic analyses of the hydrothermally heated, sediment layers of Guaymas Basin (Gulf of California, Mexico) to examine the distribution and activity patterns of bacteria and archaea along thermal, geochemical and cell count gradients. We find that the composition and distribution of metagenome-assembled genomes (MAGs), dominated by numerous lineages of Chloroflexota and Thermoproteota, correlate with biogeochemical parameters as long as temperatures remain moderate, but downcore increasing temperatures beyond ca. 45 ºC override other factors. Consistently, MAG size and diversity decrease with increasing temperature, indicating a downcore winnowing of the subsurface biosphere. By contrast, specific archaeal MAGs within the Thermoproteota and Hadarchaeota increase in relative abundance and in recruitment of transcriptome reads towards deeper, hotter sediments, marking the transition towards a specialized deep, hot biosphere.
A promising perovskite primary explosive
Authors: Feng Yongan , Zhang Jichuan , Cao Weiguo , Zhang Jiaheng , Shreeve Jean’ne M.
Published: November 2023

A primary explosive is an ideal chemical substance for performing ignition in military and commercial applications. For over 150 years, nearly all of the developed primary explosives have suffered from various issues, such as troublesome syntheses, high toxicity, poor stability or/and weak ignition performance. Now we report an interesting example of a primary explosive with double perovskite framework, {(C6H14N2)2[Na(NH4)(IO4)6]}n (DPPE-1), which was synthesized using a simple green one-pot method in an aqueous solution at room temperature. DPPE-1 is free of heavy metals, toxic organic components, and doesn’t involve any explosive precursors. It exhibits good stability towards air, moisture, sunlight, and heat and has acceptable mechanical sensitivities. It affords ignition performance on par with the most powerful primary explosives reported to date. DPPE-1 promises to meet the challenges existing with current primary explosives, and this work could trigger more extensive applications of perovskite.
Ultra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration
Authors: Yang Yuxuan , Zhao Xiaodan , Wang Shuang , Zhang Yanfeng , Yang Aiming , Cheng Yilong , Chen Xuesi
Published: November 2023

Osteoarthritis is a worldwide prevalent disease that imposes a significant socioeconomic burden on individuals and healthcare systems. Achieving cartilage regeneration in patients with osteoarthritis remains challenging clinically. In this work, we construct a multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin by polyaddition reaction as a cell-free scaffold for in vivo cartilage regeneration, which features ultra-durable mechanical properties and stage-dependent drug release behavior. We demonstrate that the hydrogel can withstand 28000 loading-unloading mechanical cycles and exhibits fast shape memory at body temperature (30 s) with the potential for minimally invasive surgery. We find that the hydrogel can also alleviate the inflammatory reaction and regulate oxidative stress in situ to establish a microenvironment conducive to healing. We show that the sequential release of tannic acid and Kartogenin can promote the migration of bone marrow mesenchymal stem cells into the hydrogel scaffold, followed by the induction of chondrocyte differentiation, thus leading to full-thickness cartilage regeneration in vivo. This work may provide a promising solution to address the problem of cartilage regeneration.
Anomalous efficiency elevation of quantum-dot light-emitting diodes induced by operational degradation
Authors: He Siyu , Tang Xiaoqi , Deng Yunzhou , Yin Ni , Jin Wangxiao , Lu Xiuyuan , Chen Desui , Wang Chenyang , Sun Tulai , Chen Qi , Jin Yizheng
Published: November 2023

Quantum-dot light-emitting diodes promise a new generation of high-performance and solution-processed electroluminescent light sources. Understanding the operational degradation mechanisms of quantum-dot light-emitting diodes is crucial for their practical applications. Here, we show that quantum-dot light-emitting diodes may exhibit an anomalous degradation pattern characterized by a continuous increase in electroluminescent efficiency upon electrical stressing, which deviates from the typical decrease in electroluminescent efficiency observed in other light-emitting diodes. Various in-situ/operando characterizations were performed to investigate the evolutions of charge dynamics during the efficiency elevation, and the alterations in electric potential landscapes in the active devices. Furthermore, we carried out selective peel-off-and-rebuild experiments and depth-profiling analyses to pinpoint the critical degradation site and reveal the underlying microscopic mechanism. The results indicate that the operation-induced efficiency increase results from the degradation of electron-injection capability at the electron-transport layer/cathode interface, which in turn leads to gradually improved charge balance. Our work provides new insights into the degradation of red quantum-dot light-emitting diodes and has far-reaching implications for the design of charge-injection interfaces in solution-processed light-emitting diodes.
LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins
Authors: Ansell T. Bertie , Song Wanling , Coupland Claire E. , Carrique Loic , Corey Robin A. , Duncan Anna L. , Cassidy C. Keith , Geurts Maxwell M. G. , Rasmussen Tim , Ward Andrew B. , Siebold Christian , Stansfeld Phillip J. , Sansom Mark S. P.
Published: November 2023

Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.
OVOL2 sustains postnatal thymic epithelial cell identity
Authors: Zhong Xue , Peddada Nagesh , Wang Jianhui , Moresco James J. , Zhan Xiaowei , Shelton John M. , SoRelle Jeffrey A. , Keller Katie , Lazaro Danielle Renee , Moresco Eva Marie Y. , Choi Jin Huk , Beutler Bruce
Published: November 2023

Distinct pathways and molecules may support embryonic versus postnatal thymic epithelial cell (TEC) development and maintenance. Here, we identify a mechanism by which TEC numbers and function are maintained postnatally. A viable missense allele (C120Y) of Ovol2, expressed ubiquitously or specifically in TECs, results in lymphopenia, in which T cell development is compromised by loss of medullary TECs and dysfunction of cortical TECs. We show that the epithelial identity of TECs is aberrantly subverted towards a mesenchymal state in OVOL2-deficient mice. We demonstrate that OVOL2 inhibits the epigenetic regulatory BRAF-HDAC complex, specifically disrupting RCOR1-LSD1 interaction. This causes inhibition of LSD1-mediated H3K4me2 demethylation, resulting in chromatin accessibility and transcriptional activation of epithelial genes. Thus, OVOL2 controls the epigenetic landscape of TECs to enforce TEC identity. The identification of a non-redundant postnatal mechanism for TEC maintenance offers an entry point to understanding thymic involution, which normally begins in early adulthood.
Time-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle
Authors: Hu Shuyao , Zhang Yufeng , Yi Qianqian , Yang Cuiwei , Liu Yanfen , Bai Yun
Published: November 2023

Stress granules (SGs) are dynamic, membrane-less organelles. With their formation and disassembly processes characterized, it remains elusive how compositional transitions are coordinated during prolonged stress to meet changing functional needs. Here, using time-resolved proteomic profiling of the acute to prolonged heat-shock SG life cycle, we identify dynamic SG proteins, further segregated into early and late proteins. Comparison of different groups of SG proteins suggests that their biochemical properties help coordinate SG compositional and functional transitions. In particular, early proteins, with high phase-separation-propensity, drive the rapid formation of the initial SG platform, while late proteins are subsequently recruited as discrete modules to further functionalize SGs. This model, supported by immunoblotting and immunofluorescence imaging, provides a conceptual framework for the compositional transitions throughout the acute to prolonged SG life cycle. Additionally, an early SG constituent, non-muscle myosin II, is shown to promote SG formation by increasing SG fusion, underscoring the strength of this dataset in revealing the complexity of SG regulation.
RNA is a key component of extracellular DNA networks in Pseudomonas aeruginosa biofilms
Authors: Mugunthan Sudarsan , Wong Lan Li , Winnerdy Fernaldo Richtia , Summers Stephen , Bin Ismail Muhammad Hafiz , Foo Yong Hwee , Jaggi Tavleen Kaur , Meldrum Oliver W. , Tiew Pei Yee , Chotirmall Sanjay H. , Rice Scott A. , Phan Anh Tuân , Kjelleberg Staffan , Seviour Thomas
Published: November 2023

The extracellular matrix of bacterial biofilms consists of diverse components including polysaccharides, proteins and DNA. Extracellular RNA (eRNA) can also be present, contributing to the structural integrity of biofilms. However, technical difficulties related to the low stability of RNA make it difficult to understand the precise roles of eRNA in biofilms. Here, we show that eRNA associates with extracellular DNA (eDNA) to form matrix fibres in Pseudomonas aeruginosa biofilms, and the eRNA is enriched in certain bacterial RNA transcripts. Degradation of eRNA associated with eDNA led to a loss of eDNA fibres and biofilm viscoelasticity. Compared with planktonic and biofilm cells, the biofilm matrix was enriched in specific mRNA transcripts, including lasB (encoding elastase). The mRNA transcripts colocalised with eDNA fibres in the biofilm matrix, as shown by single molecule inexpensive FISH microscopy (smiFISH). The lasB mRNA was also observed in eDNA fibres in a clinical sputum sample positive for P. aeruginosa. Thus, our results indicate that the interaction of specific mRNAs with eDNA facilitates the formation of viscoelastic networks in the matrix of Pseudomonas aeruginosa biofilms.
Ancient diversity in host-parasite interaction genes in a model parasitic nematode
Authors: Stevens Lewis , Martínez-Ugalde Isaac , King Erna , Wagah Martin , Absolon Dominic , Bancroft Rowan , Gonzalez de la Rosa Pablo , Hall Jessica L. , Kieninger Manuela , Kloch Agnieszka , Pelan Sarah , Robertson Elaine , Pedersen Amy B. , Abreu-Goodger Cei , Buck Amy H. , Blaxter Mark
Published: November 2023

Host-parasite interactions exert strong selection pressures on the genomes of both host and parasite. These interactions can lead to negative frequency-dependent selection, a form of balancing selection that is hypothesised to explain the high levels of polymorphism seen in many host immune and parasite antigen loci. Here, we sequence the genomes of several individuals of Heligmosomoides bakeri, a model parasite of house mice, and Heligmosomoides polygyrus, a closely related parasite of wood mice. Although H. bakeri is commonly referred to as H. polygyrus in the literature, their genomes show levels of divergence that are consistent with at least a million years of independent evolution. The genomes of both species contain hyper-divergent haplotypes that are enriched for proteins that interact with the host immune response. Many of these haplotypes originated prior to the divergence between H. bakeri and H. polygyrus, suggesting that they have been maintained by long-term balancing selection. Together, our results suggest that the selection pressures exerted by the host immune response have played a key role in shaping patterns of genetic diversity in the genomes of parasitic nematodes.
Molecular basis for the catalytic mechanism of human neutral sphingomyelinases 1 (hSMPD2)
Authors: Yi Jingbo , Qi Boya , Yin Jian , Li Ruochong , Chen Xudong , Hu Junhan , Li Guohui , Zhang Sensen , Zhang Yuebin , Yang Maojun
Published: November 2023

Enzymatic breakdown of sphingomyelin by sphingomyelinase (SMase) is the main source of the membrane lipids, ceramides, which are involved in many cellular physiological processes. However, the full-length structure of human neutral SMase has not been resolved; therefore, its catalytic mechanism remains unknown. Here, we resolve the structure of human full-length neutral SMase, sphingomyelinase 1 (SMPD2), which reveals that C-terminal transmembrane helices contribute to dimeric architecture of hSMPD2 and that D111 − K116 loop domain is essential for substrate hydrolysis. Coupled with molecular docking, we clarify the binding pose of sphingomyelin, and site-directed mutagenesis further confirms key residues responsible for sphingomyelin binding. Hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamic (MD) simulations are utilized to elaborate the catalysis of hSMPD2 with the reported in vitro substrates, sphingomyelin and lyso-platelet activating fator (lyso-PAF). Our study provides mechanistic details that enhance our knowledge of lipid metabolism and may lead to an improved understanding of ceramide in disease and in cancer treatment.
Non-equilibrium dynamics of spin-lattice coupling
Authors: Ueda Hiroki , Mankowsky Roman , Paris Eugenio , Sander Mathias , Deng Yunpei , Liu Biaolong , Leroy Ludmila , Nag Abhishek , Skoropata Elizabeth , Wang Chennan , Ukleev Victor , Perren Gérard Sylvester , Dössegger Janine , Gurung Sabina , Svetina Cristian , Abreu Elsa , Savoini Matteo , Kimura Tsuyoshi , Patthey Luc , Razzoli Elia , Lemke Henrik Till , Johnson Steven Lee , Staub Urs
Published: November 2023

Quantifying the dynamics of normal modes and how they interact with other excitations is of central importance in condensed matter. Spin-lattice coupling is relevant to several sub-fields of condensed matter physics; examples include spintronics, high-Tc superconductivity, and topological materials. However, experimental approaches that can directly measure it are rare and incomplete. Here we use time-resolved X-ray diffraction to directly access the ultrafast motion of atoms and spins following the coherent excitation of an electromagnon in a multiferroic hexaferrite. One striking outcome is the different phase shifts relative to the driving field of the two different components. This phase shift provides insight into the excitation process of such a coupled mode. This direct observation of combined lattice and magnetization dynamics paves the way to access the mode-selective spin-lattice coupling strength, which remains a missing fundamental parameter for ultrafast control of magnetism and is relevant to a wide variety of materials.
Resting-state global brain activity affects early β-amyloid accumulation in default mode network
Authors: Han Feng , Liu Xufu , Mailman Richard B. , Huang Xuemei , Liu Xiao
Published: November 2023

It remains unclear why β-amyloid (Aβ) plaque, a hallmark pathology of Alzheimer’s disease (AD), first accumulates cortically in the default mode network (DMN), years before AD diagnosis. Resting-state low-frequency ( < 0.1 Hz) global brain activity recently was linked to AD, presumably due to its role in glymphatic clearance. Here we show that the preferential Aβ accumulation in the DMN at the early stage of Aβ pathology was associated with the preferential reduction of global brain activity in the same regions. This can be partly explained by its failure to reach these regions as propagating waves. Together, these findings highlight the important role of resting-state global brain activity in early preferential Aβ deposition in the DMN.
CAR+ and CAR− T cells share a differentiation trajectory into an NK-like subset after CD19 CAR T cell infusion in patients with B cell malignancies
Authors: Louie Raymond Hall Yip , Cai Curtis , Samir Jerome , Singh Mandeep , Deveson Ira W. , Ferguson James M. , Amos Timothy G. , McGuire Helen Marie , Gowrishankar Kavitha , Adikari Thiruni , Balderas Robert , Bonomi Martina , Ruella Marco , Bishop David , Gottlieb David , Blyth Emily , Micklethwaite Kenneth , Luciani Fabio
Published: November 2023

Chimeric antigen receptor (CAR) T cell therapy is effective in treating B cell malignancies, but factors influencing the persistence of functional CAR+ T cells, such as product composition, patients’ lymphodepletion, and immune reconstitution, are not well understood. To shed light on this issue, here we conduct a single-cell multi-omics analysis of transcriptional, clonal, and phenotypic profiles from pre- to 1-month post-infusion of CAR+ and CAR− T cells from patients from a CARTELL study (ACTRN12617001579381) who received a donor-derived 4-1BB CAR product targeting CD19. Following infusion, CAR+ T cells and CAR− T cells shows similar differentiation profiles with clonally expanded populations across heterogeneous phenotypes, demonstrating clonal lineages and phenotypic plasticity. We validate these findings in 31 patients with large B cell lymphoma treated with CD19 CAR T therapy. For these patients, we identify using longitudinal mass-cytometry data an association between NK-like subsets and clinical outcomes at 6 months with both CAR+ and CAR− T cells. These results suggest that non-CAR-derived signals can provide information about patients’ immune recovery and be used as correlate of clinically relevant parameters.
DNA polymerase ε harmonizes topological states and R-loops formation to maintain genome integrity in Arabidopsis
Authors: Li Qin , Zhou Jincong , Li Shuai , Zhang Weifeng , Du Yingxue , Li Kuan , Wang Yingxiang , Sun Qianwen
Published: November 2023

Genome topology is tied to R-loop formation and genome stability. However, the regulatory mechanism remains to be elucidated. By establishing a system to sense the connections between R-loops and genome topology states, we show that inhibiting DNA topoisomerase 1 (TOP1i) triggers the global increase of R-loops (called topoR-loops) and DNA damages, which are exacerbated in the DNA damage repair-compromised mutant atm. A suppressor screen identifies a mutation in POL2A, the catalytic subunit of DNA polymerase ε, rescuing the TOP1i-induced topoR-loop accumulation and genome instability in atm. Importantly we find that a highly conserved junction domain between the exonuclease and polymerase domains in POL2A is required for modulating topoR-loops near DNA replication origins and facilitating faithful DNA replication. Our results suggest that DNA replication acts in concert with genome topological states to fine-tune R-loops and thereby maintain genome integrity, revealing a likely conserved regulatory mechanism of TOP1i resistance in chemotherapy for ATM-deficient cancers.
Lithium carbonate-promoted mixed rare earth oxides as a generalized strategy for oxidative coupling of methane with exceptional yields
Authors: Zhao Kun , Gao Yunfei , Wang Xijun , Lis Bar Mosevitzky , Liu Junchen , Jin Baitang , Smith Jacob , Huang Chuande , Gao Wenpei , Wang Xiaodong , Wang Xin , Zheng Anqing , Huang Zhen , Hu Jianli , Schömacker Reinhard , Wachs Israel E. , Li Fanxing
Published: November 2023

The oxidative coupling of methane to higher hydrocarbons offers a promising autothermal approach for direct methane conversion, but its progress has been hindered by yield limitations, high temperature requirements, and performance penalties at practical methane partial pressures (~1 atm). In this study, we report a class of Li2CO3-coated mixed rare earth oxides as highly effective redox catalysts for oxidative coupling of methane under a chemical looping scheme. This catalyst achieves a single-pass C2+ yield up to 30.6%, demonstrating stable performance at 700 °C and methane partial pressures up to 1.4 atm. In-situ characterizations and quantum chemistry calculations provide insights into the distinct roles of the mixed oxide core and Li2CO3 shell, as well as the interplay between the Pr oxidation state and active peroxide formation upon Li2CO3 coating. Furthermore, we establish a generalized correlation between Pr4+ content in the mixed lanthanide oxide and hydrocarbons yield, offering a valuable optimization strategy for this class of oxidative coupling of methane redox catalysts.
Ocean fronts as decadal thermostats modulating continental warming hiatus
Authors: Sung Mi-Kyung , An Soon-Il , Shin Jongsoo , Park Jae-Heung , Yang Young-Min , Kim Hyo-Jeong , Chang Minhee
Published: November 2023

Over the past decade, an unexpected cooling trend has been observed in East Asia and North America during winter. Climate model simulations suggest that this pattern of stalled warming, besides accelerated warming, will repeat throughout the course of global warming, influenced by the natural decade-long variations in the climate system. However, understanding the exact factors affecting the pace of warming remains a challenge. Here we show that a pause in warming over continental areas—namely, local warming hiatus—can be accompanied by excessive heat accumulation north of the ocean fronts. This oceanic condition, often manifesting in the form of marine heatwaves, constrains the subseasonal growth of atmospheric planetary waves, significantly increasing the likelihood of cold extremes in downstream continents. Our results underscore the importance of closely monitoring changing ocean fronts in response to human-induced warming, which can potentially reshape the inherent decade-long fluctuations within regional climates over the long term.
COPI vesicle formation and N-myristoylation are targetable vulnerabilities of senescent cells
Authors: McHugh Domhnall , Sun Bin , Gutierrez-Muñoz Carmen , Hernández-González Fernanda , Mellone Massimiliano , Guiho Romain , Duran Imanol , Pombo Joaquim , Pietrocola Federico , Birch Jodie , Kallemeijn Wouter W. , Khadayate Sanjay , Dharmalingam Gopuraja , Vernia Santiago , Tate Edward W. , Martínez-Barbera Juan Pedro , Withers Dominic J. , Thomas Gareth J. , Serrano Manuel , Gil Jesús
Published: November 2023

Drugs that selectively kill senescent cells (senolytics) improve the outcomes of cancer, fibrosis and age-related diseases. Despite their potential, our knowledge of the molecular pathways that affect the survival of senescent cells is limited. To discover senolytic targets, we performed RNAi screens and identified coatomer complex I (COPI) vesicle formation as a liability of senescent cells. Genetic or pharmacological inhibition of COPI results in Golgi dispersal, dysfunctional autophagy, and unfolded protein response-dependent apoptosis of senescent cells, and knockdown of COPI subunits improves the outcomes of cancer and fibrosis in mouse models. Drugs targeting COPI have poor pharmacological properties, but we find that N-myristoyltransferase inhibitors (NMTi) phenocopy COPI inhibition and are potent senolytics. NMTi selectively eliminated senescent cells and improved outcomes in models of cancer and non-alcoholic steatohepatitis. Our results suggest that senescent cells rely on a hyperactive secretory apparatus and that inhibiting trafficking kills senescent cells with the potential to treat various senescence-associated diseases.
Loss-of-function gs3 allele decreases methane emissions and increases grain yield in rice
Authors: Kwon Youngho , Lee Ji-Yoon , Choi Jisu , Lee So-Myeong , Kim Dajeong , Cha Jin-Kyung , Park Hyeonjin , Kang Ju-Won , Kim Tae Hee , Chae Ho Gyeong , Kabange Nkulu Rolly , Oh Ki-Won , Kim Pil Joo , Kwak Youn-Sig , Lee Jong-Hee , Ryu Choong-Min
Published: November 2023

Rice paddies are a major source of methane emissions. To meet the food demand of the growing population and to cope with global warming, reducing greenhouse gases and enhancing yields are critical. Here we demonstrate that a loss-of-function rice allele, gs3, mitigates methane emissions from methanogens by allocating more photosynthates to the grain and less to the root and increases yield by enlarging grain size and weight.
Comparison of a gelatin thrombin versus a modified absorbable polymer as a unique treatment for severe hepatic hemorrhage in swine
Authors: Sánchez del Valle Francisco José , De Nicolás Luis , Fernández Guillermo , Fernández Pedro , Gómez Esther , Aranaz Corral Inmaculada
Published: November 2023

There are many surgical techniques (packing, Pringle maneuver, etc.) and hemostatic agents to manage hepatic bleeding in trauma surgery. This study compares the effectiveness of two different types of hemostatic agents, one is an active flowable hemostat and the other is a passive hemostat made of modified absorbable polymers [MAP]. Both surgical technique and hemostatic agents can be used together as a means of controlling bleeding. We have hypothesized that a single hemostatic agent might be as effective as a unique hemostatic surgical technique. Twenty swine were prospectively randomized to receive either active Flowable (Floseal) or passive MAP powder (PerClot) hemostatic agents. We used a novel severe liver injury model that caused exsanguinating hemorrhage. The main outcome measure was total blood loss volume. The total volume of blood loss, from hepatic injury to minute 120, was significantly lower in the Flowable group (407.5 cm3; IqR: 195.0–805.0 cm3) compared to MAP group (1107.5 cm3; IqR: 822.5 to 1544.5 cm3) (Hodges–Lehmann median difference: − 645.0 cm3; 95% CI: − 1144.0 to − 280.0 cm3; p = 0.0087). The rate of blood loss was significantly lower in the flowable group compared with the MAP group as measured from time of injury to minutes 3, 9, 12, and 120 (except for 6 min). The mean arterial pressure gradually recovered in the flowable group by 24 h, whereas in the MAP group, the mean arterial pressure was consistently stayed below baseline values. Kaplan–Meier survival analysis indicated similar rates of death between study groups (Logrank test p = 0.3395). Both the flowable and the MAP hemostatic agents were able to effectively control surgical bleeding in a novel severe liver injury model, however, the flowable gelatin–thrombin agent provided quicker and better bleed control.
Attention-based solubility prediction of polysulfide and electrolyte analysis for lithium–sulfur batteries
Authors: Lee Jaewan , Yang Hongjun , Park Changyoung , Park Seong-Hyo , Jang Eunji , Kwack Hobeom , Lee Chang Hoon , Song Chang-ik , Choi Young Cheol , Han Sehui , Lee Honglak
Published: November 2023

During the continuous charge and discharge process in lithium-sulfur batteries, one of the next-generation batteries, polysulfides are generated in the battery’s electrolyte, and impact its performance in terms of power and capacity by involving the process. The amount of polysulfides in the electrolyte could be estimated by the change of the Gibbs free energy of the electrolyte, $$\Delta _{mix}\textrm{G}$$

Δ

mix

G

in the presence of polysulfide. However, obtaining $$\Delta _{mix}\textrm{G}$$

Δ

mix

G

of the diverse mixtures of components in the electrolyte is a complex and expensive task that shows itself as a bottleneck in optimization of electrolytes. In this work, we present a machine-learning approach for predicting $$\Delta _{mix}\textrm{G}$$

Δ

mix

G

of electrolytes. The proposed architecture utilizes (1) an attention-based model (Attentive FP), a contrastive learning model (MolCLR) or morgan fingerprints to represent chemical components, and (2) transformers to account for the interactions between chemicals in the electrolyte. This architecture was not only capable of predicting electrolyte properties, including those of chemicals not used during training, but also providing insights into chemical interactions within electrolytes. It revealed that interactions with other chemicals relate to the logP and molecular weight of the chemicals.
Social opportunities and mate preference improve breeding success in Caribbean iguanas
Authors: Lemm Jeffrey M. , Martin Meghan S.
Published: November 2023

Conservation breeding of West Indian rock iguanas (Cyclura) has met with limited success historically. Many facilities witness high levels of aggression and mate incompatibility resulting in failed breeding introductions which often require animals to be separated. This may be due, in part, to lack of knowledge of how mate familiarity and preference affect reproductive outcomes in these species. We investigated whether social exposure during the pre-breeding season influenced copulation success, egg production, and breeding behaviors. Additionally, we examined whether mate preference, as determined by pre-mating dichotomous choice tests, increased these reproductive outcomes. Female rock iguanas that were socialized with males prior to breeding opportunities copulated with familiar males for longer periods of time than females that were not socialized. Socialization opportunities did not alter male reproductive success measurements or breeding behavior. Female rock iguanas introduced for mating to their preferred partners had a higher probability of successful copulations, higher average number of copulations, and less resting behavior during introductions than females mated to non-preferred males. Male mate preference had no effect on reproductive success measurements during mating introductions. These results indicate that socializing animals and providing mate choice opportunities increase breeding success of rock iguanas under managed care.
Assessment of green technology innovation on energy-environmental efficiency in China under the influence of environmental regulation considering spatial effects
Authors: Li Wei , Xu Xiaomin , Huang Shengzhong , Cheng Tong , Liu Mengkai , Zhang Can
Published: November 2023

Enhancing energy-environmental efficiency (EEE) is crucial for achieving energy conservation and emission reduction goals. Investigating the mechanism through which green technology innovation (GTI) affects EEE and understanding the role of environmental regulation (ER) in this process provides a theoretical basis for efficient utilization of GTI and ER. This study employs a Dynamic Spatial Durbin Model and utilizes panel data from 2003 to 2017 for 30 Chinese provinces to examine the impact of GTI on EEE in the presence of ER. The empirical results reveal: (1) GTI has a U-shaped impact on EEE, primarily driven by SubGI. (2) GTI’s influence on EEE is predominantly reflected in PTE, also stemming from SubGI. (3) The interaction term between ER and GTI is 0.0022, while the GTI coefficient is − 0.0741, and the GTI quadratic term coefficient is 0.0007, all statistically significant. This implies that ER mitigates the negative impact of GTI on EEE while strengthening its positive effect. These findings provide empirical evidence and policy insights for more effectively utilizing GTI and ER to enhance EEE and achieve energy conservation and emissions reduction goals.
Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach
Authors: Furlong Melissa A. , Liu Tuo , Snider Justin M. , Tfaily Malak M. , Itson Christian , Beitel Shawn , Parsawar Krishna , Keck Kristen , Galligan James , Walker Douglas I. , Gulotta John J. , Burgess Jefferey L.
Published: November 2023

Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers.
Exploring ceRNA networks for key biomarkers in breast cancer subtypes and immune regulation
Authors: Shariatmadar Taleghani Alireza , Zohrab Beigi Yasaman , Zare-Mirakabad Fatemeh , Masoudi-Nejad Ali
Published: November 2023

Breast cancer is a major global health concern, and recent researches have highlighted the critical roles of non-coding RNAs in both cancer and the immune system. The competing endogenous RNA hypothesis suggests that various types of RNA, including coding and non-coding RNAs, compete for microRNA targets, acting as molecular sponges. This study introduces the Pre_CLM_BCS pipeline to investigate the potential of long non-coding RNAs and circular RNAs as biomarkers in breast cancer subtypes. The pipeline identifies specific modules within each subtype that contain at least one long non-coding RNA or circular RNA exhibiting significantly distinct expression patterns when compared to other subtypes. The results reveal potential biomarker genes for each subtype, such as circ_001845, circ_001124, circ_003925, circ_000736, and circ_003996 for the basal-like subtype, circ_00306 and circ_00128 for the luminal B subtype, circ_000709 and NPHS1 for the normal-like subtype, CAMKV and circ_001855 for the luminal A subtype, and circ_00128 and circ_00173 for the HER2+ subtype. Additionally, certain long non-coding RNAs and circular RNAs, including RGS5-AS1, C6orf223, HHLA3-AS1, circ_000349, circ_003996, circ_003925, circ_002665, circ_001855, and DLEU1, are identified as potential regulators of T cell mechanisms, underscoring their importance in understanding breast cancer progression in various subtypes. This pipeline provides valuable insights into cancer and immune-related processes in breast cancer subtypes.
A comparative cradle-to-gate life cycle assessment of three cotton stalk waste sustainable applications
Authors: Ibrahim Rana Adel , Inan Hatice , Fahim Irene S.
Published: November 2023

This paper presents a novel approach to utilizing agricultural waste. It compares three different applications for cotton stalks: fabrication of wood composites, bioethanol production, and biogas cradle-to-gate Life cycle assessment production processes. Cotton cultivation generates a lot of debris, mostly cotton stalks, which are incinerated or landfilled, Sustainable resource management is critical for maintaining the ecosystem, and economic stability, and promoting social fairness since it ensures the long-term availability of resources while minimizing environmental damage. The investigation uses the Ecological Footprint, Impact 2002 +, Global Warming Damage Potential, Greenhouse Gas Protocol, Recipe Midpoint, Ecosystem Damage Potential, and CML IA Baseline—open LCA-enabled environmental sustainability assessments. The analysis showed that bioethanol has a lower carbon footprint and climate change impact than both wood composite and biogas production processes, as a result, this could cause a preference for bioethanol production as an environmentally friendly strategy for cotton stalks utilization. While human toxicity was higher in the biogas production process, it emits less fossil CO2 than biogenic CO2. The total climate change of wood composite, bioethanol, and biogas production processes was 0.01761, 0.011300, and 0.01083 points, respectively. This research helps accomplish wider ecological and economic aims by giving insights into sustainable waste management practices.
Ecological correlates and predictors of Lassa fever incidence in Ondo State, Nigeria 2017–2021: an emerging urban trend
Authors: Cadmus Simeon , Taiwo Olalekan John , Akinseye Victor , Cadmus Eniola , Famokun Gboyega , Fagbemi Stephen , Ansumana Rashid , Omoluabi Anddy , Ayinmode Adekunle , Oluwayelu Daniel , Odemuyiwa Solomon , Tomori Oyewale
Published: November 2023

Lassa fever (LF) is prevalent in many West African countries, including Nigeria. Efforts to combat LF have primarily focused on rural areas where interactions between rodents and humans are common. However, recent studies indicate a shift in its occurrence from rural to urban areas. We analysed secondary data of reported LF outbreaks from 2017 to 2021 in Ondo State, Nigeria to identify the distribution pattern, ecological variations, and other determinants of disease spread from the ward level using nearest neighbour statistics and regression analysis. Data utilised include LF incidence, ecological variables involving population, nighttime light intensity, vegetation, temperature, market presence, road length, and building area coverage. ArcGIS Pro 3.0 software was employed for spatial analysis. Results revealed spatio-temporal clustering of LF incidents between 2017 and 2021, with an increasing trend followed by a decline in 2021. All wards in Owo Local Government Area were identified as LF hotspots. The ecological variables exhibited significant correlations with the number of LF cases in the wards, except for maximum temperature. Notably, these variables varied significantly between wards with confirmed LF and those without. Therefore, it is important to prioritise strategies for mitigating LF outbreaks in urban areas of Nigeria and other LF-endemic countries.
Long noncoding RNA NONHSAT160169.1 promotes resistance via hsa-let-7c-3p/SOX2 axis in gastric cancer
Authors: Zhao Xuan , Xu Zijian , Meng Bi , Ren Tong , Wang Xu , Hou Rui , Li Sijin , Ma Wen , Liu Dan , Zheng Junnian , Shi Ming
Published: November 2023

In clinical trials involving patients with HER2 (ERBB2 receptor tyrosine kinase 2) positive gastric cancer, the efficacy of the HER2-targeted drug lapatinib has proven to be disappointingly poor. Under the persistent pressure exerted by targeted drug therapy, a subset of tumor cells exhibit acquired drug resistance through the activation of novel survival signaling cascades, alongside the proliferation of tumor cells that previously harbored mutations conferring resistance to the drug. This study was undertaken with the aim of elucidating in comprehensive detail the intricate mechanisms behind adaptive resistance and identifying novel therapeutic targets that hold promise in the development of effective lapatinib-based therapies for the specific subset of patients afflicted with gastric cancer. We have successfully established a gastric cancer cell line with acquired lapatinib resistance, designated as HGC-27-LR cells. Utilizing comprehensive coding and noncoding transcriptome sequencing analysis, we have identified key factors that regulate lapatinib resistance in HGC-27 cells. We have compellingly validated that among all the lncRNAs identified in HGC-27-LR cells, a novel lncRNA (long noncoding RNA) named NONHSAT160169.1 was found to be most notably upregulated following exposure to lapatinib treatment. The upregulation of NONHSAT160169.1 significantly augmented the migratory, invasive, and stemness capabilities of HGC-27-LR cells. Furthermore, we have delved into the mechanism by which NONHSAT160169.1 regulates lapatinib resistance. The findings have revealed that NONHSAT160169.1, which is induced by the p-STAT3 (signal transducer and activator of transcription 3) nuclear transport pathway, functions as a decoy that competitively interacts with hsa-let-7c-3p and thereby abrogates the inhibitory effect of hsa-let-7c-3p on SOX2 (SRY-box transcription factor 2) expression. Hence, our study has unveiled the NONHSAT160169.1/hsa-let-7c-3p/SOX2 signaling pathway as a novel and pivotal axis for comprehending and surmounting lapatinib resistance in the treatment of HER2-positive gastric cancer.
A human bispecific antibody neutralizes botulinum neurotoxin serotype A
Authors: Lu Jiansheng , Jiang Yujia , Guo Jiazheng , Chen Lei , Liu Fujia , Li Zhiying , Liu Xuyang , Du Peng , Yu Yunzhou , Wang Rong , Yang Zhixin
Published: November 2023

Botulinum neurotoxin (BoNT) shows high lethality and toxicity, marking it as an important biological threat. The only effective post-exposure therapy is botulinum antitoxin; however, such products have great potential for improvement. To prevent or treat BoNT, monoclonal antibodies (mAbs) are promising agents. Herein, we aimed to construct a bispecific antibody (termed LUZ-A1-A3) based on the anti-BoNT/A human monoclonal antibodies (HMAb) A1 and A3. LUZ-A1-A3 binds to the Hc and L-HN domains of BoNT/A, displaying potent neutralization activity against BoNT/A (124 × higher than that of HMAb A1 or HMAb A3 alone and 15 × higher than that of the A1 + A3 combination). LUZ-A1-A3 provided effective protection against BoNT/A in an in vivo mouse model. Mice were protected from infection with 500 × LD50 of BoNT/A by LUZ-A1-A3 from up to 7 days before intraperitoneal administration of BoNT/A. We also demonstrated the effective therapeutic capacity of LUZ-A1-A3 against BoNT/A in a mouse model. LUZ-A1-A3 (5 μg/mouse) neutralized 20 × LD50 of BoNT/A at 3 h after intraperitoneal BoNT/A administration and complete neutralized 20 × LD50 of BoNT/A at 0.5 h after intraperitoneal BoNT/A administration. Thus, LUZ-A1-A3 is a promising agent for the pre-exposure prophylaxis and post-exposure treatment of BoNT/A.
Sea level anomalies affect the ocean circulation at abyssal depths
Authors: Frey D. I. , Morozov E. G. , Smirnova D. A.
Published: November 2023

Abyssal channels are the key points controlling bottom circulation of the World Ocean. They provide meridional transport of the coldest Antarctic Bottom Water between deep-water basins influencing the meridional overturning circulation and the climate on a global scale. Here we show that the synoptic variability of deep-water flows including blocking abyssal currents between deep ocean basins is related to sea level anomalies observed over the channels. Our results demonstrate that processes at the ocean surface have a more significant connection with the bottom circulation than it was considered earlier. This study opens a discussion of the importance of mesoscale eddies and air-sea interactions on water exchange between abyssal basins, meridional heat transport in the ocean, and possible responses of the ocean to the observed sea level rise in a changing climate.
Label-free quantitative proteomics analysis for type 2 diabetes mellitus early diagnostic marker discovery using data-independent acquisition mass spectrometry (DIA-MS)
Authors: Nimer Refat M. , Alfaqih Mahmoud A. , Shehabat Eman R. , Mujammami Muhammad , Abdel Rahman Anas M.
Published: November 2023

Type-2 diabetes mellitus (T2DM) therapy requires early diagnosis and complication avoidance. Unfortunately, current diagnostic markers do not meet these needs. Data-independent acquisition mass spectrometry (DIA-MS) offers a solution for clinical diagnosis, providing reliable and precise sample quantification. This study utilized DIA-MS to investigate proteomic differential expression in the serum of recently diagnosed T2DM patients. The study conducted a comparative protein expression analysis between healthy and recently diagnosed T2DM groups (discovery cohort). A candidate protein was then validated using enzyme-linked immune assay (ELISA) on serum samples collected from T2DM patients (n = 87) and healthy control (n = 60) (validation cohort). A total of 1074 proteins were identified, and 90 were significantly dysregulated between the two groups, including 32 newly associated with T2DM. Among these proteins, the expression of S100 calcium-binding protein A6 (S100A6) was validated by ELISA. It showed a significant increase in T2DM samples compared to the control group. It was evaluated as a biomarker using the receiver operating characteristic (ROC) curve, consistent with the DIA-MS results. Novel proteins are reported to be involved in the development and progression of T2DM. Further studies are required to investigate the differential expression of candidate marker proteins in a larger population of T2DM patients.
Fault-tolerant attitude control of the satellite in the presence of simultaneous actuator and sensor faults
Authors: Fazlyab Ali Reza , Fani Saberi Farhad , Kabganian Mansour
Published: November 2023

In this paper, a robust attitude control algorithm is developed based on backstepping sliding mode control for a satellite using reaction wheels and thrusters that can perform its mission despite faulty actuators. In this method, the actuator dynamics have been considered to design the controller and the asymptotic stability of the proposed algorithm has been proven based on the Lyapunov theory. The designed controller can converge the attitude of the system into the desired path in the presence of faulty actuators. Then a fault-tolerant attitude estimation system is designed based on federated unscented Kalman filters that can be effectively employed to detect and isolate sensor faults. Finally, the performance of the designed attitude estimation and controller is investigated by simulation in the presence of both actuator and sensor faults.