bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrically insulating PBO/MXene film with superior thermal conductivity, mechanical properties, thermal stability, and flame retardancy
Authors: Liu Yong , Zou Weizhi , Zhao Ning , Xu Jian
Published: September 2023

Constructing flexible and robust thermally conductive but electrically insulating composite films for efficient and safe thermal management has always been a sought-after research topic. Herein, a nacre-inspired high-performance poly(p-phenylene-2,6-benzobisoxazole) (PBO)/MXene nanocomposite film was prepared by a sol-gel-film conversion method with a homogeneous gelation process. Because of the as-formed optimized brick and mortar structure, and the strong bridging and caging effects of the fine PBO nanofibre network on the MXene nanosheets, the resulting nanocomposite film is electrically insulating (2.5 × 109 Ω cm), and exhibits excellent mechanical properties (tensile strength of 416.7 MPa, Young’s modulus of 9.1 GPa and toughness of 97.3 MJ m−3). More importantly, the synergistic orientation of PBO nanofibres and MXene nanosheets endows the film with an in-plane thermal conductivity of 42.2 W m−1 K−1. The film also exhibits excellent thermal stability and flame retardancy. This work broadens the ideas for preparing high-performance thermally conductive but electrically insulating composites.
Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial
Authors: Monjazeb Arta M. , Daly Megan E. , Luxardi Guillaume , Maverakis Emanual , Merleev Alexander A. , Marusina Alina I. , Borowsky Alexander , Mirhadi Amin , Shiao Stephen L. , Beckett Laurel , Chen Shuai , Eastham David , Li Tianhong , Vick Logan V. , McGee Heather M. , Lara Frances , Garcia Leslie , Morris Leigh Anne , Canter Robert J. , Riess Jonathan W. , Schalper Kurt A. , Murphy William J. , Kelly Karen
Published: September 2023

Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes. We initiated a multi-institutional single-arm phase I study (NCT02599454) enrolling twenty patients with the primary endpoint of maximum tolerated dose (MTD); secondary endpoints of safety and efficacy; and exploratory mechanistic correlatives. Treatment is well tolerated and full dose atezolizumab (1200 mg) is the MTD. Efficacy signals include early responses (after 2 cycles of ICI, before initiation of SABR) in 17% of patients. Biomarkers of functional adaptive immunity, including T cell activation in the tumor and response to ex-vivo stimulation by circulating T cells, are highly predictive of benefit. These results require validation and are being tested in a phase III randomized trial.
Theranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway
Authors: Zhou Huiling , Tang Dongsheng , Yu Yingjie , Zhang Lingpu , Wang Bin , Karges Johannes , Xiao Haihua
Published: September 2023

Tumor metastases are considered the leading cause of cancer-associated deaths. While clinically applied drugs have demonstrated to efficiently remove the primary tumor, metastases remain poorly accessible. To overcome this limitation, herein, the development of a theranostic nanomaterial by incorporating a chromophore for imaging and a photosensitizer for treatment of metastatic tumor sites is presented. The mechanism of action reveals that the nanoparticles are able to intervene by local generation of cellular damage through photodynamic therapy as well as by systemic induction of an immune response by immunotherapy upon inhibition of the mTOR signaling pathway which is of crucial importance for tumor onset, progression and metastatic spreading. The nanomaterial is able to strongly reduce the volume of the primary tumor as well as eradicates tumor metastases in a metastatic breast cancer and a multi-drug resistant patient-derived hepatocellular carcinoma models in female mice.
Enhancing photosynthetic CO2 fixation by assembling metal-organic frameworks on Chlorella pyrenoidosa
Authors: Li Dingyi , Dong Hong , Cao Xupeng , Wang Wangyin , Li Can
Published: September 2023

The CO2 concentration at ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is crucial to improve photosynthetic efficiency for biomass yield. However, how to concentrate and transport atmospheric CO2 towards the Rubisco carboxylation is a big challenge. Herein, we report the self-assembly of metal-organic frameworks (MOFs) on the surface of the green alga Chlorella pyrenoidosa that can greatly enhance the photosynthetic carbon fixation. The chemical CO2 concentrating approach improves the apparent photo conversion efficiency to about 1.9 folds, which is up to 9.8% in ambient air from an intrinsic 5.1%. We find that the efficient carbon fixation lies in the conversion of the captured CO2 to the transportable HCO3− species at bio-organic interface. This work demonstrates a chemical approach of concentrating atmospheric CO2 for enhancing biomass yield of photosynthesis.
Epigenetic inheritance is unfaithful at intermediately methylated CpG sites
Authors: Hay Amir D. , Kessler Noah J. , Gebert Daniel , Takahashi Nozomi , Tavares Hugo , Teixeira Felipe K. , Ferguson-Smith Anne C.
Published: September 2023

DNA methylation at the CpG dinucleotide is considered a stable epigenetic mark due to its presumed long-term inheritance through clonal expansion. Here, we perform high-throughput bisulfite sequencing on clonally derived somatic cell lines to quantitatively measure methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity, and is not coordinately maintained between neighbouring sites. We determine that the probabilistic changes that occur at intermediately methylated sites are likely due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the current epigenetic inheritance model and has direct implications for both the functional relevance and general interpretability of DNA methylation as a stable epigenetic mark.
Low-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models
Authors: Porter L. H. , Zhu J. J. , Lister N. L. , Harrison S. G. , Keerthikumar S. , Goode D. L. , Urban R. Quezada , Byrne D. J. , Azad A. , Vela I. , Hofman M. S. , Neeson P. J. , Darcy P. K. , Trapani J. A. , Taylor R. A. , Risbridger G. P.
Published: September 2023

Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR T cells are less efficient against solid tumors, largely due to poor infiltration resulting from the immunosuppressive nature of the tumor microenvironment (TME). Here, we assessed the efficacy of Lewis Y antigen (LeY)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer. In vitro, LeY CAR T cells directly killed organoids derived from androgen receptor (AR)-positive or AR-null PDXs. In vivo, although LeY CAR T cells alone did not reduce tumor growth, a single prior dose of carboplatin reduced tumor burden. Carboplatin had a pro-inflammatory effect on the TME that facilitated early and durable CAR T cell infiltration, including an altered cancer-associated fibroblast phenotype, enhanced extracellular matrix degradation and re-oriented M1 macrophage differentiation. In a PDX less sensitive to carboplatin, CAR T cell infiltration was dampened; however, a reduction in tumor burden was still observed with increased T cell activation. These findings indicate that carboplatin improves the efficacy of CAR T cell treatment, with the extent of the response dependent on changes induced within the TME.
Structure-based design of a strain transcending AMA1-RON2L malaria vaccine
Authors: Patel Palak N. , Dickey Thayne H. , Diouf Ababacar , Salinas Nichole D. , McAleese Holly , Ouahes Tarik , Long Carole A. , Miura Kazutoyo , Lambert Lynn E. , Tolia Niraj H.
Published: September 2023

Apical membrane antigen 1 (AMA1) is a key malaria vaccine candidate and target of neutralizing antibodies. AMA1 binds to a loop in rhoptry neck protein 2 (RON2L) to form the moving junction during parasite invasion of host cells, and this complex is conserved among apicomplexan parasites. AMA1-RON2L complex immunization achieves higher growth inhibitory activity than AMA1 alone and protects mice against Plasmodium yoelii challenge. Here, three single-component AMA1-RON2L immunogens were designed that retain the structure of the two-component AMA1-RON2L complex: one structure-based design (SBD1) and two insertion fusions. All immunogens elicited high antibody titers with potent growth inhibitory activity, yet these antibodies did not block RON2L binding to AMA1. The SBD1 immunogen induced significantly more potent strain-transcending neutralizing antibody responses against diverse strains of Plasmodium falciparum than AMA1 or AMA1-RON2L complex vaccination. This indicates that SBD1 directs neutralizing antibody responses to strain-transcending epitopes in AMA1 that are independent of RON2L binding. This work underscores the importance of neutralization mechanisms that are distinct from RON2 blockade. The stable single-component SBD1 immunogen elicits potent strain-transcending protection that may drive the development of next-generation vaccines for improved malaria and apicomplexan parasite control.
Deciphering early human pancreas development at the single-cell level
Authors: Ma Zhuo , Zhang Xiaofei , Zhong Wen , Yi Hongyan , Chen Xiaowei , Zhao Yinsuo , Ma Yanlin , Song Eli , Xu Tao
Published: September 2023

Understanding pancreas development can provide clues for better treatments of pancreatic diseases. However, the molecular heterogeneity and developmental trajectory of the early human pancreas are poorly explored. Here, we performed large-scale single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing of human embryonic pancreas tissue obtained from first-trimester embryos. We unraveled the molecular heterogeneity, developmental trajectories and regulatory networks of the major cell types. The results reveal that dorsal pancreatic multipotent cells in humans exhibit different gene expression patterns than ventral multipotent cells. Pancreato-biliary progenitors that generate ventral multipotent cells in humans were identified. Notch and MAPK signals from mesenchymal cells regulate the differentiation of multipotent cells into trunk and duct cells. Notably, we identified endocrine progenitor subclusters with different differentiation potentials. Although the developmental trajectories are largely conserved between humans and mice, some distinct gene expression patterns have also been identified. Overall, we provide a comprehensive landscape of early human pancreas development to understand its lineage transitions and molecular complexity.
Compact all-fiber quantum-inspired LiDAR with over 100 dB noise rejection and single photon sensitivity
Authors: Liu Han , Qin Changhao , Papangelakis Georgios , Iu Meng Lon , Helmy Amr S.
Published: September 2023

Entanglement and correlation of quantum light can enhance LiDAR sensitivity in the presence of strong background noise. However, the power of such quantum sources is fundamentally limited to a stream of single photons and cannot compete with the detection range of high-power classical LiDAR transmitters. To circumvent this, we develop and demonstrate a quantum-inspired LiDAR prototype based on coherent measurement of classical time-frequency correlation. This system uses a high-power classical source and maintains the high noise rejection advantage of quantum LiDARs. In particular, we show that it can achieve over 100dB rejection (with 100ms integration time) of indistinguishable (with statistically identical properties in every degree of freedom) in-band noise while still being sensitive to single photon signals. In addition to the LiDAR demonstration, we also discuss the potential of the proposed LiDAR receiver for quantum information applications. In particular, we propose the chaotic quantum frequency conversion technique for coherent manipulation of high dimensional quantum states of light. It is shown that this technique can provide improved performance in terms of selectivity and efficiency as compared to pulse-based quantum frequency conversion.
Decadal decrease in Los Angeles methane emissions is much smaller than bottom-up estimates
Authors: Zeng Zhao-Cheng , Pongetti Thomas , Newman Sally , Oda Tomohiro , Gurney Kevin , Palmer Paul I. , Yung Yuk L. , Sander Stanley P.
Published: September 2023

Methane, a powerful greenhouse gas, has a short atmospheric lifetime ( ~ 12 years), so that emissions reductions will have a rapid impact on climate forcing. In megacities such as Los Angeles (LA), natural gas (NG) leakage is the primary atmospheric methane source. The magnitudes and trends of fugitive NG emissions are largely unknown and need to be quantified to verify compliance with emission reduction targets. Here we use atmospheric remote sensing data to show that, in contrast to the observed global increase in methane emissions, LA area emissions decreased during 2011-2020 at a mean rate of (–1.57 ± 0.41) %/yr. However, the NG utility calculations indicate a much larger negative emissions trend of −5.8 %/yr. The large difference between top-down and bottom-up trends reflects the uncertainties in estimating the achieved emissions reductions. Actions taken in LA can be a blueprint for COP28 and future efforts to reduce methane emissions.
Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma
Authors: Coffey David G. , Maura Francesco , Gonzalez-Kozlova Edgar , Diaz-Mejia J. Javier , Luo Ping , Zhang Yong , Xu Yuexin , Warren Edus H. , Dawson Travis , Lee Brian , Xie Hui , Smith Eric , Ciardiello Amanda , Cho Hearn J. , Rahman Adeeb , Kim-Schulze Seunghee , Diamond Benjamin , Lesokhin Alexander , Kazandjian Dickran , Pugh Trevor J. , Green Damian J. , Gnjatic Sacha , Landgren Ola
Published: September 2023

The role of the immune microenvironment in maintaining disease remission in patients with multiple myeloma (MM) is not well understood. In this study, we comprehensively profile the immune system in patients with newly diagnosed MM receiving continuous lenalidomide maintenance therapy with the aim of discovering correlates of long-term treatment response. Leveraging single-cell RNA sequencing and T cell receptor β sequencing of the peripheral blood and CyTOF mass cytometry of the bone marrow, we longitudinally characterize the immune landscape in 23 patients before and one year after lenalidomide exposure. We compare patients achieving sustained minimal residual disease (MRD) negativity to patients who never achieved or were unable to maintain MRD negativity. We observe that the composition of the immune microenvironment in both the blood and the marrow varied substantially according to both MRD negative status and history of autologous stem cell transplant, supporting the hypothesis that the immune microenvironment influences the depth and duration of treatment response.
From Stoner to local moment magnetism in atomically thin Cr2Te3
Authors: Zhong Yong , Peng Cheng , Huang Haili , Guan Dandan , Hwang Jinwoong , Hsu Kuan H. , Hu Yi , Jia Chunjing , Moritz Brian , Lu Donghui , Lee Jun-Sik , Jia Jin-Feng , Devereaux Thomas P. , Mo Sung-Kwan , Shen Zhi-Xun
Published: September 2023

The field of two-dimensional (2D) ferromagnetism has been proliferating over the past few years, with ongoing interests in basic science and potential applications in spintronic technology. However, a high-resolution spectroscopic study of the 2D ferromagnet is still lacking due to the small size and air sensitivity of the exfoliated nanoflakes. Here, we report a thickness-dependent ferromagnetism in epitaxially grown Cr2Te3 thin films and investigate the evolution of the underlying electronic structure by synergistic angle-resolved photoemission spectroscopy, scanning tunneling microscopy, x-ray absorption spectroscopy, and first-principle calculations. A conspicuous ferromagnetic transition from Stoner to Heisenberg-type is directly observed in the atomically thin limit, indicating that dimensionality is a powerful tuning knob to manipulate the novel properties of 2D magnetism. Monolayer Cr2Te3 retains robust ferromagnetism, but with a suppressed Curie temperature, due to the drastic drop in the density of states near the Fermi level. Our results establish atomically thin Cr2Te3 as an excellent platform to explore the dual nature of localized and itinerant ferromagnetism in 2D magnets.
Cell-inspired design of cascade catalysis system by 3D spatially separated active sites
Authors: Wang Qiuping , Chen Kui , Jiang Hui , Chen Cai , Xiong Can , Chen Min , Xu Jie , Gao Xiaoping , Xu Suowen , Zhou Huang , Wu Yuen
Published: September 2023

Cells possess isolated compartments that spatially confine different enzymes, enabling high-efficiency enzymatic cascade reactions. Herein, we report a cell-inspired design of biomimetic cascade catalysis system by immobilizing Fe single atoms and Au nanoparticles on the inner and outer layers of three-dimensional nanocapsules, respectively. The different metal sites catalyze independently and work synergistically to enable engineered and cascade glucose detection. The biomimetic catalysis system demonstrates ~ 9.8- and 2-fold cascade activity enhancement than conventional mixing and coplanar construction systems, respectively. Furthermore, the biomimetic catalysis system is successfully demonstrated for the colorimetric glucose detection with high catalytic activity and selectivity. Also, the proposed gel-based sensor is integrated with smartphone to enable real-time and visual determination of glucose. More importantly, the gel-based sensor exhibits a high correlation with a commercial glucometer in real samples detection. These findings provide a strategy to design an efficient biomimetic catalysis system for applications in bioassays and nanobiomedicines.
Prediction of base editor off-targets by deep learning
Authors: Zhang Chengdong , Yang Yuan , Qi Tao , Zhang Yuening , Hou Linghui , Wei Jingjing , Yang Jingcheng , Shi Leming , Ong Sang-Ging , Wang Hongyan , Wang Hui , Yu Bo , Wang Yongming
Published: September 2023

Due to the tolerance of mismatches between gRNA and targeting sequence, base editors frequently induce unwanted Cas9-dependent off-target mutations. Here, to develop models to predict such off-targets, we design gRNA-off- target pairs for adenine base editors (ABEs) and cytosine base editors (CBEs) and stably integrate them into the human cells. After five days of editing, we obtain valid efficiency datasets of 54,663 and 55,727 off-targets for ABEs and CBEs, respectively. We use the datasets to train deep learning models, resulting in ABEdeepoff and CBEdeepoff, which can predict off-target sites. We use these tools to predict off-targets for a panel of endogenous loci and achieve Spearman correlation values varying from 0.710 to 0.859. Finally, we develop an integrated tool that is freely accessible via an online web server http://www.deephf.com/#/bedeep/bedeepoff. These tools could facilitate minimizing the off-target effects of base editing.
Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice
Authors: Inamdar Sahil , Suresh Abhirami P. , Mangal Joslyn L. , Ng Nathan D. , Sundem Alison , Wu Christopher , Lintecum Kelly , Thumsi Abhirami , Khodaei Taravat , Halim Michelle , Appel Nicole , Jaggarapu Madhan Mohan Chandra Sekhar , Esrafili Arezoo , Yaron Jordan R. , Curtis Marion , Acharya Abhinav P.
Published: September 2023

Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.1 tumours in immunocompetent female mice. Furthermore, to test the versatility of this strategy, adoptive DC therapy is developed with formulations that incorporate F16BP, poly(IC) as adjuvant and mRNA derived from B16F10 cells as antigens in established B16F10 tumours in immunocompetent female mice. F16BP vaccine formulations rescue DCs in vitro and in vivo, significantly improve the survival of mice, and generate cytotoxic T cell (Tc) responses by elevating Tc1 and Tc17 cells within the tumour. Overall, these results demonstrate that rescuing glycolysis of DCs using metabolite-based formulations can be utilized to generate immunotherapy even in the presence of glycolytic inhibitor.
MAVS integrates glucose metabolism and RIG-I-like receptor signaling
Authors: He Qiao-qiao , Huang Yu , Nie Longyu , Ren Sheng , Xu Gang , Deng Feiyan , Cheng Zhikui , Zuo Qi , Zhang Lin , Cai Huanhuan , Wang Qiming , Wang Fubing , Ren Hong , Yan Huan , Xu Ke , Zhou Li , Lu Mengji , Lu Zhibing , Zhu Ying , Liu Shi
Published: September 2023

MAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling in mitochondria, peroxisomes, and mitochondria-associated ER membranes (MAMs). However, the role of MAVS in glucose metabolism and RLR signaling cross-regulation and how these signaling pathways are coordinated among these organelles have not been defined. This study reports that RLR action drives a switch from glycolysis to the pentose phosphate pathway (PPP) and the hexosamine biosynthesis pathway (HBP) through MAVS. We show that peroxisomal MAVS is responsible for glucose flux shift into PPP and type III interferon (IFN) expression, whereas MAMs-located MAVS is responsible for glucose flux shift into HBP and type I IFN expression. Mechanistically, peroxisomal MAVS interacts with G6PD and the MAVS signalosome forms at peroxisomes by recruiting TNF receptor-associated factor 6 (TRAF6) and interferon regulatory factor 1 (IRF1). By contrast, MAMs-located MAVS interact with glutamine-fructose-6-phosphate transaminase, and the MAVS signalosome forms at MAMs by recruiting TRAF6 and TRAF2. Our findings suggest that MAVS mediates the interaction of RLR signaling and glucose metabolism.
Associations of modern initial antiretroviral therapy regimens with all-cause mortality in people living with HIV in resource-limited settings: a retrospective multicenter cohort study in China
Authors: Wu Xinsheng , Wu Guohui , Ma Ping , Wang Rugang , Li Linghua , Chen Yuanyi , Xu Junjie , Li Yuwei , Li Quanmin , Yang Yuecheng , Wang Lijing , Xin Xiaoli , Qiao Ying , Fu Gengfeng , Huang Xiaojie , Su Bin , Zhang Tong , Wang Hui , Zou Huachun
Published: September 2023

Despite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others [including darunavir, raltegravie, elvitegravir and rilpivirine]) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.
Anisotropic flexibility and rigidification in a TPE-based Zr-MOFs with scu topology
Authors: Meng Sha-Sha , Xu Ming , Guan Hanxi , Chen Cailing , Cai Peiyu , Dong Bo , Tan Wen-Shu , Gu Yu-Hao , Tang Wen-Qi , Xie Lan-Gui , Yuan Shuai , Han Yu , Kong Xueqian , Gu Zhi-Yuan
Published: September 2023

Tetraphenylethylene (TPE)-based ligands are appealing for constructing metal-organic frameworks (MOFs) with new functions and responsiveness. Here, we report a non-interpenetrated TPE-based scu Zr-MOF with anisotropic flexibility, that is, Zr-TCPE (H4TCPE = 1,1,2,2-tetra(4-carboxylphenyl)ethylene), remaining two anisotropic pockets. The framework flexibility is further anisotropically rigidified by installing linkers individually at specific pockets. By individually installing dicarboxylic acid L1 or L2 at pocket A or B, the framework flexibility along the b-axis or c-axis is rigidified, and the intermolecular or intramolecular motions of organic ligands are restricted, respectively. Synergistically, with dual linker installation, the flexibility is completely rigidified with the restriction of ligand motion, resulting in MOFs with enhanced stability and improved separation ability. Furthermore, in situ observation of the flipping of the phenyl ring and its rigidification process is made by 2H solid-state NMR. The anisotropic rigidification of flexibility in scu Zr-MOFs guides the directional control of ligand motion for designing stimuli-responsive emitting or efficient separation materials.
Self-adaptive amorphous CoOxCly electrocatalyst for sustainable chlorine evolution in acidic brine
Authors: Xiao Mengjun , Wu Qianbao , Ku Ruiqi , Zhou Liujiang , Long Chang , Liang Junwu , Mavrič Andraž , Li Lei , Zhu Jing , Valant Matjaz , Li Jiong , Zeng Zhenhua , Cui Chunhua
Published: September 2023

Electrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOxClycatalyst that has been deposited in situ in an acidic saline electrolyte containing Co2+and Cl-ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm−2and high stability over 500 h. In situ spectroscopic studies and theoretical calculations reveal that the electrochemical introduction of Cl-prevents the Co sites from charging to a higher oxidation state thus suppressing the O-O bond formation for oxygen evolution. Consequently, the chlorine evolution selectivity has been enhanced on the Cl-constrained Co-O*sites via the Volmer-Heyrovsky pathway. This study provides fundamental insights into how the reactant Cl-itself can work as a promoter toward enhancing chlorine evolution in acidic brine.
Coordinated peptidoglycan synthases and hydrolases stabilize the bacterial cell wall
Authors: Zhang Huan , Venkatesan Srutha , Ng Emily , Nan Beiyan
Published: September 2023

Peptidoglycan (PG) defines cell shape and protects bacteria against osmotic stress. The growth and integrity of PG require coordinated actions between synthases that insert new PG strands and hydrolases that generate openings to allow the insertion. However, the mechanisms of their coordination remain elusive. Moenomycin that inhibits a family of PG synthases known as Class-A penicillin-binding proteins (aPBPs), collapses rod shape despite aPBPs being non-essential for rod-like morphology in the bacterium Myxococcus xanthus. Here, we demonstrate that inhibited PBP1a2, an aPBP, accelerates the degradation of cell poles by DacB, a hydrolytic PG peptidase. Moenomycin promotes the binding between DacB and PG and thus reduces the mobility of DacB through PBP1a2. Conversely, DacB also regulates the distribution and dynamics of aPBPs. Our findings clarify the action of moenomycin and suggest that disrupting the coordination between PG synthases and hydrolases could be more lethal than eliminating individual enzymes.
Protein fibers with self-recoverable mechanical properties via dynamic imine chemistry
Authors: Sun Jing , He Haonan , Zhao Kelu , Cheng Wenhao , Li Yuanxin , Zhang Peng , Wan Sikang , Liu Yawei , Wang Mengyao , Li Ming , Wei Zheng , Li Bo , Zhang Yi , Li Cong , Sun Yao , Shen Jianlei , Li Jingjing , Wang Fan , Ma Chao , Tian Yang , Su Juanjuan , Chen Dong , Fan Chunhai , Zhang Hongjie , Liu Kai
Published: September 2023

The manipulation of internal interactions at the molecular level within biological fibers is of particular importance but challenging, severely limiting their tunability in macroscopic performances and applications. It thus becomes imperative to explore new approaches to enhance biological fibers’ stability and environmental tolerance and to impart them with diverse functionalities, such as mechanical recoverability and stimulus-triggered responses. Herein, we develop a dynamic imine fiber chemistry (DIFC) approach to engineer molecular interactions to fabricate strong and tough protein fibers with recoverability and actuating behaviors. The resulting DIF fibers exhibit extraordinary mechanical performances, outperforming many recombinant silks and synthetic polymer fibers. Remarkably, impaired DIF fibers caused by fatigue or strong acid treatment are quickly recovered in water directed by the DIFC strategy. Reproducible mechanical performance is thus observed. The DIF fibers also exhibit exotic mechanical stability at extreme temperatures (e.g., −196 °C and 150 °C). When triggered by humidity, the DIFC endows the protein fibers with diverse actuation behaviors, such as self-folding, self-stretching, and self-contracting. Therefore, the established DIFC represents an alternative strategy to strengthen biological fibers and may pave the way for their high-tech applications.
Reversal of trends in global fine particulate matter air pollution
Authors: Li Chi , van Donkelaar Aaron , Hammer Melanie S. , McDuffie Erin E. , Burnett Richard T. , Spadaro Joseph V. , Chatterjee Deepangsu , Cohen Aaron J. , Apte Joshua S. , Southerland Veronica A. , Anenberg Susan C. , Brauer Michael , Martin Randall V.
Published: September 2023

Ambient fine particulate matter (PM2.5) is the world’s leading environmental health risk factor. Quantification is needed of regional contributions to changes in global PM2.5 exposure. Here we interpret satellite-derived PM2.5 estimates over 1998-2019 and find a reversal of previous growth in global PM2.5 air pollution, which is quantitatively attributed to contributions from 13 regions. Global population-weighted (PW) PM2.5 exposure, related to both pollution levels and population size, increased from 1998 (28.3 μg/m3) to a peak in 2011 (38.9 μg/m3) and decreased steadily afterwards (34.7 μg/m3 in 2019). Post-2011 change was related to exposure reduction in China and slowed exposure growth in other regions (especially South Asia, the Middle East and Africa). The post-2011 exposure reduction contributes to stagnation of growth in global PM2.5-attributable mortality and increasing health benefits per µg/m3 marginal reduction in exposure, implying increasing urgency and benefits of PM2.5 mitigation with aging population and cleaner air.
Metallic W/WO2 solid-acid catalyst boosts hydrogen evolution reaction in alkaline electrolyte
Authors: Chen Zhigang , Gong Wenbin , Wang Juan , Hou Shuang , Yang Guang , Zhu Chengfeng , Fan Xiyue , Li Yifan , Gao Rui , Cui Yi
Published: September 2023

The lack of available protons severely lowers the activity of alkaline hydrogen evolution reaction process than that in acids, which can be efficiently accelerated by tuning the coverage and chemical environment of protons on catalyst surface. However, the cycling of active sites by proton transfer is largely dependent on the utilization of noble metal catalysts because of the appealing electronic interaction between noble metal atoms and protons. Herein, an all-non-noble W/WO2 metallic heterostructure serving as an efficient solid-acid catalyst exhibits remarkable hydrogen evolution reaction performance with an ultra-low overpotential of −35 mV at −10 mA/cm2 and a small Tafel slope (−34 mV/dec), as well as long-term durability of hydrogen production (>50 h) at current densities of −10 and −50 mA/cm2 in alkaline electrolyte. Multiple in situ and ex situ spectroscopy characterizations combining with first-principle density functional theory calculations discover that a dynamic proton-concentrated surface can be constructed on W/WO2 solid-acid catalyst under ultra-low overpotentials, which enables W/WO2 catalyzing alkaline hydrogen production to follow a kinetically fast Volmer-Tafel pathway with two neighboring protons recombining into a hydrogen molecule. Our strategy of solid-acid catalyst and utilization of multiple spectroscopy characterizations may provide an interesting route for designing advanced all-non-noble catalytic system towards boosting hydrogen evolution reaction performance in alkaline electrolyte.
Sulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish
Authors: Sun Wenwei , Wang Meimei , Zhao Jun , Zhao Shuang , Zhu Wenchao , Wu Xiaoting , Li Feifei , Liu Wei , Wang Zhuo , Gao Meng , Zhang Yiyue , Xu Jin , Zhang Meijia , Wang Qiang , Wen Zilong , Shen Juan , Zhang Wenqing , Huang Zhibin
Published: September 2023

Nonsteroidal anti-inflammatory drugs compose one of the most widely used classes of medications, but the risks for early development remain controversial, especially in the nervous system. Here, we utilized zebrafish larvae to assess the potentially toxic effects of nonsteroidal anti-inflammatory drugs and found that sulindac can selectively induce apoptosis of GABAergic neurons in the brains of zebrafish larvae brains. Zebrafish larvae exhibit hyperactive behaviour after sulindac exposure. We also found that akt1 is selectively expressed in GABAergic neurons and that SC97 (an Akt1 activator) and exogenous akt1 mRNA can reverse the apoptosis caused by sulindac. Further studies showed that sulindac binds to retinoid X receptor alpha (RXRα) and induces autophagy in GABAergic neurons, leading to activation of the mitochondrial apoptotic pathway. Finally, we verified that sulindac can lead to hyperactivity and selectively induce GABAergic neuron apoptosis in mice. These findings suggest that excessive use of sulindac may lead to early neurodevelopmental toxicity and increase the risk of hyperactivity, which could be associated with damage to GABAergic neurons.
Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy
Authors: Zhang Liang , Song An , Yang Qi-Chao , Li Shu-Jin , Wang Shuo , Wan Shu-Cheng , Sun Jianwei , Kwok Ryan T. K. , Lam Jacky W. Y. , Deng Hexiang , Tang Ben Zhong , Sun Zhi-Jun
Published: September 2023

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response and boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable of triggering both pyroptosis and ferroptosis remains limited. Here we show the construction of a covalent organic framework (COF-919) from planar and twisted AIEgen-based motifs as a dual-inducer of pyroptosis and ferroptosis for efficient antitumor immunity. Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, and longer lifetime to favor the generation of reactive oxygen species (ROS) and photothermal conversion, triggering pyroptosis. Because of its good ROS production capability, it upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. Additionally, the induction of pyroptosis and ferroptosis by COF-919 effectively inhibits tumor metastasis and recurrence, resulting in over 90% tumor growth inhibition and cure rates exceeding 80%.
Interpreting biologically informed neural networks for enhanced proteomic biomarker discovery and pathway analysis
Authors: Hartman Erik , Scott Aaron M. , Karlsson Christofer , Mohanty Tirthankar , Vaara Suvi T. , Linder Adam , Malmström Lars , Malmström Johan
Published: September 2023

The incorporation of machine learning methods into proteomics workflows improves the identification of disease-relevant biomarkers and biological pathways. However, machine learning models, such as deep neural networks, typically suffer from lack of interpretability. Here, we present a deep learning approach to combine biological pathway analysis and biomarker identification to increase the interpretability of proteomics experiments. Our approach integrates a priori knowledge of the relationships between proteins and biological pathways and biological processes into sparse neural networks to create biologically informed neural networks. We employ these networks to differentiate between clinical subphenotypes of septic acute kidney injury and COVID-19, as well as acute respiratory distress syndrome of different aetiologies. To gain biological insight into the complex syndromes, we utilize feature attribution-methods to introspect the networks for the identification of proteins and pathways important for distinguishing between subtypes. The algorithms are implemented in a freely available open source Python-package (https://github.com/InfectionMedicineProteomics/BINN).
FAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination
Authors: Lei Chuxiang , Kan Haoxuan , Xian Xiangyu , Chen Wenlin , Xiang Wenxuan , Song Xiaohong , Wu Jianqiang , Yang Dan , Zheng Yuehong
Published: September 2023

Reprogramming of vascular smooth muscle cell (VSMC) differentiation plays an essential role in abdominal aortic aneurysm (AAA). However, the underlying mechanisms are still unclear. We explore the expression of FAM3A, a newly identified metabolic cytokine, and whether and how FAM3A regulates VSMC differentiation in AAA. We discover that FAM3A is decreased in the aortas and plasma in AAA patients and murine models. Overexpression or supplementation of FAM3A significantly attenuate the AAA formation, manifested by maintenance of the well-differentiated VSMC status and inhibition of VSMC transformation toward macrophage-, chondrocyte-, osteogenic-, mesenchymal-, and fibroblast-like cell subpopulations. Importantly, FAM3A induces KLF4 ubiquitination and reduces its phosphorylation and nuclear localization. Here, we report FAM3A as a VSMC fate-shaping regulator in AAA and reveal the underlying mechanism associated with KLF4 ubiquitination and stability, which may lead to the development of strategies based on FAM3A to restore VSMC homeostasis in AAA.
TAZ2 truncation confers overactivation of p300 and cellular vulnerability to HDAC inhibition
Authors: Xu Longxia , Xuan Hongwen , He Wei , Zhang Liang , Huang Mengying , Li Kuai , Wen Hong , Xu Han , Shi Xiaobing
Published: September 2023

The histone acetyltransferase p300/CBP is composed of several conserved domains, among which, the TAZ2 domain is known as a protein-protein interaction domain that binds to E1A and various transcription factors. Here we show that TAZ2 has a HAT autoinhibitory function. Truncating p300/CBP at TAZ2 leads to hyperactive HAT and elevated histone H3K27 and H3K18 acetylation in cells. Mechanistically, TAZ2 cooperates with other HAT neighboring domains to maintain the HAT active site in a ‘closed’ state. Truncating TAZ2 or binding of transcription factors to TAZ2 induces a conformational change that ‘opens’ the active site for substrate acetylation. Importantly, genetic mutations that lead to p300/CBP TAZ2 truncations are found in human cancers, and cells with TAZ2 truncations are vulnerable to histone deacetylase inhibitors. Our study reveals a function of the TAZ2 domain in HAT autoinhibitory regulation and provides a potential therapeutic strategy for the treatment of cancers harboring p300/CBP TAZ2 truncations.
Ultra-fast interpretable machine-learning potentials
Authors: Xie Stephen R. , Rupp Matthias , Hennig Richard G.
Published: September 2023

All-atom dynamics simulations are an indispensable quantitative tool in physics, chemistry, and materials science, but large systems and long simulation times remain challenging due to the trade-off between computational efficiency and predictive accuracy. To address this challenge, we combine effective two- and three-body potentials in a cubic B-spline basis with regularized linear regression to obtain machine-learning potentials that are physically interpretable, sufficiently accurate for applications, as fast as the fastest traditional empirical potentials, and two to four orders of magnitude faster than state-of-the-art machine-learning potentials. For data from empirical potentials, we demonstrate the exact retrieval of the potential. For data from density functional theory, the predicted energies, forces, and derived properties, including phonon spectra, elastic constants, and melting points, closely match those of the reference method. The introduced potentials might contribute towards accurate all-atom dynamics simulations of large atomistic systems over long-time scales.
Frequency-insensitive spatiotemporal shaping of single photon in multiuser quantum network
Authors: Huang Yiwen , Qi Zhantong , Yang Yilin , Li Yuanhua , Sun Yiwei , Tang Yongzhi , Ni Fengchao , Li Lanting , Zheng Yuanlin , Chen Xianfeng
Published: September 2023

Exploiting the fundamental features of quantum mechanics, an entanglement-based quantum network offers a promising platform for many dramatic applications such as multi-user cryptography. Nevertheless, the implementation of a large-scale quantum network in real-world scenarios remains challenging owing to the multiple scattering events in complex environment, particularly those frequency-sensitive scatterings that disturb quantum correlation both spatially and temporally. Here, we demonstrate the frequency-insensitive spatiotemporal control of entangled photons in a fully connected network by leveraging a Fourier-transform setup and the genetic algorithm. Such an approach can effectively improve the entanglement distribution process through a multimode fiber while the quantum characteristic of the network can be maintained well after the spatiotemporal shaping. Our scheme can serve as a bridging technology to establish entanglement between remote nodes of spectrally interconnected quantum systems and has great potential applications in future real-world quantum networks.
Model-independent quantum phases classifier
Authors: Mahlow F. , Luiz F. S. , Malvezzi A. L. , Fanchini F. F.
Published: September 2023

Machine learning has transformed science and technology. In this article, we present a model-independent classifier that uses the k-Nearest Neighbors algorithm to classify phases of a model for which it has never been trained. This is done by studying three different spin-1 chains with some common phases: the XXZ chains with uniaxial single-ion-type anisotropy, the bond alternating XXZ chains, and the bilinear biquadratic chain. We show that the algorithm trained with two of these models can, with high probability, determine phases common to the third one. This is the first step towards a universal classifier, where an algorithm can recognize an arbitrary phase without knowing the Hamiltonian, since it knows only partial information about the quantum state.
Effect of antenatal depression on ANC service utilization in northwest Ethiopia
Authors: Beyene Getnet Mihretie , Azale Telake , Gelaye Kassahun Alemu , Ayele Tadesse Awoke
Published: September 2023

Maternal morbidity and mortality remain high among women who did not attend antenatal care (ANC). Antenatal care is one of the interventions given to pregnant women to detect existed problems or problems that can develop during pregnancy, which harm the health of pregnant women and fetuses. In Ethiopia, however, there is limited evidence that revealed the effect of antenatal depression on ANC service utilization. Hence, this study aimed to see the effect of antenatal depression on ANC visits among women in urban northwest Ethiopia. A population-based, prospective cohort study was done from June 2019 to March 2020. The Edinburgh postnatal depression scale was administered to 970 women in the second and third trimesters of pregnancy to screen for antenatal depression. Additional data were collected on ANC visits, the mother’s socio-demographic, obstetric, clinical, psychosocial, and behavioral factors. A logistic regression model was used to adjust confounders and determine associations between antenatal depression and inadequate ANC visits. The cumulative incidence of inadequate ANC visits was 62.58% (95% CI: 59.43, 65.63). The cumulative incidence of inadequate ANC visits among depressed pregnant women was 75% as compared to 56% in non-depressed. The incidence of inadequate ANC visits in the exposed group due to antenatal depression was 25.33%. After multivariable analysis, antenatal depression at the second and third trimesters of pregnancy remained a potential predictor of inadequate ANC visits (AOR = 1.96: (95% CI 1.22, 3.16)). In addition, antenatal depression, long travel time for ANC visits (AOR = 1.83 (95% CI 1.166, 2.870)), and late initiation of ANC visits (AOR = 2.20 (95% CI 1.393, 3.471)) were the predictors of inadequate ANC visits as compared to their counterpart. This study suggested that antenatal depression affects ANC visits in Ethiopian urban settings. Therefore, early detecting and treating depression symptoms during the antenatal period reduced significantly the impacts of depression on the health of the mother and fetus.
In vitro synergy screens of FDA-approved drugs reveal novel zidovudine- and azithromycin-based combinations with last-line antibiotics against Klebsiella pneumoniae
Authors: Gómara-Lomero Marta , López-Calleja Ana Isabel , Rezusta Antonio , Aínsa José Antonio , Ramón-García Santiago
Published: September 2023

Treatment of infections caused by multi-drug resistant (MDR) enterobacteria remains challenging due to the limited therapeutic options available. Drug repurposing could accelerate the development of new urgently needed successful interventions. This work aimed to identify and characterise novel drug combinations against Klebsiella pneumoniae based on the concepts of synergy and drug repurposing. We first performed a semi-qualitative high-throughput synergy screen (sHTSS) with tigecycline, colistin and fosfomycin (last-line antibiotics against MDR Enterobacteriaceae) against a FDA-library containing 1430 clinically approved drugs; a total of 109 compounds potentiated any of the last-line antibiotics. Selected hits were further validated by secondary checkerboard (CBA) and time-kill (TKA) assays, obtaining 15.09% and 65.85% confirmation rates, respectively. Accordingly, TKA were used for synergy classification based on determination of bactericidal activities at 8, 24 and 48 h, selecting 27 combinations against K. pneumoniae. Among them, zidovudine or azithromycin combinations with last-line antibiotics were further evaluated by TKA against a panel of 12 MDR/XDR K. pneumoniae strains, and their activities confronted with those clinical combinations currently used for MDR enterobacteria treatment; these combinations showed better bactericidal activities than usual treatments without added cytotoxicity. Our studies show that sHTSS paired to TKA are powerful tools for the identification and characterisation of novel synergistic drug combinations against K. pneumoniae. Further pre-clinical studies might support the translational potential of zidovudine- and azithromycin-based combinations for the treatment of these infections.