bluuebunny/crossref_metadata_2025 huggingface dataset:
The Signal‐to‐Noise Paradox in ENSO Prediction: Role of ENSO Growth Rate and Period
Authors: Jin Yishuai
Published: June 2022

This paper investigates the relationship between heterogeneous predictability and homogeneous predictability for El Niño‐Southern Oscillation (ENSO) prediction. Previous studies showed that a larger heterogeneous predictability than homogeneous predictability, referred as the signal‐to‐noise paradox, is caused by a higher persistence in the observations than in the model. By using the recharge oscillator model, it is found analytically and numerically that both ENSO growth rate and period contribute to this paradox. A larger ENSO growth rate in the observation can lead to a higher persistence and heterogeneous predictability. However, a larger ENSO growth rate associated with a shortened ENSO period can also lead to this paradox although the persistence of the observation is lower than forecast model. Finally, we apply it to explain the paradox after 1960 is caused by a larger ENSO growth rate and a shortened ENSO period.
Current Challenges in Visibility Improvement in Sichuan Basin
Authors: Zhao Gang , Hu Min , Zhang Zirui , Tang Lizi , Shang Dongjie , Ren Jie , Meng Xiangxinyue , Zhang Yuan , Feng Miao , Luo Yina , Yang Shishi , Tan Qinwen , Song Danlin , Guo Song , Wu Zhijun , Zeng Limin , Zhang Yuanhang , Xie Shaodong
Published: June 2022

The visibility in the Sichuan Basin (SB) was worse than that in the North China Plain (NCP) for the same level of PM2.5. One well‐known reason is that the aerosol extinction enhancement due to hygroscopic growth in the SB was stronger than that in the NCP because the relative humidity (RH) in the SB was higher than that in the NCP. However, the visibility was worse in the SB under the same PM2.5 and RH levels. The volume extinction efficiency (VEE) is kept between 7 and 8 for different PM2.5 in the SB, while the VEE increased from 4.6 to 7.2 when the PM2.5 level increased from 20 to 180 μg/m3 in the NCP. The difference in VEE resulted from the different particle number size distributions. Our research demonstrates that the VEE is an important factor that influences visibility and provides new insight into visibility impairment for the SB.
Geologic Evidence of Lithostatic Pore Fluid Pressures at the Base of the Subduction Seismogenic Zone
Authors: Condit C. B. , French M. E.
Published: June 2022

Geophysical and rheological work below the subduction seismogenic zone suggest that elevated pore fluid pressures (Pfs) may facilitate slow slip and tremor. However, quantification of Pf and its variation in this environment remain indirect and incomplete. We examine brittle‐frictional deformation within metasedimentary rocks from an exhumed subduction zone. Here, penetrative foliation formed under viscous deformation conditions by pressure‐solution creep at 0.9 GPa, 300–350°C, and differential stresses <35 MPa. Three sets of crack‐seal veins, precipitated at peak subduction temperatures, cross‐cut this foliation. Mechanical inversions of these veins indicate they formed within a single stress field orientation with foliation, but at different magnitudes of differential stress. These deformation structures reveal near‐lithostatic Pf that fluctuated in time by perhaps only ∼4 MPa, resulting in cyclic mode I and shear fracturing and viscous flow, and support slow slip and tremor mechanisms that require or are enhanced by high Pf and low differential stress.
Key Factors Modulating the Threat of the Arabian Sea's Tropical Cyclones to the Gulf Countries
Authors: Francis Diana , Fonseca Ricardo , Nelli Narendra
Published: June 2022

Tropical cyclones (TC) are one of the biggest natural hazards with significant threat to life and property due to storm surge, flooding and extreme winds. Combined, these hazards substantially increase the potential for loss of life and damage especially in populated landfall‐locations such as the countries on the Arabian Gulf and Sea of Oman. Hence, it is important to identify the factors that modulate the trajectory of TC in order to better predict their lifetime and dynamics. Since 1900, only two TCs moved into the Sea of Oman and made landfall on the southeastern coast of the Arabian Peninsula (AP): TC Shaheen in 2021 and Gonu in 2007. In this study, the mechanisms behind the exceptional trajectories of these two TCs are investigated. Both TCs developed during the active phase of the Madden‐Julian Oscillation, and benefited from above‐average sea surface temperatures (SSTs), ocean heat content and reduced vertical wind shear. Their paths over the Indian Ocean were controlled by large‐scale forcings, whereas regional‐scale processes, such as the local SST gradients and the Arabian Heat Low (AHL) defined their trajectories near landfall location over the AP. An exceptionally deep AHL was present during these events. The AHL is found to interact two‐way with TCs: its associated circulation drags the TCs inland while the TCs, through the advection of cooler marine‐air inland, cause the collapse of the AHL. It is recommended to account for the AHL as fluctuations in its position and strength can determine where future TCs make landfall.
A Model of the Spatiotemporal Dynamics of Soil Carbon Following Coastal Wetland Loss Applied to a Louisiana Salt Marsh in the Mississippi River Deltaic Plain
Authors: Schoolmaster Donald R. , Stagg Camille L. , Creamer Courtney , Laurenzano Claudia , Ward Eric J. , Waldrop Mark P. , Baustian Melissa M. , Aw Tiong , Merino Sergio , Villani Rachel , Scott Laura
Published: June 2022

The potential for carbon sequestration in coastal wetlands is high due to protection of carbon (C) in flooded soils. However, excessive flooding can result in the conversion of the vegetated wetland to open water. This transition results in the loss of wetland habitat in addition to the potential loss of soil carbon. Thus, in areas experiencing rapid wetland submergence, such as the Mississippi River Delta, coastal wetlands could become a significant source of carbon emissions if land loss is not mitigated. To accurately assess the capacity of wetlands to store (or emit) carbon in dynamic environments, it is critical to understand the fate of soil carbon following the transition from vegetated wetland to open water. We developed a simple soil carbon model representing soil depths to 1 m using the data collected from a Louisiana coastal salt marsh in the Mississippi River Deltaic Plain to predict soil carbon density and stock following the transition from a vegetated salt marsh to an open water pond. While immediate effects of ponding on the distribution of carbon within the 1‐m soil profile were apparent, there were no effects of ponding on the overall, integrated, carbon stocks 14 years, following wetland submergence. Rather, the model predicts that soil carbon losses in the first meter will be realized over long periods of time (∼200 years) due to changes in the source of carbon (biomass vs. mineral sediment) with minimal losses through mineralization.
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
Authors: He Ming , Cao Chaoguo , Ni Zhihao , Liu Yongbo , Song Peilu , Hao Shuang , He Yuna , Sun Xiuyun , Rao Yu
Published: June 2022

PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin–proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article “PROTACs: great opportunities for academia and industry” in the journal, summarizing the representative compounds of PROTACs reported before the end of 2019. In the past 2 years, the entire field of protein degradation has experienced rapid development, including not only a large increase in the number of research papers on protein-degradation technology but also a rapid increase in the number of small-molecule degraders that have entered the clinical and will enter the clinical stage. In addition to PROTAC and molecular glue technology, other new degradation technologies are also developing rapidly. In this article, we mainly summarize and review the representative PROTACs of related targets published in 2020–2021 to present to researchers the exciting developments in the field of protein degradation. The problems that need to be solved in this field will also be briefly introduced.
Signaling pathways of chronic kidney diseases, implications for therapeutics
Authors: Yuan Qian , Tang Ben , Zhang Chun
Published: June 2022

Chronic kidney disease (CKD) is a chronic renal dysfunction syndrome that is characterized by nephron loss, inflammation, myofibroblasts activation, and extracellular matrix (ECM) deposition. Lipotoxicity and oxidative stress are the driving force for the loss of nephron including tubules, glomerulus, and endothelium. NLRP3 inflammasome signaling, MAPK signaling, PI3K/Akt signaling, and RAAS signaling involves in lipotoxicity. The upregulated Nox expression and the decreased Nrf2 expression result in oxidative stress directly. The injured renal resident cells release proinflammatory cytokines and chemokines to recruit immune cells such as macrophages from bone marrow. NF-κB signaling, NLRP3 inflammasome signaling, JAK-STAT signaling, Toll-like receptor signaling, and cGAS-STING signaling are major signaling pathways that mediate inflammation in inflammatory cells including immune cells and injured renal resident cells. The inflammatory cells produce and secret a great number of profibrotic cytokines such as TGF-β1, Wnt ligands, and angiotensin II. TGF-β signaling, Wnt signaling, RAAS signaling, and Notch signaling evoke the activation of myofibroblasts and promote the generation of ECM. The potential therapies targeted to these signaling pathways are also introduced here. In this review, we update the key signaling pathways of lipotoxicity, oxidative stress, inflammation, and myofibroblasts activation in kidneys with chronic injury, and the targeted drugs based on the latest studies. Unifying these pathways and the targeted therapies will be instrumental to advance further basic and clinical investigation in CKD.
Roles of exosomal circRNAs in tumour immunity and cancer progression
Authors: Tuo Baojing , Chen Zhuang , Dang Qin , Chen Chen , Zhang Hao , Hu Shengyun , Sun Zhenqiang
Published: June 2022

Tumour immunity plays an important role in the development of cancer. Tumour immunotherapy is an important component of antitumour therapy. Exosomes, a type of extracellular vesicle, act as mediators of intercellular communication and molecular transfer and play an essential role in tumour immunity. Circular RNAs (circRNAs) are a new type of noncoding RNA that are enriched within exosomes. In this review, we describe the effects of exosomal circRNAs on various immune cells and the mechanisms of these effects, including macrophages, neutrophils, T cells, and Natural killer (NK) cells. Next, we elaborate on the latest progress of exosome extraction. In addition, the function of exosomal circRNAs as a potential prognostic and drug sensitivity marker is described. We present the great promise of exosomal circRNAs in regulating tumour immunity, predicting patient outcomes, and evaluating drug efficacy.
Small molecule targeting FOXM1 DNA binding domain exhibits anti-tumor activity in ovarian cancer
Authors: Zhang Zaixin , Xue Si-tu , Gao Yan , Li Yingwei , Zhou Ziying , Wang Jing , Li Zhuorong , Liu Zhaojian
Published: June 2022

FOXM1 is a potent oncogenic transcription factor essential for cancer initiation, progression, and drug resistance. FOXM1 regulatory network is a major predictor of adverse outcomes in various human cancers. Inhibition of FOXM1 transcription factor function is a potential strategy in cancer treatment. In this study, we performed structure-based in silico screening to discover small molecules targeting the FOXM1 DNA-binding domain (DBD). Compound XST-20 was identified to effectively suppress FOXM1 transcriptional activities and inhibit ovarian cancer cell proliferation. XST-20 directly interacts with the FOXM1 DNA-binding domain determined by SPR assay. Furthermore, XST-20 was found to significantly reduce the colony-forming efficiency and induce cell cycle arrest and apoptosis. Our study provides a lead compound of FOXM1 inhibitor which may serve as a potential targeted therapy agent for ovarian cancer.
Sorafenib inhibits LPS-induced inflammation by regulating Lyn-MAPK-NF-kB/AP-1 pathway and TLR4 expression
Authors: Li Xiaolian , Xu Mingkun , Shen Jiaojiao , Li Yuqin , Lin Shaoping , Zhu Min , Pang Qiongni , Tan Xiujuan , Tang Jing
Published: June 2022

Sorafenib is an anti-tumor drug widely used in clinical treatment, which can inhibit tyrosine kinase receptor on cell surface and serine/threonine kinase in downstream Ras/MAPK cascade signaling pathway of cells. Tyrosine kinase phosphorylation plays an important role in inflammatory mechanism, such as TLR4 tyrosine phosphorylation, MAPK pathway protein activation, and activation of downstream NF-кB. However, the effects of sorafenib on LPS-induced inflammatory reaction and its specific mechanism have still remained unknown. We found that sorafenib inhibited the phosphorylation of tyrosine kinase Lyn induced by LPS, thereby reducing the phosphorylation level of p38 and JNK, inhibiting the activation of c-Jun and NF-κB, and then inhibiting the expression of inflammatory factors IL-6, IL-1β, and TNF-α. Furthermore, sorafenib also decreased the expression of TLR4 on the macrophage membrane to inhibit the expression of inflammatory factors latterly, which may be related to the inactivation of Lyn. These results provide a new perspective and direction for the clinical treatment of sepsis.
Excited-state spin-resonance spectroscopy of V$${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ defect centers in hexagonal boron nitride
Authors: Mathur Nikhil , Mukherjee Arunabh , Gao Xingyu , Luo Jialun , McCullian Brendan A. , Li Tongcang , Vamivakas A. Nick , Fuchs Gregory D.
Published: June 2022

The recently discovered spin-active boron vacancy (V$${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$

B

−

) defect center in hexagonal boron nitride (hBN) has high contrast optically-detected magnetic resonance (ODMR) at room-temperature, with a spin-triplet ground-state that shows promise as a quantum sensor. Here we report temperature-dependent ODMR spectroscopy to probe spin within the orbital excited-state. Our experiments determine the excited-state spin Hamiltonian, including a room-temperature zero-field splitting of 2.1 GHz and a g-factor similar to that of the ground-state. We confirm that the resonance is associated with spin rotation in the excited-state using pulsed ODMR measurements, and we observe Zeeman-mediated level anti-crossings in both the orbital ground- and excited-state. Our observation of a single set of excited-state spin-triplet resonance from 10 to 300 K is suggestive of symmetry-lowering of the defect system from D3h to C2v. Additionally, the excited-state ODMR has strong temperature dependence of both contrast and transverse anisotropy splitting, enabling promising avenues for quantum sensing.
Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network
Authors: Coutant Bérénice , Frontera Jimena Laura , Perrin Elodie , Combes Adèle , Tarpin Thibault , Menardy Fabien , Mailhes-Hamon Caroline , Perez Sylvie , Degos Bertrand , Venance Laurent , Léna Clément , Popa Daniela
Published: June 2022

Chronic Levodopa therapy, the gold-standard treatment for Parkinson’s Disease (PD), leads to the emergence of involuntary movements, called levodopa-induced dyskinesia (LID). Cerebellar stimulation has been shown to decrease LID severity in PD patients. Here, in order to determine how cerebellar stimulation induces LID alleviation, we performed daily short trains of optogenetic stimulations of Purkinje cells (PC) in freely moving LID mice. We demonstrated that these stimulations are sufficient to suppress LID or even prevent their development. This symptomatic relief is accompanied by the normalization of aberrant neuronal discharge in the cerebellar nuclei, the motor cortex and the parafascicular thalamus. Inhibition of the cerebello-parafascicular pathway counteracted the beneficial effects of cerebellar stimulation. Moreover, cerebellar stimulation reversed plasticity in D1 striatal neurons and normalized the overexpression of FosB, a transcription factor causally linked to LID. These findings demonstrate LID alleviation and prevention by daily PC stimulations, which restore the function of a wide motor network, and may be valuable for LID treatment.
Waning effectiveness of the third dose of the BNT162b2 mRNA COVID-19 vaccine
Authors: Patalon Tal , Saciuk Yaki , Peretz Asaf , Perez Galit , Lurie Yoav , Maor Yasmin , Gazit Sivan
Published: June 2022

The duration of protection of the third (booster) dose of the BioNTech/Pfizer BNT162b2 mRNA Coronavirus Disease 2019 vaccine has been the subject of recent investigations, as global discussions around the necessity and effectiveness of a fourth dose are already underway. By conducting a retrospective study implementing a test-negative case-control design, analyzing 546,924 PCR tests performed throughout January 2022 by 389,265 persons who received at least two doses, we find that the effectiveness in each month-since-vaccination decreases significantly. Compared to those vaccinated five months prior to the outcome period, on August 2021, relative protection against infection waned from 53.4% a month after vaccination to 16.5% three months after vaccination. These results suggest that there is a significant waning of vaccine effectiveness against the Omicron variant of the third dose of the BNT162b2 vaccine within a few months after administration. Additional information could assist to comprehensively estimate the effectiveness of the three-dose-strategy.
Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci
Authors: Fadista João , Skotte Line , Karjalainen Juha , Abner Erik , Sørensen Erik , Ullum Henrik , Werge Thomas ,   iPSYCH Group, Werge Thomas , Hougaard David M. , Børglum Anders D. , Nordentoft Merete , Mortensen Preben B. , Esko Tõnu , Milani Lili , Palotie Aarno , Daly Mark ,   FinnGen Consortium, Melbye Mads , Feenstra Bjarke , Geller Frank
Published: June 2022

Hernias are characterized by protrusion of an organ or tissue through its surrounding cavity and often require surgical repair. In this study we identify 65,492 cases for five hernia types in the UK Biobank and perform genome-wide association study scans for these five types and two combined groups. Our results show associated variants in all scans. Inguinal hernia has the most associations and we conduct a follow-up study with 23,803 additional cases from four study groups giving 84 independently associated variants. Identified variants from all scans are collapsed into 81 independent loci. Further testing shows that 26 loci are associated with more than one hernia type, suggesting substantial overlap between the underlying genetic mechanisms. Pathway analyses identify several genes with a strong link to collagen and/or elastin (ADAMTS6, ADAMTS16, ADAMTSL3, LOX, ELN) in the vicinity of associated loci for inguinal hernia, which substantiates an essential role of connective tissue morphology.
Niobium-doped layered cathode material for high-power and low-temperature sodium-ion batteries
Authors: Shi Qinhao , Qi Ruijuan , Feng Xiaochen , Wang Jing , Li Yong , Yao Zhenpeng , Wang Xuan , Li Qianqian , Lu Xionggang , Zhang Jiujun , Zhao Yufeng
Published: June 2022

The application of sodium-based batteries in grid-scale energy storage requires electrode materials that facilitate fast and stable charge storage at various temperatures. However, this goal is not entirely achievable in the case of P2-type layered transition-metal oxides because of the sluggish kinetics and unfavorable electrode|electrolyte interphase formation. To circumvent these issues, we propose a P2-type Na0.78Ni0.31Mn0.67Nb0.02O2 (P2-NaMNNb) cathode active material where the niobium doping enables reduction in the electronic band gap and ionic diffusion energy barrier while favoring the Na-ion mobility. Via physicochemical characterizations and theoretical calculations, we demonstrate that the niobium induces atomic scale surface reorganization, hindering metal dissolution from the cathode into the electrolyte. We also report the testing of the cathode material in coin cell configuration using Na metal or hard carbon as anode active materials and ether-based electrolyte solutions. Interestingly, the Na||P2-NaMNNb cell can be cycled up to 9.2 A g−1 (50 C), showing a discharge capacity of approximately 65 mAh g−1 at 25 °C. Furthermore, the Na||P2-NaMNNb cell can also be charged/discharged for 1800 cycles at 368 mA g−1 and −40 °C, demonstrating a capacity retention of approximately 76% and a final discharge capacity of approximately 70 mAh g−1.
A boundary migration model for imaging within volumetric scattering media
Authors: Du Dongyu , Jin Xin , Deng Rujia , Kang Jinshi , Cao Hongkun , Fan Yihui , Li Zhiheng , Wang Haoqian , Ji Xiangyang , Song Jingyan
Published: June 2022

Effectively imaging within volumetric scattering media is of great importance and challenging especially in macroscopic applications. Recent works have demonstrated the ability to image through scattering media or within the weak volumetric scattering media using spatial distribution or temporal characteristics of the scattered field. Here, we focus on imaging Lambertian objects embedded in highly scattering media, where signal photons are dramatically attenuated during propagation and highly coupled with background photons. We address these challenges by providing a time-to-space boundary migration model (BMM) of the scattered field to convert the scattered measurements in spectral form to the scene information in the temporal domain using all of the optical signals. The experiments are conducted under two typical scattering scenarios: 2D and 3D Lambertian objects embedded in the polyethylene foam and the fog, which demonstrate the effectiveness of the proposed algorithm. It outperforms related works including time gating in terms of reconstruction precision and scattering strength. Even though the proportion of signal photons is only 0.75%, Lambertian objects located at more than 25 transport mean free paths (TMFPs), corresponding to the round-trip scattering length of more than 50 TMFPs, can be reconstructed. Also, the proposed method provides low reconstruction complexity and millisecond-scale runtime, which significantly benefits its application.
Drought-exposure history increases complementarity between plant species in response to a subsequent drought
Authors: Chen Yuxin , Vogel Anja , Wagg Cameron , Xu Tianyang , Iturrate-Garcia Maitane , Scherer-Lorenzen Michael , Weigelt Alexandra , Eisenhauer Nico , Schmid Bernhard
Published: June 2022

Growing threats from extreme climatic events and biodiversity loss have raised concerns about their interactive consequences for ecosystem functioning. Evidence suggests biodiversity can buffer ecosystem functioning during such climatic events. However, whether exposure to extreme climatic events will strengthen the biodiversity-dependent buffering effects for future generations remains elusive. We assess such transgenerational effects by exposing experimental grassland communities to eight recurrent summer droughts versus ambient conditions in the field. Seed offspring of 12 species are then subjected to a subsequent drought event in the glasshouse, grown individually, in monocultures or in 2-species mixtures. Comparing productivity between mixtures and monocultures, drought-selected plants show greater between-species complementarity than ambient-selected plants when recovering from the subsequent drought, causing stronger biodiversity effects on productivity and better recovery of drought-selected mixtures after the drought. These findings suggest exposure to recurrent climatic events can improve ecosystem responses to future events through transgenerational reinforcement of species complementarity.
Subsurface oxygen defects electronically interacting with active sites on In2O3 for enhanced photothermocatalytic CO2 reduction
Authors: Wei Weiqin , Wei Zhen , Li Ruizhe , Li Zhenhua , Shi Run , Ouyang Shuxin , Qi Yuhang , Philips David Lee , Yuan Hong
Published: June 2022

Oxygen defects play an important role in many catalytic reactions. Increasing surface oxygen defects can be done through reduction treatment. However, excessive reduction blocks electron channels and deactivates the catalyst surface due to electron-trapped effects by subsurface oxygen defects. How to effectively extract electrons from subsurface oxygen defects which cannot directly interact with reactants is challenging and remains elusive. Here, we report a metallic In-embedded In2O3 nanoflake catalyst over which the turnover frequency of CO2 reduction into CO increases by a factor of 866 (7615 h−1) and 376 (2990 h−1) at the same light intensity and reaction temperature, respectively, compared to In2O3. Under electron-delocalization effect of O-In-(O)Vo-In-In structural units at the interface, the electrons in the subsurface oxygen defects are extracted and gather at surface active sites. This improves the electronic coupling with CO2 and stabilizes intermediate. The study opens up new insights for exquisite electronic manipulation of oxygen defects.
Biomimetic non-classical crystallization drives hierarchical structuring of efficient circularly polarized phosphors
Authors: Feng Li-Zhe , Wang Jing-Jing , Ma Tao , Yin Yi-Chen , Song Kuang-Hui , Li Zi-Du , Zhou Man-Man , Jin Shan , Zhuang Taotao , Fan Feng-Jia , Zhu Man-Zhou , Yao Hong-Bin
Published: June 2022

Hierarchically structured chiral luminescent materials hold promise for achieving efficient circularly polarized luminescence. However, a feasible chemical route to fabricate hierarchically structured chiral luminescent polycrystals is still elusive because of their complex structures and complicated formation process. We here report a biomimetic non-classical crystallization (BNCC) strategy for preparing efficient hierarchically structured chiral luminescent polycrystals using well-designed highly luminescent homochiral copper(I)-iodide hybrid clusters as basic units for non-classical crystallization. By monitoring the crystallization process, we unravel the BNCC mechanism, which involves crystal nucleation, nanoparticles aggregation, oriented attachment, and mesoscopic transformation processes. We finally obtain the circularly polarized phosphors with both high luminescent efficiency of 32% and high luminescent dissymmetry factor of 1.5 × 10−2, achieving the demonstration of a circularly polarized phosphor converted light emitting diode with a polarization degree of 1.84% at room temperature. Our designed BNCC strategy provides a simple, reliable, and large-scale synthetic route for preparing bright circularly polarized phosphors.
Structural basis of ligand binding modes of human EAAT2
Authors: Zhang Zhenglai , Chen Huiwen , Geng Ze , Yu Zhuoya , Li Hang , Dong Yanli , Zhang Hongwei , Huang Zhuo , Jiang Juquan , Zhao Yan
Published: June 2022

In the central nervous system (CNS), excitatory amino acid transporters (EAATs) mediate the uptake of excitatory neurotransmitter glutamate and maintain its low concentrations in the synaptic cleft for avoiding neuronal cytotoxicity. Dysfunction of EAATs can lead to many psychiatric diseases. Here we report cryo-EM structures of human EAAT2 in an inward-facing conformation, in the presence of substrate glutamate or selective inhibitor WAY-213613. The glutamate is coordinated by extensive hydrogen bonds and further stabilized by HP2. The inhibitor WAY-213613 occupies a similar binding pocket to that of the substrate glutamate. Upon association with the WAY-213613, the HP2 undergoes a substantial conformational change, and in turn stabilizes the inhibitor binding by forming hydrophobic interactions. Electrophysiological experiments elucidate that the unique S441 plays pivotal roles in the binding of hEAAT2 with glutamate or WAY-213613, and the I464-L467-V468 cluster acts as a key structural determinant for the selective inhibition of this transporter by WAY-213613.
Underwater wireless communication via TENG-generated Maxwell’s displacement current
Authors: Zhao Hongfa , Xu Minyi , Shu Mingrui , An Jie , Ding Wenbo , Liu Xiangyu , Wang Siyuan , Zhao Cong , Yu Hongyong , Wang Hao , Wang Chuan , Fu Xianping , Pan Xinxiang , Xie Guangming , Wang Zhong Lin
Published: June 2022

Underwater communication is a critical and challenging issue, on account of the complex underwater environment. This study introduces an underwater wireless communication approach via Maxwell’s displacement current generated by a triboelectric nanogenerator. Underwater electric field can be generated through a wire connected to a triboelectric nanogenerator, while current signal can be inducted in an underwater receiver certain distance away. The received current signals are basically immune to disturbances from salinity, turbidity and submerged obstacles. Even after passing through a 100 m long spiral water pipe, the electric signals are not distorted in waveform. By modulating and demodulating the current signals generated by a sound driven triboelectric nanogenerator, texts and images can be transmitted in a water tank at 16 bits/s. An underwater lighting system is operated by the triboelectric nanogenerator-based voice-activated controller wirelessly. This triboelectric nanogenerator-based approach can form the basis for an alternative wireless communication in complex underwater environments.
An in vitro model of neuronal ensembles
Authors: Rabadan M. Angeles , De La Cruz Estanislao Daniel , Rao Sneha B. , Chen Yannan , Gong Cheng , Crabtree Gregg , Xu Bin , Markx Sander , Gogos Joseph A. , Yuste Rafael , Tomer Raju
Published: June 2022

Advances in 3D neuronal cultures, such as brain spheroids and organoids, are allowing unprecedented in vitro access to some of the molecular, cellular and developmental mechanisms underlying brain diseases. However, their efficacy in recapitulating brain network properties that encode brain function remains limited, thereby precluding development of effective in vitro models of complex brain disorders like schizophrenia. Here, we develop and characterize a Modular Neuronal Network (MoNNet) approach that recapitulates specific features of neuronal ensemble dynamics, segregated local-global network activities and a hierarchical modular organization. We utilized MoNNets for quantitative in vitro modelling of schizophrenia-related network dysfunctions caused by highly penetrant mutations in SETD1A and 22q11.2 risk loci. Furthermore, we demonstrate its utility for drug discovery by performing pharmacological rescue of alterations in neuronal ensembles stability and global network synchrony. MoNNets allow in vitro modelling of brain diseases for investigating the underlying neuronal network mechanisms and systematic drug discovery.
Ultrafast self-heating synthesis of robust heterogeneous nanocarbides for high current density hydrogen evolution reaction
Authors: Li Chenyu , Wang Zhijie , Liu Mingda , Wang Enze , Wang Bolun , Xu Longlong , Jiang Kaili , Fan Shoushan , Sun Yinghui , Li Jia , Liu Kai
Published: June 2022

Designing cost-effective and high-efficiency catalysts to electrolyze water is an effective way of producing hydrogen. Practical applications require highly active and stable hydrogen evolution reaction catalysts working at high current densities (≥1000 mA cm−2). However, it is challenging to simultaneously enhance the catalytic activity and interface stability of these catalysts. Herein, we report a rapid, energy-saving, and self-heating method to synthesize high-efficiency Mo2C/MoC/carbon nanotube hydrogen evolution reaction catalysts by ultrafast heating and cooling. The experiments and density functional theory calculations reveal that numerous Mo2C/MoC hetero-interfaces offer abundant active sites with a moderate hydrogen adsorption free energy ΔGH* (0.02 eV), and strong chemical bonding between the Mo2C/MoC catalysts and carbon nanotube heater/electrode significantly enhances the mechanical stability owing to instantaneous high temperature. As a result, the Mo2C/MoC/carbon nanotube catalyst achieves low overpotentials of 233 and 255 mV at 1000 and 1500 mA cm−2 in 1 M KOH, respectively, and the overpotential shows only a slight change after working at 1000 mA cm−2 for 14 days, suggesting the excellent activity and stability of the high-current-density hydrogen evolution reaction catalyst. The promising activity, excellent stability, and high productivity of our catalyst can fulfil the demands of hydrogen production in various applications.
Sacituzumab govitecan as second-line treatment for metastatic triple-negative breast cancer—phase 3 ASCENT study subanalysis
Authors: Carey Lisa A. , Loirat Delphine , Punie Kevin , Bardia Aditya , Diéras Véronique , Dalenc Florence , Diamond Jennifer R. , Fontaine Christel , Wang Grace , Rugo Hope S. , Hurvitz Sara A. , Kalinsky Kevin , O’Shaughnessy Joyce , Loibl Sibylle , Gianni Luca , Piccart Martine , Zhu Yanni , Delaney Rosemary , Phan See , Cortés Javier
Published: June 2022

Patients with triple-negative breast cancer (TNBC) who relapse early after (neo)adjuvant chemotherapy have more aggressive disease. In the ASCENT trial, sacituzumab govitecan (SG), an antibody-drug conjugate composed of an anti-Trop–2 antibody coupled to SN-38 via a hydrolyzable linker, improved outcomes over single-agent chemotherapy of physician’s choice (TPC) in metastatic TNBC (mTNBC). Of 468 patients without known baseline brain metastases, 33/235 vs 32/233 patients (both 14%) in the SG vs TPC arms, respectively, received one line of therapy in the metastatic setting and experienced disease recurrence ≤12 months after (neo)adjuvant chemotherapy. SG prolonged progression-free survival (median 5.7 vs 1.5 months [HR, 0.41; 95% CI, 0.22–0.76]) and overall survival (median 10.9 vs 4.9 months [HR, 0.51; 95% CI, 0.28–0.91]) vs TPC, with a manageable safety profile in this subgroup consistent with the overall population. In this second-line setting, as with later-line therapy, SG improved survival over conventional chemotherapy for patients with mTNBC.
Generalized Wilson loop method for nonlinear light-matter interaction
Authors: Wang Hua , Tang Xiuyu , Xu Haowei , Li Ju , Qian Xiaofeng
Published: June 2022

Nonlinear light–matter interaction, as the core of ultrafast optics, bulk photovoltaics, nonlinear optical sensing and imaging, and efficient generation of entangled photons, has been traditionally studied by first-principles theoretical methods with the sum-over-states approach. However, this indirect method often suffers from the divergence at band degeneracy and optical zeros as well as convergence issues and high computation costs when summing over the states. Here, using shift vector and shift current conductivity tensor as an example, we present a gauge-invariant generalized approach for efficient and direct calculations of nonlinear optical responses by representing interband Berry curvature, quantum metric, and shift vector in a generalized Wilson loop. This generalized Wilson loop method avoids the above cumbersome challenges and allows for easy implementation and efficient calculations. More importantly, the Wilson loop representation provides a succinct geometric interpretation of nonlinear optical processes and responses based on quantum geometric tensors and quantum geometric potentials and can be readily applied to studying other excited-state responses.
Explainable machine learning for precise fatigue crack tip detection
Authors: Melching David , Strohmann Tobias , Requena Guillermo , Breitbarth Eric
Published: June 2022

Data-driven models based on deep learning have led to tremendous breakthroughs in classical computer vision tasks and have recently made their way into natural sciences. However, the absence of domain knowledge in their inherent design significantly hinders the understanding and acceptance of these models. Nevertheless, explainability is crucial to justify the use of deep learning tools in safety-relevant applications such as aircraft component design, service and inspection. In this work, we train convolutional neural networks for crack tip detection in fatigue crack growth experiments using full-field displacement data obtained by digital image correlation. For this, we introduce the novel architecture ParallelNets—a network which combines segmentation and regression of the crack tip coordinates—and compare it with a classical U-Net-based architecture. Aiming for explainability, we use the Grad-CAM interpretability method to visualize the neural attention of several models. Attention heatmaps show that ParallelNets is able to focus on physically relevant areas like the crack tip field, which explains its superior performance in terms of accuracy, robustness, and stability.
Metagenomics to characterize sediment microbial biodiversity associated with fishing exposure within the Stellwagen Bank National Marine Sanctuary
Authors: Bruce Spencer A. , Aytur Semra A. , Andam Cheryl P. , Bucci John P.
Published: June 2022

Microbes in marine sediments constitute a large percentage of the global marine ecosystem and function to maintain a healthy food web. In continental shelf habitats such as the Gulf of Maine (GoM), relatively little is known of the microbial community abundance, biodiversity, and natural product potential. This report is the first to provide a time-series assessment (2017–2020) of the sediment microbial structure in areas open and closed to fishing within the Stellwagen Bank National Marine Sanctuary (SBNMS). A whole metagenome sequencing (WMS) approach was used to characterize the sediment microbial community. Taxonomic abundance was calculated across seven geographic sites with 14 individual sediment samples collected during the summer and fall seasons. Bioinformatics analyses identified more than 5900 different species across multiple years. Non-metric multidimensional scaling methods and generalized linear models demonstrated that species richness was inversely associated with fishing exposure levels and varied by year. Additionally, the discovery of 12 unique biosynthetic gene clusters (BGCs) collected across sites confirmed the potential for medically relevant natural product discovery in the SBNMS. This study provides a practical assessment of how fishing exposure and temporal trends may affect microbial community structure in a coastal marine sanctuary.
Functional and morphologic dysfunctions in the airways of rats submitted to an experimental model of obesity-exacerbated asthma
Authors: Ferreira Sarah Rebeca Dantas , Pessoa Rayane Fernandes , Figueiredo Indyra Alencar Duarte , Lima João Pedro Moura , de Moura Thayna Maria Costa Fernandes , Bezerra Cleyton Oliveira , de Oliveira Martins Alissa Maria , de Carvalho Leila Moreira , Madruga Marta Suely , Cavalcante Hassler Clementino , de Souza Aquino Jailane , de Brito Alves José Luiz , Alves Adriano Francisco , Vasconcelos Luiz Henrique César , de Andrade Cavalcante Fabiana
Published: June 2022

The obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aim of this study was to standardize an obesity-exacerbated asthma model by a high glycemic level index (HGLI) diet and ovalbumin (OVA) sensitization and challenges in Wistar rats. Animals were divided into groups: control (Ctrl), obese (Ob), asthmatic (Asth), obese asthmatic (Ob + Asth) and obese asthmatic treated with dexamethasone (Ob + Asth + Dexa), and in vivo and in vitro functional and morphological parameters were measured. After HGLI consumption, there was an increase in body weight, fasting blood glucose, abdominal circumferences, body mass index and adiposity index. Respiratory function showed a reduction in pulmonary tidal volume and ventilation. In isolated tracheas, carbachol showed an increase in contractile efficacy in the Ob, Ob + Asth and Ob + Asth + Dexa, but mostly on Ob + Asth. Histological analysis of lungs showed peribronchovascular inflammation and smooth muscle hypertrophy and extracellular remodeling on Ob + Asth and Ob + Asth + Dexa. An obesity-exacerbated asthma model was successfully established. Therefore, this model allows further molecular investigations and the search for new therapies for the treatment and relief of symptoms of patients with obesity-induced resistant asthma.
DNA databases of an important tropical timber tree species Shorea leprosula (Dipterocarpaceae) for forensic timber identification
Authors: Ng Chin Hong , Ng Kevin Kit Siong , Lee Soon Leong , Zakaria Nurul-Farhanah , Lee Chai Ting , Tnah Lee Hong
Published: June 2022

International timber trade communities are increasingly demanding that timber in the wood supply chain be sourced from sustainably harvested forests and certified plantations. This is to combat illegal logging activities to prevent further depletion of our precious forests worldwide. Hence, timber tracking tools are important to support law enforcement officials in ensuring only sustainably harvested timbers are traded in the market. In this study, we developed chloroplast DNA (cpDNA) and simple sequence repeat (SSR) databases as tracking tools for an important tropical timber tree species, Shorealeprosula from Peninsular Malaysia. A total of 1410 individual trees were sampled from 44 natural populations throughout Peninsular Malaysia. Four cpDNA regions were used to generate a cpDNA haplotype database, resulting in a haplotype map comprising 22 unique haplotypes derived from 28 informative intraspecific variable sites. This cpDNA database can be used to trace the origin of an unknown log at the regional level. Ten SSR loci were used to develop the SSR allele frequency database. Bayesian cluster analysis divided the 44 populations into two genetic clusters corresponding to Region A and Region B. Based on conservativeness evaluation of the SSR databases for individual identification, the coancestry coefficients (θ) were adjusted to 0.1900 and 0.1500 for Region A and B, respectively. These databases are useful tools to complement existing timber tracking systems in ensuring only legally sourced timbers are allowed to enter the wood supply chain.
Factors associated to the duration of COVID-19 lockdowns in Chile
Authors: Pavani Jessica , Cerda Jaime , Gutiérrez Luis , Varas Inés , Gutiérrez Iván , Jofré Leonardo , Ortiz Oscar , Arriagada Gabriel
Published: June 2022

During the first year of the COVID-19 pandemic, several countries have implemented non-pharmacologic measures, mainly lockdowns and social distancing, to reduce the spread of the SARS-CoV-2 virus. These strategies varied widely across nations, and their efficacy is currently being studied. This study explores demographic, socioeconomic, and epidemiological factors associated with the duration of lockdowns applied in Chile between March 25th and December 25th, 2020. Joint models for longitudinal and time-to-event data were used. In this case, the number of days under lockdown for each Chilean commune and longitudinal information were modeled jointly. Our results indicate that overcrowding, number of active cases, and positivity index are significantly associated with the duration of lockdowns, being identified as risk factors for longer lockdown duration. In short, joint models for longitudinal and time-to-event data permit the identification of factors associated with the duration of lockdowns in Chile. Indeed, our findings suggest that demographic, socioeconomic, and epidemiological factors should be used to define both entering and exiting lockdown.
Pan-cancer analysis of genomic scar patterns caused by homologous repair deficiency (HRD)
Authors: Rempel E. , Kluck K. , Beck S. , Ourailidis I. , Kazdal D. , Neumann O. , Volckmar A. L. , Kirchner M. , Goldschmid H. , Pfarr N. , Weichert W. , Hübschmann D. , Fröhling S. , Sutter C. , Schaaf C. P. , Schirmacher P. , Endris V. , Stenzinger A. , Budczies J.
Published: June 2022

Homologous repair deficiency (HRD) is present in many cancer types at variable prevalence and can indicate response to platinum-based chemotherapy and PARP inhibition. We developed a tumor classification system based on the loss of function of genes in the homologous recombination repair (HRR) pathway. To this end, somatic and germline alterations inBRCA1/2and 140 other HRR genes were included and assessed for the impact on gene function. Additionally, information on the allelic hit type and onBRCA1promoter hypermethylation was included. The HRDsum score including LOH, LST, and TAI was calculated for 8847 tumors of the TCGA cohort starting from genotyping data and for the subcohort of ovarian cancer also starting from WES data. Pan-cancer, deleteriousBRCA1/2alterations were detected in 4% of the tumors, while 18% of the tumors were HRD-positive (HRDsum ≥ 42). Across 33 cancer types, bothBRCA1/2alterations and HRD-positivity were most prevalent in ovarian cancer (20% and 69%). Pan-cancer, tumors with biallelic deleterious alterations inBRCA1/2were separated strongly from tumors without relevant alterations (AUC = 0.89), while separation for tumors with monoallelic deleteriousBRCA1/2alterations was weak (AUC = 0.53). Tumors with biallelic deleterious alterations in other HHR genes were separated moderately from tumors without relevant alterations (AUC = 0.63), while separation for tumors with such monoallelic alterations was weaker (AUC = 0.57). In ovarian cancer, HRDsum scores calculated from WES data correlated strongly with HRDsum scores calculated from genotyping data (R = 0.87) and were slightly (4%) higher. We comprehensively analyzed HRD scores and their association with mutations in HRR genes in common cancer types. Our study identifies important parameters influencing HRD measurement and argues for an integration of HRDsum score with specific mutational profiles.
Larix species range dynamics in Siberia since the Last Glacial captured from sedimentary ancient DNA
Authors: Schulte Luise , Meucci Stefano , Stoof-Leichsenring Kathleen R. , Heitkam Tony , Schmidt Nicola , von Hippel Barbara , Andreev Andrei A. , Diekmann Bernhard , Biskaborn Boris K. , Wagner Bernd , Melles Martin , Pestryakova Lyudmila A. , Alsos Inger G. , Clarke Charlotte , Krutovsky Konstantin V. , Herzschuh Ulrike
Published: June 2022

Climate change is expected to cause major shifts in boreal forests which are in vast areas of Siberia dominated by two species of the deciduous needle tree larch (Larix). The species differ markedly in their ecosystem functions, thus shifts in their respective ranges are of global relevance. However, drivers of species distribution are not well understood, in part because paleoecological data at species level are lacking. This study tracks Larix species distribution in time and space using target enrichment on sedimentary ancient DNA extracts from eight lakes across Siberia. We discovered that Larix sibirica, presently dominating in western Siberia, likely migrated to its northern distribution area only in the Holocene at around 10,000 years before present (ka BP), and had a much wider eastern distribution around 33 ka BP. Samples dated to the Last Glacial Maximum (around 21 ka BP), consistently show genotypes of L. gmelinii. Our results suggest climate as a strong determinant of species distribution in Larix and provide temporal and spatial data for species projection in a changing climate.