bluuebunny/crossref_metadata_2025 huggingface dataset:
P130cas-FAK interaction is essential for YAP-mediated radioresistance of non-small cell lung cancer
Authors: Li Jingduo , Zhang Xiupeng , Hou Zaiyu , Cai Siqi , Guo Yingxue , Sun Limei , Li Ailin , Li Qingchang , Wang Enhua , Miao Yuan
Published: September 2022

Based on the RNA-sequencing data, previous studies revealed that extracellular matrix receptor interaction and focal adhesion signaling pathways were enriched in radioresistant non-small cell lung cancer (NSCLC) cell lines. As the principal members of these signaling pathways, recent studies showed that FAK controlled YAP’s nuclear translocation and activation in response to mechanical activation. However, the underlying mechanisms are largely unknown. This study was designed to determine whether P130cas plays a role in FAK-YAP axis-mediated radioresistance. We found that P130cas promoted proliferation, altered the cell cycle profile, and enhanced tumor growth using cell lines and xenograft mouse models. After treating the cell lines and xenograft models with a single dose of 5 Gy irradiation, we observed that P130cas effectively induced radioresistance in vitro and in vivo. We confirmed that P130cas interacted with and promoted YAP stabilization, thereby facilitating YAP’s activation and nuclear translocation and downregulating the radiosensitivity of NSCLC. Our data also revealed that P130cas and FAK directly interacted with each other and worked together to regulate YAP’s activation and nuclear translocation. Furthermore, the present study identified that P130cas, FAK and YAP formed a triple complex to induce radioresistance. Using P130cas-ΔSH3, FAK- P712/715A mutant, YAP-ΔSH3bm and YAP-ΔWW mutant, our results showed that targeting P130cas-FAK interaction may be a more cost-effective way to overcome the YAP activation mediated radioresistance in NSCLC. Using the data of the public database and our clinical samples, the present study suggested that the expression of P130cas correlated with YAP expression and indicated a poor overall response rate of NSCLC patients who underwent radiation therapy. Overall, our study extends the knowledge of FAK-YAP interaction and provides new insight into understanding the underlying mechanisms to overcome the radioresistance of NSCLC.
PLGA-microspheres-carried circGMCL1 protects against Crohn’s colitis through alleviating NLRP3 inflammasome-induced pyroptosis by promoting autophagy
Authors: Zhao Jie , Sun Ye , Yang Haojun , Qian Jun , Zhou Yan , Gong Yu , Dai Yi , Jiao Yuwen , Zhu Weiming , Wang Honggang , Lin Zhiliang , Tang Liming
Published: September 2022

This study aimed to at explore exploring the biological functions of dysregulated circRNA in Crohn’s disease (CD) pathogenesis, with the overarching goal of and providing potential novel therapeutic targets. CircRNA microarray and quantitative real time-polymerase chain reaction (qRT-PCR) analyses were performed to investigate and verify the candidate dysregulated circRNA. The Next, clinical, in vivo, and in vitro studies were performed to investigate explore the biological function and mechanisms of the candidate circRNA in CD. The therapeutic effect of poly (lactic-co-glycolic acid)-microspheres (PLGA MSs)-carried oe-circGMCL1 in experimental colitis models of IL-10 knock-out mice was assessed. CircGMCL1 was identified as the candidate circRNA by microarray and qRT-PCR analyses. Results showed that circGMCL1 expression was negatively correlated with CD-associated inflammatory indices, suggesting that it is a CD-associated circRNA. Microarray and bioinformatics analyses identified miR-124-3p and Annexin 7 (ANXA7) as its downstream mechanisms. The in vitro studies revealed that circGMCL1 mediates its effects on autophagy and NLRP3 inflammasome-mediated pyroptosis in epithelial cells through the ceRNA network. Moreover, the in vivo studies identified the therapeutic effect of PLGA MSs-carried oe-circGMCL1 in experimental colitis models. This study suggests that circGMCL1 protects intestinal barrier function against Crohn’s colitis through alleviating NLRP3 inflammasome-mediated epithelial pyroptosis by promoting autophagy through regulating ANXA7 via sponging miR-124-3p. Therefore, circGMCL1 can serve as a potential biological therapeutic target for Crohn’s colitis.
Transcription factor Foxp1 stimulates angiogenesis in adult rats after myocardial infarction
Authors: Wang Dinghui , Liu Bin , Xiong Tianhua , Yu Wenlong , Yang Huiping , Wang Jing , Jing Xiaodong , She Qiang
Published: September 2022

Forkhead box protein P1 (FoxP1) is essential for cardiac development and the regulation of neovascularization, but its potential for cardiac angiogenesis has not been explored. This study aims to investigate the angiogenic role of FoxP1 in a rat model of myocardial infarction (MI). Adult male rats were subjected to MI, and Foxp1 was knocked down with lentivirus FoxP1 siRNA. Endothelial cell proliferation, angiogenesis, and cardiac function were also assessed. Cell scratch assay and tubule formation analysis were used to detect the migration ability and tube formation ability of human umbilical vein endothelial cells (HUVECs). Compared with that in the sham group, results showed that the expression of FoxP1 was significantly increased in the MI group. Foxp1 knockdown decreases FoxP1 expression, reduces angiogenesis, and increases collagen deposition. When Foxp1 was knocked down in HUVECs using FoxP1 siRNA lentivirus, cell proliferation, migration, and tube formation abilities decreased significantly. Our study showed that FoxP1 elicits pleiotropic beneficial actions on angiogenesis in the post-MI heart by promoting the proliferation of endothelial cells. FoxP1 should be considered a candidate for therapeutic cardiac angiogenesis.
Diverse cell-specific patterns of alternative polyadenylation in Drosophila
Authors: Lee Seungjae , Chen Yen-Chung ,   FCA Consortium, Gillen Austin E. , Taliaferro J. Matthew , Deplancke Bart , Li Hongjie , Lai Eric C.
Published: September 2022

Most genes in higher eukaryotes express isoforms with distinct 3’ untranslated regions (3’ UTRs), generated by alternative polyadenylation (APA). Since 3’ UTRs are predominant locations of post-transcriptional regulation, APA can render such programs conditional, and can also alter protein sequences via alternative last exon (ALE) isoforms. We previously used 3’-sequencing from diverseDrosophilasamples to define multiple tissue-specific APA landscapes. Here, we exploit comprehensive single nucleus RNA-sequencing data (Fly Cell Atlas) to elucidate cell-type expression of 3’ UTRs across >250 adultDrosophilacell types. We reveal the cellular bases of multiple tissue-specific APA/ALE programs, such as 3’ UTR lengthening in differentiated neurons and 3’ UTR shortening in spermatocytes and spermatids. We trace dynamic 3’ UTR patterns across cell lineages, including in the male germline, and discover new APA patterns in the intestinal stem cell lineage. Finally, we correlate expression of RNA binding proteins (RBPs), miRNAs and global levels of cleavage and polyadenylation (CPA) factors in several cell types that exhibit characteristic APA landscapes, yielding candidate regulators of transcriptome complexity. These analyses provide a comprehensive foundation for future investigations of mechanisms and biological impacts of alternative 3’ isoforms across the major cell types of this widely-studied model organism.
Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen
Authors: Poole Andrew , Karuppiah Vijaykumar , Hartt Annabelle , Haidar Jaafar N. , Moureau Sylvie , Dobrzycki Tomasz , Hayes Conor , Rowley Christopher , Dias Jorge , Harper Stephen , Barnbrook Keir , Hock Miriam , Coles Charlotte , Yang Wei , Aleksic Milos , Lin Aimee Bence , Robinson Ross , Dukes Joe D. , Liddy Nathaniel , Van der Kamp Marc , Plowman Gregory D. , Vuidepot Annelise , Cole David K. , Whale Andrew D. , Chillakuri Chandramouli
Published: September 2022

Neoantigens derived from somatic mutations are specific to cancer cells and are ideal targets for cancer immunotherapy. KRAS is the most frequently mutated oncogene and drives the pathogenesis of several cancers. Here we show the identification and development of an affinity-enhanced T cell receptor (TCR) that recognizes a peptide derived from the most common KRAS mutant, KRASG12D, presented in the context of HLA-A*11:01. The affinity of the engineered TCR is increased by over one million-fold yet fully able to distinguish KRASG12D over KRASWT. While crystal structures reveal few discernible differences in TCR interactions with KRASWT versus KRASG12D, thermodynamic analysis and molecular dynamics simulations reveal that TCR specificity is driven by differences in indirect electrostatic interactions. The affinity enhanced TCR, fused to a humanized anti-CD3 scFv, enables selective killing of cancer cells expressing KRASG12D. Our work thus reveals a molecular mechanism that drives TCR selectivity and describes a soluble bispecific molecule with therapeutic potential against cancers harboring a common shared neoantigen.
Wilkes subglacial basin ice sheet response to Southern Ocean warming during late Pleistocene interglacials
Authors: Crotti Ilaria , Quiquet Aurélien , Landais Amaelle , Stenni Barbara , Wilson David J. , Severi Mirko , Mulvaney Robert , Wilhelms Frank , Barbante Carlo , Frezzotti Massimo
Published: September 2022

The response of the East Antarctic Ice Sheet to past intervals of oceanic and atmospheric warming is still not well constrained but is critical for understanding both past and future sea-level change. Furthermore, the ice sheet in the Wilkes Subglacial Basin appears to have undergone thinning and ice discharge events during recent decades. Here we combine glaciological evidence on ice sheet elevation from the TALDICE ice core with offshore sedimentological records and ice sheet modelling experiments to reconstruct the ice dynamics in the Wilkes Subglacial Basin over the past 350,000 years. Our results indicate that the Wilkes Subglacial Basin experienced an extensive retreat 330,000 years ago and a more limited retreat 125,000 years ago. These changes coincide with warmer Southern Ocean temperatures and elevated global mean sea level during those interglacial periods, confirming the sensitivity of the Wilkes Subglacial Basin ice sheet to ocean warming and its potential role in sea-level change.
An analysis modality for vascular structures combining tissue-clearing technology and topological data analysis
Authors: Takahashi Kei , Abe Ko , Kubota Shimpei I. , Fukatsu Noriaki , Morishita Yasuyuki , Yoshimatsu Yasuhiro , Hirakawa Satoshi , Kubota Yoshiaki , Watabe Tetsuro , Ehata Shogo , Ueda Hiroki R. , Shimamura Teppei , Miyazono Kohei
Published: September 2022

The blood and lymphatic vasculature networks are not yet fully understood even in mouse because of the inherent limitations of imaging systems and quantification methods. This study aims to evaluate the usefulness of the tissue-clearing technology for visualizing blood and lymphatic vessels in adult mouse. Clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) enables us to capture the high-resolution 3D images of organ- or area-specific vascular structures. To evaluate these 3D structural images, signals are first classified from the original captured images by machine learning at pixel base. Then, these classified target signals are subjected to topological data analysis and non-homogeneous Poisson process model to extract geometric features. Consequently, the structural difference of vasculatures is successfully evaluated in mouse disease models. In conclusion, this study demonstrates the utility of CUBIC for analysis of vascular structures and presents its feasibility as an analysis modality in combination with 3D images and mathematical frameworks.
Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm
Authors: Rai Shivam , Grockowiak Elodie , Hansen Nils , Luque Paz Damien , Stoll Cedric B. , Hao-Shen Hui , Mild-Schneider Gabriele , Dirnhofer Stefan , Farady Christopher J. , Méndez-Ferrer Simón , Skoda Radek C.
Published: September 2022

Interleukin-1β (IL-1β) is a master regulator of inflammation. Increased activity of IL-1β has been implicated in various pathological conditions including myeloproliferative neoplasms (MPNs). Here we show that IL-1β serum levels and expression of IL-1 receptors on hematopoietic progenitors and stem cells correlate withJAK2-V617F mutant allele fraction in peripheral blood of patients with MPN. We show that the source of IL-1β overproduction in a mouse model of MPN areJAK2-V617F expressing hematopoietic cells. Knockout ofIL-1βin hematopoietic cells ofJAK2-V617F mice reduces inflammatory cytokines, prevents damage to nestin-positive niche cells and reduces megakaryopoiesis, resulting in decrease of myelofibrosis and osteosclerosis. Inhibition of IL-1β inJAK2-V617F mutant mice by anti-IL-1β antibody also reduces myelofibrosis and osteosclerosis and shows additive effects with ruxolitinib. These results suggest that inhibition of IL-1β with anti-IL-1β antibody alone or in combination with ruxolitinib could have beneficial effects on the clinical course in patients with myelofibrosis.
Wide field imaging of van der Waals ferromagnet Fe3GeTe2 by spin defects in hexagonal boron nitride
Authors: Huang Mengqi , Zhou Jingcheng , Chen Di , Lu Hanyi , McLaughlin Nathan J. , Li Senlei , Alghamdi Mohammed , Djugba Dziga , Shi Jing , Wang Hailong , Du Chunhui Rita
Published: September 2022

Emergent color centers with accessible spins hosted by van der Waals materials have attracted substantial interest in recent years due to their significant potential for implementing transformative quantum sensing technologies. Hexagonal boron nitride (hBN) is naturally relevant in this context due to its remarkable ease of integration into devices consisting of low-dimensional materials. Taking advantage of boron vacancy spin defects in hBN, we report nanoscale quantum imaging of low-dimensional ferromagnetism sustained in Fe3GeTe2/hBN van der Waals heterostructures. Exploiting spin relaxometry methods, we have further observed spatially varying magnetic fluctuations in the exfoliated Fe3GeTe2 flake, whose magnitude reaches a peak value around the Curie temperature. Our results demonstrate the capability of spin defects in hBN of investigating local magnetic properties of layered materials in an accessible and precise way, which can be extended readily to a broad range of miniaturized van der Waals heterostructure systems.
Record high-Tc and large practical utilization level of electric polarization in metal-free molecular antiferroelectric solid solutions
Authors: Xu Haojie , Guo Wuqian , Ma Yu , Liu Yi , Hu Xinxin , Hua Lina , Han Shiguo , Liu Xitao , Luo Junhua , Sun Zhihua
Published: September 2022

Metal-free antiferroelectric materials are holding a promise for energy storage application, owing to their unique merits of wearability, environmental friendliness, and structure tunability. Despite receiving great interests, metal-free antiferroelectrics are quite limited and it is a challenge to acquire new soft antiferroelectric candidates. Here, we have successfully exploited binary CMBrxI1-x and CMBrxCl1-x solid solution as single crystals (0 ≤ x ≤ 1, where CM is cyclohexylmethylammonium). A molecule-level modification can effectively enhance Curie temperature. Emphatically, the binary CM-chloride salt shows the highest antiferroelectric-to-paraelectric Curie temperature of ~453 K among the known molecular antiferroelectrics. Its characteristic double electrical hysteresis loops provide a large electric polarization up to ~11.4 μC/cm2, which endows notable energy storage behaviors. To our best knowledge, this work provides an effective solid-solution methodology to the targeted design of new metal-free antiferroelectric candidates toward biocompatible energy storage devices.
Identifying and tailoring C–N coupling site for efficient urea synthesis over diatomic Fe–Ni catalyst
Authors: Zhang Xiaoran , Zhu Xiaorong , Bo Shuowen , Chen Chen , Qiu Mengyi , Wei Xiaoxiao , He Nihan , Xie Chao , Chen Wei , Zheng Jianyun , Chen Pinsong , Jiang San Ping , Li Yafei , Liu Qinghua , Wang Shuangyin
Published: September 2022

Electrocatalytic urea synthesis emerged as the promising alternative of Haber–Bosch process and industrial urea synthetic protocol. Here, we report that a diatomic catalyst with bonded Fe–Ni pairs can significantly improve the efficiency of electrochemical urea synthesis. Compared with isolated diatomic and single-atom catalysts, the bonded Fe–Ni pairs act as the efficient sites for coordinated adsorption and activation of multiple reactants, enhancing the crucial C–N coupling thermodynamically and kinetically. The performance for urea synthesis up to an order of magnitude higher than those of single-atom and isolated diatomic electrocatalysts, a high urea yield rate of 20.2 mmol h−1 g−1 with corresponding Faradaic efficiency of 17.8% has been successfully achieved. A total Faradaic efficiency of about 100% for the formation of value-added urea, CO, and NH3 was realized. This work presents an insight into synergistic catalysis towards sustainable urea synthesis via identifying and tailoring the atomic site configurations.
The primeval optical evolving matter by optical binding inside and outside the photon beam
Authors: Huang Chih-Hao , Louis Boris , Bresolí-Obach Roger , Kudo Tetsuhiro , Camacho Rafael , Scheblykin Ivan G. , Sugiyama Teruki , Hofkens Johan , Masuhara Hiroshi
Published: September 2022

Optical binding has recently gained considerable attention because it enables the light-induced assembly of many-body systems; however, this phenomenon has only been described between directly irradiated particles. Here, we demonstrate that optical binding can occur outside the focal spot of a single tightly focused laser beam. By trapping at an interface, we assemble up to three gold nanoparticles with a linear arrangement which fully-occupies the laser focus. The trapping laser is efficiently scattered by this linear alignment and interacts with particles outside the focus area, generating several discrete arc-shape potential wells with a half-wavelength periodicity. Those external nanoparticles inside the arcs show a correlated motion not only with the linear aligned particles, but also between themselves even both are not directly illuminated. We propose that the particles are optically bound outside the focal spot by the back-scattered light and multi-channel light scattering, forming a dynamic optical binding network.
Chang’E-5 samples reveal high water content in lunar minerals
Authors: Zhou Chuanjiao , Tang Hong , Li Xiongyao , Zeng Xiaojia , Mo Bing , Yu Wen , Wu Yanxue , Zeng Xiandi , Liu Jianzhong , Wen Yuanyun
Published: September 2022

The formation and distribution of lunar surficial water remains ambiguous. Here, we show the prominence of water (OH/H2O) attributed to solar wind implantation on the uppermost surface of olivine, plagioclase, and pyroxene grains from Chang’E-5 samples. The results of spectral and microstructural analyses indicate that solar wind-derived water is affected by exposure time, crystal structure, and mineral composition. Our estimate of a minimum of 170 ppm water content in lunar soils in the Chang’E-5 region is consistent with that reported by the Moon Minerology Mapper and Chang’E-5 lander. By comparing with remote sensing data and through lunar soil maturity analysis, the amount of water in Chang’E-5 provides a reference for the distribution of surficial water in middle latitude of the Moon. We conclude that minerals in lunar soils are important reservoirs of water, and formation and retention of water originating from solar wind occurs on airless bodies.
Holocene seasonal temperature evolution and spatial variability over the Northern Hemisphere landmass
Authors: Zhang Wenchao , Wu Haibin , Cheng Jun , Geng Junyan , Li Qin , Sun Yong , Yu Yanyan , Lu Huayu , Guo Zhengtang
Published: September 2022

The origin of the temperature divergence between Holocene proxy reconstructions and model simulations remains controversial, but it possibly results from potential biases in the seasonality of reconstructions or in the climate sensitivity of models. Here we present an extensive dataset of Holocene seasonal temperatures reconstructed using 1310 pollen records covering the Northern Hemisphere landmass. Our results indicate that both summer and winter temperatures warmed from the early to mid-Holocene (~11–7 ka BP) and then cooled thereafter, but with significant spatial variability. Strong early Holocene warming trend occurred mainly in Europe, eastern North America and northern Asia, which can be generally captured by model simulations and is likely associated with the retreat of continental ice sheets. The subsequent cooling trend is pervasively recorded except for northern Asia and southeastern North America, which may reflect the cross-seasonal impact of the decreasing summer insolation through climatic feedbacks, but the cooling in winter season is not well reproduced by climate models. Our results challenge the proposal that seasonal biases in proxies are the main origin of model–data discrepancies and highlight the critical impact of insolation and associated feedbacks on temperature changes, which warrant closer attention in future climate modelling.
Unconventional interfacial water structure of highly concentrated aqueous electrolytes at negative electrode polarizations
Authors: Li Chao-Yu , Chen Ming , Liu Shuai , Lu Xinyao , Meng Jinhui , Yan Jiawei , Abruña Héctor D. , Feng Guang , Lian Tianquan
Published: September 2022

Water-in-salt electrolytes are an appealing option for future electrochemical energy storage devices due to their safety and low toxicity. However, the physicochemical interactions occurring at the interface between the electrode and the water-in-salt electrolyte are not yet fully understood. Here, via in situ Raman spectroscopy and molecular dynamics simulations, we investigate the electrical double-layer structure occurring at the interface between a water-in-salt electrolyte and an Au(111) electrode. We demonstrate that most interfacial water molecules are bound with lithium ions and have zero, one, or two hydrogen bonds to feature three hydroxyl stretching bands. Moreover, the accumulation of lithium ions on the electrode surface at large negative polarizations reduces the interfacial field to induce an unusual “hydrogen-up” structure of interfacial water and blue shift of the hydroxyl stretching frequencies. These physicochemical behaviours are quantitatively different from aqueous electrolyte solutions with lower concentrations. This atomistic understanding of the double-layer structure provides key insights for designing future aqueous electrolytes for electrochemical energy storage devices.
Immunologically “cold” triple negative breast cancers engraft at a higher rate in patient derived xenografts
Authors: Petrosyan Varduhi , Dobrolecki Lacey E. , LaPlante Emily L. , Srinivasan Ramakrishnan Rajaram , Bailey Matthew H. , Welm Alana L. , Welm Bryan E. , Lewis Michael T. , Milosavljevic Aleksandar
Published: September 2022

TNBC is a heterogeneous subtype of breast cancer, and only a subset of TNBC can be established as PDXs. Here, we show that there is an engraftment bias toward TNBC with low levels of immune cell infiltration. Additionally, TNBC that failed to engraft show gene expression consistent with a cancer-promoting immunological state, leading us to hypothesize that the immunological state of the tumor and possibly the state of the immune system of the host may be essential for engraftment.
A flexible and scalable scheme for mixing computed formation energies from different levels of theory
Authors: Kingsbury Ryan S. , Rosen Andrew S. , Gupta Ayush S. , Munro Jason M. , Ong Shyue Ping , Jain Anubhav , Dwaraknath Shyam , Horton Matthew K. , Persson Kristin A.
Published: September 2022

Computational materials discovery efforts are enabled by large databases of properties derived from high-throughput density functional theory (DFT), which now contain millions of calculations at the generalized gradient approximation (GGA) level of theory. It is now feasible to carry out high-throughput calculations using more accurate methods, such as meta-GGA DFT; however recomputing an entire database with a higher-fidelity method would not effectively leverage the enormous investment of computational resources embodied in existing (GGA) calculations. Instead, we propose here a general procedure by which higher-fidelity, low-coverage calculations (e.g., meta-GGA calculations for selected chemical systems) can be combined with lower-fidelity, high-coverage calculations (e.g., an existing database of GGA calculations) in a robust and scalable manner. We then use legacy PBE(+U) GGA calculations and new r2SCAN meta-GGA calculations from the Materials Project database to demonstrate that our scheme improves solid and aqueous phase stability predictions, and discuss practical considerations for its implementation.
Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects
Authors: Ho Philip Wing-Lok , Chang Eunice Eun-Seo , Leung Chi-Ting , Liu Huifang , Malki Yasine , Pang Shirley Yin-Yu , Choi Zoe Yuen-Kiu , Liang Yingmin , Lai Weng Seng , Ruan Yuefei , Leung Kenneth Mei-Yee , Yung Susan , Mak Judith Choi-Wo , Kung Michelle Hiu-Wai , Ramsden David B. , Ho Shu-Leong
Published: September 2022

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in nigrostriatal and cortical brain regions associated with pathogenic α-synuclein (αSyn) aggregate/oligomer accumulation. LRRK2 hyperactivity is a disease-modifying therapeutic target in PD. However, LRRK2 inhibition may be associated with peripheral effects, albeit with unclear clinical consequences. Here, we significantly reduced αSyn oligomer accumulation in mouse striatum through long-term LRRK2 inhibition using GNE-7915 (specific brain-penetrant LRRK2 inhibitor) without causing adverse peripheral effects. GNE-7915 concentrations in wild-type (WT) mouse sera and brain samples reached a peak at 1 h, which gradually decreased over 24 h following a single subcutaneous (100 mg/kg) injection. The same dose in young WT and LRRK2R1441G mutant mice significantly inhibited LRRK2 kinase activity (Thr73-Rab10 and Ser106-Rab12 phosphorylation) in the lung, which dissipated by 72 h post-injection. 14-month-old mutant mice injected with GNE-7915 twice weekly for 18 weeks (equivalent to ~13 human years) exhibited reduced striatal αSyn oligomer and cortical pSer129-αSyn levels, correlating with inhibition of LRRK2 hyperactivity in brain and lung to WT levels. No GNE-7915-treated mice showed increased mortality or morbidity. Unlike reports of abnormalities in lung and kidney at acute high doses of LRRK2 inhibitors, our GNE-7915-treated mice did not exhibit swollen lamellar bodies in type II pneumocytes or abnormal vacuolation in the kidney. Functional and histopathological assessments of lung, kidney and liver, including whole-body plethysmography, urinary albumin-creatinine ratio (ACR), serum alanine aminotransferase (ALT) and serum interleukin-6 (inflammatory marker) did not reveal abnormalities after long-term GNE-7915 treatment. Long-term inhibition of mutant LRRK2 hyper-kinase activity to physiological levels presents an efficacious and safe disease-modifying therapy to ameliorate synucleinopathy in PD.
Spin supersolidity in nearly ideal easy-axis triangular quantum antiferromagnet Na2BaCo(PO4)2
Authors: Gao Yuan , Fan Yu-Chen , Li Han , Yang Fan , Zeng Xu-Tao , Sheng Xian-Lei , Zhong Ruidan , Qi Yang , Wan Yuan , Li Wei
Published: September 2022

Prototypical models and their material incarnations are cornerstones to the understanding of quantum magnetism. Here we show theoretically that the recently synthesized magnetic compound Na2BaCo(PO4)2 (NBCP) is a rare, nearly ideal material realization of the S = 1/2 triangular-lattice antiferromagnet with significant easy-axis spin exchange anisotropy. By combining the automatic parameter searching and tensor-network simulations, we establish a microscopic model description of this material with realistic model parameters, which can not only fit well the experimental thermodynamic data but also reproduce the measured magnetization curves without further adjustment of parameters. According to the established model, the NBCP hosts a spin supersolid state that breaks both the lattice translation symmetry and the spin rotational symmetry. Such a state is a spin analog of the long-sought supersolid state, thought to exist in solid Helium and optical lattice systems, and share similar traits. The NBCP therefore represents an ideal material-based platform to explore the physics of supersolidity as well as its quantum and thermal melting.
Quantitative 3D OPT and LSFM datasets of pancreata from mice with streptozotocin-induced diabetes
Authors: Hahn Max , Nord Christoffer , van Krieken Pim P. , Berggren Per-Olof , Ilegems Erwin , Cheddad Abbas , Ahlgren Ulf
Published: September 2022

Mouse models for streptozotocin (STZ) induced diabetes probably represent the most widely used systems for preclinical diabetes research, owing to the compound’s toxic effect on pancreatic β-cells. However, a comprehensive view of pancreatic β-cell mass distribution subject to STZ administration is lacking. Previous assessments have largely relied on the extrapolation of stereological sections, which provide limited 3D-spatial and quantitative information. This data descriptor presents multiple ex vivo tomographic optical image datasets of the full β-cell mass distribution in mice subject to single high and multiple low doses of STZ administration, and in glycaemia recovered mice. The data further include information about structural features, such as individual islet β-cell volumes, spatial coordinates, and shape as well as signal intensities for both insulin and GLUT2. Together, they provide the most comprehensive anatomical record of the effects of STZ administration on the islet of Langerhans in mice. As such, this data descriptor may serve as reference material to facilitate the planning, use and (re)interpretation of this widely used disease model.
Intravital microscopy datasets examining key nephron segments of transplanted decellularized kidneys
Authors: Corridon Peter R.
Published: September 2022

This study contains intravital microscopy (IVM) data examining the microarchitecture of acellular kidney scaffolds. Acellular scaffolds are cell-free collagen-based matrices derived from native organs that can be used as templates for regenerative medicine applications. This data set contains in vivo assays that evaluate the effectiveness of decellularization and how these acellular nephron compartments perform in the post-transplantation environment. Qualitative and quantitative assessments of scaffold DNA concentrations, tissue fluorescence signals, and structural and functional integrities of decellularized tubular and peritubular capillary segments were acquired and compared to the native (non-transplanted) organ. Cohorts of 2–3-month-old male Sprague Dawley rats were used: non-transplanted (n = 4), transplanted day 0 (n = 4), transplanted day 1 (n = 4), transplanted day 2 (n = 4), and transplanted day 7 (n = 4). Micrographs and supporting measurements are provided to illustrate IVM processes used to perform this study and are publicly available in a data repository to assist scientific reproducibility and extend the use of this powerful imaging application to analyze other scaffold systems.

Measurements(s)
DNA quantification • tissue fluorescence • microvascular leakage • tubular and peritubular capillary integrity

Technology Type(s)
intravital microscopy • multiphoton microscopy • UV-visible spectroscopy

Sample Characterization(s)
rats • native and decellularized kidneys
Differences in acute phase response to bacterial, fungal and viral antigens in greater mouse-eared bats (Myotis myotis)
Authors: Seltmann Anne , Troxell Sara A. , Schad Julia , Fritze Marcus , Bailey Liam D. , Voigt Christian C. , Czirják Gábor Á.
Published: September 2022

The acute phase response (APR) is an evolutionarily well-conserved part of the innate immune defense against pathogens. However, recent studies in bats yielded surprisingly diverse results compared to previous APR studies on both vertebrate and invertebrate species. This is especially interesting due to the known role of bats as reservoirs for viruses and other intracellular pathogens, while being susceptible to extracellular microorganisms such as some bacteria and fungi. To better understand these discrepancies and the reservoir-competence of bats, we mimicked bacterial, viral and fungal infections in greater mouse-eared bats (Myotis myotis) and quantified different aspects of the APR over a two-day period. Individuals reacted most strongly to a viral (PolyI:C) and a bacterial (LPS) antigen, reflected by an increase of haptoglobin levels (LPS) and an increase of the neutrophil-to-lymphocyte-ratio (PolyI:C and LPS). We did not detect fever, leukocytosis, body mass loss, or a change in the overall functioning of the innate immunity upon challenge with any antigen. We add evidence that bats respond selectively with APR to specific pathogens and that the activation of different parts of the immune system is species-specific.
Entrance and origin of the extracranial vertebral artery found on computed tomography angiography
Authors: Yi Xueting , Xie Ping , Zhang Lianwei , Lu Fengxia , Chen Hao , Liu Kefu
Published: September 2022

To investigated morphological variability of vertebral artery (VA) origin and its entrance level into cervical transverse foramina by computed tomography angiography (CTA). To retrospectively investigated CTA of 223 subjects (446 VA courses). Investigated were origin of the VA and its level of entrance into vertebral transverse foramen with notification of the sex and side of variation. The VA entered the C6 transverse process in 91.70% of specimens (409 out of 446 VA courses). Abnormal entrance of VA was observed in 8.30% of specimens (37 VA courses), with the level of entrance into the C3, C4, C5, or C7 transverse foramen at 0.22%, 2.47%, 4.71% and 0.90% respectively. Comparably, the overall variability of abnormal origin of VA was 1.57% (7 out of 466 VA courses), in which the left vertebral arteries all arose from aortic arch. The variation rate of vertebral entrance rose up to 50% in abnormal origin subgroup. When comparing subgroups of subjects with normal and abnormal origin, there was significance difference in the frequency of entrance variation in the level of transverse foramen (p < 0.001). Abnormal entrance and origin of VA were observed in 8.30% and 1.57% of VA courses, which can be accurately appeared by CTA. Regarding to the subgroups of abnormal origin, the frequency of entrance variation was significantly increased in the level of transverse foramen compared to that of normal origin.
Bacillus velezensis strain Ag75 as a new multifunctional agent for biocontrol, phosphate solubilization and growth promotion in maize and soybean crops
Authors: Mosela Mirela , Andrade Galdino , Massucato Luana Rainieri , de Araújo Almeida Suelen Regina , Nogueira Alison Fernando , de Lima Filho Renato Barros , Zeffa Douglas Mariani , Mian Silas , Higashi Allan Yukio , Shimizu Gabriel Danilo , Teixeira Gustavo Manoel , Branco Kelvin Shinohata , Faria Marcos Ventura , Giacomin Renata Mussoi , Scapim Carlos Alberto , Gonçalves Leandro Simões Azeredo
Published: September 2022

Soybean and maize are some of the main drivers of Brazilian agribusiness. However, biotic and abiotic factors are of great concern, causing huge grain yield and quality losses. Phosphorus (P) deficiency is important among the abiotic factors because most Brazilian soils have a highly P-fixing nature. Thus, large amounts of phosphate fertilizers are regularly applied to overcome the rapid precipitation of P. Searching for alternatives to improve the use of P by crops is essential to reduce the demand for P input. The use of multifunctional rhizobacteria can be considered one of these alternatives. In this sense, the objective of the present work was to select and validate bacterial strains with triple action (plant growth promoter, phosphate solubilizer, and biocontrol agent) in maize and soybean, aiming to develop a multifunctional microbial inoculant for Brazilian agriculture. Bacterial strains with high indole acetic acid (IAA) production, phosphate solubilization, and antifungal activity against soil pathogenic fungi (Rhizoctonia solani, Macrophomina phaseolina, and Fusarium solani) were selected from the maize rhizosphere. Then, they were evaluated as growth promoters in maize under greenhouse conditions. Based on this study, strain 03 (Ag75) was selected due to its high potential for increasing biomass (root and shoot) and shoot P content in maize. This strain was identified through genomic sequencing as Bacillus velezensis. In field experiments, the inoculation of this bacterium increased maize and soybean yields by 17.8 and 26.5%, respectively, compared to the control (25 kg P2O5). In addition, the inoculation results did not differ from the control with 84 kg P2O5, indicating that it is possible to reduce the application of phosphate in these crops. Thus, the Ag75 strain has great potential for developing a multifunctional microbial inoculant that combines the ability to solubilize phosphate, promote plant growth, and be a biocontrol agent for several phytopathogenic fungi.
Design, synthesis and insecticidal activity and mechanism research of Chasmanthinine derivatives
Authors: Song Ziyu , Li Xiangyu , Xu Ke , Sun Guoqing , Yang Liu , Huang Linyu , Liu Junqi , Yin Pengyuan , Huang Shuai , Gao Feng , Zhou Xianli , Chen Lin
Published: September 2022

Unrestricted reproduction and spread of pest had caused great damage to the quality and yield of crops in recent years. Besides the use of traditional chemical pesticides, natural products also make a huge contribution against pests. Chasmanthinine, a diterpenoid alkaloid isolated from Aconitum franchetii var. villosulum, shown extremely antifeedant activity against Spodoptera exigua. Therefore, a series of novel Chasmanthinine derivatives were synthesized and their biological activity was studied in this work. Compound 33 showed the strongest antifeedant activity (EC50 = 0.10 mg/cm2) among all the test compounds. The mechanism research of 33 revealed that its antifeedant effect was related to the inhibition of carboxylesterase (CES), and proved the thiophene acyl group could form a strong binding effect with CES by molecular docking. Moreover, compound 10 exhibited the strongest cytotoxicity (IC50 = 12.87 μM) against Sf9 cell line and moderate contact toxicity. The mechanism research indicated that compound 10 could induce Sf9 cells apoptosis. In summary, the results lay a foundation for the application of diterpene alkaloids in plant protection.
Polarization-probe polarization-imaging system in near-infrared regime using a polarization grating
Authors: Sakamoto Moritsugu , Nhan Huynh Thanh , Noda Kohei , Sasaki Tomoyuki , Tanaka Masayuki , Kawatsuki Nobuhiro , Ono Hiroshi
Published: September 2022

A polarization-probe polarization-imaging (PPPI) system was developed for the near-infrared (NIR) regime. This system comprises two components operating as a polarization generator and a polarization analyzer to enable polarization image capture under polarized light illumination. The captured polarization images contain considerable object information because the illuminating polarized light beams are affected by many of the Mueller matrix elements. By assembling the polarization camera using two liquid crystal retarders and a polarization grating, the PPPI system offers the potential to measure the Stokes parameters fully with a high extinction ratio, even in the NIR region. The PPPI system’s feasibility was demonstrated experimentally. Its dependence on the state of polarization (SoP) of the illuminating polarized light was discussed. The polarization image acquired by the PPPI system is strongly dependent on the illuminating light’s SoP, so the appropriate SoP must be selected for each object to enhance the polarization image contrast. This PPPI system should expand the range of polarization imaging applications, including LiDAR, product inspection, and bio-imaging.
Empirical analysis of the role of the environmental accountability system in energy conservation and emission reduction in China
Authors: Cui Chunying , Li Jing , Lu Zhaoying , Yan Ziwei
Published: September 2022

Many developing countries are facing the difficulty of choosing between economic growth and energy conservation and emission reduction (ECER). China has strengthened the implementation of ECER by setting environmental accountability as the development goal of local governments, hoping to have better governance effects. To evaluate the actual intervention effect of this approach, this paper constructs panel data covering 46 countries from 1995 to 2014 and uses the difference-in-differences (DID) method and the composite control method to quantitatively analyse the policy effect. The results show that China can effectively curb energy consumption and carbon emission intensity per unit of GDP by adding ECER targets to the government’s five-year plan, which has significant effects on ECER. Furthermore, we use an intermediary mechanism to test and identify low-carbon alternatives and an ECER promotion mechanism for technological advancement. The conclusion shows that economic development is compatible with low carbon and energy consumption. Combined with China’s long-term goals for ECER, it can be considered that on the road to achieving carbon peaking and carbon neutrality in the future, the economy and tertiary industry should be rationally developed, the degree of urbanization should receive more attention, and the proportion of thermal power generation should be reduced.
Incidence of nephrotoxicity associated with intravenous colistimethate sodium administration for the treatment of multidrug-resistant gram-negative bacterial infections
Authors: Sadyrbaeva-Dolgova Svetlana , García-Fumero Ricardo , Exposito-Ruiz Manuela , Pasquau-Liaño Juan , Jiménez-Morales Alberto , Hidalgo-Tenorio Carmen
Published: September 2022

Colistimethate sodium (CMS) is the inactive prodrug of colistin, CMS has a narrow antibacterial spectrum with concentration-dependent bactericidal activity against multidrug-resistant gram-negative bacteria, including Pseudomonas aeruginosa and Acinetobacter baumannii. This study aimed to analyze potential correlations between clinical features and the development of CMS-induced nephrotoxicity. This retrospective cohort study was conducted in a tertiary-care university hospital between 1 January 2015 and 31 December 2019. A total of 163 patients received CMS therapy. 75 patients (46%) developed nephrotoxicity attributable to colistin treatment, although only 14 patients (8.6%) discontinued treatment for this reason. 95.7% of CMS were prescribed as target therapy. Acinetobacter baumannii spp. was the most commonly identified pathogen (72.4%) followed by P. aeruginosa (19.6%). Several risk factors associated with nephrotoxicity were identified, among these were age (HR 1.033, 95%CI 1.016–1.052, p < 0.001), Charlson Index (HR 1.158, 95%CI 1.0462–1.283; p = 0.005) and baseline creatinine level (HR 1.273, 95%CI 1.071–1.514, p = 0.006). In terms of in-hospital mortality, risk factors were age (HR 2.43, 95%CI 1.021–1.065, p < 0.001); Charlson Index (HR 1.274, 95%CI 1.116–1.454, p = 0.043), higher baseline creatinine levels (HR 1.391, 95%CI 1.084–1.785, p = 0.010) and nephrotoxicity due to CMS treatment (HR 5.383, 95%CI 3.126–9.276, p < 0.001). In-hospital mortality rate were higher in patients with nephrotoxicity (log rank test p < 0.001). In conclusion, the nephrotoxicity was reported in almost half of the patients. Its complex management, continuous renal dose adjustment and monitoring creatinine levels at least every 48 h leads to a high percentage of inappropriate use and treatment failure.
Investigation on pollination approaches, reproductive biology and essential oil variation during floral development in German chamomile (Matricaria chamomilla L.)
Authors: Yadav Niketa , Shakya Pooja , Kumar Ajay , Gautam Rahul Dev , Chauhan Ramesh , Kumar Dinesh , Kumar Ashok , Singh Sanatsujat , Singh Satbeer
Published: September 2022

German chamomile is an important medicinal and aromatic herb known for its blue essential oil. It lacks studies on anthesis, breeding systems and floral development with their impact on the essential oil. Therefore, the study investigated floral development and divided it into six reproductive stages (RS-1 to RS-6). The first four stages (5–6 days long) were identified as the floral enlargement and differentiation, followed by the fifth stage (10 days long) of three anthesis flushes, i.e., anther dehiscence, ray and disc florets' style branches flush. Anther dehiscence started 1–2 days before style branches flushes showed protandry and overlapped later with style branches flushes. Pollen production started from RS-3 and showed maximum viability (89%) at anther dehiscence (RS-5.1). Pollen showed dispersal through the air up to 0.7 m distance. Seed setting in controlled pollination experiments showed that removing disc florets could be successfully used as the emasculation alternate in German chamomile. The maximum essential oil content (0.40%) at the full blossomed floral stage (RS-4 &-5) suggested the right time for capitula harvesting. The findings on reproductive biology and breeding systems would offer several tools and techniques to support future breeding programs for genetic improvement of German chamomile.
Effects of contoured insoles with different materials on plantar pressure offloading in diabetic elderly during gait
Authors: Shi Qiu Qiong , Li Pui Ling , Yick Kit-Lun , Li Nga-Wun , Jiao Jiao
Published: September 2022

To investigate the effect of contoured insoles constructed of different insole materials, including Nora Lunalastik EVA, Nora Lunalight A fresh, Pe-Lite, and PORON Medical 4708 with Langer Biomechanics longitudinal PPT arch pads on offloading plantar pressure on the foot of the elderly with Type 1 or 2 diabetes during gait. Twenty-two elderly with Type 1 or 2 diabetes participated in the study. Their plantar pressure was measured by using an insole measurement system, while the participants walked 10 m in their bare feet or used each experimental insole in random order. The plantar surface was divided into four specific regions including the toes, forefoot, midfoot, and rearfoot. The mean peak pressure (MPP) and pressure–time integral (PTI) of ten steps with or without wearing one of the four insoles were analyzed on the dominant foot and the four specific plantar regions. After completion of the activities, the participants scored each insole from 1 (the least comfortable) to 10 (the most comfortable). The analysis of variance (ANOVA) factor of the insoles had significant effects on the MPP (P < 0.001) and PTI (P = 0.004) in the dominant foot during gait. Pairwise comparison results showed that the MPP and PTI in the dominant foot were significantly lower (P < 0.001) with PORON Medical 4708 than barefoot, Nora Lunalight A fresh, and Pe-Lite. Additionally, the insole materials had a significant effect for the forefoot (P < 0.001) and rearfoot (P < 0.001) in terms of the MPP and PTI compared with the barefoot condition during gait. Regardless of the plantar region, the MPP and PTI values were the lowest when PORON Medical 4708 was used as the insole material among four insole materials. Meanwhile, a significantly lower MPP and PTI can be found in the forefoot and rearfoot with the use of the four experimental insoles when compared with barefoot. The soft insole materials (i.e., PORON medical 4708 and Nora Lunalastik EVA) had a better performance than the rigid insole materials (i.e., Nora Lunalight A fresh, and Pe-Lite) on plantar pressure offloading for diabetic elderly.
Recent advances in antibiotic resistance diagnosis using SERS: focus on the “Big 5” challenges
Authors: Hassanain Waleed A. , Johnson Christopher L. , Faulds Karen , Graham Duncan , Keegan Neil
Published: September 2022

SERS for antibiotic resistance diagnosis.