bluuebunny/crossref_metadata_2025 huggingface dataset:
Underthrusting of Tarim Lower Crust Beneath the Tibetan Plateau Revealed by Receiver Function Imaging
Authors: Wu Chenglong , Xu Tao , Tian Xiaobo , Mitchell Ross N. , Lin Jiyan , Yang Jianfeng , Wang Xin , Lu Zhanwu
Published: January 2024

The left‐lateral Altyn Tagh Fault (ATF) system is the northern boundary of the Tibetan Plateau resulted from the India–Eurasia continental collision. How intracontinental deformation across the central ATF responds to the distal collision remains elusive, primarily due to unclear crustal structure. We obtained detailed crustal structure across the central ATF using receiver functions recorded by ∼NW–SE oriented linear dense array. The images reveal the Tarim lower crust is underthrusting beneath the Tibetan Plateau and reaches to a maximum depth of ∼75 km and undergoing partial eclogitization. The two south‐dipping interfaces imaged beneath the Altyn Tagh Range (ATR) represent the thrusting Northern Altyn Fault and its branch fault. Oblique convergent forces extruded upper crustal materials along the thrust faults, creating the pop‐up structure of ATR, supported by low Vp/Vs ratios. Our balanced cross‐section for the Moho suggests intracontinental deformation in the ATR has accelerated since the late Miocene.
Data-driven connectivity profiles relate to smoking cessation outcomes
Authors: Murray Laura , Frederick Blaise B. , Janes Amy C.
Published: January 2024

At a group level, nicotine dependence is linked to differences in resting-state functional connectivity (rs-FC) within and between three large-scale brain networks: the salience network (SN), default mode network (DMN), and frontoparietal network (FPN). Yet, individuals may display distinct patterns of rs-FC that impact treatment outcomes. This study used a data-driven approach, Group Iterative Multiple Model Estimation (GIMME), to characterize shared and person-specific rs-FC features linked with clinically-relevant treatment outcomes. 49 nicotine-dependent adults completed a resting-state fMRI scan prior to a two-week smoking cessation attempt. We used GIMME to identify group, subgroup, and individual-level networks of SN, DMN, and FPN connectivity. Regression models assessed whether within- and between-network connectivity of individual rs-FC models was associated with baseline cue-induced craving, and craving and use of regular cigarettes (i.e., “slips”) during cessation. As a group, participants displayed shared patterns of connectivity within all three networks, and connectivity between the SN-FPN and DMN-SN. However, there was substantial heterogeneity across individuals. Individuals with greater within-network SN connectivity experienced more slips during treatment, while individuals with greater DMN-FPN connectivity experienced fewer slips. Individuals with more anticorrelated DMN-SN connectivity reported lower craving during treatment, while SN-FPN connectivity was linked to higher craving. In conclusion, in nicotine-dependent adults, GIMME identified substantial heterogeneity within and between the large-scale brain networks. Individuals with greater SN connectivity may be at increased risk for relapse during treatment, while a greater positive DMN-FPN and negative DMN-SN connectivity may be protective for individuals during smoking cessation treatment.
Electrophysiological signatures of anxiety in Parkinson’s disease
Authors: Yassine Sahar , Almarouk Sourour , Gschwandtner Ute , Auffret Manon , Fuhr Peter , Verin Marc , Hassan Mahmoud
Published: January 2024

Anxiety is a common non-motor symptom in Parkinson’s disease (PD) occurring in up to 31% of the patients and affecting their quality of life. Despite the high prevalence, anxiety symptoms in PD are often underdiagnosed and, therefore, undertreated. To date, functional and structural neuroimaging studies have contributed to our understanding of the motor and cognitive symptomatology of PD. Yet, the underlying pathophysiology of anxiety symptoms in PD remains largely unknown and studies on their neural correlates are missing. Here, we used resting-state electroencephalography (RS-EEG) of 68 non-demented PD patients with or without clinically-defined anxiety and 25 healthy controls (HC) to assess spectral and functional connectivity fingerprints characterizing the PD-related anxiety. When comparing the brain activity of the PD anxious group (PD-A, N = 18) to both PD non-anxious (PD-NA, N = 50) and HC groups (N = 25) at baseline, our results showed increased fronto-parietal delta power and decreased frontal beta power depicting the PD-A group. Results also revealed hyper-connectivity networks predominating in delta, theta and gamma bands against prominent hypo-connectivity networks in alpha and beta bands as network signatures of anxiety in PD where the frontal, temporal, limbic and insular lobes exhibited the majority of significant connections. Moreover, the revealed EEG-based electrophysiological signatures were strongly associated with the clinical scores of anxiety and followed their progression trend over the course of the disease. We believe that the identification of the electrophysiological correlates of anxiety in PD using EEG is conducive toward more accurate prognosis and can ultimately support personalized psychiatric follow-up and the development of new therapeutic strategies.
Targeted immunotherapy: harnessing the immune system to battle multiple myeloma
Authors: Xu Limei , Wen Caining , Xia Jiang , Zhang Hao , Liang Yujie , Xu Xiao
Published: January 2024

Multiple myeloma (MM) remains an incurable hematological malignancy disease characterized by the progressive dysfunction of the patient’s immune system. In this context, immunotherapy for MM has emerged as a prominent area of research in recent years. Various targeted immunotherapy strategies, such as monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cells/natural killer (NK) cells, and checkpoint inhibitors have been developed for MM. This review aims to discuss promising experimental and clinical evidence as well as the mechanisms of action underlying these immunotherapies. Specifically, we will explore the design of exosome-based bispecific monoclonal antibodies that offer cell-free immunotherapy options. The treatment landscape for myeloma continues to evolve with the development of numerous emerging immunotherapies. Given their significant advantages in modulating the MM immune environment through immune-targeted therapy, these approaches provide novel perspectives in selecting cutting-edge treatments for MM.
Despite structural identity, ace-1 heterogenous duplication resistance alleles are quite diverse in Anopheles mosquitoes
Authors: Claret Jean-Loup , Di-Liegro Marion , Namias Alice , Assogba Benoit , Makoundou Patrick , Koffi Alphonsine , Pennetier Cédric , Weill Mylène , Milesi Pascal , Labbé Pierrick
Published: January 2024

Anopheles gambiae s.l. has been the target of intense insecticide treatment since the mid-20th century to try and control malaria. A substitution in the ace-1 locus has been rapidly selected for, allowing resistance to organophosphate and carbamate insecticides. Since then, two types of duplication of the ace-1 locus have been found in An. gambiae s.l. populations: homogeneous duplications that are composed of several resistance copies, or heterogeneous duplications that contain both resistance and susceptible copies. The substitution induces a trade-off between resistance in the presence of insecticides and disadvantages in their absence: the heterogeneous duplications allow the fixation of the intermediate heterozygote phenotype. So far, a single heterogeneous duplication has been described in An. gambiae s.l. populations (in contrast with the multiple duplicated alleles found in Culex pipiens mosquitoes). We used a new approach, combining long and short-read sequencing with Sanger sequencing to precisely identify and describe at least nine different heterogeneous duplications, in two populations of An. gambiae s.l. We show that these alleles share the same structure as the previously identified heterogeneous and homogeneous duplications, namely 203-kb tandem amplifications with conserved breakpoints. Our study sheds new light on the origin and maintenance of these alleles in An. gambiae s.l. populations, and their role in mosquito adaptation.
Rising rainfall intensity induces spatially divergent hydrological changes within a large river basin
Authors: Wu Yiping , Yin Xiaowei , Zhou Guoyi , Bruijnzeel L. Adrian , Dai Aiguo , Wang Fan , Gentine Pierre , Zhang Guangchuang , Song Yanni , Zhou Decheng
Published: January 2024

Droughts or floods are usually attributed to precipitation deficits or surpluses, both of which may become more frequent and severe under continued global warming. Concurring large-scale droughts in the Southwest and flooding in the Southeast of China in recent decades have attracted considerable attention, but their causes and interrelations are not well understood. Here, we examine spatiotemporal changes in hydrometeorological variables and investigate the mechanism underlying contrasting soil dryness/wetness patterns over a 54-year period (1965–2018) across a representative mega-watershed in South China—the West River Basin. We demonstrate that increasing rainfall intensity leads to severe drying upstream with decreases in soil water storage, water yield, and baseflow, versus increases therein downstream. Our study highlights a simultaneous occurrence of increased drought and flooding risks due to contrasting interactions between rainfall intensification and topography across the river basin, implying increasingly vulnerable water and food security under continued climate change.
Trajectory inference across multiple conditions with condiments
Authors: Roux de Bézieux Hector , Van den Berge Koen , Street Kelly , Dudoit Sandrine
Published: January 2024

In single-cell RNA sequencing (scRNA-Seq), gene expression is assessed individually for each cell, allowing the investigation of developmental processes, such as embryogenesis and cellular differentiation and regeneration, at unprecedented resolution. In such dynamic biological systems, cellular states form a continuum, e.g., for the differentiation of stem cells into mature cell types. This process is often represented via a trajectory in a reduced-dimensional representation of the scRNA-Seq dataset. While many methods have been suggested for trajectory inference, it is often unclear how to handle multiple biological groups or conditions, e.g., inferring and comparing the differentiation trajectories of wild-type and knock-out stem cell populations. In this manuscript, we presentcondiments, a method for the inference and downstream interpretation of cell trajectories across multiple conditions. Our framework allows the interpretation of differences between conditions at the trajectory, cell population, and gene expression levels. We start by integrating datasets from multiple conditions into a single trajectory. By comparing the cell’s conditions along the trajectory’s path, we can detect large-scale changes, indicative of differential progression or fate selection. We also demonstrate how to detect subtler changes by finding genes that exhibit different behaviors between these conditions along a differentiation path.
Global distribution of surface soil organic carbon in urban greenspaces
Authors: Guo Hongbo , Du Enzai , Terrer César , Jackson Robert B.
Published: January 2024

Urban greenspaces continue to grow with global urbanization. The global distribution and stock of soil organic carbon (SOC) in urban greenspaces remain largely undescribed and missing in global carbon (C) budgets. Here, we synthesize data of 420 observations from 257 cities in 52 countries to evaluate the global pattern of surface SOC density (0–20 cm depth) in urban greenspaces. Surface SOC density in urban greenspaces increases significantly at higher latitudes and decreases significantly with higher mean annual temperature, stronger temperature and precipitation seasonality, as well as lower urban greenness index. By mapping surface SOC density using a random forest model, we estimate an average SOC density of 55.2 (51.9–58.6) Mg C ha−1 and a SOC stock of 1.46 (1.37–1.54) Pg C in global urban greenspaces. Our findings present a comprehensive assessment of SOC in global urban greenspaces and provide a baseline for future urban soil C assessment under continuing urbanization.
Intensifying rice production to reduce imports and land conversion in Africa
Authors: Yuan Shen , Saito Kazuki , van Oort Pepijn A. J. , van Ittersum Martin K. , Peng Shaobing , Grassini Patricio
Published: January 2024

Africa produces around 60% of the rice the continent consumes, relying heavily on rice imports to fulfill the rest of the domestic demand. Over the past 10 years, the rice-agricultural area increased nearly 40%, while average yield remained stagnant. Here we used a process-based crop simulation modelling approach combined with local weather, soil, and management datasets to evaluate the potential to increase rice production on existing cropland area in Africa and assess cropland expansion and rice imports by year 2050 for different scenarios of yield intensification. We find that Africa can avoid further increases in rice imports, and even reduce them, through a combination of cropland expansion following the historical trend together with closure of the current exploitable yield gap by half or more. Without substantial increase in rice yields, meeting future rice demand will require larger rice imports and/or land conversion than now.
Three-dimensional covalent organic frameworks with nia nets for efficient separation of benzene/cyclohexane mixtures
Authors: Chang Jianhong , Chen Fengqian , Li Hui , Suo Jinquan , Zheng Haorui , Zhang Jie , Wang Zitao , Zhu Liangkui , Valtchev Valentin , Qiu Shilun , Fang Qianrong
Published: January 2024

The synthesis of three-dimensional covalent organic frameworks with highly connected building blocks presents a significant challenge. In this study, we report two 3D COFs with the nia topology, named JUC-641 and JUC-642, by introducing planar hexagonal and triangular prism nodes. Notably, our adsorption studies and breakthrough experiments reveal that both COFs exhibit exceptional separation capabilities, surpassing previously reported 3D COFs and most porous organic polymers, with a separation factor of up to 2.02 for benzene and cyclohexane. Additionally, dispersion-corrected density functional theory analysis suggests that the good performance of these 3D COFs can be attributed to the incorporation of highly aromatic building blocks and the presence of extensive pore structures. Consequently, this research not only expands the diversity of COFs but also highlights the potential of functional COF materials as promising candidates for environmentally-friendly separation applications.
Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation
Authors: An Luye , Kim Dahihm , Donahue Leanne R. , Mejooli Menansili Abraham , Eom Chi-Yong , Nishimura Nozomi , White Andrew C.
Published: January 2024

Vitiligo is an autoimmune skin disease caused by cutaneous melanocyte loss. Although phototherapy and T cell suppression therapy have been widely used to induce epidermal re-pigmentation, full pigmentation recovery is rarely achieved due to our poor understanding of the cellular and molecular mechanisms governing this process. Here, we identify unique melanocyte stem cell (McSC) epidermal migration rates between male and female mice, which is due to sexually dimorphic cutaneous inflammatory responses generated by ultra-violet B exposure. Using genetically engineered mouse models, and unbiased bulk and single-cell mRNA sequencing approaches, we determine that manipulating the inflammatory response through cyclooxygenase and its downstream prostaglandin product regulates McSC proliferation and epidermal migration in response to UVB exposure. Furthermore, we demonstrate that a combinational therapy that manipulates both macrophages and T cells (or innate and adaptive immunity) significantly promotes epidermal melanocyte re-population. With these findings, we propose a novel therapeutic strategy for repigmentation in patients with depigmentation conditions such as vitiligo.
Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging
Authors: Jiménez-Loygorri Juan Ignacio , Villarejo-Zori Beatriz , Viedma-Poyatos Álvaro , Zapata-Muñoz Juan , Benítez-Fernández Rocío , Frutos-Lisón María Dolores , Tomás-Barberán Francisco A. , Espín Juan Carlos , Area-Gómez Estela , Gomez-Duran Aurora , Boya Patricia
Published: January 2024

Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice. Transcriptomic analysis shows marked upregulation of the type I interferon response in the retina of old mice, which correlates with increased levels of cytosolic mtDNA and activation of the cGAS/STING pathway. Crucially, these same alterations are replicated in primary human fibroblasts from elderly donors. In old mice, pharmacological induction of mitophagy with urolithin A attenuates cGAS/STING activation and ameliorates deterioration of neurological function. These findings point to mitophagy induction as a strategy to decrease age-associated inflammation and increase healthspan.
In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing
Authors: Chen Shuiling , Luo Yang , He Yang , Li Ming , Liu Yongjian , Zhou Xishen , Hou Jianwen , Zhou Shaobing
Published: January 2024

Surgery is the mainstay of treatment modality for malignant melanoma. However, the deteriorative hypoxic microenvironment after surgery is recognized as a stemming cause for tumor recurrence/metastasis and delayed wound healing. Here we design and construct a sprayable therapeutic hydrogel (HIL@Z/P/H) encapsulating tumor-targeted nanodrug and photosynthetic cyanobacteria (PCC 7942) to prevent tumor recurrence/metastasis while promote wound healing. In a postsurgical B16F10 melanoma model in female mice, the nanodrug can disrupt cellular redox homeostasis via the photodynamic therapy-induced cascade reactions within tumor cells. Besides, the photosynthetically generated O2 by PCC 7942 can not only potentiate the oxidative stress-triggered cell death to prevent local recurrence of residual tumor cells, but also block the signaling pathway of hypoxia-inducible factor 1α to inhibit their distant metastasis. Furthermore, the long-lasting O2 supply and PCC 7942-secreted extracellular vesicles can jointly promote angiogenesis and accelerate the wound healing process. Taken together, the developed HIL@Z/P/H capable of preventing tumor recurrence/metastasis while promoting wound healing shows great application potential for postsurgical cancer therapy.
Hydrogen bond unlocking-driven pore structure control for shifting multi-component gas separation function
Authors: Yang Rong , Wang Yu , Cao Jian-Wei , Ye Zi-Ming , Pham Tony , Forrest Katherine A. , Krishna Rajamani , Chen Hongwei , Li Libo , Ling Bo-Kai , Zhang Tao , Gao Tong , Jiang Xue , Xu Xiang-Ou , Ye Qian-Hao , Chen Kai-Jie
Published: January 2024

Purification of ethylene (C2H4) as the most extensive and output chemical, from complex multi-components is of great significance but highly challenging. Herein we demonstrate that precise pore structure tuning by controlling the network hydrogen bonds in two highly-related porous coordination networks can shift the efficient C2H4 separation function from C2H2/C2H4/C2H6 ternary mixture to CO2/C2H2/C2H4/C2H6 quaternary mixture system. Single-crystal X-ray diffraction revealed that the different amino groups on the triazolate ligands resulted in the change of the hydrogen bonding in the host network, which led to changes in the pore shape and pore chemistry. Gas adsorption isotherms, adsorption kinetics and gas-loaded crystal structure analysis indicated that the coordination network Zn-fa-atz (2) weakened the affinity for three C2 hydrocarbons synchronously including C2H4 but enhanced the CO2 adsorption due to the optimized CO2-host interaction and the faster CO2 diffusion, leading to effective C2H4 production from the CO2/C2H2/C2H4/C2H6 mixture in one step based on the experimental and simulated breakthrough data. Moreover, it can be shaped into spherical pellets with maintained porosity and separation performance.
Reconstitution of human PDAC using primary cells reveals oncogenic transcriptomic features at tumor onset
Authors: Xu Yi , Nipper Michael H. , Dominguez Angel A. , Ye Zhenqing , Akanuma Naoki , Lopez Kevin , Deng Janice J. , Arenas Destiny , Sanchez Ava , Sharkey Francis E. , Court Colin M. , Singhi Aatur D. , Wang Huamin , Fernandez-Zapico Martin E. , Sun Lu-Zhe , Zheng Siyuan , Chen Yidong , Liu Jun , Wang Pei
Published: January 2024

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations. The acinar organoids undergo dramatic transcriptional alterations but maintain a recognizable DNA methylation signature. The transcriptomes of acinar organoids are similar to those of disease-specific cell populations. Oncogenic KRAS alone do not transform acinar organoids. However, acinar organoids can form PDAC in vivo after acquiring the four most common driver mutations of this disease. Similarly, sorted ductal cells carrying these genetic mutations can also form PDAC, thus experimentally proving that PDACs can originate from both human acinar and ductal cells. RNA-seq analysis reveal the transcriptional shift from normal acinar cells towards PDACs with enhanced proliferation, metabolic rewiring, down-regulation of MHC molecules, and alterations in the coagulation and complement cascade. By comparing PDAC-like cells with normal pancreas and PDAC samples, we identify a group of genes with elevated expression during early transformation which represent potential early diagnostic biomarkers.
BacPE: a versatile prime-editing platform in bacteria by inhibiting DNA exonucleases
Authors: Zhang Hongyuan , Ma Jiacheng , Wu Zhaowei , Chen Xiaoyang , Qian Yangyang , Chen Weizhong , Wang Zhipeng , Zhang Ya , Zhu Huanhu , Huang Xingxu , Ji Quanjiang
Published: January 2024

Prime editing allows precise installation of any single base substitution and small insertions and deletions without requiring homologous recombination or double-strand DNA breaks in eukaryotic cells. However, the applications in bacteria are hindered and the underlying mechanisms that impede efficient prime editing remain enigmatic. Here, we report the determination of vital cellular factors that affect prime editing in bacteria. Genetic screening of 129 Escherichia coli transposon mutants identified sbcB, a 3ʹ→5ʹ DNA exonuclease, as a key genetic determinant in impeding prime editing in E. coli, combinational deletions of which with two additional 3ʹ→5ʹ DNA exonucleases, xseA and exoX, drastically enhanced the prime editing efficiency by up to 100-fold. Efficient prime editing in wild-type E. coli can be achieved by simultaneously inhibiting the DNA exonucleases via CRISPRi. Our results pave the way for versatile applications of prime editing for bacterial genome engineering.
Consistent stoichiometric long-term relationships between nutrients and chlorophyll-a across shallow lakes
Authors: Graeber Daniel , McCarthy Mark J. , Shatwell Tom , Borchardt Dietrich , Jeppesen Erik , Søndergaard Martin , Lauridsen Torben L. , Davidson Thomas A.
Published: January 2024

Aquatic ecosystems are threatened by eutrophication from nutrient pollution. In lakes, eutrophication causes a plethora of deleterious effects, such as harmful algal blooms, fish kills and increased methane emissions. However, lake-specific responses to nutrient changes are highly variable, complicating eutrophication management. These lake-specific responses could result from short-term stochastic drivers overshadowing lake-independent, long-term relationships between phytoplankton and nutrients. Here, we show that strong stoichiometric long-term relationships exist between nutrients and chlorophyll a (Chla) for 5-year simple moving averages (SMA, median R² = 0.87) along a gradient of total nitrogen to total phosphorus (TN:TP) ratios. These stoichiometric relationships are consistent across 159 shallow lakes (defined as average depth < 6 m) from a cross-continental, open-access database. We calculate 5-year SMA residuals to assess short-term variability and find substantial short-term Chla variation which is weakly related to nutrient concentrations (median R² = 0.12). With shallow lakes representing 89% of the world’s lakes, the identified stoichiometric long-term relationships can globally improve quantitative nutrient management in both lakes and their catchments through a nutrient-ratio-based strategy.
Bioinspired light-driven chloride pump with helical porphyrin channels
Authors: Li Chao , Zhai Yi , Jiang Heming , Li Siqi , Liu Pengxiang , Gao Longcheng , Jiang Lei
Published: January 2024

Halorhodopsin, a light-driven chloride pump, utilizes photonic energy to drive chloride ions across biological membranes, regulating the ion balance and conveying biological information. In the light-driven chloride pump process, the chloride-binding chromophore (protonated Schiff base) is crucial, able to form the active center by absorbing light and triggering the transport cycle. Inspired by halorhodopsin, we demonstrate an artificial light-driven chloride pump using a helical porphyrin channel array with excellent photoactivity and specific chloride selectivity. The helical porphyrin channels are formed by a porphyrin-core star block copolymer, and the defects along the channels can be effectively repaired by doping a small number of porphyrins. The well-repaired porphyrin channel exhibits the light-driven Cl− migration against a 3-fold concentration gradient, showing the ion pumping behavior. The bio-inspired artificial light-driven chloride pump provides a prospect for designing bioinspired responsive ion channel systems and high-performance optogenetics.
Phase transitions associated with magnetic-field induced topological orbital momenta in a non-collinear antiferromagnet
Authors: Deng Sihao , Gomonay Olena , Chen Jie , Fischer Gerda , He Lunhua , Wang Cong , Huang Qingzhen , Shen Feiran , Tan Zhijian , Zhou Rui , Hu Ze , Šmejkal Libor , Sinova Jairo , Wernsdorfer Wolfgang , Sürgers Christoph
Published: January 2024

Resistivity measurements are widely exploited to uncover electronic excitations and phase transitions in metallic solids. While single crystals are preferably studied to explore crystalline anisotropies, these usually cancel out in polycrystalline materials. Here we show that in polycrystalline Mn3Zn0.5Ge0.5N with non-collinear antiferromagnetic order, changes in the diagonal and, rather unexpected, off-diagonal components of the resistivity tensor occur at low temperatures indicating subtle transitions between magnetic phases of different symmetry. This is supported by neutron scattering and explained within a phenomenological model which suggests that the phase transitions in magnetic field are associated with field induced topological orbital momenta. The fact that we observe transitions between spin phases in a polycrystal, where effects of crystalline anisotropy are cancelled suggests that they are only controlled by exchange interactions. The observation of an off-diagonal resistivity extends the possibilities for realising antiferromagnetic spintronics with polycrystalline materials.
Accurate prediction of the optical properties of nanoalloys with both plasmonic and magnetic elements
Authors: Coviello Vito , Badocco Denis , Pastore Paolo , Fracchia Martina , Ghigna Paolo , Martucci Alessandro , Forrer Daniel , Amendola Vincenzo
Published: January 2024

The alloying process plays a pivotal role in the development of advanced multifunctional plasmonic materials within the realm of modern nanotechnology. However, accurate in silico predictions are only available for metal clusters of just a few nanometers, while the support of modelling is required to navigate the broad landscape of components, structures and stoichiometry of plasmonic nanoalloys regardless of their size. Here we report on the accurate calculation and conceptual understanding of the optical properties of metastable alloys of both plasmonic (Au) and magnetic (Co) elements obtained through a tailored laser synthesis procedure. The model is based on the density functional theory calculation of the dielectric function with the Hubbard-corrected local density approximation, the correction for intrinsic size effects and use of classical electrodynamics. This approach is built to manage critical aspects in modelling of real samples, as spin polarization effects due to magnetic elements, short-range order variability, and size heterogeneity. The method provides accurate results also for other magnetic-plasmonic (Au-Fe) and typical plasmonic (Au-Ag) nanoalloys, thus being available for the investigation of several other nanomaterials waiting for assessment and exploitation in fundamental sectors such as quantum optics, magneto-optics, magneto-plasmonics, metamaterials, chiral catalysis and plasmon-enhanced catalysis.
Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and viral vaccines
Authors: Zhu Wenjun , Wei Ting , Xu Yuchun , Jin Qiutong , Chao Yu , Lu Jiaqi , Xu Jun , Zhu Jiafei , Yan Xiaoying , Chen Muchao , Chen Qian , Liu Zhuang
Published: January 2024

Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform based on biocompatible fluorocarbon modified chitosan (FCS) is developed to achieve highly efficient non-invasive delivery of biomacromolecules including antibodies and antigens. The formed nanocomplexes exhibits effective transdermal penetration ability via both intercellular and transappendageal routes. Non-invasive transdermal delivery of immune checkpoint blockade antibodies induces stronger immune responses for melanoma in female mice and reduces systemic toxicity compared to intravenous injection. Moreover, transdermal delivery of a SARS-CoV-2 vaccine in female mice results in comparable humoral immunity as well as improved cellular immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Additionally, FCS-based protein delivery systems demonstrate transdermal ability for rabbit and porcine skins. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of bio-therapeutics.
Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis
Authors: Dong Ting , Hu Guangan , Fan Zhongqi , Wang Huirui , Gao Yinghui , Wang Sisi , Xu Hao , Yaffe Michael B. , Vander Heiden Matthew G. , Lv Guoyue , Chen Jianzhu
Published: January 2024

Kupffer cells are liver resident macrophages and play critical role in fatty liver disease, yet the underlying mechanisms remain unclear. Here, we show that activation of G-protein coupled receptor 3 (GPR3) in Kupffer cells stimulates glycolysis and protects mice from obesity and fatty liver disease. GPR3 activation induces a rapid increase in glycolysis via formation of complexes between β-arrestin2 and key glycolytic enzymes as well as sustained increase in glycolysis through transcription of glycolytic genes. In mice, GPR3 activation in Kupffer cells results in enhanced glycolysis, reduced inflammation and inhibition of high-fat diet induced obesity and liver pathogenesis. In human fatty liver biopsies, GPR3 activation increases expression of glycolytic genes and reduces expression of inflammatory genes in a population of disease-associated macrophages. These findings identify GPR3 activation as a pivotal mechanism for metabolic reprogramming of Kupffer cells and as a potential approach for treating fatty liver disease.
Two-component nematic superconductivity in 4Hb-TaS2
Authors: Silber I. , Mathimalar S. , Mangel I. , Nayak A. K. , Green O. , Avraham N. , Beidenkopf H. , Feldman I. , Kanigel A. , Klein A. , Goldstein M. , Banerjee A. , Sela E. , Dagan Y.
Published: January 2024

Most superconductors have an isotropic, single component order parameter and are well described by the standard (BCS) theory for superconductivity. Unconventional, multiple-component superconductors are exceptionally rare and are much less understood. Here, we combine scanning tunneling microscopy and angle-resolved macroscopic transport for studying the candidate chiral superconductor, 4Hb-TaS2. We reveal quasi-periodic one-dimensional modulations in the tunneling conductance accompanied by two-fold symmetric superconducting critical field. The strong modulation of the in-plane critical field, Hc2, points to a nematic, unconventional order parameter. However, the imaged vortex core is isotropic at low temperatures. We suggest a model that reconciles this apparent discrepancy and takes into account previously observed spontaneous time-reversal symmetry breaking at low temperatures. The model describes a competition between a dominating chiral superconducting order parameter and a nematic one. The latter emerges close to the normal phase. Our results strongly support the existence of two-component superconductivity in 4Hb-TaS2 and can provide valuable insights into other systems with coexistent charge order and superconductivity.
Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model
Authors: Li Zhifang , Guo Ruochen , Sun Xiaozhi , Li Guoling , Shao Zhuang , Huo Xiaona , Yang Rongrong , Liu Xinyu , Cao Xi , Zhang Hainan , Zhang Weihong , Zhang Xiaoyin , Ma Shuangyu , Zhang Meiling , Liu Yuanhua , Yao Yinan , Shi Jinqi , Yang Hui , Hu Chunyi , Zhou Yingsi , Xu Chunlong
Published: January 2024

Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (408 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB from Deinococcus radiodurans (ISDra2 TnpB) in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA (ωRNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-ωRNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and corrected the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.
Single-cell multiomics decodes regulatory programs for mouse secondary palate development
Authors: Yan Fangfang , Suzuki Akiko , Iwaya Chihiro , Pei Guangsheng , Chen Xian , Yoshioka Hiroki , Yu Meifang , Simon Lukas M. , Iwata Junichi , Zhao Zhongming
Published: January 2024

Perturbations in gene regulation during palatogenesis can lead to cleft palate, which is among the most common congenital birth defects. Here, we perform single-cell multiome sequencing and profile chromatin accessibility and gene expression simultaneously within the same cells (n = 36,154) isolated from mouse secondary palate across embryonic days (E) 12.5, E13.5, E14.0, and E14.5. We construct five trajectories representing continuous differentiation of cranial neural crest-derived multipotent cells into distinct lineages. By linking open chromatin signals to gene expression changes, we characterize the underlying lineage-determining transcription factors. In silico perturbation analysis identifies transcription factors SHOX2 and MEOX2 as important regulators of the development of the anterior and posterior palate, respectively. In conclusion, our study charts epigenetic and transcriptional dynamics in palatogenesis, serving as a valuable resource for further cleft palate research.
High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer
Authors: Mei Jie , Cai Yun , Zhu Hongjun , Jiang Ying , Fu Ziyi , Xu Junying , Chen Lingyan , Yang Kai , Zhao Jinlu , Song Chenghu , Zhang Yan , Mao Wenjun , Yin Yongmei
Published: January 2024

Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancers, but exhibits higher chemotherapeutic and immunotherapeutic responses due to its unique immunogenicity. Thus, appropriate discrimination of subtypes is critical for guiding therapeutic options in clinical practice. In this research, using multiple in-house and public cohorts, we investigated the expression features and immuno-correlations of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in a mouse model. We also developed a novel classifier combining B7-H3 and PD-L1 expression in TNBC. B7-H3 was revealed to be related to immuno-cold features and accumulated collagen in TNBC. In addition, targeting B7-H3 using the monoclonal antibody significantly suppressed mouse TNBC growth, reversed the armored-cold phenotype, and also boosted anti-PD-1 immunotherapy. In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.
Image-guided programming deep brain stimulation improves clinical outcomes in patients with Parkinson’s disease
Authors: Torres Viviana , Del Giudice Kirsys , Roldán Pedro , Rumià Jordi , Muñoz Esteban , Cámara Ana , Compta Yaroslau , Sánchez-Gómez Almudena , Valldeoriola Francesc
Published: January 2024

Deep brain stimulation (DBS) is an effective treatment for patients with Parkinson’s disease (PD). However, some patients may not respond optimally to clinical programming adjustments. Advances in DBS technology have led to more complex and time-consuming programming. Image-guided programming (IGP) could optimize and improve programming leading to better clinical outcomes in patients for whom DBS programming is not ideal due to sub-optimal response. We conducted a prospective single-center study including 31 PD patients with subthalamic nucleus (STN) DBS and suboptimal responses refractory to clinical programming. Programming settings were adjusted according to the volumetric reconstruction of the stimulation field using commercial postoperative imaging software. Clinical outcomes were assessed at baseline and at 3-month follow-up after IGP, using motor and quality of life (QoL) scales. Additionally, between these two assessment points, follow-up visits for fine-tuning amplitude intensity and medication were conducted at weeks 2, 4, 6, and 9. After IGP, twenty-six patients (83.9%) experienced motor and QoL improvements, with 25.8% feeling much better and 38.7% feeling moderately better according to the patient global impression scale. Five patients (16.1%) had no clinical or QoL changes after IGP. The MDS-UPDRS III motor scale showed a 21.9% improvement and the DBS-IS global score improved by 41.5%. IGP optimizes STN-DBS therapy for PD patients who are experiencing suboptimal clinical outcomes. These findings support using IGP as a standard tool in clinical practice, which could save programming time and improve patients’ QoL.
Quantifying the effect of gate errors on variational quantum eigensolvers for quantum chemistry
Authors: Dalton Kieran , Long Christopher K. , Yordanov Yordan S. , Smith Charles G. , Barnes Crispin H. W. , Mertig Normann , Arvidsson-Shukur David R. M.
Published: January 2024

Variational quantum eigensolvers (VQEs) are leading candidates to demonstrate near-term quantum advantage. Here, we conduct density-matrix simulations of leading gate-based VQEs for a range of molecules. We numerically quantify their level of tolerable depolarizing gate-errors. We find that: (i) The best-performing VQEs require gate-error probabilities between 10−6 and 10−4 (10−4 and 10−2 with error mitigation) to predict, within chemical accuracy, ground-state energies of small molecules with 4 − 14 orbitals. (ii) ADAPT-VQEs that construct ansatz circuits iteratively outperform fixed-circuit VQEs. (iii) ADAPT-VQEs perform better with circuits constructed from gate-efficient rather than physically-motivated elements. (iv) The maximally-allowed gate-error probability, pc, for any VQE to achieve chemical accuracy decreases with the number NII of noisy two-qubit gates as $${p}_{c}\mathop{\propto }\limits_{\displaystyle{ \sim }}{N}_{{{{\rm{II}}}}}^{-1}$$

p

c

∝

~

N

II

−
1

. Additionally, pc decreases with system size, even with error mitigation, implying that larger molecules require even lower gate-errors. Thus, quantum advantage via gate-based VQEs is unlikely unless gate-error probabilities are decreased by orders of magnitude.
Controlling the photon number coherence of solid-state quantum light sources for quantum cryptography
Authors: Karli Yusuf , Vajner Daniel A. , Kappe Florian , Hagen Paul C. A. , Hansen Lena M. , Schwarz René , Bracht Thomas K. , Schimpf Christian , Covre da Silva Saimon F. , Walther Philip , Rastelli Armando , Axt Vollrath Martin , Loredo Juan C. , Remesh Vikas , Heindel Tobias , Reiter Doris E. , Weihs Gregor
Published: January 2024

Quantum communication networks rely on quantum cryptographic protocols including quantum key distribution (QKD) based on single photons. A critical element regarding the security of QKD protocols is the photon number coherence (PNC), i.e., the phase relation between the vacuum and one-photon Fock state. To obtain single photons with the desired properties for QKD protocols, optimal excitation schemes for quantum emitters need to be selected. As emitters, we consider semiconductor quantum dots, that are known to generate on-demand single photons with high purity and indistinguishability. Exploiting two-photon excitation of a quantum dot combined with a stimulation pulse, we demonstrate the generation of high-quality single photons with a controllable degree of PNC. The main tuning knob is the pulse area giving full control from minimal to maximal PNC, while without the stimulating pulse the PNC is negligible in our setup for all pulse areas. Our approach provides a viable route toward secure communication in quantum networks.
Cerebro-cerebellar gray matter abnormalities associated with cognitive impairment in patients with recent-onset and chronic schizophrenia
Authors: Kang Naok , Chung Subin , Lee Sang-Hyuk , Bang Minji
Published: January 2024

Although the role of the cerebellum in schizophrenia has gained attention, its contribution to cognitive impairment remains unclear. We aimed to investigate volumetric alterations in the cerebro-cerebellar gray matter (GM) in patients with recent-onset schizophrenia (ROS) and chronic schizophrenia (CS) compared with healthy controls (HCs). Seventy-two ROS, 43 CS, and 127 HC participants were recruited, and high-resolution T1-weighted structural magnetic resonance images of the brain were acquired. We compared cerebellar GM volumes among the groups using voxel-based morphometry and examined the cerebro-cerebellar GM volumetric correlations in participants with schizophrenia. Exploratory correlation analysis investigated the functional relevance of cerebro-cerebellar GM volume alterations to cognitive function in the schizophrenia group. The ROS and CS participants demonstrated smaller cerebellar GM volumes, particularly in Crus I and II, than HCs. Extracted cerebellar GM volumes demonstrated significant positive correlations with the cerebral GM volume in the fronto-temporo-parietal association areas engaged in higher-order association. The exploratory analysis showed that smaller cerebellar GM in the posterior lobe regions was associated with poorer cognitive performance in participants with schizophrenia. Our study suggests that cerebellar pathogenesis is present in the early stages of schizophrenia and interconnected with structural abnormalities in the cerebral cortex. Integrating the cerebellum into the pathogenesis of schizophrenia will help advance our understanding of the disease and identify novel treatment targets concerning dysfunctional cerebro-cerebellar interactions.
Short-term neonatal and long-term neurodevelopmental outcome of children born term low birth weight
Authors: Kim Ho Yeon , Cho Geum Joon , Ahn Ki Hoon , Hong Soon-Cheol , Oh Min-Jeong , Kim Hai-Joong
Published: January 2024

This study aimed to examine the impact of term LBW on short-term neonatal and long-term neurodevelopmental outcomes in children 5–7 years of age. This is a population-based cohort study that merged national data from the Korea National Health Insurance claims and National Health Screening Program for Infants and Children. The participants were women who gave birth at a gestational age of ≥ 37 weeks between 2013 and 2015 in the Republic of Korea, and were tracked during 2020 for the neurodevelopmental surveillance of their children. Among 830,806 women who gave birth during the study period, 31,700 (3.8%) of their babies weighed less than 2500 g. By Cox proportional hazard analysis, children aged 5–7 years who had LBW were associated with any developmental, motor developmental delay, cognitive developmental delay, autism spectrum, attention deficit hyperactivity disorders, and epileptic and febrile seizures.Children born with term LBW were more vulnerable to neurodevelopmental disorders at 5–7 years of age than those with normal and large birth weights. This study further substantiates counseling parents regarding the long-term outcomes of children being born underweight.