bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukemia inhibitory factor drives glucose metabolic reprogramming to promote breast tumorigenesis
Authors: Yue Xuetian , Wang Jianming , Chang Chun-yuan , Liu Juan , Yang Xue , Zhou Fan , Qiu Xia , Bhatt Vrushank , Guo Jessie Yanxiang , Su Xiaoyang , Zhang Lanjing , Feng Zhaohui , Hu Wenwei
Published: April 2022

LIF, a multifunctional cytokine, is frequently overexpressed in many types of solid tumors, including breast cancer, and plays an important role in promoting tumorigenesis. Currently, how LIF promotes tumorigenesis is not well-understood. Metabolic reprogramming is a hallmark of cancer cells and a key contributor to cancer progression. However, the role of LIF in cancer metabolic reprogramming is unclear. In this study, we found that LIF increases glucose uptake and drives glycolysis, contributing to breast tumorigenesis. Blocking glucose uptake largely abolishes the promoting effect of LIF on breast tumorigenesis. Mechanistically, LIF overexpression enhances glucose uptake via activating the AKT/GLUT1 axis to promote glycolysis. Blocking the AKT signaling by shRNA or its inhibitors greatly inhibits glycolysis driven by LIF and largely abolishes the promoting effect of LIF on breast tumorigenesis. These results demonstrate an important role of LIF overexpression in glucose metabolism reprogramming in breast cancers, which contributes to breast tumorigenesis. This study also reveals an important mechanism underlying metabolic reprogramming of breast cancers, and identifies LIF and its downstream signaling as potential therapeutic targets for breast cancers, especially those with LIF overexpression.
xCT contributes to colorectal cancer tumorigenesis through upregulation of the MELK oncogene and activation of the AKT/mTOR cascade
Authors: Tang Bufu , Zhu Jinyu , Liu Fangming , Ding Jiayi , Wang Yajie , Fang Shiji , zheng Liyun , Qiu Rongfang , Chen Minjiang , Shu Gaofeng , Xu Min , Lu Chenying , Zhao Zhongwei , Yang Yang , Ji Jiansong
Published: April 2022

Colorectal cancer (CRC) is one of the most commonly diagnosed and deadly malignant tumors globally, and its occurrence and progression are closely related to the poor histological features and complex molecular characteristics among patients. It is urgent to identify specific biomarkers for effective treatment of CRC. In this study, we performed comprehensive experiments to validate the role of xCT expression in CRC tumorigenesis and stemness and confirmed xCT knockdown significantly suppressed the proliferation, migration, and stemness of CRC cells in vitro and effectively inhibited CRC tumorigenesis and metastasis in vivo. In addition, bioinformatic analysis and luciferase assays were used to identify E2F1 as a critical upstream transcription factor of SLC7A11 (the gene encoding for xCT) that facilitated CRC progression and cell stemness. Subsequent RNA sequencing, western blotting, rescue assay, and immunofluorescence assays revealed MELK directly co-expressed with xCT in CRC cells, and its upregulation significantly attenuated E2F1/xCT-mediated tumorigenesis and stemness in CRC. Further molecular mechanism exploration confirmed that xCT knockdown may exert an antitumor effect by controlling the activation of MELK-mediated Akt/mTOR signaling. Erastin, a specific inhibitor of xCT, was also proven to effectively inhibit CRC tumorigenesis and cell stemness. Altogether, our study showed that E2F1/xCT is a promising therapeutic target of CRC that promotes tumorigenesis and cell stemness. Erastin is also an effective antitumoral agent for CRC.
The miR-532-E2F1 feedback loop contributes to gastric cancer progression
Authors: Gao Shanting , Bu Xiaomin , Gao Yongyue , Bao Zengtao , Shi Wenchao , Luan Lipeng , Chen Huiyu , Zhang Baoming , Tian Qingshui , Guan Wenxian , Yang Liuqing
Published: April 2022

Gastric cancer (GC) ranks fourth in incidence and mortality worldwide, ascertaining the pathogenesis of GC is crucial for its treatment. E2F1, which regulates the transcription of genes encoding proteins involved in DNA repair, DNA replication, mitosis and survival of cancer patients, functions as a key regulator in GC progression. However, the underneath mechanism of these processes is not fully elucidated. Here, TCGA database analysis, microarray immunohistochemical technique and western blot showed that E2F1 was highly upregulated in clinical GC tissues and correlated with tumor malignancy. In vitro and in vivo assays confirmed the oncogenic function of E2F1. MiR-532 was decreased and negatively correlated with E2F1 in GC tissues. MiR-532 directly targeted and inhibited E2F1 expression, leading to the decrease of ASK1 and elevation of TXNIP, and affected proliferation, cell cycle, apoptosis and DNA damage in vitro and tumor growth in vivo. Moreover, E2F1 serves as a transcriptional repressor to suppress miR-532 expression and a double-negative feedback loop was formed between them. This study demonstrates the significant roles of the E2F1-miR-532 double-negative feedback loop in GC progression and may represent a potential target for GC therapy.
Dehydroepiandrosterone exacerbates nigericin-induced abnormal autophagy and pyroptosis via GPER activation in LPS-primed macrophages
Authors: Cao Ji , Li Longlong , Yao Yao , Xing Yuxiao , Ma Haitian
Published: April 2022

As a widely acknowledged FDA-approved dietary supplement or over-the-counter medicines, dehydroepiandrosterone (DHEA) exerts anti-inflammatory and immunomodulatory function. Pyroptosis is an important form of programmed cell death (PCD), and which acts a key role in the body’s anti-infection and inflammatory responses. But the effects and mechanisms of DHEA on pyroptosis remain unclear. Here, we found that DHEA inhibited the NLRP3 inflammasome components expression by blocking inflammatory signals in lipopolysaccharide (LPS)-primed macrophages, and prevented the bacterial toxin nigericin (Nig)-induced NLRP3 inflammasome assembly. However, DHEA exacerbated NLRP3-independent cell death in Nig-treated inflammatory macrophages. During this process, DHEA induced the abnormal autophagy, which reflected as the blocking of autophagic flux and the accumulation of autophagy receptor p62 (SQSTM1) protein. In addition, DHEA caused a burst of reactive oxygen species (ROS) and activated extracellular signal-regulated kinase (ERK) phosphorylation in LPS plus Nig-stimulated macrophages but not in LPS-treated macrophages. Mechanistically, the present study certified that the activation of G protein-coupled estrogen receptor (GPER) signal mediated the cell death induced by DHEA in Nig-stimulated inflammatory macrophages, as GPER specific inhibitor G15 alleviated the abnormal autophagy and ultimately prevented the gasdermin D (GSDMD)-mediated pyroptosis induced by DHEA. Collectively, DHEA can exacerbate Nig-induced abnormal autophagy and pyroptosis via activation of GPER in LPS-primed macrophages, which prompts us the potential application value of DHEA in anti-infection or anti-tumor immunity.
Collective interactions among organometallics are exotic bonds hidden on lab shelves
Authors: Sowlati-Hashjin Shahin , Šadek Vojtěch , Sadjadi SeyedAbdolreza , Karttunen Mikko , Martín-Pendás Angel , Foroutan-Nejad Cina
Published: April 2022

Recent discovery of an unusual bond between Na and B in NaBH3− motivated us to look for potentially similar bonds, which remained unnoticed among systems isoelectronic with NaBH3−. Here, we report a novel family of collective interactions and a measure called exchange-correlation interaction collectivity index (ICIXC; $${ICI}\in \left[{{{{\mathrm{0,1}}}}}\right]$$
I
C
I
∈

0, 1

) to characterize the extent of collective versus pairwise bonding. Unlike conventional bonds in which ICIXC remains close to one, in collective interactions ICIXC may approach zero. We show that collective interactions are commonplace among widely used organometallics, as well as among boron and aluminum complexes with the general formula [Ma+AR3]b− (A: C, B or Al). In these species, the metal atom interacts more efficiently with the substituents (R) on the central atoms than the central atoms (A) upon forming efficient collective interactions. Furthermore, collective interactions were also found among fluorine atoms of XFn systems (X: B or C). Some of organolithium and organomagnesium species have the lowest ICIXC among the more than 100 studied systems revealing the fact that collective interactions are rather a rule than an exception among organometallic species.
Reversible Power-to-Gas systems for energy conversion and storage
Authors: Glenk Gunther , Reichelstein Stefan
Published: April 2022

In the transition to decarbonized energy systems, Power-to-Gas (PtG) processes have the potential to connect the existing markets for electricity and hydrogen. Specifically, reversible PtG systems can convert electricity to hydrogen at times of ample power supply, yet they can also operate in the reverse direction to deliver electricity during times when power is relatively scarce. Here we develop a model for determining when reversible PtG systems are economically viable. We apply the model to the current market environment in both Germany and Texas and find that the reversibility feature of unitized regenerative fuel cells (solid oxide) makes them already cost-competitive at current hydrogen prices, provided the fluctuations in electricity prices are as pronounced as currently observed in Texas. We further project that, due to their inherent flexibility, reversible PtG systems would remain economically viable at substantially lower hydrogen prices in the future, provided recent technological trends continue over the coming decade.
A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population
Authors: Qu Yuanyuan , Feng Jinwen , Wu Xiaohui , Bai Lin , Xu Wenhao , Zhu Lingli , Liu Yang , Xu Fujiang , Zhang Xuan , Yang Guojian , Lv Jiacheng , Chen Xiuping , Shi Guo-Hai , Wang Hong-Kai , Cao Da-Long , Xiang Hang , Li Lingling , Tan Subei , Gan Hua-Lei , Sun Meng-Hong , Qiu Jiange , Zhang Hailiang , Zhao Jian-Yuan , Ye Dingwei , Ding Chen
Published: April 2022

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC tumors into three subtypes (GP1–3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.
High-quality genome and methylomes illustrate features underlying evolutionary success of oaks
Authors: Sork Victoria L. , Cokus Shawn J. , Fitz-Gibbon Sorel T. , Zimin Aleksey V. , Puiu Daniela , Garcia Jesse A. , Gugger Paul F. , Henriquez Claudia L. , Zhen Ying , Lohmueller Kirk E. , Pellegrini Matteo , Salzberg Steven L.
Published: April 2022

The genusQuercus, which emerged ∼55 million years ago during globally warm temperatures, diversified into ∼450 extant species. We present a high-quality de novo genome assembly of a California endemic oak,Quercus lobata, revealing features consistent with oak evolutionary success. Effective population size remained large throughout history despite declining since early Miocene. Analysis of 39,373 mapped protein-coding genes outlined copious duplications consistent with genetic and phenotypic diversity, both by retention of genes created during the ancient γ whole genome hexaploid duplication event and by tandem duplication within families, including numerous resistance genes and a very large block of duplicated DUF247 genes, which have been found to be associated with self-incompatibility in grasses. An additional surprising finding is that subcontext-specific patterns of DNA methylation associated with transposable elements reveal broadly-distributed heterochromatin in intergenic regions, similar to grasses. Collectively, these features promote genetic and phenotypic variation that would facilitate adaptability to changing environments.
Generation of human islet cell type-specific identity genesets
Authors: van Gurp Léon , Fodoulian Leon , Oropeza Daniel , Furuyama Kenichiro , Bru-Tari Eva , Vu Anh Nguyet , Kaddis John S. , Rodríguez Iván , Thorel Fabrizio , Herrera Pedro L.
Published: April 2022

Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics meta-analysis to identify robustly expressed markers used to build genesets describing the identity of human α-, β-, γ- and δ-cells. These genesets define islet cellular identities better than previously published genesets. We show their efficacy to outline cell identity changes and unravel some of their underlying genetic mechanisms, whether during embryonic pancreas development or in experimental setups aiming at developing glucose-responsive insulin-secreting cells, such as pluripotent stem-cell differentiation or in adult islet cell reprogramming protocols. These islet cell type-specific genesets represent valuable tools that accurately benchmark gain and loss in islet cell identity traits.
Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes
Authors: Lee Hyo-Jung , Song Kwon-Ho , Oh Se Jin , Kim Suyeon , Cho Eunho , Kim Jungwon , Park Yun gyu , Lee Kyung-Mi , Yee Cassian , Song Seung-Hwa , Chang Suhwan , Choi Jungmin , Jung Sang Taek , Kim Tae Woo
Published: April 2022

Immunotherapy has emerged as a powerful approach to cancer treatment. However, immunotherapeutic resistance limits its clinical application. Therefore, identifying immune-resistant factors, which can be targeted by clinically available drugs and it also can be a companion diagnostic marker, is needed to develop combination strategies. Here, using the transcriptome data of patients, and immune-refractory tumor models, we identify TCTP as an immune-resistance factor that correlates with clinical outcome of anti-PD-L1 therapy and confers immune-refractory phenotypes, decreased T cell trafficking to the tumor and resistance to cytotoxic T lymphocyte-mediated tumor cell killing. Mechanistically, TCTP activates the EGFR-AKT-MCL-1/CXCL10 pathway by phosphorylation-dependent interaction with Na, K ATPase. Furthermore, treatment with dihydroartenimsinin, the most effective agent impending the TCTP-mediated-refractoriness, synergizes with T cell-mediated therapy to control immune-refractory tumors. Thus, our findings suggest a role of TCTP in promoting immune-refractoriness, thereby encouraging a rationale for combination therapies to enhance the efficacy of T cell-mediated therapy.
New seasonal pattern of pollution emerges from changing North American wildfires
Authors: Buchholz Rebecca R. , Park Mijeong , Worden Helen M. , Tang Wenfu , Edwards David P. , Gaubert Benjamin , Deeter Merritt N. , Sullivan Thomas , Ru Muye , Chin Mian , Levy Robert C. , Zheng Bo , Magzamen Sheryl
Published: April 2022

Rising emissions from wildfires over recent decades in the Pacific Northwest are known to counteract the reductions in human-produced aerosol pollution over North America. Since amplified Pacific Northwest wildfires are predicted under accelerating climate change, it is essential to understand both local and transported contributions to air pollution in North America. Here, we find corresponding increases for carbon monoxide emitted from the Pacific Northwest wildfires and observe significant impacts on both local and down-wind air pollution. Between 2002 and 2018, the Pacific Northwest atmospheric carbon monoxide abundance increased in August, while other months showed decreasing carbon monoxide, so modifying the seasonal pattern. These seasonal pattern changes extend over large regions of North America, to the Central USA and Northeast North America regions, indicating that transported wildfire pollution could potentially impact the health of millions of people.
A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation
Authors: Llimos Gerard , Gardeux Vincent , Koch Ute , Kribelbauer Judith F. , Hafner Antonina , Alpern Daniel , Pezoldt Joern , Litovchenko Maria , Russeil Julie , Dainese Riccardo , Moia Riccardo , Mahmoud Abdurraouf Mokhtar , Rossi Davide , Gaidano Gianluca , Plass Christoph , Lutsik Pavlo , Gerhauser Clarissa , Waszak Sebastian M. , Boettiger Alistair , Radtke Freddy , Deplancke Bart
Published: April 2022

Non-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. These molecularly coordinated regions are named “variable chromatin modules” (VCMs), providing a conceptual framework of how regulatory variation might shape complex traits. To better understand the molecular mechanisms underlying VCM formation, here, we mechanistically dissect a VCM-modulating noncoding variant that is associated with reduced chronic lymphocytic leukemia (CLL) predisposition and disease progression. This common, germline variant constitutes a 5-bp indel that controls the activity of an AXIN2 gene-linked VCM by creating a MEF2 binding site, which, upon binding, activates a super-enhancer-like regulatory element. This triggers a large change in TF binding activity and chromatin state at an enhancer cluster spanning >150 kb, coinciding with subtle, long-range chromatin compaction and robust AXIN2 up-regulation. Our results support a model in which the indel acts as an AXIN2 VCM-activating TF nucleation event, which modulates CLL pathology.
The neural coding framework for learning generative models
Authors: Ororbia Alexander , Kifer Daniel
Published: April 2022

Neural generative models can be used to learn complex probability distributions from data, to sample from them, and to produce probability density estimates. We propose a computational framework for developing neural generative models inspired by the theory of predictive processing in the brain. According to predictive processing theory, the neurons in the brain form a hierarchy in which neurons in one level form expectations about sensory inputs from another level. These neurons update their local models based on differences between their expectations and the observed signals. In a similar way, artificial neurons in our generative models predict what neighboring neurons will do, and adjust their parameters based on how well the predictions matched reality. In this work, we show that the neural generative models learned within our framework perform well in practice across several benchmark datasets and metrics and either remain competitive with or significantly outperform other generative models with similar functionality (such as the variational auto-encoder).
Inhibition of the succinyl dehydrogenase complex in acute myeloid leukemia leads to a lactate-fuelled respiratory metabolic vulnerability
Authors: Erdem Ayşegül , Marin Silvia , Pereira-Martins Diego A. , Geugien Marjan , Cunningham Alan , Pruis Maurien G. , Weinhäuser Isabel , Gerding Albert , Bakker Barbara M. , Wierenga Albertus T. J. , Rego Eduardo M. , Huls Gerwin , Cascante Marta , Schuringa Jan Jacob
Published: April 2022

Metabolic programs can differ substantially across genetically distinct subtypes of acute myeloid leukemia (AML). These programs are not static entities but can change swiftly as a consequence of extracellular changes or in response to pathway-inhibiting drugs. Here, we uncover that AML patients with FLT3 internal tandem duplications (FLT3-ITD+) are characterized by a high expression of succinate-CoA ligases and high activity of mitochondrial electron transport chain (ETC) complex II, thereby driving high mitochondrial respiration activity linked to the Krebs cycle. While inhibition of ETC complex II enhances apoptosis in FLT3-ITD+ AML, cells also quickly adapt by importing lactate from the extracellular microenvironment. 13C3-labelled lactate metabolic flux analyses reveal that AML cells use lactate as a fuel for mitochondrial respiration. Inhibition of lactate transport by blocking Monocarboxylic Acid Transporter 1 (MCT1) strongly enhances sensitivity to ETC complex II inhibition in vitro as well as in vivo. Our study highlights a metabolic adaptability of cancer cells that can be exploited therapeutically.
A natural allele of OsMS1 responds to temperature changes and confers thermosensitive genic male sterility
Authors: Wu Lunying , Jing Xiaohui , Zhang Baolan , Chen Shoujun , Xu Ran , Duan Penggen , Zou Danni , Huang Shengjian , Zhou Tingbo , An Chengcai , Luo Yuehua , Li Yunhai
Published: April 2022

Changes in ambient temperature influence crop fertility and production. Understanding of how crops sense and respond to temperature is thus crucial for sustainable agriculture. The thermosensitive genic male-sterile (TGMS) lines are widely used for hybrid rice breeding and also provide a good system to investigate the mechanisms underlying temperature sensing and responses in crops. Here, we show that OsMS1 is a histone binding protein, and its natural allele OsMS1wenmin1 confers thermosensitive male sterility in rice. OsMS1 is primarily localized in nuclei, while OsMS1wenmin1 is localized in nuclei and cytoplasm. Temperature regulates the abundances of OsMS1 and OsMS1wenmin1 proteins. The high temperature causes more reduction of OsMS1wenmin1 than OsMS1 in nuclei. OsMS1 associates with the transcription factor TDR to regulate expression of downstream genes in a temperature-dependent manner. Thus, our findings uncover a thermosensitive mechanism that could be useful for hybrid crop breeding.
A decade of cold Eurasian winters reconstructed for the early 19th century
Authors: Reichen Lukas , Burgdorf Angela-Maria , Brönnimann Stefan , Franke Jörg , Hand Ralf , Valler Veronika , Samakinwa Eric , Brugnara Yuri , Rutishauser This
Published: April 2022

Annual-to-decadal variability in northern midlatitude temperature is dominated by the cold season. However, climate field reconstructions are often based on tree rings that represent the growing season. Here we present cold-season (October-to-May average) temperature field reconstructions for the northern midlatitudes, 1701-1905, based on extensive phenological data (freezing and thawing dates of rivers, plant observations). Northern midlatitude land temperatures exceeded the variability range of the 18th and 19th centuries by the 1940s, to which recent warming has added another 1.5 °C. A sequences of cold winters 1808/9-1815/6 can be explained by two volcanic eruptions and unusual atmospheric flow. Weak southwesterlies over Western Europe in early winter caused low Eurasian temperatures, which persisted into spring even though the flow pattern did not. Twentieth century data and model simulations confirm this persistence and point to increased snow cover as a cause, consistent with sparse information on Eurasian snow in the early 19th century.
Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF
Authors: Aljahani Abrar , Hua Peng , Karpinska Magdalena A. , Quililan Kimberly , Davies James O. J. , Oudelaar A. Marieke
Published: April 2022

Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date (20 bp resolution) and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.
Reconfigurable halide perovskite nanocrystal memristors for neuromorphic computing
Authors: John Rohit Abraham , Demirağ Yiğit , Shynkarenko Yevhen , Berezovska Yuliia , Ohannessian Natacha , Payvand Melika , Zeng Peng , Bodnarchuk Maryna I. , Krumeich Frank , Kara Gökhan , Shorubalko Ivan , Nair Manu V. , Cooke Graham A. , Lippert Thomas , Indiveri Giacomo , Kovalenko Maksym V.
Published: April 2022

Many in-memory computing frameworks demand electronic devices with specific switching characteristics to achieve the desired level of computational complexity. Existing memristive devices cannot be reconfigured to meet the diverse volatile and non-volatile switching requirements, and hence rely on tailored material designs specific to the targeted application, limiting their universality. “Reconfigurable memristors” that combine both ionic diffusive and drift mechanisms could address these limitations, but they remain elusive. Here we present a reconfigurable halide perovskite nanocrystal memristor that achieves on-demand switching between diffusive/volatile and drift/non-volatile modes by controllable electrochemical reactions. Judicious selection of the perovskite nanocrystals and organic capping ligands enable state-of-the-art endurance performances in both modes – volatile (2 × 106 cycles) and non-volatile (5.6 × 103 cycles). We demonstrate the relevance of such proof-of-concept perovskite devices on a benchmark reservoir network with volatile recurrent and non-volatile readout layers based on 19,900 measurements across 25 dynamically-configured devices.
Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model
Authors: Lian Qizhou , Zhang Kui , Zhang Zhao , Duan Fuyu , Guo Liyan , Luo Weiren , Mok Bobo Wing-Yee , Thakur Abhimanyu , Ke Xiaoshan , Motallebnejad Pedram , Nicolaescu Vlad , Chen Jonathan , Ma Chui Yan , Zhou Xiaoya , Han Shuo , Han Teng , Zhang Wei , Tan Adrian Y. , Zhang Tuo , Wang Xing , Xu Dong , Xiang Jenny , Xu Aimin , Liao Can , Huang Fang-Ping , Chen Ya-Wen , Na Jie , Randall Glenn , Tse Hung-fat , Chen Zhiwei , Chen Yin , Chen Huanhuan Joyce
Published: April 2022

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity.
Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function
Authors: Cheng Hung-Wei , Mörbe Urs , Lütge Mechthild , Engetschwiler Céline , Onder Lucas , Novkovic Mario , Gil-Cruz Cristina , Perez-Shibayama Christian , Hehlgans Thomas , Scandella Elke , Ludewig Burkhard
Published: April 2022

Innate lymphoid cells (ILCs) govern immune cell homeostasis in the intestine and protect the host against microbial pathogens. Various cell-intrinsic pathways have been identified that determine ILC development and differentiation. However, the cellular components that regulate ILC sustenance and function in the intestinal lamina propria are less known. Using single-cell transcriptomic analysis of lamina propria fibroblasts, we identify fibroblastic reticular cells (FRCs) that underpin cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Genetic ablation of lymphotoxin-β receptor expression inCcl19-expressing FRCs blocks the maturation of CPs into mature ILFs. Interactome analysis shows the major niche factors and processes underlying FRC-ILC crosstalk. In vivo validation confirms that a sustained lymphotoxin-driven feedforward loop of FRC activation including IL-7 generation is critical for the maintenance of functional ILC populations. In sum, our study indicates critical fibroblastic niches within the intestinal lamina propria that control ILC homeostasis and functionality and thereby secure protective gut immunity.
Defects engineering simultaneously enhances activity and recyclability of MOFs in selective hydrogenation of biomass
Authors: Xu Wenlong , Zhang Yuwei , Wang Junjun , Xu Yixiu , Bian Li , Ju Qiang , Wang Yuemin , Fang Zhenlan
Published: April 2022

The development of synthetic methodologies towards enhanced performance in biomass conversion is desirable due to the growing energy demand. Here we design two types of Ru impregnated MIL-100-Cr defect engineered metal-organic frameworks (Ru@DEMOFs) by incorporating defective ligands (DLs), aiming at highly efficient catalysts for biomass hydrogenation. Our results show that Ru@DEMOFs simultaneously exhibit boosted recyclability, selectivity and activity with the turnover frequency being about 10 times higher than the reported values of polymer supported Ru towards D-glucose hydrogenation. This work provides in-depth insights into (i) the evolution of various defects in the cationic framework upon DLs incorporation and Ru impregnation, (ii) the special effect of each type of defects on the electron density of Ru nanoparticles and activation of reactants, and (iii) the respective role of defects, confined Ru particles and metal single active sites in the catalytic performance of Ru@DEMOFs for D-glucose selective hydrogenation as well as their synergistic catalytic mechanism.
DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion
Authors: Chen Baiwen , Hu Jiajia , Hu Xianting , Chen Huifang , Bao Rujuan , Zhou Yatao , Ye Youqiong , Zhan Meixiao , Cai Wei , Li Huabin , Li Hua-Bing
Published: April 2022

RNA-binding proteins (RBPs) can recognize thousands of RNAs that help to maintain cell homeostasis, and RBP dysfunction is frequently observed in various cancers. However, whether specific RBPs are involved in tumor immune evasion by regulating programmed death ligand-1 (PD-L1) is unclear. Here, we perform targeted RBP CRISPR/Cas9 screening and identify density regulated re-initiation and release factor (DENR) as a PD-L1 regulator. DENR-depleted cancer cells exhibit reduced PD-L1 expression in vitro and in vivo. DENR depletion significantly suppresses tumor growth and enhances the tumor-killing activity of CD8+ T cells. Mechanistically, DENR antagonizes the translational repression of three consecutive upstream open reading frames (uORFs) upstream of Janus kinase 2 (Jak2); thus, DENR deficiency impairs JAK2 translation and the IFNγ-JAK-STAT signaling pathway, resulting in reduced PD-L1 expression in tumors. Overall, we discover an RBP DENR that could regulate PD-L1 expression for tumor immune evasion, and highlight the potential of DENR as a therapeutic target for immunotherapy.
Honeybee gut Lactobacillus modulates host learning and memory behaviors via regulating tryptophan metabolism
Authors: Zhang Zijing , Mu Xiaohuan , Cao Qina , Shi Yao , Hu Xiaosong , Zheng Hao
Published: April 2022

Honeybees are highly social insects with a rich behavioral repertoire and are a versatile model for neurobiological research. Their gut microbiota comprises a limited number of host-restricted bacterial phylotypes that are important for honeybee health. However, it remains unclear how specific gut members affect honeybee behaviors. Here, we find that antibiotic exposure disturbs the gut community and influences honeybee phenotypes under field conditions. Using laboratory-generated gnotobiotic bees, we show that a normal gut microbiota is required for olfactory learning and memory abilities. Brain transcriptomic profiling reveals distinct brain gene expression patterns between microbiota-free and conventional bees. Subsequent metabolomic analyses of both hemolymph and gut samples show that the microbiota mainly regulates tryptophan metabolism. Our results indicate that host-specific Lactobacillus strains promote memory behavior by transforming tryptophan to indole derivatives that activate the host aryl hydrocarbon receptor. Our findings highlight the contributions of specific gut members to honeybee neurological processes, thus providing a promising model to understand host-microbe interactions.
Local structure-function relationships in human brain networks across the lifespan
Authors: Zamani Esfahlani Farnaz , Faskowitz Joshua , Slack Jonah , Mišić Bratislav , Betzel Richard F.
Published: April 2022

A growing number of studies have used stylized network models of communication to predict brain function from structure. Most have focused on a small set of models applied globally. Here, we compare a large number of models at both global and regional levels. We find that globally most predictors perform poorly. At the regional level, performance improves but heterogeneously, both in terms of variance explained and the optimal model. Next, we expose synergies among predictors by using pairs to jointly predict FC. Finally, we assess age-related differences in global and regional coupling across the human lifespan. We find global decreases in the magnitude of structure-function coupling with age. We find that these decreases are driven by reduced coupling in sensorimotor regions, while higher-order cognitive systems preserve local coupling with age. Our results describe patterns of structure-function coupling across the cortex and how this may change with age.
Two octave supercontinuum generation in a non-silica graded-index multimode fiber
Authors: Eslami Zahra , Salmela Lauri , Filipkowski Adam , Pysz Dariusz , Klimczak Mariusz , Buczynski Ryszard , Dudley John M. , Genty Goëry
Published: April 2022

The generation of a two-octave supercontinuum from the visible to mid-infrared (700–2800 nm) in a non-silica graded-index multimode fiber is reported. The fiber design is based on a nanostructured core comprised of two types of drawn lead-bismuth-gallate glass rods with different refractive indices. This yields an effective parabolic index profile and ten times increased nonlinearity when compared to silica fibers. Using femtosecond pulse pumping at wavelengths in both normal and anomalous dispersion regimes, a detailed study is carried out into the supercontinuum generating mechanisms and instabilities seeded by periodic self-imaging. Significantly, suitable injection conditions in the high power regime are found to result in the output beam profile showing clear signatures of beam self-cleaning from nonlinear mode mixing. Experimental observations are interpreted using spatio-temporal 3+1D numerical simulations of the generalized nonlinear Schrödinger equation, and simulated spectra are in excellent agreement with experiment over the full two-octave spectral bandwidth. Experimental comparison with the generation of supercontinuum in a silica graded-index multimode fiber shows that the enhanced nonlinear refractive index of the lead-bismuth-gallate fiber yields a spectrum with a significantly larger bandwidth. These results demonstrate a new pathway towards the generation of bright, ultrabroadband light sources in the mid-infrared.
Q-dependent collective relaxation dynamics of glass-forming liquid Ca0.4K0.6(NO3)1.4 investigated by wide-angle neutron spin-echo
Authors: Luo Peng , Zhai Yanqin , Falus Peter , García Sakai Victoria , Hartl Monika , Kofu Maiko , Nakajima Kenji , Faraone Antonio , Z Y
Published: April 2022

The relaxation behavior of glass formers exhibits spatial heterogeneity and dramatically changes upon cooling towards the glass transition. However, the underlying mechanisms of the dynamics at different microscopic length scales are not fully understood. Employing the recently developed wide-angle neutron spin-echo spectroscopy technique, we measured the Q-dependent coherent intermediate scattering function of a prototypical ionic glass former Ca0.4K0.6(NO3)1.4, in the highly viscous liquid state. In contrast to the structure modulated dynamics for Q < 2.4 Å−1, i.e., at and below the structure factor main peak, for Q > 2.4 Å−1, beyond the first minimum above the structure factor main peak, the stretching exponent exhibits no temperature dependence and concomitantly the relaxation time shows smaller deviations from Arrhenius behavior. This finding indicates a change in the dominant relaxation mechanisms around a characteristic length of 2π/(2.4 Å−1) ≈ 2.6 Å, below which the relaxation process exhibits a temperature independent distribution and more Arrhenius-like behavior.
An evolutionarily conserved stop codon enrichment at the 5′ ends of mammalian piRNAs
Authors: Bornelöv Susanne , Czech Benjamin , Hannon Gregory J.
Published: April 2022

PIWI-interacting RNAs (piRNAs) are small RNAs required to recognize and silence transposable elements. The 5’ ends of mature piRNAs are defined through cleavage of long precursor transcripts, primarily by Zucchini (Zuc). Zuc-dependent cleavage typically occurs immediately upstream of a uridine. However, Zuc lacks sequence preference in vitro, pointing towards additional unknown specificity factors. Here, we examine murine piRNAs and reveal a strong and specific enrichment of three sequences (UAA, UAG, UGA)—corresponding to stop codons—at piRNA 5’ ends. Stop codon sequences are also enriched immediately after piRNA processing intermediates, reflecting their Zuc-dependent tail-to-head arrangement. Further analyses reveal that a Zuc in vivo cleavage preference at four sequences (UAA, UAG, UGA, UAC) promotes 5’ end stop codons. This observation is conserved across mammals and possibly further. Our work provides new insights into Zuc-dependent cleavage and may point to a previously unrecognized connection between piRNA biogenesis and the translational machinery.
Accuracy of portable spirometers in the diagnosis of chronic obstructive pulmonary disease A meta-analysis
Authors: Zhou Jiawei , Li Xiaomeng , Wang Xingjian , Yu Na , Wang Wei
Published: April 2022

Portable spirometers has been approved for diagnosing chronic obstructive pulmonary disease (COPD). However, their diagnostic accuracy has not been reviewed. Therefore, the purpose of this study was to systematically evaluate the diagnostic value of portable spirometers in detecting COPD. A comprehensive literature search for relevant studies was conducted in PubMed, Embase, CNKI, Wan Fang, and Web of Science databases. Pooled sensitivity, specificity, summary receiver operating characteristic (SROC), area under the curve (AUC), and other related indices were calculated using the bivariate mixed-effect model. Subgroup analysis was performed to explore the source of heterogeneity. Thirty one studies were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), SROC, and AUC of the SROC of portable spirometers were 0.85 (0.81–0.88), 0.85 (0.81–0.88), 5.6 (4.4–7.3), 0.18 (0.15–0.22), 31 (21–46) and 0.91 (0.89–0.94), respectively. Among the three commonly used types of portable spirometers, the accuracy of PIKO-6 was higher (0.95) than that of COPD-6 (0.91) and PEF (0.82). Subgroup analysis indicated that the accuracy of a multi-indices portable spirometer was higher than that of a single-index one (P < 0.05). In addition, portable spirometry performed by professional technicians in tertiary hospitals was more accurate than for those conducted by trained technicians in primary care facilities and communities (P < 0.05). Moreover, the accuracy of studies conducted in developing country was superior to developed country (P < 0.05). Portable spirometers have high accuracy in the diagnosis of COPD. Multi-index COPD-6 and PIKO-6 displayed higher accuracy than others. Standardized training of instrument operators should be considered to achieve reliable results.
A review of advances in freeze desalination and future prospects
Authors: Najim Abdul
Published: April 2022

Freeze desalination (FD) has several benefits compared to vaporization-based and membrane-based desalination methods. The FD process needs approximately 1/7th of the latent heat required by the vaporization-based desalination processes. The involvement of sub-zero temperature in FD reduces the risk of corrosion and scaling. This paper reviews the advances in FD methods involving stand-alone and hybrid methods that operate with and without utilizing the energy released during the re-gasification of liquefied natural gas. Moreover, the paper discusses the future focus areas for research and development to make FD a commercially feasible technology. Potable water was produced from brackish water and seawater by FD wherein the nucleation was achieved by ice seeding, the mixing of rejected salt from ice into the liquid phase was controlled appropriately, growth of ice crystals was slow, and liquid subcooling was maintained at approximately 4 K. The post-treatment of obtained ice is needed to produce potable water if the process is instigated without ice seeding. The plant capacity of stand-alone progressive FD was higher than the stand-alone suspension FD of seawater. The integration of the falling-film, fractional thawing, and block FD method showed significantly improved plant capacity than the stand-alone suspension FD method. The energy consumption of stand-alone PFC and SFC-based desalination with latent heat recovery was reported close to the reverse osmosis (RO) method. The hybrid (integration of the suspension FD method with membrane distillation) FD method utilizing LNG cold energy consumed less energy than the conventional RO method.
Addressing a systematic error correcting for free and mixed convection when measuring mean radiant temperature with globe thermometers
Authors: Teitelbaum Eric , Alsaad Hayder , Aviv Dorit , Kim Alexander , Voelker Conrad , Meggers Forrest , Pantelic Jovan
Published: April 2022

It is widely accepted that most people spend the majority of their lives indoors. Most individuals do not realize that while indoors, roughly half of heat exchange affecting their thermal comfort is in the form of thermal infrared radiation. We show that while researchers have been aware of its thermal comfort significance over the past century, systemic error has crept into the most common evaluation techniques, preventing adequate characterization of the radiant environment. Measuring and characterizing radiant heat transfer is a critical component of both building energy efficiency and occupant thermal comfort and productivity. Globe thermometers are typically used to measure mean radiant temperature (MRT), a commonly used metric for accounting for the radiant effects of an environment at a point in space. In this paper we extend previous field work to a controlled laboratory setting to (1) rigorously demonstrate that existing correction factors used in the American Society of Heating Ventilation and Air-conditioning Engineers (ASHRAE) Standard 55 or ISO7726 for using globe thermometers to quantify MRT are not sufficient; (2) develop a correction to improve the use of globe thermometers to address problems in the current standards; and (3) show that mean radiant temperature measured with ping-pong ball-sized globe thermometers is not reliable due to a stochastic convective bias. We also provide an analysis of the maximum precision of globe sensors themselves, a piece missing from the domain in contemporary literature.
Optimization of the pulse electric field assisted extraction of black rice grain for antioxidant and sirtuin1 enzyme stimulation activities
Authors: Salee Nuttinee , Chaiyana Wantida , Yawootti Artit , Naruenartwongsakul Srisuwan , Klangpetch Wannaporn , Walter Ponjan , Utama-ang Niramon
Published: April 2022

Cyanidin-3-glucoside (C3G) and peonidin-3-glucoside (P3G) in black rice grain (BRG) demonstrate many beneficial health effects, including antioxidant and anti-aging properties. This research aimed to study on pulsed electric field assisted water extraction (PEF-AWE) on BRG using pre-treatment technique, which was determined for enhanced yields of C3G and P3G, antioxidant and sirtuin1 enzyme stimulation activities. The effects of operating parameters for PEF-AWE (intensity of electric field, X1: 3–5 kV/cm, number of pulse, X2: 1000–3000 pulse and BRG/water ratio, X3: 0.1–0.5 g/mL) were determined using regression analysis and optimized PEF-AWE condition using the response surface methodology. Regression models showed the intensity of electric field and BRG/water ratio were the strong influence parameters significantly on C3G (p < 0.01). The results highlighted optimized conditions of PEF-AWE followed by 5 kV/cm, 3000 pulse and 0.5 g/mL leading to achieve higher C3G (92.59 ± 4.79 mg/g) and P3G (4.59 ± 0.27 mg/g) than no pre-treatment by PEF process, approximately 60%. Additionally, PEF extracts of BRG can modulate the ability of surtuin1 enzyme to deacetylate substrate proteins (26.78 ± 0.50 FIR). Thus, PEF-AWE can be applied to produce BRG extract as natural antioxidant compound and functional ingredient.
Quantifying social segregation in large-scale networks
Authors: Reme Bjørn-Atle , Kotsadam Andreas , Bjelland Johannes , Sundsøy Pål Roe , Lind Jo Thori
Published: April 2022

We present a measure of social segregation which combines mobile phone data and income register data in Oslo, Norway. In addition to measuring the extent of social segregation, our study shows that social segregation is strong, robust, and that social networks are particularly clustered among the richest. Using location data on the areas where people work, we also examine whether exposure to other social strata weakens measured segregation. Lastly, we extend our analysis to a large South Asian city and show that our main results hold across two widely different societies.