bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Liquid Splitting Behavior at Intersections on Infiltration Dynamics in an Unsaturated Fracture Network
Authors: Xue Song , Yang Zhibing , Zhou Zexiong , Hu Ran , Chen Yi‐Feng 
Published: September 2023

AbstractUnderstanding the macro‐scale flow characteristics in the fractured vadose zone is of great importance for subsurface hydrological and environmental applications. Here we develop an idealized fracture network model composed of a series of linked intersections, aiming to reveal the roles of local fluid flow, storage and splitting behaviors at intersections in controlling macroscopic unsaturated flow in a fracture network. By setting different local flow rules, unsaturated flow dynamics and structure in networks are systematically investigated. Numerical simulations suggest that avalanche infiltration mode, that is, sudden release of a large amount of water from the network, emerges spontaneously, and is modulated by the local splitting behavior. In terms of water infiltration structure, we find that uneven liquid splitting at intersections inevitably leads to preferential flow in networks. The preferential paths strongly rely on the competition between gravitational and capillary forces, relating to network structure and water saturation. When flow is dominated by gravity, preferential paths extend along large‐aperture routes; conversely, when flow is dominated by capillarity, the small‐aperture paths are preferred. In terms of infiltration dynamics, we show that the power spectral density of the water saturation time series in the network follows a power law with an exponent of −2 for all simulations with different structural parameters and local flow rules, suggesting a universal self‐organized criticality behavior for unsaturated flow in fractured rocks. The improved understanding from this study may shed new light on the complex flow dynamics for unsaturated flow in fractured media.
Transcriptional profiling of dental sensory and proprioceptive trigeminal neurons using single-cell RNA sequencing
Authors: Lee Pa Reum , Kim Jihoon , Rossi Heather Lynn , Chung Sena , Han Seung Yub , Kim Junhyong , Oh Seog Bae 
Published: September 2023

AbstractDental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.
Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines
Authors: Peng Ye , Zhang Lin , Mok Chris K. P. , Ching Jessica Y. L. , Zhao Shilin , Wong Matthew K. L. , Zhu Jie , Chen Chunke , Wang Shilan , Yan Shuai , Qin Biyan , Liu Yingzhi , Zhang Xi , Cheung Chun Pun , Cheong Pui Kuan , Ip Ka Long , Fung Adrian C. H. , Wong Kenneth K. Y. , Hui David S. C. , Chan Francis K. L. , Ng Siew C. , Tun Hein M. 
Published: September 2023

AbstractThe role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.
Cultivation and genomic characterization of novel and ubiquitous marine nitrite-oxidizing bacteria from the Nitrospirales
Authors: Mueller Anna J , Daebeler Anne , Herbold Craig W , Kirkegaard Rasmus H , Daims Holger 
Published: September 2023

Abstract
Nitrospirales, including the genus Nitrospira, are environmentally widespread chemolithoautotrophic nitrite-oxidizing bacteria. These mostly uncultured microorganisms gain energy through nitrite oxidation, fix CO2, and thus play vital roles in nitrogen and carbon cycling. Over the last decade, our understanding of their physiology has advanced through several new discoveries, such as alternative energy metabolisms and complete ammonia oxidizers (comammox Nitrospira). These findings mainly resulted from studies of terrestrial species, whereas less attention has been given to marine Nitrospirales. In this study, we cultured three new marine Nitrospirales enrichments and one isolate. Three of these four NOB represent new Nitrospira species while the fourth represents a novel genus. This fourth organism, tentatively named “Ca. Nitronereus thalassa”, represents the first cultured member of a Nitrospirales lineage that encompasses both free-living and sponge-associated nitrite oxidizers, is highly abundant in the environment, and shows distinct habitat distribution patterns compared to the marine Nitrospira species. Partially explaining this, “Ca. Nitronereus thalassa” harbors a unique combination of genes involved in carbon fixation and respiration, suggesting differential adaptations to fluctuating oxygen concentrations. Furthermore, “Ca. Nitronereus thalassa” appears to have a more narrow substrate range compared to many other marine nitrite oxidizers, as it lacks the genomic potential to utilize formate, cyanate, and urea. Lastly, we show that the presumed marine Nitrospirales lineages are not restricted to oceanic and saline environments, as previously assumed.
Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
Authors: Cao Yaoquan , Tang Haibo , Wang Guohui , Li Pengzhou , Song Zhi , Li Weizheng , Sun Xulong , Zhong Xiaoxiao , Yu Qianqian , Zhu Shaihong , Zhu Liyong 
Published: September 2023

AbstractThe inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.
SMCHD1 has separable roles in chromatin architecture and gene silencing that could be targeted in disease
Authors: Tapia del Fierro Andres , den Hamer Bianca , Benetti Natalia , Jansz Natasha , Chen Kelan , Beck Tamara , Vanyai Hannah , Gurzau Alexandra D. , Daxinger Lucia , Xue Shifeng , Ly Thanh Thao Nguyen , Wanigasuriya Iromi , Iminitoff Megan , Breslin Kelsey , Oey Harald , Krom Yvonne D. , van der Hoorn Dinja , Bouwman Linde F. , Johanson Timothy M. , Ritchie Matthew E. , Gouil Quentin A. , Reversade Bruno , Prin Fabrice , Mohun Timothy , van der Maarel Silvère M. , McGlinn Edwina , Murphy James M. , Keniry Andrew , de Greef Jessica C. , Blewitt Marnie E. 
Published: September 2023

AbstractThe interplay between 3D chromatin architecture and gene silencing is incompletely understood. Here, we report a novel point mutation in the non-canonical SMC protein SMCHD1 that enhances its silencing capacity at endogenous developmental targets. Moreover, it also results in enhanced silencing at the facioscapulohumeral muscular dystrophy associated macrosatellite-array, D4Z4, resulting in enhanced repression of DUX4 encoded by this repeat. Heightened SMCHD1 silencing perturbs developmental Hox gene activation, causing a homeotic transformation in mice. Paradoxically, the mutant SMCHD1 appears to enhance insulation against other epigenetic regulators, including PRC2 and CTCF, while depleting long range chromatin interactions akin to what is observed in the absence of SMCHD1. These data suggest that SMCHD1’s role in long range chromatin interactions is not directly linked to gene silencing or insulating the chromatin, refining the model for how the different levels of SMCHD1-mediated chromatin regulation interact to bring about gene silencing in normal development and disease.
Myo9b mutations are associated with altered dendritic cell functions and increased susceptibility to autoimmune diabetes onset
Authors: Zhang Jing , Zou Yuan , Chen Longmin , Sun Fei , Xu Qianqian , Zhou Qing , Wang Yi , Luo Xi , Wang Na , Li Yang , Zhang Shu , Xiong Fei , Yang Ping , Liu Shiwei , Yang Tao , Weng Jianping , Eizirik Décio L. , Yan Jinhua , Zhou Zhiguang , Wang Cong-Yi 
Published: September 2023

AbstractThe regulation of autoimmunity against pancreatic islet β cells for type 1 diabetes (T1D) onset is still unclear. NOD/ShiLtJ (NOD) mice are prone to the onset of autoimmune diabetes, but its congenic strain, ALR/Lt (ALR), is not. Here we show that dendritic cells (DC) in ALR mice have impaired migratory and T-cell priming capability. Genomic comparative analysis maps a 33-bp deletion in the ALR Myosin IXb (Myo9b) gene when compared with NOD genome; meanwhile, data from knock-in models show that this ALR Myo9b allele impairs phenotypic and functional maturation of DCs, and prevents the development and progression of spontaneous autoimmune diabetes in NOD mice. In parallel, while the ALR 33-bp deletion of Myo9b is not conserved in human, we find a MYO9B R133Q polymorphism associating with increased risk of T1D and enhanced DC function in patients with T1D. Our results thus hint that alterations in Myo9b may contribute to altered DC function and autoimmune diabetes onset.
A net-zero emissions strategy for China’s power sector using carbon-capture utilization and storage
Authors: Fan Jing-Li , Li Zezheng , Huang Xi , Li Kai , Zhang Xian , Lu Xi , Wu Jianzhong , Hubacek Klaus , Shen Bo 
Published: September 2023

AbstractDecarbonized power systems are critical to mitigate climate change, yet methods to achieve a reliable and resilient near-zero power system are still under exploration. This study develops an hourly power system simulation model considering high-resolution geological constraints for carbon-capture-utilization-and-storage to explore the optimal solution for a reliable and resilient near-zero power system. This is applied to 31 provinces in China by simulating 10,450 scenarios combining different electricity storage durations and interprovincial transmission capacities, with various shares of abated fossil power with carbon-capture-utilization-and-storage. Here, we show that allowing up to 20% abated fossil fuel power generation in the power system could reduce the national total power shortage rate by up to 9.0 percentages in 2050 compared with a zero fossil fuel system. A lowest-cost scenario with 16% abated fossil fuel power generation in the system even causes 2.5% lower investment costs in the network (or $16.8 billion), and also increases system resilience by reducing power shortage during extreme climatic events.
A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators
Authors: Chang Yi-Cheng , Lee Hsiao-Lin , Yang Wenjin , Hsieh Meng-Lun , Liu Cai-Cin , Lee Tung-Yuan , Huang Jing-Yong , Nong Jiun-Yi , Li Fu-An , Chuang Hsiao-Li , Ding Zhi-Zhong , Su Wei-Lun , Chueh Li-Yun , Tsai Yi-Ting , Chen Che-Hong , Mochly-Rosen Daria , Chuang Lee-Ming 
Published: September 2023

AbstractObesity and type 2 diabetes have reached pandemic proportion. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal. A missense Glu504Lys mutation of the ALDH2 gene is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We find that male Aldh2 knock-in mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver due to reduced adaptive thermogenesis and energy expenditure. We find reduced activity of ALDH2 of the brown adipose tissue from the male Aldh2 homozygous knock-in mice. Proteomic analyses of the brown adipose tissue from the male Aldh2 knock-in mice identifies increased 4-hydroxynonenal-adducted proteins involved in mitochondrial fatty acid oxidation and electron transport chain, leading to markedly decreased fatty acid oxidation rate and mitochondrial respiration of brown adipose tissue, which is essential for adaptive thermogenesis and energy expenditure. AD-9308 is a water-soluble, potent, and highly selective ALDH2 activator. AD-9308 treatment ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male Aldh2 wild-type and knock-in mice. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for metabolic diseases.
Deep learning-enabled realistic virtual histology with ultraviolet photoacoustic remote sensing microscopy
Authors: Martell Matthew T. , Haven Nathaniel J. M. , Cikaluk Brendyn D. , Restall Brendon S. , McAlister Ewan A. , Mittal Rohan , Adam Benjamin A. , Giannakopoulos Nadia , Peiris Lashan , Silverman Sveta , Deschenes Jean , Li Xingyu , Zemp Roger J. 
Published: September 2023

AbstractThe goal of oncologic surgeries is complete tumor resection, yet positive margins are frequently found postoperatively using gold standard H&E-stained histology methods. Frozen section analysis is sometimes performed for rapid intraoperative margin evaluation, albeit with known inaccuracies. Here, we introduce a label-free histological imaging method based on an ultraviolet photoacoustic remote sensing and scattering microscope, combined with unsupervised deep learning using a cycle-consistent generative adversarial network for realistic virtual staining. Unstained tissues are scanned at rates of up to 7 mins/cm2, at resolution equivalent to 400x digital histopathology. Quantitative validation suggests strong concordance with conventional histology in benign and malignant prostate and breast tissues. In diagnostic utility studies we demonstrate a mean sensitivity and specificity of 0.96 and 0.91 in breast specimens, and respectively 0.87 and 0.94 in prostate specimens. We also find virtual stain quality is preferred (P = 0.03) compared to frozen section analysis in a blinded survey of pathologists.
Characterization and structure-based protein engineering of a regiospecific saponin acetyltransferase from Astragalus membranaceus
Authors: Wang Linlin , Jiang Zhihui , Zhang Jiahe , Chen Kuan , Zhang Meng , Wang Zilong , Wang Binju , Ye Min , Qiao Xue 
Published: September 2023

AbstractAcetylation contributes to the bioactivity of numerous medicinally important natural products. However, little is known about the acetylation on sugar moieties. Here we report a saponin acetyltransferase fromAstragalus membranaceus. AmAT7-3 is discovered through a stepwise gene mining approach and characterized as the xylose C3′/C4′-O-acetyltransferse of astragaloside IV (1). To elucidate its catalytic mechanism, complex crystal structures of AmAT7-3/1and AmAT7-3A310G/1are obtained, which reveal a large active pocket decided by a specific sequence AADAG. Combining with QM/MM computation, the regiospecificity of AmAT7-3 is determined by sugar positioning modulated by surrounding amino acids including #A310 and #L290. Furthermore, a small mutant library is built using semi-rational design, where variants A310G and A310W are found to catalyze specific C3′-Oand C4′-Oacetylation, respectively. AmAT7-3 and its variants are also employed to acetylate other bioactive saponins. This work expands the understanding of saponin acetyltransferases, and provide efficient catalytic tools for saponin acetylation.
Blockade of interferon signaling decreases gut barrier integrity and promotes severe West Nile virus disease
Authors: Lin Shih-Ching , Zhao Fang R. , Janova Hana , Gervais Adrian , Rucknagel Summer , Murray Kristy O. , Casanova Jean-Laurent , Diamond Michael S. 
Published: September 2023

AbstractThe determinants of severe disease caused by West Nile virus (WNV) and why only ~1% of individuals progress to encephalitis remain poorly understood. Here, we use human and mouse enteroids, and a mouse model of pathogenesis, to explore the capacity of WNV to directly infect gastrointestinal (GI) tract cells and contribute to disease severity. At baseline, WNV poorly infects human and mouse enteroid cultures and enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI tract cells become infected, and this is associated with augmented GI tract and blood-brain barrier (BBB) permeability, accumulation of gut-derived molecules in the brain, and more severe WNV disease. The increased gut permeability requires TNF-α signaling, and is absent in WNV-infected IFN-deficient germ-free mice. To link these findings to human disease, we measured auto-antibodies against type I IFNs in serum from WNV-infected human cohorts. A greater frequency of auto- and neutralizing antibodies against IFN-α2 or IFN-ω is present in patients with severe WNV infection, whereas virtually no asymptomatic WNV-infected subjects have such antibodies (odds ratio 24 [95% confidence interval: 3.0 − 192.5;P = 0.003]). Overall, our experiments establish that blockade of type I IFN signaling extends WNV tropism to enterocytes, which correlates with increased gut and BBB permeability, and more severe disease.
Structural insights into the mechanism of GTP initiation of microtubule assembly
Authors: Zhou Ju , Wang Anhui , Song Yinlong , Liu Nan , Wang Jia , Li Yan , Liang Xin , Li Guohui , Chu Huiying , Wang Hong-Wei 
Published: September 2023

AbstractIn eukaryotes, the dynamic assembly of microtubules (MT) plays an important role in numerous cellular processes. The underlying mechanism of GTP triggering MT assembly is still unknown. Here, we present cryo-EM structures of tubulin heterodimer at their GTP- and GDP-bound states, intermediate assembly states of GTP-tubulin, and final assembly stages of MT. Both GTP- and GDP-tubulin heterodimers adopt similar curved conformations with subtle flexibility differences. In head-to-tail oligomers of tubulin heterodimers, the inter-dimer interface of GDP-tubulin exhibits greater flexibility, particularly in tangential bending. Cryo-EM of the intermediate assembly states reveals two types of tubulin lateral contacts, “Tube-bond” and “MT-bond”. Further, molecular dynamics (MD) simulations show that GTP triggers lateral contact formation in MT assembly in multiple sequential steps, gradually straightening the curved tubulin heterodimers. Therefore, we propose a flexible model of GTP-initiated MT assembly, including the formation of longitudinal and lateral contacts, to explain the nucleation and assembly of MT.
Magnetically-dressed CrSBr exciton-polaritons in ultrastrong coupling regime
Authors: Wang Tingting , Zhang Dingyang , Yang Shiqi , Lin Zhongchong , Chen Quan , Yang Jinbo , Gong Qihuang , Chen Zuxin , Ye Yu , Liu Wenjing 
Published: September 2023

AbstractOver the past few decades, exciton-polaritons have attracted substantial research interest due to their half-light-half-matter bosonic nature. Coupling exciton-polaritons with magnetic orders grants access to rich many-body phenomena, but has been limited by the availability of material systems that exhibit simultaneous exciton resonances and magnetic ordering. Here we report magnetically-dressed microcavity exciton-polaritons in the van der Waals antiferromagnetic (AFM) semiconductor CrSBr coupled to a Tamm plasmon microcavity. Using angle-resolved spectroscopy, we reveal an exceptionally high exciton-photon coupling strength, up to 169 meV, demonstrating ultrastrong coupling that persists up to room temperature. By performing temperature-dependent spectroscopy, we show the magnetic nature of the exciton-polaritons in CrSBr microcavity as the magnetic order changes from AFM to paramagnetic. By applying an out-of-plane magnetic field, we achieve effective tuning of the polariton energy while maintaining the ultrastrong exciton-photon coupling strength. We attribute this to the spin canting process that modulates the interlayer exciton interaction.
Evolution of lasR mutants in polymorphic Pseudomonas aeruginosa populations facilitates chronic infection of the lung
Authors: Zhao Kelei , Yang Xiting , Zeng Qianglin , Zhang Yige , Li Heyue , Yan Chaochao , Li Jing Shirley , Liu Huan , Du Liangming , Wu Yi , Huang Gui , Huang Ting , Zhang Yamei , Zhou Hui , Wang Xinrong , Chu Yiwen , Zhou Xikun 
Published: September 2023

AbstractChronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.