bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis
Authors: Ruan Xianhui , Yan Wei , Cao Minghui , Daza Ray Anthony M. , Fong Miranda Y. , Yang Kaifu , Wu Jun , Liu Xuxiang , Palomares Melanie , Wu Xiwei , Li Arthur , Chen Yuan , Jandial Rahul , Spitzer Nicholas C. , Hevner Robert F. , Wang Shizhen Emily 
Published: May 2024

AbstractBreast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.
Haplotype-resolved gapless genome and chromosome segment substitution lines facilitate gene identification in wild rice
Authors: Huang Jingfen , Zhang Yilin , Li Yapeng , Xing Meng , Lei Cailin , Wang Shizhuang , Nie Yamin , Wang Yanyan , Zhao Mingchao , Han Zhenyun , Sun Xianjun , Zhou Han , Wang Yan , Zheng Xiaoming , Xiao Xiaorong , Fan Weiya , Liu Ziran , Guo Wenlong , Zhang Lifang , Cheng Yunlian , Qian Qian , He Hang , Yang Qingwen , Qiao Weihua 
Published: May 2024

AbstractThe abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.
Low-temperature strain-free encapsulation for perovskite solar cells and modules passing multifaceted accelerated ageing tests
Authors: Mariani Paolo , Molina-García Miguel Ángel , Barichello Jessica , Zappia Marilena Isabella , Magliano Erica , Castriotta Luigi Angelo , Gabatel Luca , Thorat Sanjay Balkrishna , Del Rio Castillo Antonio Esaú , Drago Filippo , Leonardi Enrico , Pescetelli Sara , Vesce Luigi , Di Giacomo Francesco , Matteocci Fabio , Agresti Antonio , De Giorgi Nicole , Bellani Sebastiano , Di Carlo Aldo , Bonaccorso Francesco 
Published: May 2024

AbstractPerovskite solar cells promise to be part of the future portfolio of photovoltaic technologies, but their instability is slow down their commercialization. Major stability assessments have been recently achieved but reliable accelerated ageing tests on beyond small-area cells are still poor. Here, we report an industrial encapsulation process based on the lamination of highly viscoelastic semi-solid/highly viscous liquid adhesive atop the perovskite solar cells and modules. Our encapsulant reduces the thermomechanical stresses at the encapsulant/rear electrode interface. The addition of thermally conductive two-dimensional hexagonal boron nitride into the polymeric matrix improves the barrier and thermal management properties of the encapsulant. Without any edge sealant, encapsulated devices withstood multifaceted accelerated ageing tests, retaining >80% of their initial efficiency. Our encapsulation is applicable to the most established cell configurations (direct/inverted, mesoscopic/planar), even with temperature-sensitive materials, and extended to semi-transparent cells for building-integrated photovoltaics and Internet of Things systems.
Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips
Authors: Izadifar Zohreh , Cotton Justin , Chen Siyu , Horvath Viktor , Stejskalova Anna , Gulati Aakanksha , LoGrande Nina T. , Budnik Bogdan , Shahriar Sanjid , Doherty Erin R. , Xie Yixuan , To Tania , Gilpin Sarah E. , Sesay Adama M. , Goyal Girija , Lebrilla Carlito B. , Ingber Donald E. 
Published: May 2024

AbstractModulation of the cervix by steroid hormones and commensal microbiome play a central role in the health of the female reproductive tract. Here we describe organ-on-a-chip (Organ Chip) models that recreate the human cervical epithelial-stromal interface with a functional epithelial barrier and production of mucus with biochemical and hormone-responsive properties similar to living cervix. When Cervix Chips are populated with optimal healthy versus dysbiotic microbial communities (dominated by Lactobacillus crispatus and Gardnerella vaginalis, respectively), significant differences in tissue innate immune responses, barrier function, cell viability, proteome, and mucus composition are observed that are similar to those seen in vivo. Thus, human Cervix Organ Chips represent physiologically relevant in vitro models to study cervix physiology and host-microbiome interactions, and hence may be used as a preclinical testbed for development of therapeutic interventions to enhance women’s health.
Catalytic asymmetric synthesis of planar-chiral dianthranilides via (Dynamic) kinetic resolution
Authors: Guan Chun-Yan , Zou Shuai , Luo Can , Li Zhen-Yu , Huang Mingjie , Huang Lihua , Xiao Xiao , Wei Donghui , Wang Min-Can , Mei Guang-Jian 
Published: May 2024

AbstractChirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C2- or C1-symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies.
Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD
Authors: Verschuren Lars , Mak Anne Linde , van Koppen Arianne , Özsezen Serdar , Difrancesco Sonia , Caspers Martien P. M. , Snabel Jessica , van der Meer David , van Dijk Anne-Marieke , Rashu Elias Badal , Nabilou Puria , Werge Mikkel Parsberg , van Son Koen , Kleemann Robert , Kiliaan Amanda J. , Hazebroek Eric J. , Boonstra André , Brouwer Willem P. , Doukas Michail , Gupta Saurabh , Kluft Cornelis , Nieuwdorp Max , Verheij Joanne , Gluud Lise Lotte , Holleboom Adriaan G. , Tushuizen Maarten E. , Hanemaaijer Roeland 
Published: May 2024

AbstractAccurate non-invasive biomarkers to diagnose metabolic dysfunction-associated steatotic liver disease (MASLD)-related fibrosis are urgently needed. This study applies a translational approach to develop a blood-based biomarker panel for fibrosis detection in MASLD. A molecular gene expression signature identified from a diet-induced MASLD mouse model (LDLr−/−.Leiden) is translated into human blood-based biomarkers based on liver biopsy transcriptomic profiles and protein levels in MASLD patient serum samples. The resulting biomarker panel consists of IGFBP7, SSc5D and Sema4D. LightGBM modeling using this panel demonstrates high accuracy in predicting MASLD fibrosis stage (F0/F1: AUC = 0.82; F2: AUC = 0.89; F3/F4: AUC = 0.87), which is replicated in an independent validation cohort. The overall accuracy of the model outperforms predictions by the existing markers Fib-4, APRI and FibroScan. In conclusion, here we show a disease mechanism-related blood-based biomarker panel with three biomarkers which is able to identify MASLD patients with mild or advanced hepatic fibrosis with high accuracy.
Rapid response of fly populations to gene dosage across development and generations
Authors: Li Xueying C. , Gandara Lautaro , Ekelöf Måns , Richter Kerstin , Alexandrov Theodore , Crocker Justin 
Published: May 2024

AbstractAlthough the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges remains limited. Here, we have examined the phenotypic consequences of disturbing the bicoid regulatory network in early Drosophila embryos. We generated flies with two extra copies of bicoid, which causes a posterior shift of the network’s regulatory outputs and a decrease in fitness. We subjected these flies to EMS mutagenesis, followed by experimental evolution. After only 8–15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level.
Temporal interference stimulation disrupts spike timing in the primate brain
Authors: Vieira Pedro G. , Krause Matthew R. , Pack Christopher C. 
Published: May 2024

AbstractElectrical stimulation can regulate brain activity, producing clear clinical benefits, but focal and effective neuromodulation often requires surgically implanted electrodes. Recent studies argue that temporal interference (TI) stimulation may provide similar outcomes non-invasively. During TI, scalp electrodes generate multiple electrical fields in the brain, modulating neural activity only at their intersection. Despite considerable enthusiasm for this approach, little empirical evidence demonstrates its effectiveness, especially under conditions suitable for human use. Here, using single-neuron recordings in non-human primates, we establish that TI reliably alters the timing, but not the rate, of spiking activity. However, we show that TI requires strategies—high carrier frequencies, multiple electrodes, and amplitude-modulated waveforms—that also limit its effectiveness. Combined, these factors make TI 80 % weaker than other forms of non-invasive brain stimulation. Although unlikely to cause widespread neuronal entrainment, TI may be ideal for disrupting pathological oscillatory activity, a hallmark of many neurological disorders.
Observation of phonon Stark effect
Authors: Huang Zhiheng , Bai Yunfei , Zhao Yanchong , Liu Le , Zhao Xuan , Wu Jiangbin , Watanabe Kenji , Taniguchi Takashi , Yang Wei , Shi Dongxia , Xu Yang , Zhang Tiantian , Zhang Qingming , Tan Ping-Heng , Sun Zhipei , Meng Sheng , Wang Yaxian , Du Luojun , Zhang Guangyu 
Published: May 2024

AbstractStark effect, the electric-field analogue of magnetic Zeeman effect, is one of the celebrated phenomena in modern physics and appealing for emergent applications in electronics, optoelectronics, as well as quantum technologies. While in condensed matter it has prospered only for excitons, whether other collective excitations can display Stark effect remains elusive. Here, we report the observation of phonon Stark effect in a two-dimensional quantum system of bilayer 2H-MoS2. The longitudinal acoustic phonon red-shifts linearly with applied electric fields and can be tuned over ~1 THz, evidencing giant Stark effect of phonons. Together with many-body ab initio calculations, we uncover that the observed phonon Stark effect originates fundamentally from the strong coupling between phonons and interlayer excitons (IXs). In addition, IX-mediated electro-phonon intensity modulation up to ~1200% is discovered for infrared-active phonon A2u. Our results unveil the exotic phonon Stark effect and effective phonon engineering by IX-mediated mechanism, promising for a plethora of exciting many-body physics and potential technological innovations.
Low-frequency conductivity of low wear high-entropy alloys
Authors: Yeh Cheng-Hsien , Hsu Wen-Dung , Liu Bernard Haochih , Yang Chan-Shan , Kuan Chen-Yun , Chang Yuan-Chun , Huang Kai-Sheng , Jhang Song-Syun , Lu Chia-Yen , Liaw Peter K. , Shih Chuan-Feng 
Published: May 2024

AbstractHigh-entropy alloys (HEAs) provide new research avenues for alloy combinations in the periodic table, opening numerous possibilities in novel-alloy applications. However, their electrical characteristics have been relatively underexplored. The challenge in establishing an HEA electrical conductivity model lies in the changes in electronic characteristics caused by lattice distortion and complexity of nanostructures. Here we show a low-frequency electrical conductivity model for the Nb-Mo-Ta-W HEA system. The cocktail effect is found to explain trends in electrical-conductivity changes in HEAs, while the magnitude of the reduction is understood by the calculated plasma frequency, free electron density, and measured relaxation time by terahertz spectroscopy. As a result, the refractory HEA Nb15Mo35Ta15W35 thin film exhibits both high hardness and excellent conductivity. This combination of Nb15Mo35Ta15W35 makes it suitable for applications in atomic force microscopy probe coating, significantly improving their wear resistance and atomic-scale image resolution.
Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills
Authors: Vassiliadis Pierre , Beanato Elena , Popa Traian , Windel Fabienne , Morishita Takuya , Neufeld Esra , Duque Julie , Derosiere Gerard , Wessel Maximilian J. , Hummel Friedhelm C. 
Published: May 2024

AbstractReinforcement feedback can improve motor learning, but the underlying brain mechanisms remain underexplored. In particular, the causal contribution of specific patterns of oscillatory activity within the human striatum is unknown. To address this question, we exploited a recently developed non-invasive deep brain stimulation technique called transcranial temporal interference stimulation (tTIS) during reinforcement motor learning with concurrent neuroimaging, in a randomized, sham-controlled, double-blind study. Striatal tTIS applied at 80 Hz, but not at 20 Hz, abolished the benefits of reinforcement on motor learning. This effect was related to a selective modulation of neural activity within the striatum. Moreover, 80 Hz, but not 20 Hz, tTIS increased the neuromodulatory influence of the striatum on frontal areas involved in reinforcement motor learning. These results show that tTIS can non-invasively and selectively modulate a striatal mechanism involved in reinforcement learning, expanding our tools for the study of causal relationships between deep brain structures and human behaviour.
Van der Waals polarity-engineered 3D integration of 2D complementary logic
Authors: Guo Yimeng , Li Jiangxu , Zhan Xuepeng , Wang Chunwen , Li Min , Zhang Biao , Wang Zirui , Liu Yueyang , Yang Kaining , Wang Hai , Li Wanying , Gu Pingfan , Luo Zhaoping , Liu Yingjia , Liu Peitao , Chen Bo , Watanabe Kenji , Taniguchi Takashi , Chen Xing-Qiu , Qin Chengbing , Chen Jiezhi , Sun Dongming , Zhang Jing , Wang Runsheng , Liu Jianpeng , Ye Yu , Li Xiuyan , Hou Yanglong , Zhou Wu , Wang Hanwen , Han Zheng 
Published: May 2024

AbstractVertical three-dimensional integration of two-dimensional (2D) semiconductors holds great promise, as it offers the possibility to scale up logic layers in the z axis1–3. Indeed, vertical complementary field-effect transistors (CFETs) built with such mixed-dimensional heterostructures4,5, as well as hetero-2D layers with different carrier types6–8, have been demonstrated recently. However, so far, the lack of a controllable doping scheme (especially p-doped WSe2 (refs. 9–17) and MoS2 (refs. 11,18–28)) in 2D semiconductors, preferably in a stable and non-destructive manner, has greatly impeded the bottom-up scaling of complementary logic circuitries. Here we show that, by bringing transition metal dichalcogenides, such as MoS2, atop a van der Waals (vdW) antiferromagnetic insulator chromium oxychloride (CrOCl), the carrier polarity in MoS2 can be readily reconfigured from n- to p-type via strong vdW interfacial coupling. The consequential band alignment yields transistors with room-temperature hole mobilities up to approximately 425 cm2 V−1 s−1, on/off ratios reaching 106 and air-stable performance for over one year. Based on this approach, vertically constructed complementary logic, including inverters with 6 vdW layers, NANDs with 14 vdW layers and SRAMs with 14 vdW layers, are further demonstrated. Our findings of polarity-engineered p- and n-type 2D semiconductor channels with and without vdW intercalation are robust and universal to various materials and thus may throw light on future three-dimensional vertically integrated circuits based on 2D logic gates.
Structural basis for pegRNA-guided reverse transcription by a prime editor
Authors: Shuto Yutaro , Nakagawa Ryoya , Zhu Shiyou , Hoki Mizuki , Omura Satoshi N. , Hirano Hisato , Itoh Yuzuru , Zhang Feng , Nureki Osamu 
Published: May 2024

AbstractThe prime editor system composed of Streptococcus pyogenes Cas9 nickase (nSpCas9) and engineered Moloney murine leukaemia virus reverse transcriptase (M-MLV RT) collaborates with a prime editing guide RNA (pegRNA) to facilitate a wide variety of precise genome edits in living cells1. However, owing to a lack of structural information, the molecular mechanism of pegRNA-guided reverse transcription by the prime editor remains poorly understood. Here we present cryo-electron microscopy structures of the SpCas9–M-MLV RTΔRNaseH–pegRNA–target DNA complex in multiple states. The termination structure, along with our functional analysis, reveals that M-MLV RT extends reverse transcription beyond the expected site, resulting in scaffold-derived incorporations that cause undesired edits at the target loci. Furthermore, structural comparisons among the pre-initiation, initiation and elongation states show that M-MLV RT remains in a consistent position relative to SpCas9 during reverse transcription, whereas the pegRNA–synthesized DNA heteroduplex builds up along the surface of SpCas9. On the basis of our structural insights, we rationally engineered pegRNA variants and prime-editor variants in which M-MLV RT is fused within SpCas9. Collectively, our findings provide structural insights into the stepwise mechanism of prime editing, and will pave the way for the development of a versatile prime editing toolbox.
A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits
Authors: Wietek Jonas , Nozownik Adrianna , Pulin Mauro , Saraf-Sinik Inbar , Matosevich Noa , Gowrishankar Raajaram , Gat Asaf , Malan Daniela , Brown Bobbie J. , Dine Julien , Imambocus Bibi Nusreen , Levy Rivka , Sauter Kathrin , Litvin Anna , Regev Noa , Subramaniam Suraj , Abrera Khalid , Summarli Dustin , Goren Eva Madeline , Mizrachi Gili , Bitton Eyal , Benjamin Asaf , Copits Bryan A. , Sasse Philipp , Rost Benjamin R. , Schmitz Dietmar , Bruchas Michael R. , Soba Peter , Oren-Suissa Meital , Nir Yuval , Wiegert J. Simon , Yizhar Ofer 
Published: May 2024

AbstractInformation is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.
Respiratory muscle strength can improve the prognostic assessment in COPD
Authors: Silva Rebeca Nunes , Goulart Cássia da Luz , de Oliveira Claudio R. , Mendes Renata Gonçalves , Arena Ross , Myers Jonathan , Borghi-Silva Audrey 
Published: May 2024

AbstractImpaired lung function, respiratory muscle weakness and exercise intolerance are present in COPD and contribute to poor prognosis. However, the contribution of the combination of these manifestations to define prognosis in COPD is still unknown. This study aimed to define cut-off points for both inspiratory and expiratory muscle strength (MIP and MEP, respectively) for mortality prediction over 42-months in patients with COPD, and to investigate its combination with other noninvasive established prognostic measures (FEV1, V̇O2peak and 6MWD) to improve risk identification. Patients with COPD performed pulmonary function, respiratory muscle strength, six-minute walk and cardiopulmonary exercise tests, and were followed over 42 months to analyze all-cause mortality. A total of 79 patients were included. The sample was mostly (91.1%) comprised of severe (n = 37) and very severe (n = 34) COPD, and 43 (54%) patients died during the follow-up period. Cut-points of ≤ 55 and ≤ 80 cmH2O for MIP and MEP, respectively, were associated with increased risk of death (log-rank p = 0.0001 for both MIP and MEP) in 42 months. Furthermore, MIP and MEP substantially improved the mortality risk assessment when combined with FEV1 (log-ranks p = 0.006 for MIP and p < 0.001 for MEP), V̇O2peak (log-rank: p < 0.001 for both MIP and MEP) and 6MWD (log-ranks: p = 0.005 for MIP; p = 0.015 for MEP). Thus, patients severely affected by COPD presenting MIP ≤ 55 and/or MEP ≤ 80 cmH2O are at increased risk of mortality. Furthermore, MIP and MEP substantially improve the mortality risk assessment when combined with FEV1, V̇O2peak and 6MWD in patients with COPD.