bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant oncolytic adenovirus armed with CCL5, IL-12, and IFN-γ promotes CAR-T infiltration and proliferation in vivo to eradicate local and distal tumors
Authors: Fang Lin , Yuan Sen , Wang Meng , Zhang Chen , Wang Xueyan , Li Hailong , Yang Jie , Li Wanjing , Sun Nan , Zhang Qi , Zhang Yuxin , Chai Dafei , Li Huizhong , Zheng Junnian , Wang Gang 
Published: September 2023

AbstractThe efficacy of chimeric antigen receptor T (CAR-T) cells for solid tumors remains unsatisfactory due to the limited tumor infiltration and immunosuppressive microenvironment. To overcome these limitations, the genetically engineered recombinant oncolytic adenoviruses (OAVs) that conditionally replicate in tumor cells were developed to modify the tumor microenvironment (TME) to facilitate CAR-T-mediated tumor eradication. Here in the present study, a novel recombinant OAV carrying CCL5, IL12, and IFN-γ controlled by Ki67 promoter was constructed (named AdKi67-C3). The antitumor activity of AdKi67-C3 was tested in vitro and in vivo by using mono administration or combing with CAR-T cells targeting B7H3. It proved that CCL5 expressed by AdKi67-C3 indeed induced more CAR-T migration in vitro and CAR-T infiltration in tumor mass in vivo. Meanwhile, cytokines of IFN-γ and IL12 secreted by AdKi67-C3-infected tumor cells significantly promoted proliferation and persistence of CAR-T cells in vitro and in vivo. In tumor-bearing xenograft mouse models of kidney, prostate or pancreatic cancer, local pretreatment with AdKi67-C3 dramatically enhanced CAR-T cell efficacy and eliminated local and distant tumors. More importantly, mice achieving complete tumor regression resisted to re-challenge with the same tumor cells, suggesting establishment of long-term antitumor immune response. Therefore, OAVs armored with cytokines could be developed as a bioenhancer to defeat the immunosuppressive microenvironment and improve therapeutic efficacy of CAR-T in solid tumors.
Flexible and broadband colloidal quantum dots photodiode array for pixel-level X-ray to near-infrared image fusion
Authors: Liu Jing , Liu Peilin , Shi Tailong , Ke Mo , Xiong Kao , Liu Yuxuan , Chen Long , Zhang Linxiang , Liang Xinyi , Li Hao , Lu Shuaicheng , Lan Xinzheng , Niu Guangda , Zhang Jianbing , Fei Peng , Gao Liang , Tang Jiang 
Published: September 2023

AbstractCombining information from multispectral images into a fused image is informative and beneficial for human or machine perception. Currently, multiple photodetectors with different response bands are used, which require complicated algorithms and systems to solve the pixel and position mismatch problem. An ideal solution would be pixel-level multispectral image fusion, which involves multispectral image using the same photodetector and circumventing the mismatch problem. Here we presented the potential of pixel-level multispectral image fusion utilizing colloidal quantum dots photodiode array, with a broadband response range from X-ray to near infrared and excellent tolerance for bending and X-ray irradiation. The colloidal quantum dots photodiode array showed a specific detectivity exceeding 1012 Jones in visible and near infrared range and a favorable volume sensitivity of approximately 2 × 105 μC Gy−1 cm−3 for X-ray irradiation. To showcase the advantages of pixel-level multispectral image fusion, we imaged a capsule enfolding an iron wire and soft plastic, successfully revealing internal information through an X-ray to near infrared fused image.
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

AbstractConstructing 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

AbstractStereotactic 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

AbstractTumor 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

AbstractThe 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

AbstractDNA 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

AbstractChimeric 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

AbstractApical 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

AbstractUnderstanding 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

AbstractEntanglement 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

AbstractMethane, 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

AbstractThe 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

AbstractThe 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

AbstractCells 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

AbstractDue 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.