bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design principles for NASICON super-ionic conductors
Authors: Wang Jingyang , He Tanjin , Yang Xiaochen , Cai Zijian , Wang Yan , Lacivita Valentina , Kim Haegyeom , Ouyang Bin , Ceder Gerbrand 
Published: August 2023

AbstractNa Super Ionic Conductor (NASICON) materials are an important class of solid-state electrolytes owing to their high ionic conductivity and superior chemical and electrochemical stability. In this paper, we combine first-principles calculations, experimental synthesis and testing, and natural language-driven text-mined historical data on NASICON ionic conductivity to achieve clear insights into how chemical composition influences the Na-ion conductivity. These insights, together with a high-throughput first-principles analysis of the compositional space over which NASICONs are expected to be stable, lead to the successful synthesis and electrochemical investigation of several new NASICONs solid-state conductors. Among these, a high ionic conductivity of 1.2 mS cm−1 could be achieved at 25 °C. We find that the ionic conductivity increases with average metal size up to a certain value and that the substitution of PO4 polyanions by SiO4 also enhances the ionic conductivity. While optimal ionic conductivity is found near a Na content of 3 per formula unit, the exact optimum depends on other compositional variables. Surprisingly, the Na content enhances the ionic conductivity mostly through its effect on the activation barrier, rather than through the carrier concentration. These deconvoluted design criteria may provide guidelines for the design of optimized NASICON conductors.
Infrared spectroscopic laser scanning confocal microscopy for whole-slide chemical imaging
Authors: Yeh Kevin , Sharma Ishaan , Falahkheirkhah Kianoush , Confer Matthew P. , Orr Andres C. , Liu Yen-Ting , Phal Yamuna , Ho Ruo-Jing , Mehta Manu , Bhargava Ankita , Mei Wenyan , Cheng Georgina , Cheville John C. , Bhargava Rohit 
Published: August 2023

AbstractChemical imaging, especially mid-infrared spectroscopic microscopy, enables label-free biomedical analyses while achieving expansive molecular sensitivity. However, its slow speed and poor image quality impede widespread adoption. We present a microscope that provides high-throughput recording, low noise, and high spatial resolution where the bottom-up design of its optical train facilitates dual-axis galvo laser scanning of a diffraction-limited focal point over large areas using custom, compound, infinity-corrected refractive objectives. We demonstrate whole-slide, speckle-free imaging in ~3 min per discrete wavelength at 10× magnification (2 μm/pixel) and high-resolution capability with its 20× counterpart (1 μm/pixel), both offering spatial quality at theoretical limits while maintaining high signal-to-noise ratios (>100:1). The data quality enables applications of modern machine learning and capabilities not previously feasible – 3D reconstructions using serial sections, comprehensive assessments of whole model organisms, and histological assessments of disease in time comparable to clinical workflows. Distinct from conventional approaches that focus on morphological investigations or immunostaining techniques, this development makes label-free imaging of minimally processed tissue practical.
Projecting RNA measurements onto single cell atlases to extract cell type-specific expression profiles using scProjection
Authors: Johansen Nelson , Hu Hongru , Quon Gerald 
Published: August 2023

AbstractMulti-modal single cell RNA assays capture RNA content as well as other data modalities, such as spatial cell position or the electrophysiological properties of cells. Compared to dedicated scRNA-seq assays however, they may unintentionally capture RNA from multiple adjacent cells, exhibit lower RNA sequencing depth compared to scRNA-seq, or lack genome-wide RNA measurements. We present scProjection, a method for mapping individual multi-modal RNA measurements to deeply sequenced scRNA-seq atlases to extract cell type-specific, single cell gene expression profiles. We demonstrate several use cases of scProjection, including identifying spatial motifs from spatial transcriptome assays, distinguishing RNA contributions from neighboring cells in both spatial and multi-modal single cell assays, and imputing expression measurements of un-measured genes from gene markers. scProjection therefore combines the advantages of both multi-modal and scRNA-seq assays to yield precise multi-modal measurements of single cells.
Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions
Authors: Gao Xiang , Han Tian-Jiao , Li Bei-Bei , Hou Xiao-Xiao , Hua Yuan-Zhao , Jia Shi-Kun , Xiao Xiao , Wang Min-Can , Wei Donghui , Mei Guang-Jian 
Published: August 2023

AbstractThe catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.
Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain
Authors: Wu Arum , Salom David , Hong John D. , Tworak Aleksander , Watanabe Kohei , Pardon Els , Steyaert Jan , Kandori Hideki , Katayama Kota , Kiser Philip D. , Palczewski Krzysztof 
Published: August 2023

AbstractRhodopsin is a prototypical G protein-coupled receptor (GPCR) critical for vertebrate vision. Research on GPCR signaling states has been facilitated using llama-derived nanobodies (Nbs), some of which bind to the intracellular surface to allosterically modulate the receptor. Extracellularly binding allosteric nanobodies have also been investigated, but the structural basis for their activity has not been resolved to date. Here, we report a library of Nbs that bind to the extracellular surface of rhodopsin and allosterically modulate the thermodynamics of its activation process. Crystal structures of Nb2 in complex with native rhodopsin reveal a mechanism of allosteric modulation involving extracellular loop 2 and native glycans. Nb2 binding suppresses Schiff base deprotonation and hydrolysis and prevents intracellular outward movement of helices five and six – a universal activation event for GPCRs. Nb2 also mitigates protein misfolding in a disease-associated mutant rhodopsin. Our data show the power of nanobodies to modulate the photoactivation of rhodopsin and potentially serve as therapeutic agents for disease-associated rhodopsin misfolding.
An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants
Authors: Liu Juan , Mao Fengfeng , Chen Jianhe , Lu Shuaiyao , Qi Yonghe , Sun Yinyan , Fang Linqiang , Yeung Man Lung , Liu Chunmei , Yu Guimei , Li Guangyu , Liu Ximing , Yao Yuansheng , Huang Panpan , Hao Dongxia , Liu Zibing , Ding Yu , Liu Haimo , Yang Fang , Chen Pan , Sa Rigai , Sheng Yao , Tian Xinxin , Peng Ran , Li Xue , Luo Junmian , Cheng Yurui , Zheng Yule , Lin Yongqing , Song Rui , Jin Ronghua , Huang Baoying , Choe Hyeryun , Farzan Michael , Yuen Kwok-Yung , Tan Wenjie , Peng Xiaozhong , Sui Jianhua , Li Wenhui 
Published: August 2023

AbstractMany of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)—the cellular receptor of SARS-CoV-2—into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses.
A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells
Authors: Najafabadi Maryam Ghaderi , Gray G. Kenneth , Kong Li Ren , Gupta Komal , Perera David , Naylor Huw , Brugge Joan S. , Venkitaraman Ashok R. , Shehata Mona 
Published: August 2023

AbstractGermline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations. Here, we report that monoallelic Brca2mut/WT mammary organoids subjected to replication stress activate a transcriptional response that selectively expands Brca2mut/WT luminal cells lacking hormone receptor expression (HR-). While CyTOF analyses reveal comparable epithelial compositions among wildtype and Brca2mut/WT mammary glands, Brca2mut/WT HR- luminal cells exhibit greater organoid formation and preferentially survive and expand under replication stress. ScRNA-seq analysis corroborates the expansion of HR- luminal cells which express elevated transcript levels of Tetraspanin-8 (Tspan8) and Thrsp, plus pathways implicated in replication stress survival including Type I interferon responses. Notably, CRISPR/Cas9-mediated deletion of Tspan8 or Thrsp prevents Brca2mut/WT HR- luminal cell expansion. Our findings indicate that Brca2mut/WT cells activate a transcriptional response after replication stress that preferentially favours outgrowth of HR- luminal cells through the expression of interferon-responsive and mammary alveolar genes.
A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy
Authors: Kang Xiaoying , Zhang Yuan , Song Jianwen , Wang Lu , Li Wen , Qi Ji , Tang Ben Zhong 
Published: August 2023

AbstractPrecise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) and a hypoxia-responsive prodrug for multifunctional image-guided combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence and photoacoustic (PA) brightness for the strong light absorption ability, as well as amplified type I and type II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating the high-performance AIEgen with a hypoxia-responsive paclitaxel (PTX) prodrug into nanoparticles, and further camouflaging with macrophage cell membrane, a tumor-targeting theranostic agent is built. The integration of fluorescence and PA imaging helps to delineate tumor site sensitively, providing accurate guidance for tumor treatment. The light-induced PDT effect could consume the local oxygen and lead to severer hypoxia, accelerating the release of PTX drug. As a result, the combination of PDT and PTX chemotherapy induces immunogenic cancer cell death, which could not only elicit strong antitumor immunity to suppress the primary tumor, but also inhibit the growth of distant tumor in 4T1 tumor-bearing female mice. Here, we report a strategy to develop theranostic agents via rational molecular design for boosting antitumor immunotherapy.
Predicting the synthesizability of crystalline inorganic materials from the data of known material compositions
Authors: Antoniuk Evan R. , Cheon Gowoon , Wang George , Bernstein Daniel , Cai William , Reed Evan J. 
Published: August 2023

AbstractReliably identifying synthesizable inorganic crystalline materials is an unsolved challenge required for realizing autonomous materials discovery. In this work, we develop a deep learning synthesizability model (SynthNN) that leverages the entire space of synthesized inorganic chemical compositions. By reformulating material discovery as a synthesizability classification task, SynthNN identifies synthesizable materials with 7× higher precision than with DFT-calculated formation energies. In a head-to-head material discovery comparison against 20 expert material scientists, SynthNN outperforms all experts, achieves 1.5× higher precision and completes the task five orders of magnitude faster than the best human expert. Remarkably, without any prior chemical knowledge, our experiments indicate that SynthNN learns the chemical principles of charge-balancing, chemical family relationships and ionicity, and utilizes these principles to generate synthesizability predictions. The development of SynthNN will allow for synthesizability constraints to be seamlessly integrated into computational material screening workflows to increase their reliability for identifying synthetically accessible materials.
Linking environmental risk factors with epigenetic mechanisms in Parkinson’s disease
Authors: Tsalenchuk Maria , Gentleman Steve M. , Marzi Sarah J. 
Published: August 2023

AbstractSporadic Parkinson’s disease (PD) is a progressive neurodegenerative disease, with a complex risk structure thought to be influenced by interactions between genetic variants and environmental exposures, although the full aetiology is unknown. Environmental factors, including pesticides, have been reported to increase the risk of developing the disease. Growing evidence suggests epigenetic changes are key mechanisms by which these environmental factors act upon gene regulation, in disease-relevant cell types. We present a systematic review critically appraising and summarising the current body of evidence of the relationship between epigenetic mechanisms and environmental risk factors in PD to inform future research in this area. Epigenetic studies of relevant environmental risk factors in animal and cell models have yielded promising results, however, research in humans is just emerging. While published studies in humans are currently relatively limited, the importance of the field for the elucidation of molecular mechanisms of pathogenesis opens clear and promising avenues for the future of PD research. Carefully designed epidemiological studies carried out in PD patients hold great potential to uncover disease-relevant gene regulatory mechanisms. Therefore, to advance this burgeoning field, we recommend broadening the scope of investigations to include more environmental exposures, increasing sample sizes, focusing on disease-relevant cell types, and recruiting more diverse cohorts.
The potential global cost-effectiveness of prospective Strep A vaccines and associated implementation efforts
Authors: Lee Jung-Seok , Mogasale Vittal , Kim Sol , Cannon Jeffrey , Giannini Fiona , Abbas Kaja , Excler Jean-Louis , Kim Jerome H. 
Published: August 2023

AbstractGroup A Streptococcus causes a wide range of diseases from relatively mild infections including pharyngitis to more severe illnesses such as invasive diseases and rheumatic heart disease (RHD). Our aim is to estimate the cost-effectiveness of a hypothetical Strep A vaccine on multiple disease manifestations at the global-level. Cost-effectiveness analyses were carried out by building on the potential epidemiological impact of vaccines that align with the WHO’s Preferred Product Characteristics for Strep A vaccines. Maximum vaccination costs for a cost-effective vaccination strategy were estimated at the thresholds of 1XGDP per capita and health opportunity costs. The maximum cost per fully vaccinated person for Strep A vaccination to be cost-effective was $385–$489 in high-income countries, $213–$312 in upper-income-income countries, $74–$132 in lower-middle-income countries, and $37–$69 in low-income countries for routine vaccination at birth and 5 years of age respectively. While the threshold costs are sensitive to vaccine characteristics such as efficacy, and waning immunity, a cost-effective Strep A vaccine will lower morbidity and mortality burden in all income settings.
Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood
Authors: Charpentier André N. Herrera , Olekanma Doris I. , Valade Christian T. , Reeves Christopher A. , Cho Bo Ram , Arguello Amy A. 
Published: August 2023

AbstractAdolescents are at increased risk to develop substance use disorders and suffer from relapse throughout life. Targeted weakening of drug-associated memories has been shown to reduce relapse-like behavior in adult rats, however this process has been understudied in adolescents. We aimed to examine whether adolescent-formed, cocaine-associated memories could be manipulated via reconsolidation mechanisms. To accomplish this objective, we used an abbreviated operant cocaine self-administration paradigm (ABRV Coc-SA). Adult and adolescent rats received jugular catheterization surgery followed by ABRV Coc-SA in a distinct context for 2 h, 2×/day over 5 days. Extinction training (EXT) occurred in a second context for 2 h, 2×/day over 4 days. To retrieve cocaine-context memories, rats were exposed to the cocaine-paired context for 15 min, followed by subcutaneous injection of vehicle or the protein synthesis inhibitor cycloheximide (2.5 mg/kg). Two additional EXT sessions were conducted before a 2 h reinstatement test in the cocaine-paired context to assess cocaine-seeking behavior. We find that both adult and adolescent cocaine-exposed rats show similar levels of cocaine-seeking behavior regardless of post-reactivation treatment. Our results suggest that systemic treatment with the protein synthesis inhibitor cycloheximide does not impair reconsolidation of cocaine-context memories and subsequent relapse during adulthood or adolescence.
Generation of multi-scrolls in corona virus disease 2019 (COVID-19) chaotic system and its impact on the zero-covid policy
Authors: Marwan Muhammad , Han Maoan , Khan Rizwan 
Published: August 2023

AbstractIn this paper, we discussed the impossibility of achieving zero-covid cases per day for all time with the help of fuzzy theory, while how a single case can trigger chaotic situation in the nearby city is elaborated using multi-scrolls. To accomplish this goal, we consider the number of new cases per day; $$x_{1}$$

x
1

to be the preferred state variable by restricting its value to the interval (0, 1). One can need to think of $$x_{1}$$

x
1

as a member of a fuzzy set and provide that set with appropriate membership functions. Moreover, how a single incident in one city can spread chaos to other cities is also addressed at length, using multi-scroll attractors and the signal excitation function. In addition, a bifurcation diagram of daily new instances vs the parameter $$\alpha _{1}$$

α
1

is shown, elaborating that daily new cases may show a decrease under strict rules and regulations, but can again lead to chaos. Apart from biologist, this paper can play vital role for engineers as well in a sense that, a signal function can be embedded in non-symmetric systems for the creation of multi-scroll attractors in all directions using a generalized algorithm that has been designed in the current work. Finally, it is our future target to show that the covid is leading towards influenza and will be no more dangerous as was in the past.
Novel VEGFR2 inhibitors with thiazoloquinoxaline scaffold targeting hepatocellular carcinoma with lower cardiotoxic impact
Authors: El-Hazek Reham M. M. , Zaher Nashwa H. , El-Gazzar Mostafa G. M. , Fadel Noha A. , El-Sabbagh Walaa A. 
Published: August 2023

AbstractHepatocellular carcinoma (HCC) is a fatal tumor which is usually diagnosed at advanced stage. Molecular targeted drugs were used recently to treat HCC, however, due to serious side effects, mainly cardiotoxicity and emergence of resistance, there is demanding to explore new chemotherapeutics. 10 novel thiazoloquinoxaline derivatives coupled with different sulfonamide moieties 4(a–j) were designed and synthesized fulfilling pharmacophoric features of VEGFR-2 inhibition. Structures of all new compounds were verified via spectral and microanalytical data. After carrying in-vitro VEGFR-2 assay for compounds 4(a–j); sulfapyridine and sulfamethoxazole derivatives 4d and 4f showed potential inhibitory effect [61.04 and 83.35 nM], respectively, comparable to standard sorafenib [51.41 nM]. Both were then further evaluated for their cytocidal activity against HepG2 cell-line and against myocardium cells using H9C2 cell-line. As a result, only sulfapyridine derivative 4d exhibited a significant inhibition of HepG2 cells viability [IC50 = 4.31 μM]. Furthermore, it showed relatively lower cytotoxic impact against normal H9C2 myocardium cells [IC50, 33.47 μM] compared to that of sorafenib [IC50, 98.07 μM]. In-vivo study was carried out to determine myocardium safety of compound 4d on irradiated mice (8 Gy). In-vivo results of sulfapyridine derivative 4d showed normal cardiac enzyme function (CK) and serum catalase activity with significant reductions in LDH, cardiac TNF-α and caspase-9 levels, alongside with its efficacy in suppressing the expression of hepatic VEGF. In conclusion, sulfapyridine derivative 4d could be considered a promising candidate as VEGFR-2 inhibitor with less myocardium side effect.
Effects of early standardized management on the growth trajectory of offspring with gestational diabetes mellitus at 0–5 years old: a preliminary longitudinal study
Authors: Guo Bingbing , Pei Jingjing , Xu Yin , Wang Yajie , Jiang Xinye 
Published: August 2023

AbstractTo explore the application value of early standardized management in the delivery of neonates of pregnant women with gestational diabetes mellitus (GDM). Parturient diagnosed with GDM and their offspring were selected in our hospital from January 1, 2015 to December 31, 2017 to underwent early standardized management. Non-GDM pregnant women and their offspring were selected as the control group. The growth and development of children aged 0–5 years in the two groups were longitudinally followed up, and the mixed linear model was used to evaluate and compare the growth trajectories. There was no significant difference in height and weight between the two groups at 1 year old (P > 0.05), but the BMI of the GDM group was significantly higher than that in the control group. After 1 year of age, both groups of offspring were similar in height, weight, and BMI, and these similarities persisted at 2, 3, 4, and 5 years of age. After controlling for covariates, the weight, length/height of the two groups of children were slightly different in the growth trajectories between 0–1 years old, 1–2 years old, 2–3 years old, 3–4 years old, and 4–5 years old with no statistical significance (P > 0.05). Although growth differences between the two groups of children were detected within 1 year of age, there were no significant differences in growth trajectories from 1 to 5 years between two groups, which proved that early standardized management has positive significance.