bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer
Authors: Diao Xiayao , Guo Chao , Zheng Hanhao , Zhao Ke , Luo Yuming , An Mingjie , Lin Yan , Chen Jiancheng , Li Yuanlong , Li Yuting , Gao Xuehan , Zhang Jiaqi , Zhou Mengxin , Bai Wenliang , Liu Lei , Wang Guige , Zhang Lanjun , He Xiaotian , Zhang Rusi , Li Zhihua , Chen Changhao , Li Shanqing 
Published: November 2023

AbstractLymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.
SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma
Authors: Wang Xin , Wen Shaodi , Du Xiaoyue , Zhang Yihan , Yang Xiao , Zou Renrui , Feng Bing , Fu Xiao , Jiang Feng , Zhou Guoren , Liu Zi , Zhu Wei , Ma Rong , Feng Jifeng , Shen Bo 
Published: November 2023

AbstractCancer stem cells (CSCs) are believed to be crucial in the initiation, progression, and recurrence of cancer. CSCs are also known to be more resistant to cancer treatments. However, the interaction between CSCs and the immune microenvironment is complex and not fully understood. In current study we used single cell RNA sequence (scRNA-Seq, public dataset) technology to identify the characteristic of CSCs. We found that the lung adenocarcinoma cancer stem population is highly inflammatory and remodels the tumor microenvironment by secreting inflammatory factors, specifically the acute phase protein serum amyloid A (SAA). Next, we developed an ex-vivo autologous patient-derived organoids (PDOs) and peripheral blood mononuclear cells (PBMCs) co-culture model to evaluate the immune biological impact of SAA. We found that SAA not only promotes chemoresistance by inducing cancer stem transformation, but also restricts anti-tumor immunity and promotes tumor fibrosis by driving type 2 immunity, and α-SAA neutralization antibody could restrict treatment resistant and tumor fibrosis. Mechanically, we found that the malignant phenotype induced by SAA is dependent on P2X7 receptor. Our data indicate that cancer stem cells secreted SAA have significant biological impact to promote treatment resistant and tumor fibrosis by driving cancer stemness transformation and type 2 immunity polarization via P2X7 receptor. Notably, α-SAA neutralization antibody shows therapeutic potential by restricting these malignant phenotypes.
c-MYC-dependent transcriptional inhibition of autophagy is implicated in cisplatin sensitivity in HPV-positive head and neck cancer
Authors: Medda Alessandro , Compagnoni Micaela , Spini Giorgio , Citro Simona , Croci Ottavio , Campaner Stefano , Tagliabue Marta , Ansarin Mohssen , Chiocca Susanna 
Published: November 2023

AbstractAutophagy is important for the removal, degradation and recycling of damaged organelles, proteins, and lipids through the degradative action of lysosomes. In addition to its catabolic function, autophagy is important in cancer and viral-mediated tumorigenesis, including Human Papillomavirus (HPV) positive cancers. HPV infection is a major risk factor in a subset of head and neck cancer (HNC), for which no targeted therapies are currently available. Herein, we assessed autophagy function in HPV-positive HNC. We showed that HPV-positive HNC cells presented a transcriptional and functional impairment of the autophagic process compared to HPV-negative cells, which were reactivated by knocking down HPV E6/E7 oncoproteins, the drivers of cellular transformation. We found that the oncoprotein c-MYC was stabilized and triggered in HPV-positive cell lines. This resulted in the reduced binding of the MiT/TFE transcription factors to their autophagy targets due to c-MYC competition. Thus, the knock-down of c-MYC induced the upregulation of autophagic and lysosomal genes in HPV-positive HNC cells, as well as the increase of autophagic markers at the protein level. Moreover, HPV oncoprotein E7 upregulated the expression of the phosphatase inhibitor CIP2A, accounting for c-MYC upregulation and stability in HPV+ HNC cells. CIP2A mRNA expression negatively correlated with autophagy gene expression in tumor tissues from HNC patients, showing, for the first time, its implication in a transcriptional autophagic context. Both CIP2A and c-MYC knock-down, as well as pharmacological downregulation of c-MYC, resulted in increased resistance to cisplatin treatment. Our results not only show a novel way by which HPV oncoproteins manipulate the host machinery but also provide more insights into the role of autophagy in chemoresistance, with possible implications for targeted HPV-positive HNC therapy.
Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2)
Authors: Raja Aroosha , Kuiper Jonas J. W. 
Published: November 2023

AbstractEndoplasmic reticulum aminopeptidase 2 (ERAP2) is a proteolytic enzyme involved in adaptive immunity. The ERAP2 gene is highly polymorphic and encodes haplotypes that confer resistance against lethal infectious diseases, but also increase the risk for autoimmune disorders. Identifying how ERAP2 influences susceptibility to these traits requires an understanding of the selective pressures that shaped and maintained allelic variation throughout human evolution. Our review discusses the genetic regulation of haplotypes and diversity in naturally occurring ERAP2 allotypes in the global population. We outline how these ERAP2 haplotypes evolved during human history and highlight the presence of Neanderthal DNA sequences in ERAP2 of modern humans. Recent evidence suggests that human adaptation during the last ~10,000 years and historic pandemics left a significant mark on the ERAP2 gene that determines susceptibility to infectious and inflammatory diseases today.
Sampling-based Bayesian inference in recurrent circuits of stochastic spiking neurons
Authors: Zhang Wen-Hao , Wu Si , Josić Krešimir , Doiron Brent 
Published: November 2023

AbstractTwo facts about cortex are widely accepted: neuronal responses show large spiking variability with near Poisson statistics and cortical circuits feature abundant recurrent connections between neurons. How these spiking and circuit properties combine to support sensory representation and information processing is not well understood. We build a theoretical framework showing that these two ubiquitous features of cortex combine to produce optimal sampling-based Bayesian inference. Recurrent connections store an internal model of the external world, and Poissonian variability of spike responses drives flexible sampling from the posterior stimulus distributions obtained by combining feedforward and recurrent neuronal inputs. We illustrate how this framework for sampling-based inference can be used by cortex to represent latent multivariate stimuli organized either hierarchically or in parallel. A neural signature of such network sampling are internally generated differential correlations whose amplitude is determined by the prior stored in the circuit, which provides an experimentally testable prediction for our framework.
The radiation continuum and the evolution of frog diversity
Authors: Morinaga Gen , Wiens John J. , Moen Daniel S. 
Published: November 2023

AbstractMost of life’s vast diversity of species and phenotypes is often attributed to adaptive radiation. Yet its contribution to species and phenotypic diversity of a major group has not been examined. Two key questions remain unresolved. First, what proportion of clades show macroevolutionary dynamics similar to adaptive radiations? Second, what proportion of overall species richness and phenotypic diversity do these adaptive-radiation-like clades contain? We address these questions with phylogenetic and morphological data for 1226 frog species across 43 families (which represent >99% of all species). Less than half of frog families resembled adaptive radiations (with rapid diversification and morphological evolution). Yet, these adaptive-radiation-like clades encompassed ~75% of both morphological and species diversity, despite rapid rates in other clades (e.g., non-adaptive radiations). Overall, we support the importance of adaptive-radiation-like evolution for explaining diversity patterns and provide a framework for characterizing macroevolutionary dynamics and diversity patterns in other groups.
Realizing reversible phase transformation of shape memory ceramics constrained in aluminum
Authors: Zheng Wangshu , Shi Yan , Zhao Lei , Jia Shuangyue , Li Linghai , Gan Chee Lip , Zhang Di , Guo Qiang 
Published: November 2023

AbstractSmall-scale shape memory ceramics exhibit superior shape memory or superelasticity properties, while their integration into a matrix material and the subsequent attainment of their reversible tetragonal-monoclinic phase transformations remains a challenge. Here, cerium-doped zirconia (CZ) reinforced aluminum (Al) matrix composite is fabricated, and both macroscopic and microscopic mechanical tests reveal more than doubled compressive strength and energy absorbance of the composites as compared with pure Al. Full austenitization in the CZ single-crystal clusters is achieved when they are constrained by the Al matrix, and reversible martensitic transformation triggered by thermal or stress stimuli is observed in the composite micro-pillars without causing fracture in the composite. These results are interpreted by the strong geometric confinement offered by the Al matrix, the robust CZ/Al interface and the local three-dimensional particle network/force-chain configuration that effectively transfer mechanical loads, and the decent flowability of the matrix that accommodates the volume change during phase transformation.
Tunable Tamm plasmon cavity as a scalable biosensing platform for surface enhanced resonance Raman spectroscopy
Authors: Sreekanth Kandammathe Valiyaveedu , Perumal Jayakumar , Dinish U. S. , Prabhathan Patinharekandy , Liu Yuanda , Singh Ranjan , Olivo Malini , Teng Jinghua 
Published: November 2023

AbstractSurface enhanced Resonance Raman spectroscopy (SERRS) is a powerful technique for enhancing Raman spectra by matching the laser excitation wavelength with the plasmonic resonance and the absorption peak of biomolecules. Here, we propose a tunable Tamm plasmon polariton (TPP) cavity based on a metal on distributed Bragg reflector (DBR) as a scalable sensing platform for SERRS. We develop a gold film-coated ultralow-loss phase change material (Sb2S3) based DBR, which exhibits continuously tunable TPP resonances in the optical wavelengths. We demonstrate SERRS by matching the TPP resonance with the absorption peak of the chromophore molecule at 785 nm wavelength. We use this platform to detect cardiac Troponin I protein (cTnI), a biomarker for early diagnosis of cardiovascular disease, achieving a detection limit of 380 fM. This scalable substrate shows great promise as a next-generation tunable biosensing platform for detecting disease biomarkers in body fluids for routine real-time clinical diagnosis.
Identifying topological corner states in two-dimensional metal-organic frameworks
Authors: Hu Tianyi , Zhong Weiliang , Zhang Tingfeng , Wang Weihua , Wang Z. F. 
Published: November 2023

AbstractDue to the diversity of molecular building blocks, the two-dimensional (2D) metal-organic frameworks (MOFs) are ideal platforms to realize exotic lattice models in condensed matter theory. In this work, we demonstrate the universal existence of topological corner states in 2D MOFs with a star lattice configuration, and confirm the intriguing higher-order nontrivial topology in the energy window between two Kagome-bands, or between Dirac-band and four-band. Furthermore, combining first-principles calculations and scanning tunneling microscopy measurements, the unique topological corner state is directly identified in monolayer Ni3(HITP)2 (HITP = 2,3,6,7,10,11-hexaiminotriphenylene) grown on the Au(111) substrate. Our results not only illustrate the first organic topological state in the experiments, but also offer an exciting opportunity to study higher-order topology in 2D MOFs with the large insulating band gap.
Decarbonization potential of electrifying 50% of U.S. light-duty vehicle sales by 2030
Authors: Woody Maxwell , Keoleian Gregory A. , Vaishnav Parth 
Published: November 2023

AbstractThe U.S. federal government has established goals of electrifying 50% of new light-duty vehicle sales by 2030 and reducing economy-wide greenhouse gas emissions 50-52% by 2030, from 2005 levels. Here we evaluate the vehicle electrification goal in the context of the economy-wide emissions goal. We use a vehicle fleet model and a life cycle emissions model to project vehicle sales, stock, and emissions. To account for state-level variability in electric vehicle adoption and electric grid emissions factors, we apply the models to each state. By 2030, greenhouse gas emissions are reduced by approximately 25% (from 2005) for the light-duty vehicle fleet, primarily due to fleet turnover of conventional vehicles. By 2035, emissions reductions approach 45% if both vehicle electrification and grid decarbonization goals (100% by 2035) are met. To meet climate goals, the transition to electric vehicles must be accompanied by an accelerated decarbonization of the electric grid and other actions.
Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments
Authors: Busby George B. , Kulm Scott , Bolli Alessandro , Kintzle Jen , Domenico Paolo Di , Bottà Giordano 
Published: November 2023

AbstractClinical implementation of new prediction models requires evaluation of their utility in a broad range of intended use populations. Here we develop and validate ancestry-specific Polygenic Risk Scores (PRSs) for Coronary Artery Disease (CAD) using 29,389 individuals from diverse cohorts and genetic ancestry groups. The CAD PRSs outperform published scores with an average Odds Ratio per Standard Deviation of 1.57 (SD = 0.14) and identify between 12% and 24% of individuals with high genetic risk. Using this risk factor to reclassify borderline or intermediate 10 year Atherosclerotic Cardiovascular Disease (ASCVD) risk improves assessments for both CAD (Net Reclassification Improvement (NRI) = 13.14% (95% CI 9.23–17.06%)) and ASCVD (NRI = 10.70 (95% CI 7.35-14.05)) in an independent cohort of 9,691 individuals. Our analyses demonstrate that using PRSs as Risk Enhancers improves ASCVD risk assessments outlining an approach for guiding ASCVD prevention with genetic information.
Dispersion engineered metasurfaces for broadband, high-NA, high-efficiency, dual-polarization analog image processing
Authors: Cotrufo Michele , Arora Akshaj , Singh Sahitya , Alù Andrea 
Published: November 2023

AbstractOptical metasurfaces performing analog image processing – such as spatial differentiation and edge detection – hold the potential to reduce processing times and power consumption, while avoiding bulky 4 F lens systems. However, current designs have been suffering from trade-offs between spatial resolution, throughput, polarization asymmetry, operational bandwidth, and isotropy. Here, we show that dispersion engineering provides an elegant way to design metasurfaces where all these critical metrics are simultaneously optimized. We experimentally demonstrate silicon metasurfaces performing isotropic and dual-polarization edge detection, with numerical apertures above 0.35 and spectral bandwidths of 35 nm around 1500 nm. Moreover, we introduce quantitative metrics to assess the efficiency of these devices. Thanks to the low loss nature and dual-polarization response, our metasurfaces feature large throughput efficiencies, approaching the theoretical maximum for a given NA. Our results pave the way for low-loss, high-efficiency and broadband optical computing and image processing with free-space metasurfaces.
A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates
Authors: Phung Ivy , Rodrigues Kristen A. , Marina-Zárate Ester , Maiorino Laura , Pahar Bapi , Lee Wen-Hsin , Melo Mariane , Kaur Amitinder , Allers Carolina , Fahlberg Marissa , Grasperge Brooke F. , Dufour Jason P. , Schiro Faith , Aye Pyone P. , Lopez Paul G. , Torres Jonathan L. , Ozorowski Gabriel , Eskandarzadeh Saman , Kubitz Michael , Georgeson Erik , Groschel Bettina , Nedellec Rebecca , Bick Michael , Kaczmarek Michaels Katarzyna , Gao Hongmei , Shen Xiaoying , Carnathan Diane G. , Silvestri Guido , Montefiori David C. , Ward Andrew B. , Hangartner Lars , Veazey Ronald S. , Burton Dennis R. , Schief William R. , Irvine Darrell J. , Crotty Shane 
Published: November 2023

AbstractAdjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-TFH cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM BPC) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation.
Both chimpanzee adenovirus-vectored and DNA vaccines induced long-term immunity against Nipah virus infection
Authors: Lu Mingqing , Yao Yanfeng , Zhang Xuekai , Liu Hang , Gao Ge , Peng Yun , Chen Miaoyu , Zhao Jiaxuan , Zhang XiaoYu , Yin Chunhong , Guo Weiwei , Yang Peipei , Hu Xue , Rao Juhong , Li Entao , Chen Tong , Chiu Sandra , Wong Gary , Yuan Zhiming , Lan Jiaming , Shan Chao 
Published: November 2023

AbstractNipah virus (NiV) is a highly lethal zoonotic paramyxovirus that poses a severe threat to humans due to its high morbidity and the lack of viable countermeasures. Vaccines are the most crucial defense against NiV infections. Here, a recombinant chimpanzee adenovirus-based vaccine (AdC68-G) and a DNA vaccine (DNA-G) were developed by expressing the codon-optimized full-length glycoprotein (G) of NiV. Strong and sustained neutralizing antibody production, accompanied by an effective T-cell response, was induced in BALB/c mice by intranasal or intramuscular administration of one or two doses of AdC68-G, as well as by priming with DNA-G and boosting with intramuscularly administered AdC68-G. Importantly, the neutralizing antibody titers were maintained for up to 68 weeks in the mice that received intramuscularly administered AdC68-G and the prime DNA-G/boost AdC68-G regimen, without a significant decline. Additionally, Syrian golden hamsters immunized with AdC68-G and DNA-G via homologous or heterologous prime/boost immunization were completely protected against a lethal NiV virus challenge, without any apparent weight loss, clinical signs, or pathological tissue damage. There was a significant reduction in but not a complete absence of the viral load and number of infectious particles in the lungs and spleen tissue following NiV challenge. These findings suggest that the AdC68-G and DNA-G vaccines against NiV infection are promising candidates for further development.
Gap-free genome assembly of Salangid icefish Neosalanx taihuensis
Authors: Zhou Yanfeng , Zhang Xizhao , Jian Jianbo , Wang Chenhe , Fang Di’an , Jiang Shulun , Ren Long , Ge You , Wang Hongqi , You Yang , Chen Chunhai 
Published: November 2023

AbstractNeosalanx taihuensisis widely distributed in freshwater and brackish water areas in China. Due to its high commercial value, it has been artificially introduced into many lakes and reservoirs, showing strong ecological adaptability. Here, a gap-free chromosome-level reference genome was constructed by combining short reads, PacBio HiFi long reads, Nanopore ultralong reads and Hi-C data. The reference genome ofN. taihuensiswas 397.29 Mb with a contig N50 of 15.61 Mb. The assembled sequences were anchored to 28 chromosomes. Furthermore, 20,024 protein-coding genes and 98.16% of the predicted genes were annotated in publicly available biological databases. This high-quality gap-free assembled genome will provide an essential reference for studying the evolution and ecological adaptability ofN. taihuensis.