bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain
Authors: Takano Tomohiro , Sato Takashi , Kotaki Ryutaro , Moriyama Saya , Fukushi Shuetsu , Shinoda Masahiro , Kabasawa Kiyomi , Shimada Nagashige , Kousaka Mio , Adachi Yu , Onodera Taishi , Terahara Kazutaka , Isogawa Masanori , Matsumura Takayuki , Shinkai Masaharu , Takahashi Yoshimasa
Published: March 2023

The immunogenicity of mRNA vaccines has not been well studied when compared to different vaccine modalities in the context of additional boosters. Here we show that longitudinal analysis reveals more sustained SARS-CoV-2 spike receptor-binding domain (RBD)-binding IgG titers with the breadth to antigenically distinct variants by the S-268019-b spike protein booster compared to the BNT162b2 mRNA homologous booster. The durability and breadth of RBD-angiotensin-converting enzyme 2 (ACE2) binding inhibitory antibodies are pronounced in the group without systemic adverse events (AEs) after the S-268019-b booster, leading to the elevated neutralizing activities against Omicron BA.1 and BA.5 variants in the stratified group. In contrast, BNT162b2 homologous booster elicited antibodies to spike N-terminal domain in proportion to the AE scores. High-dimensional immune profiling identifies early CD16+ natural killer cell dynamics with CCR3 upregulation, as one of the correlates for the distinct anti-RBD antibody responses by the S-268019-b booster. Our results illustrate the combinational effects of heterologous booster on the immune dynamics and the durability and breadth of recalled anti-RBD antibody responses against emerging virus variants.
AlphaFlow: autonomous discovery and optimization of multi-step chemistry using a self-driven fluidic lab guided by reinforcement learning
Authors: Volk Amanda A. , Epps Robert W. , Yonemoto Daniel T. , Masters Benjamin S. , Castellano Felix N. , Reyes Kristofer G. , Abolhasani Milad
Published: March 2023

Closed-loop, autonomous experimentation enables accelerated and material-efficient exploration of large reaction spaces without the need for user intervention. However, autonomous exploration of advanced materials with complex, multi-step processes and data sparse environments remains a challenge. In this work, we present AlphaFlow, a self-driven fluidic lab capable of autonomous discovery of complex multi-step chemistries. AlphaFlow uses reinforcement learning integrated with a modular microdroplet reactor capable of performing reaction steps with variable sequence, phase separation, washing, and continuous in-situ spectral monitoring. To demonstrate the power of reinforcement learning toward high dimensionality multi-step chemistries, we use AlphaFlow to discover and optimize synthetic routes for shell-growth of core-shell semiconductor nanoparticles, inspired by colloidal atomic layer deposition (cALD). Without prior knowledge of conventional cALD parameters, AlphaFlow successfully identified and optimized a novel multi-step reaction route, with up to 40 parameters, that outperformed conventional sequences. Through this work, we demonstrate the capabilities of closed-loop, reinforcement learning-guided systems in exploring and solving challenges in multi-step nanoparticle syntheses, while relying solely on in-house generated data from a miniaturized microfluidic platform. Further application of AlphaFlow in multi-step chemistries beyond cALD can lead to accelerated fundamental knowledge generation as well as synthetic route discoveries and optimization.
In situ acid etching boosts mercury accommodation capacities of transition metal sulfides
Authors: Li Hailong , Zheng Jiaoqin , Zheng Wei , Zu Hongxiao , Chen Hongmei , Yang Jianping , Qu Wenqi , Leng Lijian , Feng Yong , Yang Zequn
Published: March 2023

Transition Metal sulfides (TMSs) are effective sorbents for entrapment of highly polluting thiophiles such as elemental mercury (Hg0). However, the application of these sorbents for mercury removal is stymied by their low accommodation capacities. Among the transition metal sulfides, only CuS has demonstrated industrially relevant accommodation capacity. The rest of the transition metal sulfides have 100-fold lower capacities than CuS. In this work, we overcome these limitations and develop a simple and scalable process to enhance Hg0accommodation capacities of TMSs. We achieve this by introducing structural motifs in TMSs by in situ etching. We demonstrate that in situ acid etching produces TMSs with defective surface and pore structure. These structural motifs promote Hg0surface adsorption and diffusion across the entire TMSs architecture. The process is highly versatile and the in situ etched transition metal sulfides show over 100-fold enhancement in their Hg0accommodation capacities. The generality and the scalability of the process provides a framework to develop TMSs for a broad range of applications.
Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice
Authors: Ye Qian , Liu Yi , Zhang Guiji , Deng Haijun , Wang Xiaojun , Tuo Lin , Chen Chang , Pan Xuanming , Wu Kang , Fan Jiangao , Pan Qin , Wang Kai , Huang Ailong , Tang Ni
Published: March 2023

Metabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in MAFLD progression. Male mice with liver Pck1 deficiency fed a normal diet displayed hepatic lipid disorder and liver injury, whereas fibrosis and inflammation were aggravated in mice fed a high-fat diet with drinking water containing fructose and glucose (HFCD-HF/G). Forced expression of hepatic PCK1 by adeno-associated virus ameliorated MAFLD in male mice. PCK1 deficiency stimulated lipogenic gene expression and lipid synthesis. Moreover, loss of hepatic PCK1 activated the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increasing secretion of platelet-derived growth factor-AA (PDGF-AA), and promoting hepatic stellate cell activation. Treatment with RhoA and AKT inhibitors or gene silencing of RhoA or AKT1 alleviated MAFLD progression in vivo. Hepatic PCK1 deficiency may be important in hepatic steatosis and fibrosis development through paracrine secretion of PDGF-AA in male mice, highlighting a potential therapeutic strategy for MAFLD.
Mixed-valence molybdenum oxide as a recyclable sorbent for silver removal and recovery from wastewater
Authors: Shao Penghui , Chang Ziwen , Li Min , Lu Xiang , Jiang Wenli , Zhang Kai , Luo Xubiao , Yang Liming
Published: March 2023

Silver ions in wastewater streams are a major pollutant and a threat to human health. Given the increasing demand and relative scarcity of silver, these streams could be a lucrative source to extract metallic silver. Wastewater is a complex mixture of many different metal salts, and developing recyclable sorbents with high specificity towards silver ions remains a major challenge. Here we report that molybdenum oxide (MoOx) adsorbent with mixed-valence (Mo(V) and Mo(VI)) demonstrates high selectivity (distribution coefficient of 6437.40 mL g−1) for Ag+ and an uptake capacity of 2605.91 mg g−1. Our experimental results and density functional theory calculations illustrate the mechanism behind Ag+ adsorption and reduction. Our results show that Mo(V) species reduce Ag+ to metallic Ag, which decreases the energy barrier for subsequent Ag+ reductions, accounting for the high uptake of Ag+ from wastewater. Due to its high selectivity, MoOx favorably adsorbs Ag+ even in the presence of interfering ions. High selective recovery of Ag+ from wastewater (recovery efficiency = 97.9%) further supports the practical applications of the sorbent. Finally, MoOx can be recycled following silver recovery while maintaining a recovery efficiency of 97.1% after five cycles. The method is expected to provide a viable strategy to recover silver from wastewater.
Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis
Authors: Killarney Shane T. , Washart Rachel , Soderquist Ryan S. , Hoj Jacob P. , Lebhar Jamie , Lin Kevin H. , Wood Kris C.
Published: March 2023

During apoptosis, mitochondrial outer membrane permeabilization (MOMP) enables certain mitochondrial matrix macromolecules to escape into the cytosol. However, the fate of mitochondrial RNA (mtRNA) during apoptosis is unknown. Here, we demonstrate that MOMP results in the cytoplasmic release of mtRNA and that executioner caspases-3 and -7 (casp3/7) prevent cytoplasmic mtRNA from triggering inflammatory signaling. In the setting of genetic or pharmacological casp3/7 inhibition, apoptotic insults result in mtRNA activation of the MDA5/MAVS/IRF3 pathway to drive Type I interferon (IFN) signaling. This pathway is sufficient to activate tumor-intrinsic Type I IFN signaling in immunologically cold cancer models that lack an intact cGAS/STING signaling pathway, promote CD8+T-cell-dependent anti-tumor immunity, and overcome anti-PD1 refractoriness in vivo. Thus, a key function of casp3/7 is to inhibit inflammation caused by the cytoplasmic release of mtRNA, and pharmacological modulation of this pathway increases the immunogenicity of chemotherapy-induced apoptosis.
Litter accumulation and fire risks show direct and indirect climate-dependence at continental scale
Authors: Adams Mark A. , Neumann Mathias
Published: March 2023

Litter decomposition / accumulation are rate limiting steps in soil formation, carbon sequestration, nutrient cycling and fire risk in temperate forests, highlighting the importance of robust predictive models at all geographic scales. Using a data set for the Australian continent, we show that among a range of models, most of the variance in litter mass over a 40-year time span can be accounted for by a parsimonious model with elapsed time, and indices of climate and litter quality, as independent drivers. Climate is an important driver of variation in both the species identity of dominant eucalypts and litter accumulation across the continent. Litter quality shows emergent properties of climate-dependence and contributes to explained variance. Nonetheless, elapsed time dominated explained variance in litter mass (up to 90%) at continental scale. Results provide guidance for future decomposition studies. Algorithms reported here can significantly improve accuracy and reliability of predictions of carbon and nutrient dynamics and fire risk.
High-performance vertical field-effect organic photovoltaics
Authors: Wu Xiaomin , Gao Changsong , Chen Qizhen , Yan Yujie , Zhang Guocheng , Guo Tailiang , Chen Huipeng
Published: March 2023

Limited by the inherent energy loss (Eloss) in carrier transport process, the device efficiency of organic solar cells shows inferior to traditional inorganic photovoltaic devices. Generally, molecular design, morphology optimization and interfacial engineering are usually required to alleviate Eloss. Here, vertical field-effect organic photovoltaic (VFEOPV) by integrating an bulk-heterojunction (BHJ) organic photovoltaic (OPV) with vertical field effect transistor (VFET) is invented, in which VFET generates a large, uneven, internal electric field, eliminating the requirement for driving force to dissociate excitons and prevents non-radiative recombination in OPV. In this way, the performance of solar cell can be well controlled by the gate voltage of VFET and the Eloss of VFEOPVs based on J71: ITIC system is dramatically reduced below 0.2 eV, significantly improving power conversion efficiency (PCE) from 10% to 18% under gate voltage of 0.9 V, which only causes negligible additional power consumption (~10−4mJ/cm2). Besides, the device also exhibits multi-functionality including transistor and phototransistors with excellent photodector performance. This work provides a new and general strategy to improve the OPV performance which is compatible with present optimization methods, and can be applied to improve PCE of other types of solar cells such as Perovskite and inorganic solar cells.
Polyvinyl chloride-based dielectric elastomer with high permittivity and low viscoelasticity for actuation and sensing
Authors: Huang Jianjian , Zhang Xiaodie , Liu Ruixue , Ding Yonghui , Guo Dongjie
Published: March 2023

Dielectric elastomers (DEs) are widely used in soft actuation and sensing. Current DE actuators require high driving electrical fields because of their low permittivity. Most of DE actuators and sensors suffer from high viscoelastic effects, leading to high mechanical loss and large shifts of signals. This study demonstrates a valuable strategy to produce polyvinyl chloride (PVC)-based elastomers with high permittivity and low viscoelasticity. The introduction of cyanoethyl cellulose (CEC) into plasticized PVC gel (PVCg) not only confers a high dielectric permittivity (18.9@1 kHz) but also significantly mitigates their viscoelastic effects with a low mechanical loss (0.04@1 Hz). The CEC/PVCg actuators demonstrate higher actuation performances over the existing DE actuators under low electrical fields and show marginal displacement shifts (7.78%) compared to VHB 4910 (136.09%). The CEC/PVCg sensors display high sensitivity, fast response, and limited signal drifts, enabling their faithful monitoring of multiple human motions.
The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis
Authors: Waller Natalie J. E. , Cheung Chen-Yi , Cook Gregory M. , McNeil Matthew B.
Published: March 2023

The increasing incidence of drug resistance in Mycobacterium tuberculosis has diminished the efficacy of almost all available antibiotics, complicating efforts to combat the spread of this global health burden. Alongside the development of new drugs, optimised drug combinations are needed to improve treatment success and prevent the further spread of antibiotic resistance. Typically, antibiotic resistance leads to reduced sensitivity, yet in some cases the evolution of drug resistance can lead to enhanced sensitivity to unrelated drugs. This phenomenon of collateral sensitivity is largely unexplored in M. tuberculosis but has the potential to identify alternative therapeutic strategies to combat drug-resistant strains that are unresponsive to current treatments. Here, by using drug susceptibility profiling, genomics and evolutionary studies we provide evidence for the existence of collateral drug sensitivities in an isogenic collection M. tuberculosis drug-resistant strains. Furthermore, in proof-of-concept studies, we demonstrate how collateral drug phenotypes can be exploited to select against and prevent the emergence of drug-resistant strains. This study highlights that the evolution of drug resistance in M. tuberculosis leads to collateral drug responses that can be exploited to design improved drug regimens.
Structural insight into the intraflagellar transport complex IFT-A and its assembly in the anterograde IFT train
Authors: Ma Yuanyuan , He Jun , Li Shaobai , Yao Deqiang , Huang Chenhui , Wu Jian , Lei Ming
Published: March 2023

Intraflagellar transport (IFT) trains, the polymers composed of two multi-subunit complexes, IFT-A and IFT-B, carry out bidirectional intracellular transport in cilia, vital for cilia biogenesis and signaling. IFT-A plays crucial roles in the ciliary import of membrane proteins and the retrograde cargo trafficking. However, the molecular architecture of IFT-A and the assembly mechanism of the IFT-A into the IFT trains in vivo remains elusive. Here, we report the cryo-electron microscopic structures of the IFT-A complex from protozoa Tetrahymena thermophila. We find that IFT-A complexes present two distinct, elongated and folded states. Remarkably, comparison with the in situ cryo-electron tomography structure of the anterograde IFT train unveils a series of adjustments of the flexible arms in apo IFT-A when incorporated into the anterograde train. Our results provide an atomic-resolution model for the IFT-A complex and valuable insights into the assembly mechanism of anterograde IFT trains.
Synthetic lethality of drug-induced polyploidy and BCL-2 inhibition in lymphoma
Authors: Portelinha Ana , da Silva Ferreira Mariana , Erazo Tatiana , Jiang Man , Asgari Zahra , de Stanchina Elisa , Younes Anas , Wendel Hans-Guido
Published: March 2023

Spontaneous whole genome duplication and the adaptive mutations that disrupt genome integrity checkpoints are infrequent events in B cell lymphomas. This suggests that lymphomas might be vulnerable to therapeutics that acutely trigger genomic instability and polyploidy. Here, we report a therapeutic combination of inhibitors of the Polo-like kinase 4 and BCL-2 that trigger genomic instability and cell death in aggressive lymphomas. The synthetic lethality is selective for tumor cells and spares vital organs. Mechanistically, inhibitors of Polo-like kinase 4 impair centrosome duplication and cause genomic instability. The elimination of polyploid cells largely depends on the pro-apoptotic BAX protein. Consequently, the combination of drugs that induce polyploidy with the BCL-2 inhibitor Venetoclax is highly synergistic and safe against xenograft and PDX models. We show that B cell lymphomas are ill-equipped for acute, therapy-induced polyploidy and that BCL-2 inhibition further enhances the removal of polyploid lymphoma cells.
Visualizing defect dynamics by assembling the colloidal graphene lattice
Authors: Swinkels Piet J. M. , Gong Zhe , Sacanna Stefano , Noya Eva G. , Schall Peter
Published: March 2023

Graphene has been under intense scientific interest because of its remarkable optical, mechanical and electronic properties. Its honeycomb structure makes it an archetypical two-dimensional material exhibiting a photonic and phononic band gap with topologically protected states. Here, we assemble colloidal graphene, the analogue of atomic graphene using pseudo-trivalent patchy particles, allowing particle-scale insight into crystal growth and defect dynamics. We directly observe the formation and healing of common defects, like grain boundaries and vacancies using confocal microscopy. We identify a pentagonal defect motif that is kinetically favoured in the early stages of growth, and acts as seed for more extended defects in the later stages. We determine the conformational energy of the crystal from the bond saturation and bond angle distortions, and follow its evolution through the energy landscape upon defect rearrangement and healing. These direct observations reveal that the origins of the most common defects lie in the early stages of graphene assembly, where pentagons are kinetically favoured over the equilibrium hexagons of the honeycomb lattice, subsequently stabilized during further growth. Our results open the door to the assembly of complex 2D colloidal materials and investigation of their dynamical, mechanical and optical properties.
Cumulative burden of 144 conditions, critical care hospitalisation and premature mortality across 26 adult cancers
Authors: Chang Wai Hoong , Neal Richard D. , Forster Martin D. , Lai Alvina G.
Published: March 2023

A comprehensive evaluation of the total burden of morbidity endured by cancer survivors remains unavailable. This study quantified the burden of 144 health conditions and critical care admissions across 26 adult cancers and treatment modalities in 243,767 adults. By age 60, top conditions ranked by fold difference (cumulative burden in survivors divided by cumulative burden in controls) were haematology, immunology/infection and pulmonary conditions. Patients who had all three forms of treatment (chemotherapy, radiotherapy and surgery) experienced a high cumulative burden of late morbidities compared with patients who received radiotherapy alone. The top five cancers with the highest cumulative burden of critical care admissions by age 60 were bone (12.4 events per 100 individuals [CI: 11.6-13.1]), brain (9.0 [7.5-10.5]), spinal cord and nervous system (7.2 [6.7-7.8]), testis (6.7 [4.9-8.4]) and Hodgkin lymphoma (4.4 [3.6-5.1]). Conditions that were associated with high excess years-of-life-lost were haematological conditions (9.6 years), pulmonary conditions (8.6 years) and immunological conditions or infections (7.8 years). As the population of cancer survivors continues to grow, our results indicate that it is important to tackle long-term health consequences through enacting data-driven policies.
Giant piezoresistivity in a van der Waals material induced by intralayer atomic motions
Authors: Tang Lingyun , Mao Zhongquan , Wang Chutian , Fu Qi , Wang Chen , Zhang Yichi , Shen Jingyi , Yin Yuefeng , Shen Bin , Tan Dayong , Li Qian , Wang Yonggang , Medhekar Nikhil V. , Wu Jie , Yuan Huiqiu , Li Yanchun , Fuhrer Michael S. , Zheng Changxi
Published: March 2023

The presence of the van der Waals gap in layered materials creates a wealth of intriguing phenomena different to their counterparts in conventional materials. For example, pressurization can generate a large anisotropic lattice shrinkage along the stacking orientation and/or a significant interlayer sliding, and many of the exotic pressure-dependent properties derive from these mechanisms. Here we report a giant piezoresistivity in pressurized β′-In2Se3. Upon compression, a six-orders-of-magnitude drop of electrical resistivity is obtained below 1.2 GPa in β′-In2Se3 flakes, yielding a giant piezoresistive gauge πp of −5.33 GPa−1. Simultaneously, the sample undergoes a semiconductor-to-semimetal transition without a structural phase transition. Surprisingly, linear dichroism study and theoretical first principles modelling show that these phenomena arise not due to shrinkage or sliding at the van der Waals gap, but rather are dominated by the layer-dependent atomic motions inside the quintuple layer, mainly from the shifting of middle Se atoms to their high-symmetric location. The atomic motions link to both the band structure modulation and the in-plane ferroelectric dipoles. Our work not only provides a prominent piezoresistive material but also points out the importance of intralayer atomic motions beyond van der Waals gap.
Highly selective electrocatalytic alkynol semi-hydrogenation for continuous production of alkenols
Authors: Bu Jun , Chang Siyu , Li Jinjin , Yang Sanyin , Ma Wenxiu , Liu Zhenpeng , An Siying , Wang Yanan , Li Zhen , Zhang Jian
Published: March 2023

Alkynols semi-hydrogenation is a critical industrial process as the product, alkenols, have extensive applications in chemistry and life sciences. However, this class of reactions is plagued by the use of high-pressure hydrogen, Pd-based catalysts, and low efficiency of the contemporary thermocatalytic process. Here, we report an electrocatalytic approach for selectively hydrogenating alkynols to alkenols under ambient conditions. For representative 2-methyl-3-butene-2-ol, Cu nanoarrays derived electrochemically from CuO, achieve a high partial current density of 750 mA cm−2 and specific selectivity of 97% at −0.88 V vs. reversible hydrogen electrode in alkaline solution. Even in a large two-electrode flow electrolyser, the Cu nanoarrays deliver a single-pass alkynol conversion of 93% with continuous production of 2-methyl-3-butene-2-ol at a rate of ~169 g gCu−1 h−1. Theoretical and in situ electrochemical infrared investigations reveal that the semi-hydrogenation performance is enhanced by exothermic alkynol adsorption and alkenol desorption on the Cu surfaces. Furthermore, this electrocatalytic semi-hydrogenation strategy is shown to be applicable to a variety of alkynol substrates.
The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression
Authors: Gaurav Amit Kumar , Afrin Marjia , Yang Xian , Saha Arpita , Sayeed S. K. Abdus , Pan Xuehua , Ji Zeyang , Wong Kam-Bo , Zhang Mingjie , Zhao Yanxiang , Li Bibo
Published: March 2023

Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. Its major surface antigen VSG is expressed from subtelomeric loci in a strictly monoallelic manner. We previously showed that the telomere protein TbRAP1 binds dsDNA through its 737RKRRR741 patch to silence VSGs globally. How TbRAP1 permits expression of the single active VSG is unknown. Through NMR structural analysis, we unexpectedly identify an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. Assisted by the 737RKRRR741 patch, TbRAP1 RRM recognizes consensus sequences of VSG 3’UTRs in vitro and binds the active VSG RNA in vivo. Mutating conserved RRM residues abolishes the RNA binding activity, significantly decreases the active VSG RNA level, and derepresses silent VSGs. The competition between TbRAP1’s RNA and dsDNA binding activities suggests a VSG monoallelic expression mechanism in which the active VSG’s abundant RNA antagonizes TbRAP1’s silencing effect, thereby sustaining its full-level expression.
Decoupling body shape and mass distribution in birds and their dinosaurian ancestors
Authors: Macaulay Sophie , Hoehfurtner Tatjana , Cross Samuel R. R. , Marek Ryan D. , Hutchinson John R. , Schachner Emma R. , Maher Alice E. , Bates Karl T.
Published: March 2023

It is accepted that non-avian theropod dinosaurs, with their long muscular tails and small forelimbs, had a centre-of-mass close to the hip, while extant birds, with their reduced tails and enlarged wings have their mass centred more cranially. Transition between these states is considered crucial to two key innovations in the avian locomotor system: crouched bipedalism and powered flight. Here we use image-based models to challenge this dichotomy. Rather than a phylogenetic distinction between ‘dinosaurian’ and ‘avian’ conditions, we find terrestrial versus volant taxa occupy distinct regions of centre-of-mass morphospace consistent with the disparate demands of terrestrial bipedalism and flight. We track this decoupled evolution of body shape and mass distribution through bird evolution, including the origin of centre-of-mass positions more advantageous for flight and major reversions coincident with terrestriality. We recover modularity in the evolution of limb proportions and centre-of-mass that suggests fully crouched bipedalism evolved after powered flight.
Physics guided deep learning for generative design of crystal materials with symmetry constraints
Authors: Zhao Yong , Siriwardane Edirisuriya M. Dilanga , Wu Zhenyao , Fu Nihang , Al-Fahdi Mohammed , Hu Ming , Hu Jianjun
Published: March 2023

Discovering new materials is a challenging task in materials science crucial to the progress of human society. Conventional approaches based on experiments and simulations are labor-intensive or costly with success heavily depending on experts’ heuristic knowledge. Here, we propose a deep learning based Physics Guided Crystal Generative Model (PGCGM) for efficient crystal material design with high structural diversity and symmetry. Our model increases the generation validity by more than 700% compared to FTCP, one of the latest structure generators and by more than 45% compared to our previous CubicGAN model. Density Functional Theory (DFT) calculations are used to validate the generated structures with 1869 materials out of 2000 are successfully optimized and deposited into the Carolina Materials Database www.carolinamatdb.org, of which 39.6% have negative formation energy and 5.3% have energy-above-hull less than 0.25 eV/atom, indicating their thermodynamic stability and potential synthesizability.
Autonomous electrochemical system for ammonia oxidation reaction measurements at the International Space Station
Authors: Morales-Navas Camila , Martínez-Rodríguez Roberto A. , Vidal-Iglesias Francisco J. , Peña Armando , Soto-Pérez Joesene J. , Trinidad Pedro , Solla-Gullón José , Tzvetkov Toshko , Doan Jonathan , Smotkin Eugene S. , Nicolau Eduardo , Feliu Juan M. , Cabrera Carlos R.
Published: March 2023

An autonomous electrochemical system prototype for ammonia oxidation reaction (AOR) measurements was efficiently done inside a 4'' x 4'' x 8'' 2U Nanoracks module at the International Space Station (ISS). This device, the Ammonia Electrooxidation Lab at the ISS (AELISS), included an autonomous electrochemical system that complied with NASA ISS nondisclosure agreements, power, safety, security, size constrain, and material compatibility established for space missions. The integrated autonomous electrochemical system was tested on-ground and deployed to the International Space Station as a “proof-of-concept” ammonia oxidation reaction testing space device. Here are discussed the results of cyclic voltammetry and chronoamperometry measurements done at the ISS with a commercially available channel flow-cell with eight screen-printed electrodes, including Ag quasi-reference (Ag QRE) and carbon counter electrodes. Pt nanocubes in Carbon Vulcan XC-72R were used as the catalyst for the AOR and 2 μL drop of Pt nanocubes/ Carbon Vulcan XC-72R, 20 wt%, ink was placed on the carbon working electrodes and allowed to dry in air. After the AELISS was prepared for launch to the ISS, a 4 days delayed (2 days in the space vehicle Antares and 2 days space transit to the ISS) cause a slight shift on the Ag QRE potential. Nevertheless, the AOR cyclic voltametric peak was observed in the ISS and showed ca. 70% current density decrease due to the buoyancy effect in agreement with previous microgravity experiments done at the zero-g aircraft.
Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy
Authors: Guo Yu , Shen Xue-Ning , Huang Shu-Yi , Chen Shu-Fen , Wang Hui-Fu , Zhang Wei , Zhang Ya-Ru , Cheng Wei , Cui Mei , Dong Qiang , Yu Jin-Tai
Published: March 2023

There is a dire need for reliable biomarkers to solidify an early and accurate diagnosis of multiple system atrophy (MSA). We sought to compare the ability of emerging plasma markers in distinguishing MSA from its mimics and healthy controls in early disease stages, and to evaluate their performance in detecting disease severity and brain atrophy. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, amyloid-β (Aβ)42, and Aβ40 were measured using ultrasensitive Simoa in early-stage patients with MSA (n = 73), spinocerebellar ataxia (SCA, n = 29), Parkinson’s disease (PD, n = 28), and healthy controls (n = 100). We observed that elevated NfL outperformed other biomarkers in distinguishing MSA and its subtypes (AUC = 0.9) versus controls. Intriguingly, when separating MSA from its mimics, increased GFAP (AUC = 0.717) in MSA-C and decreased Aβ40 (AUC = 0.807) in MSA-P best discriminated from SCA and PD respectively. Plasma levels were comparable between MSA-C and MSA-P and the differentiation by plasma index alone was poor. Combining plasma markers noticeably improved the discriminatory efficacy. Of note, among MSA patients, higher GFAP and NfL were correlated with the atrophy of brain regions vulnerable to MSA (e.g., cerebellum, pons, or putamen). They could also aggravate the severity of MSA, and this association was partially mediated by cerebral volumes. In contrast, no obvious associations of phosphorylated tau and Aβ with disease severity were observed. Collectively, plasma biomarkers, especially in combination, are useful to facilitate the discriminatory work-up of MSA at early stages. Moreover, NfL and GFAP may be promising biomarkers to monitor the disease severity of MSA.
Critical parametric quantum sensing
Authors: Di Candia R. , Minganti F. , Petrovnin K. V. , Paraoanu G. S. , Felicetti S.
Published: March 2023

Critical quantum systems are a promising resource for quantum metrology applications, due to the diverging susceptibility developed in proximity of phase transitions. Here, we assess the metrological power of parametric Kerr resonators undergoing driven-dissipative phase transitions. We fully characterize the quantum Fisher information for frequency estimation, and the Helstrom bound for frequency discrimination. By going beyond the asymptotic regime, we show that the Heisenberg precision can be achieved with experimentally reachable parameters. We design protocols that exploit the critical behavior of nonlinear resonators to enhance the precision of quantum magnetometers and the fidelity of superconducting qubit readout.
Myoscaffolds reveal laminin scarring is detrimental for stem cell function while sarcospan induces compensatory fibrosis
Authors: Stearns-Reider Kristen M. , Hicks Michael R. , Hammond Katherine G. , Reynolds Joseph C. , Maity Alok , Kurmangaliyev Yerbol Z. , Chin Jesse , Stieg Adam Z. , Geisse Nicholas A. , Hohlbauch Sophia , Kaemmer Stefan , Schmitt Lauren R. , Pham Thanh T. , Yamauchi Ken , Novitch Bennett G. , Wollman Roy , Hansen Kirk C. , Pyle April D. , Crosbie Rachelle H.
Published: March 2023

We developed an on-slide decellularization approach to generate acellular extracellular matrix (ECM) myoscaffolds that can be repopulated with various cell types to interrogate cell-ECM interactions. Using this platform, we investigated whether fibrotic ECM scarring affected human skeletal muscle progenitor cell (SMPC) functions that are essential for myoregeneration. SMPCs exhibited robust adhesion, motility, and differentiation on healthy muscle-derived myoscaffolds. All SPMC interactions with fibrotic myoscaffolds from dystrophic muscle were severely blunted including reduced motility rate and migration. Furthermore, SMPCs were unable to remodel laminin dense fibrotic scars within diseased myoscaffolds. Proteomics and structural analysis revealed that excessive collagen deposition alone is not pathological, and can be compensatory, as revealed by overexpression of sarcospan and its associated ECM receptors in dystrophic muscle. Our in vivo data also supported that ECM remodeling is important for SMPC engraftment and that fibrotic scars may represent one barrier to efficient cell therapy.
Optimization of nutrient utilization efficiency and productivity for algal cultures under light and dark cycles using genome-scale model process control
Authors: Li Chien-Ting , Eng Richard , Zuniga Cristal , Huang Kai-Wen , Chen Yiqun , Zengler Karsten , Betenbaugh Michael J.
Published: March 2023

Algal cultivations are strongly influenced by light and dark cycles. In this study, genome-scale metabolic models were applied to optimize nutrient supply during alternating light and dark cycles of Chlorella vulgaris. This approach lowered the glucose requirement by 75% and nitrate requirement by 23%, respectively, while maintaining high final biomass densities that were more than 80% of glucose-fed heterotrophic culture. Furthermore, by strictly controlling glucose feeding during the alternating cycles based on model-input, yields of biomass, lutein, and fatty acids per gram of glucose were more than threefold higher with cycling compared to heterotrophic cultivation. Next, the model was incorporated into open-loop and closed-loop control systems and compared with traditional fed-batch systems. Closed-loop systems which incorporated a feed-optimizing algorithm increased biomass yield on glucose more than twofold compared to standard fed-batch cultures for cycling cultures. Finally, the performance was compared to conventional proportional-integral-derivative (PID) controllers. Both simulation and experimental results exhibited superior performance for genome-scale model process control (GMPC) compared to traditional PID systems, reducing the overall measured value and setpoint error by 80% over 8 h. Overall, this approach provides researchers with the capability to enhance nutrient utilization and productivity of cell factories systematically by combining genome-scale models and controllers into an integrated platform with superior performance to conventional fed-batch and PID methodologies.
Booster vaccination with Ad26.COV2.S or an Omicron-adapted vaccine in pre-immune hamsters protects against Omicron BA.2
Authors: Swart Maarten , van der Lubbe Joan , Schmit-Tillemans Sonja , van Huizen Ella , Verspuij Johan , Gil Ana Izquierdo , Choi Ying , Daal Chenandly , Perkasa Aditya , de Wilde Adriaan , Claassen Erwin , de Jong Rineke , Wiese Katrin E. , Cornelissen Lisette , van Es Marieke , van Heerden Marjolein , Kourkouta Eleni , Tahiri Issam , Mulders Michel , Vreugdenhil Jessica , Feddes - de Boer Karin , Muchene Leacky , Tolboom Jeroen , Dekking Liesbeth , Juraszek Jarek , Vellinga Jort , Custers Jerome , Bos Rinke , Schuitemaker Hanneke , Wegmann Frank , Roozendaal Ramon , Kuipers Harmjan , Zahn Roland
Published: March 2023

Since the original outbreak of the SARS-CoV-2 virus, several rapidly spreading SARS-CoV-2 variants of concern (VOC) have emerged. Here, we show that a single dose of Ad26.COV2.S (based on the Wuhan-Hu-1 spike variant) protects against the Gamma and Delta variants in naive hamsters, supporting the observed maintained vaccine efficacy in humans against these VOC. Adapted spike-based booster vaccines targeting Omicron variants have now been authorized in the absence of human efficacy data. We evaluated the immunogenicity and efficacy of Ad26.COV2.S.529 (encoding a stabilized Omicron BA.1 spike) in naive mice and in hamsters with pre-existing immunity to the Wuhan-Hu-1 spike. In naive mice, Ad26.COV2.S.529 elicited higher neutralizing antibody titers against SARS-CoV-2 Omicron BA.1 and BA.2, compared with Ad26.COV2.S. However, neutralizing titers against the SARS-CoV-2 B.1 (D614G) and Delta variants were lower after primary vaccination with Ad26.COV2.S.529 compared with Ad26.COV2.S. In contrast, we found comparable Omicron BA.1 and BA.2 neutralizing titers in hamsters with pre-existing Wuhan-Hu-1 spike immunity after vaccination with Ad26.COV2.S, Ad26.COV2.S.529 or a combination of the two vaccines. Moreover, all three vaccine modalities induced equivalent protection against Omicron BA.2 challenge in these animals. Overall, our data suggest that an Omicron BA.1-based booster in rodents does not improve immunogenicity and efficacy against Omicron BA.2 over an Ad26.COV2.S booster in a setting of pre-existing immunity to SARS-CoV-2.
PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application
Authors: Zhang Zhihao , Zhou Jinhu , Ni Peng , Hu Bing , Jolicoeur Normand , Deng Shuang , Xiao Qian , He Qian , Li Gai , Xia Yan , Liu Mei , Wang Cong , Fang Zhizheng , Xia Nan , Zhang Zhe-Rui , Zhang Bo , Cai Kun , Xu Yan , Liu Binlei
Published: March 2023

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and continues to have a significant impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, which is primarily responsible for the host immune response upon infection. Here we present the preclinical studies of a broadly protective SARS-CoV-2 subunit vaccine developed from our trimer domain platform using the Delta spike protein, from antigen design through purification, vaccine evaluation and manufacturability. The pre-fusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. Immunogenicity studies have shown that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous viral challenge. Neutralizing antibodies induced by this vaccine show cross-reactivity against the ancestral WA1, Delta and several Omicrons, including BA.5.2. The formulated PF-D Trimer is stable for up to six months without refrigeration. The Trimer Domain platform was proven to be a key technology in the rapid production of PF-D-Trimer vaccine and may be crucial to accelerate the development and accessibility of updated versions of SARS-CoV-2 vaccines.
SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies
Authors: Shrivastava Shikha , Carmen Joshua M. , Lu Zhongyan , Basu Shraddha , Sankhala Rajeshwer S. , Chen Wei-Hung , Nguyen Phuong , Chang William C. , King Jocelyn , Corbitt Courtney , Mayer Sandra , Bolton Jessica S. , Anderson Alexander , Swafford Isabella , Terriquez Guillermo D. , Trinh Hung V. , Kim Jiae , Jobe Ousman , Paquin-Proulx Dominic , Matyas Gary, R. , Gromowski Gregory D. , Currier Jeffrey R. , Bergmann-Leitner Elke , Modjarrad Kayvon , Michael Nelson L. , Joyce M. Gordon , Malloy Allison M. W. , Rao Mangala
Published: March 2023

This study demonstrates the impact of adjuvant on the development of T follicular helper (Tfh) and B cells, and their influence on antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted with either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel®(SpFN + AH). SpFN + ALFQ increased the size and frequency of germinal center (GC) B cells in the vaccine-draining lymph nodes and increased the frequency of antigen-specific naive B cells. A single vaccination with SpFN + ALFQ resulted in a higher frequency of IL-21-producing-spike-specific Tfh and GC B cells in the draining lymph nodes and spleen, S-2P protein-specific IgM and IgG antibodies, and elicitation of robust cross-neutralizing antibodies against SARS-CoV-2 variants as early as day 7, which was enhanced by a second vaccination. This was associated with the generation of high titer, high avidity binding antibodies. The third vaccination with SpFN + ALFQ elicited high levels of neutralizing antibodies against the Omicron variant. No cross-neutralizing antibodies against Omicron were induced with SpFN + AH. These findings highlight the importance of ALFQ in orchestrating early induction of antigen-specific Tfh and GC B cell responses and long-lived plasma cells in the bone marrow. The early engagement of S-2P specific naive B cells and high titer IgM antibodies shape the development of long-term neutralization breadth.
Optimal design of water reuse networks in cities through decision support tool development and testing
Authors: Calle Eusebi , Martínez David , Buttiglieri Gianluigi , Corominas Lluís , Farreras Miquel , Saló-Grau Joan , Vilà Pere , Pueyo-Ros Josep , Comas Joaquim
Published: March 2023

Water scarcity and droughts are an increasing issue in many parts of the world. In the context of urban water systems, the transition to circularity may imply wastewater treatment and reuse. Planning and assessment of water reuse projects require decision-makers evaluating the cost and benefits of alternative scenarios. Manual or semi-automatic approaches are still common practice for planning both drinking and reclaimed water distribution networks. This work illustrates a decision support tool that, based on open data sources and graph theory coupled to greedy optimization algorithms, is able to automatically compute the optimal reclaimed water network for a given scenario. The tool provides not only the maximum amount of served reclaimed water per unit of invested cost, but also the length and diameters of the pipes required, the location and size of storage tanks, the population served, and the construction costs, i.e., everything under the same architecture. The usefulness of the tool is illustrated in two different but complementary cities in terms of size, density, and topography. The construction cost of the optimal water reclaimed network for a city of approximately 100,000 inhabitants is estimated to be in the range of €0.17–0.22/m3 (for a payback period of 30 years).
Control of dynamic sp3-C stereochemistry
Authors: Bismillah Aisha N. , Johnson Toby G. , Hussein Burhan A. , Turley Andrew T. , Saha Promeet K. , Wong Ho Chi , Aguilar Juan A. , Yufit Dmitry S. , McGonigal Paul R.
Published: March 2023

Stereogenic sp3-hybridized carbon centres are fundamental building blocks of chiral molecules. Unlike dynamic stereogenic motifs, such as sp3-nitrogen centres or atropisomeric biaryls, sp3-carbon centres are usually fixed, requiring intermolecular reactions to undergo configurational changes. Here we report the internal enantiomerization of fluxional carbon cages and the consequences of their adaptive configurations for the transmission of stereochemical information. The sp3-carbon stereochemistry of the rigid tricyclic cages is inverted through strain-assisted Cope rearrangements, emulating the low-barrier configurational dynamics typical for sp3-nitrogen inversion or conformational isomerism. This dynamic enantiomerization can be stopped, restarted or slowed by external reagents, while the configuration of the cage is controlled by neighbouring, fixed stereogenic centres. As part of a phosphoramidite–olefin ligand, the fluxional cage acts as a conduit to transmit stereochemical information from the ligand while also transferring its dynamic properties to chiral-at-metal coordination environments, influencing catalysis, ion pairing and ligand exchange energetics.
Recent intensification of wetland methane feedback
Authors: Zhang Zhen , Poulter Benjamin , Feldman Andrew F. , Ying Qing , Ciais Philippe , Peng Shushi , Li Xin
Published: March 2023

The positive response of wetland methane (CH4) emissions to climate change is an important yet uncertain Earth-system feedback that amplifies atmospheric CH4 concentrations. Here, using a wetland model, we report intensified wetland CH4 emissions during 2000–2021, corresponding with 2020 and 2021 being exceptional years of growth. Our results highlight the need for sustained monitoring and observations of global wetland CH4 fluxes to document emerging trends, variability and underlying drivers.
Mechanosensitive extrusion of Enterovirus A71-infected cells from colonic organoids
Authors: Moshiri Jasmine , Craven Ailsa R. , Mixon Sara B. , Amieva Manuel R. , Kirkegaard Karla
Published: March 2023

Enterovirus A71 causes severe disease upon systemic infection, sometimes leading to life-threatening neurological dysfunction. However, in most cases infection is asymptomatic and limited to the gastrointestinal tract, where virus is amplified for transmission. Picornaviruses have previously been shown to exit infected cells via either cell lysis or secretion of vesicles. Here we report that entire Enterovirus A71-infected cells are specifically extruded from the apical surface of differentiated human colon organoids, as observed by confocal microscopy. Differential sensitivity to chemical and peptide inhibitors demonstrated that extrusion of virus-infected cells is dependent on force sensing via mechanosensitive ion channels rather than apoptotic cell death. When isolated and used as inoculum, intact virus-containing extruded cells can initiate new infections. In contrast, when mechanical force sensing is inhibited, large amounts of free virus are released. Thus, extrusion of live, virus-infected cells from intact epithelial tissue is likely to benefit both the integrity of host tissues and the protected spread of this faecal–oral pathogen within and between hosts.
Breaking the temporal and frequency congestion of LiDAR by parallel chaos
Authors: Chen Ruixuan , Shu Haowen , Shen Bitao , Chang Lin , Xie Weiqiang , Liao Wenchao , Tao Zihan , Bowers John E. , Wang Xingjun
Published: March 2023

The rising demand for high scanning accuracy and resolution in sensors for self-driving vehicles has led to the rapid development of parallelization in light detection and ranging (LiDAR) technologies. However, for the two major existing LiDAR categories—time-of-flight and frequency-modulated continuous wave—the light sources and measurement principles currently used for parallel detection face severe limitations from time- and frequency-domain congestion, leading to degraded measurement performance and increased system complexity. In this work we introduce a light source—the chaotic microcomb—to overcome this problem. This physical entropy light source exhibits naturally orthogonalized light channels that are immune to any congestion problem. Based on this microcomb state, we demonstrate a new type of LiDAR—parallel chaotic LiDAR—that is interference-free and has a greatly simplified system architecture. Our approach also enables the state-of-the-art ranging performance among parallel LiDARs: millimetre-level ranging accuracy and millimetre-per-second-level velocity resolution. Combining all of these desirable properties, this technology has the potential to reshape the entire LiDAR ecosystem.