bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression and risk of infectious diseases: A mendelian randomization study
Authors: Shi Luchen , Ren Junsong , Jin Ke , Li Jun
Published: June 2024

Previous observational inquiries have revealed a correlation between depression and infectious maladies. This study seeks to elucidate the causal linkages between depression, specifically Major Depressive Disorder (MDD), and infectious diseases. Nevertheless, the causative nature of the association between MDD and infectious diseases remains elusive. Two-sample Mendelian Randomization (MR) analyses was executed utilizing single nucleotide polymorphisms (SNPs) significantly connected with MDD and infectious diseases as instrumental variables (IVs). A series of sensitivity analyses were subsequently conducted. Genetic variants linked to MDD were employed as instrumental variables sourced from a genome-wide meta-analyses comprising 500,199 individuals. Summary-level data on five infectious diseases, including candidiasis, pneumonia, skin and soft tissue infections (SSTI), upper respiratory tract infections (URTI), and urinary tract infections (UTI), were acquired from the UK Biobank and FinnGen study. Our findings evinced that genetically predicted MDD exhibited a heightened risk of candidiasis (OR = 1.52, 95% CI 1.06–2.17; P = 2.38E-02), pneumonia (OR = 1.14, 95% CI 1.01–1.29; P = 3.16E-02), URTI (OR = 1.23, 95% CI 1.12–1.36; P = 3.71E-05), and UTI (OR = 1.26, 95% CI 1.12–1.42; P = 8.90E-05). Additionally, we identified bidirectional causal relationships between UTI and MDD. The associations between MDD and the risk of URTI and UTI remained consistent in multivariable MR analyses, accounting for genetically predicted smoking and body mass index. In conclusion, this investigation ascertained a causal connection between MDD and the susceptibility to infectious diseases, particularly URTI and UTI.
Association of post-COVID phenotypic manifestations with new-onset psychiatric disease
Authors: Coleman Ben , Casiraghi Elena , Callahan Tiffany J. , Blau Hannah , Chan Lauren E. , Laraway Bryan , Clark Kevin B. , Re’em Yochai , Gersing Ken R. , Wilkins Kenneth J. , Harris Nomi L. , Valentini Giorgio , Haendel Melissa A. , Reese Justin T. , Robinson Peter N.
Published: June 2024

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28–120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.
Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia
Authors: Mochmann Liliana H. , Treue Denise , Bockmayr Michael , Silva Patricia , Zasada Christin , Mastrobuoni Guido , Bayram Safak , Forbes Martin , Jurmeister Philipp , Liebig Sven , Blau Olga , Schleich Konstanze , Splettstoesser Bianca , Nordmann Thierry M. , von der Heide Eva K. , Isaakidis Konstandina , Schulze Veronika , Busch Caroline , Siddiq Hafsa , Schlee Cornelia , Hester Svenja , Fransecky Lars , Neumann Martin , Kempa Stefan , Klauschen Frederick , Baldus Claudia D.
Published: June 2024

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by genomic aberrations in oncogenes, cytogenetic abnormalities, and an aberrant epigenetic landscape. Nearly 50% of AML cases will relapse with current treatment. A major source of therapy resistance is the interaction of mesenchymal stroma with leukemic cells resulting in therapeutic protection. We aimed to determine pro-survival/anti-apoptotic protein networks involved in the stroma protection of leukemic cells. Proteomic profiling of cultured primary AML (n = 14) with Hs5 stroma cell line uncovered an up-regulation of energy-favorable metabolic proteins. Next, we modulated stroma-induced drug resistance with an epigenetic drug library, resulting in reduced apoptosis with histone deacetylase inhibitor (HDACi) treatment versus other epigenetic modifying compounds. Quantitative phosphoproteomic probing of this effect further revealed a metabolic-enriched phosphoproteome including significant up-regulation of acetyl-coenzyme A synthetase (ACSS2, S30) in leukemia-stroma HDACi treated cocultures compared with untreated monocultures. Validating these findings, we show ACSS2 substrate, acetate, promotes leukemic proliferation, ACSS2 knockout in leukemia cells inhibits leukemic proliferation and ACSS2 knockout in the stroma impairs leukemic metabolic fitness. Finally, we identify ACSS1/ACSS2-high expression AML subtype correlating with poor overall survival. Collectively, this study uncovers the leukemia-stroma phosphoproteome emphasizing a role for ACSS2 in mediating AML growth and drug resistance.
Sponging of five tumour suppressor miRNAs by lncRNA-KCNQ1OT1 activates BMPR1A/BMPR1B-ACVR2A/ACVR2B signalling and promotes chemoresistance in hepatocellular carcinoma
Authors: Majumdar Swagata , Chakraborty Anannya , Das Sumit , Gorain Mahadeo , Chatterjee Soumyabrata , Dey Indrashish , Bhowmik Sayantani , Ghosh Suchandrima , Banerjee Sanjana , Ahammed Sk. Mahiuddin , Chowdhury Abhijit , Datta Simanti , Kundu Gopal , Banerjee Soma
Published: June 2024

Diverse mechanisms have been established to understand the chemoresistance of hepatocellular carcinoma (HCC), but the contribution of non-coding RNAs is not surveyed well. Here, we aimed to explore the lncRNA-miRNA axis in Hepatitis C and B virus (HCV and HBV) infected HCC to investigate the molecular mechanism of chemoresistance and to identify a potential therapeutic target for HCC. The small RNA transcriptome analysis followed by qRT-PCR validation with the liver tissues of both HCV and HBV infected HCC patients revealed that miR-424-5p, miR-136-3p, miR-139-5p, miR-223-3p, and miR-375-3p were the most downregulated miRNAs in HCC compared to normal (log2 fold change ≤−1.5, Padj ≤ 0.05). In silico pathway analysis with the validated targets of each miRNA revealed that the signalling pathway regulating pluripotency of stem cells is commonly targeted by these five miRNAs. Subsequent validation by 3′UTR-luciferase assay and western blot analysis unveiled that these five miRNAs impeded either same or diverse genes, but all linked to BMP signalling pathway such as BMPR1A/BMPR1B by miR-139-5p, miR-136-3p, and miR-375-3p, and ACVR2A/ACVR2B by miR-424-5p and miR-223-3p. Furthermore, restoration of each miRNA in Huh7/SNU449 cells inhibited phosphorylation of downstream SMAD1/5 and ERK1/2, and attenuated Epithelial-mesenchymal transition, stemness, spheroid formation, chemoresistance, invasion and migration of cells. To investigate the mechanism of suppression of these miRNAs, “DIANA” tool was employed and lncRNA-KCNQ1OT1 was retrieved as interacting partner of all the five miRNAs. In vitro RNA pull-down assay revealed that lncRNA-KCNQ1OT1 physically interacted and sequestered these five miRNAs in the cytoplasm. Hence, KCNQ1OT1 was suppressed in Huh7/SNU449 cells using CRISPR technology and observed regression of oncogenic properties with enhanced chemosensitivity and reduced metastasis in cancer cells. Shrinkage of tumour size and volume in NOD-SCID mice injected with KCNQ1OT1-sgRNA cells further strengthened our observations. Thus, lncRNA-KCNQ1OT1 is the main regulator, which reduces the level of beneficiary miRNAs in the tumour milieu and modulates BMP signalling pathway to promote chemoresistance in HCC, suggesting lncRNA-KCNQ1OT1 might have robust potential to be a therapeutic target in HCC.
An oncogenic role of lncRNA SNHG1 promotes ATG7 expression and autophagy involving tumor progression and sunitinib resistance of Renal Cell Carcinoma
Authors: Tian Pei , Wei Jinxing , Li Jing , Ren Junkai , He Chaohong
Published: June 2024

Renal cell carcinoma (RCC) is a malignant tumor with high incidence in adult kidney. Long non-coding RNAs (lncRNAs) have recently been recognized as important regulators in the development of RCC. However, whether lncRNA SNHG1 is associated with RCC progression remains to be elucidated. Here, the role of SNHG1 in RCC autophagy and sunitinib resistance was evaluated. Expression of SNHG1 in RCC tissues and cells was assessed using RT-qPCR. Western blot was utilized to measure the levels of autophagy-related molecules and ATG7. RNA pull-down and RIP assays were performed to confirm the molecular axis between SNHG1/PTBP1/ATG7. Cell proliferation, migration, invasion and apoptosis were analyzed by CCK-8, EdU, transwell and flow cytometry, respectively. The subcellular localization of SNHG1 was determined by an intracellular fractionation assay. The fluorescence intensity of GFP-LC3 autophagosome in RCC cells was detected. IHC staining was performed to test ATG7 expression in tumor tissues from nude mice. Here, a positive correlation of upregulated SNHG1 with poor prognosis of RCC patients was observed in RCC tissues and cells. SNHG1 knockdown suppressed tumor growth and reversed sunitinib resistance and autophagy of RCC cells. Additionally, SNHG1 was found to directly bind to PTBP1, thereby positively regulating ATG7 expression. Furthermore, we verified that SNHG1 mediated the malignant behavior of RCC cells through the PTBP1/ATG7 axis. To sum up, SNHG1 regulates RCC cell autophagy and sunitinib resistance through the PTBP1/ATG7 axis, which highlights a promising therapeutic target for RCC treatment.
The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity
Authors: Serrano Joan , Boyd Jordan , Brown Ian S. , Mason Carter , Smith Kathleen R. , Karolyi Katalin , Maurya Santosh K. , Meshram Nishita N. , Serna Vanida , Link Grace M. , Gardell Stephen J. , Kyriazis George A.
Published: June 2024

The bioavailability of nicotinamide adenine dinucleotide (NAD) is vital for skeletal muscle health, yet the mechanisms or signals regulating NAD homeostasis remain unclear. Here, we uncover a pathway connecting peripheral glucose sensing to the modulation of muscle NAD through TAS1R2, the sugar-sensing G protein-coupled receptor (GPCR) initially identified in taste perception. Muscle TAS1R2 receptor stimulation by glucose and other agonists induces ERK1/2-dependent phosphorylation and activation of poly(ADP-ribose) polymerase1 (PARP1), a major NAD consumer in skeletal muscle. Consequently, muscle-specific deletion of TAS1R2 (mKO) in male mice suppresses PARP1 activity, elevating NAD levels and enhancing mitochondrial capacity and running endurance. Plasma glucose levels negatively correlate with muscle NAD, and TAS1R2 receptor deficiency enhances NAD responses across the glycemic range, implicating TAS1R2 as a peripheral energy surveyor. These findings underscore the role of GPCR signaling in NAD regulation and propose TAS1R2 as a potential therapeutic target for maintaining muscle health.
Emergent dynamics due to chemo-hydrodynamic self-interactions in active polymers
Authors: Kumar Manoj , Murali Aniruddh , Subramaniam Arvin Gopal , Singh Rajesh , Thutupalli Shashi
Published: June 2024

The field of synthetic active matter has, thus far, been led by efforts to create point-like, isolated (yet interacting) self-propelled objects (e.g. colloids, droplets, microrobots) and understanding their collective dynamics. The design of flexible, freely jointed active assemblies from autonomously powered sub-components remains a challenge. Here, we report freely-jointed active polymers created using self-propelled droplets as monomeric units. Our experiments reveal that the self-shaping chemo-hydrodynamic interactions between the monomeric droplets give rise to an emergent rigidity (the acquisition of a stereotypical asymmetric C-shape) and associated ballistic propulsion of the active polymers. The rigidity and propulsion of the chains vary systematically with their lengths. Using simulations of a minimal model, we establish that the emergent polymer dynamics are a generic consequence of quasi two-dimensional confinement and auto-repulsive trail-mediated chemical interactions between the freely jointed active droplets. Finally, we tune the interplay between the chemical and hydrodynamic fields to experimentally demonstrate oscillatory dynamics of the rigid polymer propulsion. Altogether, our work highlights the possible first steps towards synthetic self-morphic active matter.
Advanced methods for gene network identification and noise decomposition from single-cell data
Authors: Fang Zhou , Gupta Ankit , Kumar Sant , Khammash Mustafa
Published: June 2024

Central to analyzing noisy gene expression systems is solving the Chemical Master Equation (CME), which characterizes the probability evolution of the reacting species’ copy numbers. Solving CMEs for high-dimensional systems suffers from the curse of dimensionality. Here, we propose a computational method for improved scalability through a divide-and-conquer strategy that optimally decomposes the whole system into a leader system and several conditionally independent follower subsystems. The CME is solved by combining Monte Carlo estimation for the leader system with stochastic filtering procedures for the follower subsystems. We demonstrate this method with high-dimensional numerical examples and apply it to identify a yeast transcription system at the single-cell resolution, leveraging mRNA time-course experimental data. The identification results enable an accurate examination of the heterogeneity in rate parameters among isogenic cells. To validate this result, we develop a noise decomposition technique exploiting time-course data but requiring no supplementary components, e.g., dual-reporters.
Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression
Authors: Jang Hyun-Ji , Min Hye-Young , Kang Yun Pyo , Boo Hye-Jin , Kim Jisung , Ahn Jee Hwan , Oh Seung Ho , Jung Jin Hwa , Park Choon-Sik , Park Jong-Sook , Kim Seog-Young , Lee Ho-Young
Published: June 2024

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)−1-(3-pyridyl)−1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.
FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer
Authors: Wang Zifeng , Townley Scott L. , Zhang Songqi , Liu Mingyu , Li Muqing , Labaf Maryam , Patalano Susan , Venkataramani Kavita , Siegfried Kellee R. , Macoska Jill A. , Han Dong , Gao Shuai , Risbridger Gail P. , Taylor Renea A. , Lawrence Mitchell G. , He Housheng Hansen , Selth Luke A. , Cai Changmeng
Published: June 2024

FOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the chromatin binding of the androgen receptor (AR) in both normal prostate epithelial cells and the luminal subtype of prostate cancer (PCa). Recent studies have highlighted the emergence of FOXA2 as an adaptive response to AR signaling inhibition treatments. However, the role of the FOXA1 to FOXA2 transition in regulating cancer lineage plasticity remains unclear. Our study demonstrates that FOXA2 binds to distinct classes of developmental enhancers in multiple AR-independent PCa subtypes, with its binding depending on LSD1. Moreover, we reveal that FOXA2 collaborates with JUN at chromatin and promotes transcriptional reprogramming of AP-1 in lineage-plastic cancer cells, thereby facilitating cell state transitions to multiple lineages. Overall, our findings underscore the pivotal role of FOXA2 as a pan-plasticity driver that rewires AP-1 to induce the differential transcriptional reprogramming necessary for cancer cell lineage plasticity.
Effectiveness of nirmatrelvir/ritonavir in children and adolescents aged 12–17 years following SARS-CoV-2 Omicron infection: A target trial emulation
Authors: Wong Carlos K. H. , Lau Kristy T. K. , Au Ivan C. H. , Chan Sophelia H. S. , Lau Eric H. Y. , Cowling Benjamin J. , Leung Gabriel M.
Published: June 2024

Currently there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in paediatric patients with SARS-CoV-2 infection. This target trial emulation study aims to address this gap by evaluating the use of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron variant infection. Among paediatric patients diagnosed between 16th March 2022 and 5th February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or COVID-19 diagnosis. Primary outcome was 28 day all-cause mortality or all-cause hospitalization, while secondary outcomes were 28 day in-hospital disease progression, 28 day COVID-19-specific hospitalization, multisystem inflammatory syndrome in children (MIS-C), acute liver injury, acute renal failure, and acute respiratory distress syndrome. Overall, 49,378 eligible paediatric patients were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28 day all-cause hospitalization (absolute risk reduction = 0.23%, 95%CI = 0.19%–0.31%; relative risk = 0.66, 95%CI = 0.56–0.71). No events of mortality, in-hospital disease progression, or adverse clinical outcomes were observed among nirmatrelvir/ritonavir users. The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients with SARS-CoV-2 Omicron variant infection.
The Legionella collagen-like protein employs a distinct binding mechanism for the recognition of host glycosaminoglycans
Authors: Rehman Saima , Antonovic Anna Katarina , McIntire Ian E. , Zheng Huaixin , Cleaver Leanne , Baczynska Maria , Adams Carlton O. , Portlock Theo , Richardson Katherine , Shaw Rosie , Oregioni Alain , Mastroianni Giulia , Whittaker Sara B-M. , Kelly Geoff , Lorenz Christian D. , Fornili Arianna , Cianciotto Nicholas P. , Garnett James A.
Published: June 2024

Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires’ disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual trimer arrangement with a positively charged external surface and negatively charged solvent exposed internal cavity. Through molecular dynamics simulations, we show how the glycosaminoglycan chondroitin-4-sulphate associates with the Lcl-CTD surface via distinct binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate-binding mechanism.
Emergent digital bio-computation through spatial diffusion and engineered bacteria
Authors: Fedorec Alex J. H. , Treloar Neythen J. , Wen Ke Yan , Dekker Linda , Ong Qing Hsuan , Jurkeviciute Gabija , Lyu Enbo , Rutter Jack W. , Zhang Kathleen J. Y. , Rosa Luca , Zaikin Alexey , Barnes Chris P.
Published: June 2024

Biological computing is a promising field with potential applications in biosafety, environmental monitoring, and personalized medicine. Here we present work on the design of bacterial computers using spatial patterning to process information in the form of diffusible morphogen-like signals. We demonstrate, mathematically and experimentally, that single, modular, colonies can perform simple digital logic, and that complex functions can be built by combining multiple colonies, removing the need for further genetic engineering. We extend our experimental system to incorporate sender colonies as morphogen sources, demonstrating how one might integrate different biochemical inputs. Our approach will open up ways to perform biological computation, with applications in bioengineering, biomaterials and biosensing. Ultimately, these computational bacterial communities will help us explore information processing in natural biological systems.
Waning-and-waxing shape changes in ionic nanoplates upon cation exchange
Authors: Li Zhanzhao , Saruyama Masaki , Asaka Toru , Teranishi Toshiharu
Published: June 2024

Flexible control of the composition and morphology of nanocrystals (NCs) over a wide range is an essential technology for the creation of functional nanomaterials. Cation exchange (CE) is a facile method by which to finely tune the compositions of ionic NCs, providing an opportunity to obtain complex nanostructures that are difficult to form using conventional chemical synthesis procedures. However, due to their robust anion frameworks, CE cannot typically be used to modify the original morphology of the host NCs. In this study, we report an anisotropic morphological transformation of Cu1.8S NCs during CE. Upon partial CE of Cu1.8S nanoplates (NPLs) with Mn2+, the hexagonal NPLs are transformed into crescent-shaped Cu1.8S–MnS NPLs. Upon further CE, these crescent-shaped NPLs evolve back into completely hexagonal MnS NPLs. Comprehensive characterization of the intermediates reveals that this waxing-and-waning shape-evolution process is due to dissolution, redeposition, and intraparticle migration of Cu+ and S2−. Furthermore, in addition to Mn2+, this CE-induced transformation process occurs with Zn2+, Cd2+ and Fe3+. This finding presents a strategy by which to create heterostructured NCs with various morphologies and compositions under mild conditions.
LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy
Authors: Wang Ningning , Merits Andres , Veit Michael , Lello Laura Sandra , Kong Shuhan , Jiao Houqi , Chen Jie , Wang Yu , Dobrikov Georgi , Rey Félix A. , Su Shuo
Published: June 2024

Various low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.
DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells
Authors: Zhang Zhifei , Yang Haiyan , Fang Lei , Zhao Guangrong , Xiang Jun , Zheng Jialin C. , Qin Zhao
Published: June 2024

Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.
Artificial cellulosic leaf with adjustable enzymatic CO2 sequestration capability
Authors: Zhu Xing , Du Chenxi , Gao Bo , He Bin
Published: June 2024

Developing artificial leaves to address the environmental burden of CO2 is pivotal for advancing our Net Zero Future. In this study, we introduce EcoLeaf, an artificial leaf that closely mimics the characteristics of natural leaves. It harnesses visible light as its sole energy source and orchestrates the controlled expansion and contraction of stomata and the exchange of petiole materials to govern the rate of CO2 sequestration from the atmosphere. Furthermore, EcoLeaf has a cellulose composition and mechanical strength similar to those of natural leaves, allowing it to seamlessly integrate into the ecosystem during use and participate in natural degradation and nutrient cycling processes at the end of its life. We propose that the carbon sequestration pathway within EcoLeaf is adaptable and can serve as a versatile biomimetic platform for diverse biogenic carbon sequestration pathways in the future.
Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase
Authors: Tong Huawei , Wang Haoqiang , Wang Xuchen , Liu Nana , Li Guoling , Wu Danni , Li Yun , Jin Ming , Li Hengbin , Wei Yinghui , Li Tong , Yuan Yuan , Shi Linyu , Yao Xuan , Zhou Yingsi , Yang Hui
Published: June 2024

DNA base editors enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here we develop two deaminase-free glycosylase-based base editors for direct T editing (gTBE) and C editing (gCBE) by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants. By several rounds of structure-informed rational mutagenesis on UNG in cultured human cells, we obtain gTBE and gCBE with high activity of T-to-S (i.e., T-to-C or T-to-G) and C-to-G conversions, respectively. Furthermore, we conduct parallel comparison of gTBE/gCBE with those recently developed using other protein engineering strategies, and find gTBE/gCBE show the outperformance. Thus, we provide several base editors, gTBEs and gCBEs, with corresponding engineered UNG variants, broadening the targeting scope of base editors.
SOD3 suppresses early cellular immune responses to parasite infection
Authors: Li Qilong , Lv Kunying , Jiang Ning , Liu Tong , Hou Nan , Yu Liying , Yang Yixin , Feng Anni , Zhang Yiwei , Su Ziwei , Sang Xiaoyu , Feng Ying , Chen Ran , Xu Wenyue , Cui Liwang , Cao Yaming , Chen Qijun
Published: June 2024

Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.
Solvent engineering for scalable fabrication of perovskite/silicon tandem solar cells in air
Authors: Zheng Xuntian , Kong Wenchi , Wen Jin , Hong Jiajia , Luo Haowen , Xia Rui , Huang Zilong , Luo Xin , Liu Zhou , Li Hongjiang , Sun Hongfei , Wang Yurui , Liu Chenshuaiyu , Wu Pu , Gao Han , Li Manya , Bui Anh Dinh , Mo Yi , Zhang Xueling , Yang Guangtao , Chen Yifeng , Feng Zhiqiang , Nguyen Hieu T. , Lin Renxing , Li Ludong , Gao Jifan , Tan Hairen
Published: June 2024

Perovskite/silicon tandem solar cells hold great promise for realizing high power conversion efficiency at low cost. However, achieving scalable fabrication of wide-bandgap perovskite (~1.68 eV) in air, without the protective environment of an inert atmosphere, remains challenging due to moisture-induced degradation of perovskite films. Herein, this study reveals that the extent of moisture interference is significantly influenced by the properties of solvent. We further demonstrate that n-Butanol (nBA), with its low polarity and moderate volatilization rate, not only mitigates the detrimental effects of moisture in air during scalable fabrication but also enhances the uniformity of perovskite films. This approach enables us to achieve an impressive efficiency of 29.4% (certified 28.7%) for double-sided textured perovskite/silicon tandem cells featuring large-size pyramids (2–3 μm) and 26.3% over an aperture area of 16 cm2. This advance provides a route for large-scale production of perovskite/silicon tandem solar cells, marking a significant stride toward their commercial viability.
Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer
Authors: Grinshpun Albert , Russo Douglas , Ma Wen , Verma Ana , Hermida-Prado Francisco , Sherman Shira , Gaglia Giorgio , Kabraji Sheheryar , Kirkner Gregory , Hughes Melissa E. , Lin Nancy U. , Sandusky Zachary , Nardone Agostina , Guarducci Cristina , Nguyen Quang-De , Santagata Sandro , Nagy Zsuzsanna , Jeselsohn Rinath
Published: June 2024

The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.
Ocular perfusion pressure is not reduced in response to lower body negative pressure
Authors: Hall Eric A. , Whittle Richard S. , Diaz-Artiles Ana
Published: June 2024

Lower body negative pressure (LBNP) has been proposed as a countermeasure to mitigate the cephalad fluid shift occurring during spaceflight, which may be associated with the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). This study quantifies the effect of LBNP on intraocular pressure (IOP), mean arterial pressure at eye level (MAPeye), and ocular perfusion pressure (OPP). Twenty-four subjects (12 male, 12 female) were subjected to graded LBNP in 0° supine and 15° head-down tilt (HDT) postures from 0 mmHg to –50 mmHg in 10 mmHg increments. IOP decreased significantly with LBNP pressure in 0° supine (by 0.7 ± 0.09 mmHg per 10 mmHg LBNP pressure,p < 0.001) and in 15° HDT (by 1.0 ± 0.095 mmHg per 10 mmHg of LBNP pressure,p < 0.001). MAPeyesignificantly decreased by 0.9 ± 0.4 mmHg per 10 mmHg of LBNP pressure in 0° supine (p = 0.016) but did not significantly change with LBNP in 15° HDT (p = 0.895). OPP did not significantly change with LBNP in 0° supine (p = 0.539) but it significantly increased in 15° HDT at 1.0 ± 0.3 mmHg per 10 mmHg of LBNP pressure (p = 0.010). Sex did not have a significant effect on OPP, MAPeye, or IOP in any condition. In 15° HDT, the reduction in IOP during increasing negative pressure, combined with the relatively constant MAPeye, led to the increase in OPP. Furthermore, results suggest that LBNP, while effective in reducing IOP, is not effective in reducing OPP across all postures investigated.
Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial
Authors: Shing Jaimie Z. , Porras Carolina , Pinheiro Maísa , Herrero Rolando , Hildesheim Allan , Liu Danping , Gail Mitchell H. , Romero Byron , Schiller John T. , Zúñiga Michael , Mishra Sambit , Burdette Laurie , Jones Kristine , Schussler John , Ocampo Rebeca , Fang Jianwen , Liu Zhiwei , Lowy Douglas R. , Tsang Sabrina H. , Rodríguez Ana Cecilia , Schiffman Mark , Haas Cameron B. , Carvajal Loretto J. , Brown Jalen R. , Kreimer Aimée R. , Mirabello Lisa ,   Costa Rica HPV Vaccine Trial (CVT) Group, Cortés Bernal , González Paula , Herrero Rolando , Jiménez Silvia E. , Porras Carolina , Rodríguez Ana Cecilia , Hildesheim Allan , Kreimer Aimée R. , Lowy Douglas R. , Schiffman Mark , Schiller John T. , Sherman Mark , Wacholder Sholom , Pinto Ligia A. , Kemp Troy J. , Sidawy Mary K. , Quint Wim , van Doorn Leen-Jan , Struijk Linda , Palefsky Joel M. , Darragh Teresa M. , Stoler Mark H.
Published: June 2024

The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = −34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.
A Clinical Bacterial Dataset for Deep Learning in Microbiological Rapid On-Site Evaluation
Authors: Wang Xiuli , Shi Yinghan , Guo Shasha , Qu Xuzhong , Xie Fei , Duan Zhimei , Hu Ye , Fu Han , Shi Xin , Quan Tingwei , Wang Kaifei , Xie Lixin
Published: June 2024

Microbiological Rapid On-Site Evaluation (M-ROSE) is based on smear staining and microscopic observation, providing critical references for the diagnosis and treatment of pulmonary infectious disease. Automatic identification of pathogens is the key to improving the quality and speed of M-ROSE. Recent advancements in deep learning have yielded numerous identification algorithms and datasets. However, most studies focus on artificially cultured bacteria and lack clinical data and algorithms. Therefore, we collected Gram-stained bacteria images from lower respiratory tract specimens of patients with lung infections in Chinese PLA General Hospital obtained by M-ROSE from 2018 to 2022 and desensitized images to produce 1705 images (4,912 × 3,684 pixels). A total of 4,833 cocci and 6,991 bacilli were manually labelled and differentiated into negative and positive. In addition, we applied the detection and segmentation networks for benchmark testing. Data and benchmark algorithms we provided that may benefit the study of automated bacterial identification in clinical specimens.
DustSCAN: A Five Year (2018-2022) Hourly Dataset of Dust Plumes From SEVIRI
Authors: AlNasser Faisal , Entekhabi Dara
Published: June 2024

Airborne mineral dust significantly impacts air quality, human health, and the global climate. Due to sparse ground sensors, particularly in source regions, dust monitoring relies mainly on remote sensing through Aerosol Optical Depth (AOD) retrievals from polar-orbiting satellite optical instruments. These are valuable but lack the temporal resolution for precise plume tracking and source characterization. We introduce DustSCAN, a five-year, hourly dust plume dataset derived from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) images on geostationary-orbit Meteosat satellites. Using multi-channel infrared images, we detect atmospheric dust and track hourly dust-affected pixels. These are clustered into discrete plumes using the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. DustSCAN includes 9950 discrete plumes over 2018-2022 across the Sahara, the Arabian Desert, and Western and Central Asia. It complements existing resources and provides a framework for detailed analysis of dust sources, trajectories, and impacts. Its distinctive event-based and spatio-temporal detail offers an advancement in unraveling the complexities of dust storm dynamics.
A multivariate process quality correlation diagnosis method based on grouping technique
Authors: Niu Qing , Cheng Shujie , Qiu Zeyang
Published: June 2024

Correlation diagnosis in multivariate process quality management is an important and challenging issue. In this paper, a new diagnostic method based on quality component grouping is proposed. Firstly, three theorems describing the properties of the covariance matrix of multivariate process quality are established based on the statistical viewpoint of product quality, to prove the correlation decomposition theorem, which decomposes the correlation of all the quality components into a series of correlations of components pairs, and then by using the factor analysis method, all quality components are grouped in order to maximize the correlations in the same groups and minimize the ones between different groups. Finally, on the basis of correlations between different groups are ignored, T2 control charts of component pairs in the same groups are established to form the diagnostic model. Theoretical analysis and practice prove that for the multivariate process quality whose the correlations between different components vary considerably, the grouping technique enables the size of the correlation diagnostic model to be drastically reduced, thus allowing the proposed method can be used as a generalized theoretical model for the correlation diagnosis.
Assessing the oral and suprahyoid muscles in healthy adults using muscle ultrasound to inform the swallowing process: a proof-of-concept study
Authors: Kelly Eileen , Nazeer Saira , Fazzini Brigitta , Sutt Anna-Liisa , Olusanya Segun , Campion Thomas , Puthucheary Zudin
Published: June 2024

The oral and suprahyoid muscles are responsible for movements of swallowing. Our study aimed to determine the reproducibility of static and dynamic measurements of these muscles using bedside ultrasound equipment. Forty healthy participants were recruited prospectively. Primary outcomes were evaluation of mass measurements of the anterior bellies of the digastric, mylohyoid, geniohyoid and tongue in B-mode ultrasound. Secondary outcomes were evaluation of geniohyoid muscle layer thickness and function using M-mode. Muscle mass measurements demonstrated little within-participant variability. Coefficient of Variance (CoV) across muscles were: anterior belly digastric (5.0%), mylohyoid (8.7%), geniohyoid (5.0%) and tongue (3.2%). A relationship between sex (r2 = 0.131 p = 0.022) was demonstrated for the geniohyoid muscle, with males having higher transverse Cross Sectional Area (CSA) (14.3 ± 3.6 mm vs. 11.9 ± 2.5 mm, p = 0.002). Tongue size was correlated with weight (r2 = 0.356, p = 0.001), height (r2 = 0.156, p = 0.012) and sex (r2 = 0.196, p = 0.004). Resting thickness of the geniohyoid muscle layer changed with increasing bolus sizes (f = 3.898, p = 0.026). Velocity increased with bolus size (p =  < 0.001, F = 8.974). However swallow time and slope distance did not, potentially influenced by higher coefficients of variation. Oral and suprahyoid muscle mass are easily assessed using bedside ultrasound. Ultrasound may provide new information about muscle mass and function during swallowing.
Towards improving aspect-oriented software reusability estimation
Authors: Magableh Aws A. , Ata Hana’a Bani , Saifan Ahmad A. , Rawashdeh Adnan
Published: June 2024

Nowadays, large numbers of organizations may opt for Aspect-Oriented Programming (AOP), which is an enhancement to Object-Oriented Programming (OOP). This is due to the addition of a number of concepts that have assisted in the production of more flexible and reusable components. One of the most important elements added by AOP is software reuse, which is based on reusability attributes. These attributes indicate the possibility of reusing one or more components in the development of a new system. It is one of the most essential attributes to evaluate the quality of a system’s components. Thus far, little attention has been paid to the process of measuring AOP reusability, and it has not yet been standardized. The objective of the current study is to come up with a reasonable measurement for AOP software reuse, which is simultaneously a significant topic for researchers while offering several advantages for organizations. Although numerous models have been built to estimate the reusability of software, most of them are not dedicated to Aspect-Oriented Software (AOS). In this study, a model has been designed for AOS reusability estimation and measurement based on a new equation depending on five attributes that have a range of positive and negative impacts on AOS reusability. Three of those attributes, namely coupling, cohesion, and design size, have been included in previous studies. This study proposes complexity and generality as two new attributes to be considered. Each of these attributes was measured based on the metrics also proposed in this study. A new equation to calculate AOS reusability was constructed based on the most important reusability attributes and metrics. Seven aspect projects were employed as a case study to apply the proposed equation. After the proposed equation was applied to the selected projects, we obtained new values of reusability to compare with the values that resulted from applying the previous equation. The fact that new values emerged indicates that the proposed reusability metrics and attributes had a significant effect.