bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
Authors: Li Fajin , Fang Jianhuo , Yu Yifan , Hao Sijia , Zou Qin , Zeng Qinglin , Yang Xuerui 
Published: February 2023

AbstractThe quickly accumulating ribosome profiling data is an insightful resource for studying the critical details of translation regulation under various biological contexts. Rocaglamide A (RocA), an antitumor heterotricyclic natural compound, has been shown to inhibit translation initiation of a large group of mRNA species by clamping eIF4A onto poly-purine motifs in the 5′ UTRs. However, reanalysis of previous ribosome profiling datasets reveals an unexpected shift of the ribosome occupancy pattern, upon RocA treatment in various types of cells, during early translation elongation for a specific group of mRNA transcripts without poly-purine motifs over-represented in their 5′ UTRs. Such perturbation of translation elongation dynamics can be attributed to the blockage of translating ribosomes due to the binding of eIF4A to the poly-purine sequence in coding regions. In summary, our study presents the complete dual modes of RocA in blocking translation initiation and elongation, which underlie the potent antitumor effect of RocA.
Glycoside hydrolase processing of the Pel polysaccharide alters biofilm biomechanics and Pseudomonas aeruginosa virulence
Authors: Razvi Erum , Whitfield Gregory B. , Reichhardt Courtney , Dreifus Julia E. , Willis Alexandra R. , Gluscencova Oxana B. , Gloag Erin S. , Awad Tarek S. , Rich Jacquelyn D. , da Silva Daniel Passos , Bond Whitney , Le Mauff François , Sheppard Donald C. , Hatton Benjamin D. , Stoodley Paul , Reinke Aaron W. , Boulianne Gabrielle L. , Wozniak Daniel J. , Harrison Joe J. , Parsek Matthew R. , Howell P. Lynne 
Published: February 2023

AbstractPel exopolysaccharide biosynthetic loci are phylogenetically widespread biofilm matrix determinants in bacteria. In Pseudomonas aeruginosa, Pel is crucial for cell-to-cell interactions and reducing susceptibility to antibiotic and mucolytic treatments. While genes encoding glycoside hydrolases have long been linked to biofilm exopolysaccharide biosynthesis, their physiological role in biofilm development is unclear. Here we demonstrate that the glycoside hydrolase activity of P. aeruginosa PelA decreases adherent biofilm biomass and is responsible for generating the low molecular weight secreted form of the Pel exopolysaccharide. We show that the generation of secreted Pel contributes to the biomechanical properties of the biofilm and decreases the virulence of P. aeruginosa in Caenorhabditis elegans and Drosophila melanogaster. Our results reveal that glycoside hydrolases found in exopolysaccharide biosynthetic systems can help shape the soft matter attributes of a biofilm and propose that secreted matrix components be referred to as matrix associated to better reflect their influence.
Biologically informed deep learning to query gene programs in single-cell atlases
Authors: Lotfollahi Mohammad , Rybakov Sergei , Hrovatin Karin , Hediyeh-zadeh Soroor , Talavera-López Carlos , Misharin Alexander V. , Theis Fabian J. 
Published: February 2023

AbstractThe increasing availability of large-scale single-cell atlases has enabled the detailed description of cell states. In parallel, advances in deep learning allow rapid analysis of newly generated query datasets by mapping them into reference atlases. However, existing data transformations learned to map query data are not easily explainable using biologically known concepts such as genes or pathways. Here we propose expiMap, a biologically informed deep-learning architecture that enables single-cell reference mapping. ExpiMap learns to map cells into biologically understandable components representing known ‘gene programs’. The activity of each cell for a gene program is learned while simultaneously refining them and learning de novo programs. We show that expiMap compares favourably to existing methods while bringing an additional layer of interpretability to integrative single-cell analysis. Furthermore, we demonstrate its applicability to analyse single-cell perturbation responses in different tissues and species and resolve responses of patients who have coronavirus disease 2019 to different treatments across cell types.
First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial
Authors: Song Yan , Zhang Bo , Xin Dao , Kou Xiaoge , Tan Zhenbo , Zhang Shu , Sun Meili , Zhou Jin , Fan Min , Zhang Ming , Song Yongxiang , Li Suyi , Yuan Yuan , Zhuang Wu , Zhang Jingdong , Zhang Li , Jiang Hao , Gu Kangsheng , Ye Huangyang , Ke Ying , Li Jing , Wang Qingyu , Zhu Jun , Huang Jing ,   The ASTRUM-007 investigators
Published: February 2023

AbstractFirst-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m2) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m2) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48–0.75; P < 0.0001). At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively; hazard ratio, 0.68; 95% confidence interval, 0.53–0.87; P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov (NCT03958890).
Low thigh muscle strength in relation to myosteatosis in patients with type 2 diabetes mellitus
Authors: Huang Yilong , Yan Jun , Zhu Hongli , Zhang Zhenguang , Jiang Yuanming , Zhang Xuxiang , Wu Yiran , Lu Jiahang , Cun Hanxue , He Bo 
Published: February 2023

AbstractThis study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p < 0.001), while PT and TW were lower than those in the control subjects (p < 0.05). Both IMF and IMAT PDFF were negatively correlated with PT, TW in participants with T2DM (extensors: r = − 0.72, − 0.70, p < 0.001; r = − 0.62, − 0.56, p < 0.05. flexors: r = − 0.37, − 0.43, p < 0.05; r = − 0.39, − 0.46, p < 0.05). Moderate and strong correlations between HOMA-IR and muscle strength measurements, muscle PDFFs were observed in extensors and flexors. IMF PDFF and age were the statistically significant predictor of PT and TW of extensors of thigh in multivariate regression analysis. Therefore, the thigh muscle PDFF increased was associated with muscle strength decreased in T2DM patients beyond SMI. Age are also important factors influencing thigh muscle PDFF and strength in T2DM patients.
The human microbial exposome: expanding the Exposome-Explorer database with gut microbial metabolites
Authors: Neveu Vanessa , Nicolas Geneviève , Amara Adam , Salek Reza M. , Scalbert Augustin 
Published: February 2023

AbstractMetabolites produced by the gut microbiota play an important role in the cross-talk with the human host. Many microbial metabolites are biologically active and can pass the gut barrier and make it into the systemic circulation, where they form the gut microbial exposome, i.e. the totality of gut microbial metabolites in body fluids or tissues of the host. A major difficulty faced when studying the microbial exposome and its role in health and diseases is to differentiate metabolites solely or partially derived from microbial metabolism from those produced by the host or coming from the diet. Our objective was to collect data from the scientific literature and build a database on gut microbial metabolites and on evidence of their microbial origin. Three types of evidence on the microbial origin of the gut microbial exposome were defined: (1) metabolites are produced in vitro by human faecal bacteria; (2) metabolites show reduced concentrations in humans or experimental animals upon treatment with antibiotics; (3) metabolites show reduced concentrations in germ-free animals when compared with conventional animals. Data was manually collected from peer-reviewed publications and inserted in the Exposome-Explorer database. Furthermore, to explore the chemical space of the microbial exposome and predict metabolites uniquely formed by the microbiota, genome-scale metabolic models (GSMMs) of gut bacterial strains and humans were compared. A total of 1848 records on one or more types of evidence on the gut microbial origin of 457 metabolites was collected in Exposome-Explorer. Data on their known precursors and concentrations in human blood, urine and faeces was also collected. About 66% of the predicted gut microbial metabolites (n = 1543) were found to be unique microbial metabolites not found in the human GSMM, neither in the list of 457 metabolites curated in Exposome-Explorer, and can be targets for new experimental studies. This new data on the gut microbial exposome, freely available in Exposome-Explorer (http://exposome-explorer.iarc.fr/), will help researchers to identify poorly studied microbial metabolites to be considered in future studies on the gut microbiota, and study their functionalities and role in health and diseases.
Transcriptome-wide analysis reveals the coregulation of RNA-binding proteins and alternative splicing genes in the development of atherosclerosis
Authors: Wang Runqing , Xu Jin , Tang Yuning , Wang Yongxiang , Zhao Jing , Ding Liqiong , Peng Yu , Zhang Zheng 
Published: January 2023

AbstractRNA-binding proteins (RBPs) are involved in the regulation of RNA splicing, stability, and localization. How RBPs control the development of atherosclerosis, is not fully understood. To explore the relevant RNA-binding proteins (RBPs) and alternative splicing events (ASEs) in atherosclerosis. We made a comprehensive work to integrate analyses of differentially expressed genes, including differential RBPs, and variable splicing characteristics related to different stages of atherosclerosis in dataset GSE104140. A total of 3712 differentially expressed genes (DEGs) were identified, including 2921 upregulated genes and 791 downregulated genes. Further analysis screened out 54 RBP genes, and 434 AS genes overlapped DEGs. We selected high expression ten RBP genes (SAMHD1, DDX60 L, TLR7, RBM47, MYEF2, RNASE6, PARP12, APOBEC3G, SMAD9, and RNASE1) for co-expression analysis. Meanwhile, we found seven regulated alternative splicing genes (RASGs) (ABI1, FXR1, CHID1, PLEC, PRKACB, BNIP2, PPP3CB) that could be regulated by RBPs. The co-expression network was used to further elucidate the regulatory and interaction relationship between RBPs and AS genes. Apoptotic process and innate immune response, revealed by the functional enrichment analysis of RASGs regulated by RBPs were closely related to atherosclerosis. In addition, 26 of the 344 alternative splicing genes regulated by the above 10 RBPs were transcription factors (TFs), We selected high expression nine TFs (TFDP1, RBBP7, STAT2, CREB5, ERG, ELF1, HMGN3, BCLAF1, and ZEB2) for co-expression analysis. The target genes of these TFs were mainly enriched in inflammatory and immune response pathways that were associated with atherosclerosis. indicating that AS abnormalities of these TFs may have a function in atherosclerosis. Furthermore, the expression of differentially expressed RBPs and the alternative splicing events of AS genes was validated by qRT-PCR in umbilical vein endothelial cells (HUVEC). The results showed that RBM47 were remarkedly difference in HUVEC treated with ox-LDL and the splicing ratio of AS in BCLAF1which is regulated by RBM47 significantly changed. In conclusion, the differentially expressed RBPs identified in our analysis may play important roles in the development of atherosclerosis by regulating the AS of these TF genes.
Dynamics of aggregate-associated organic carbon after long-term cropland conversion in a karst region, southwest China
Authors: Wen Li , Li Dejun , Xiao Kongcao , Tang Haiming , Li Chao , Xiao Xiaoping 
Published: January 2023

AbstractCropland conversion has a major impact on soil C sequestration. However, it remains unclear about the changes in soil aggregate and their contribution to C accumulation following cropland conversion in a karst region, southwest China. In this study, three different cropland use types (sugarcane, mulberry and forage grass cultivation) were selected to replace maize-soybean cultivation. The soil was collected at a depth of 0 to 30 cm for analysis of soil aggregates and their OC content. Results showed that macro-aggregate was the predominant component underlying four cropland use types. Forage grass cultivation remarkably increased the OC stock and aggregate stability (MWD and GMD). OC content and stock associated with aggregate varied with cropland use types and soil depth, but were typically highest in forage grass fields. Macro-aggregates contained higher OC content and stock than other aggregate fractions, along with soil depth underlying four cropland use types. The increases in OC stock in forage grass field was mainly due to increased OC stocks within macro-aggregates, which is further attributed to the increase in OC content within macro-aggregates. Overall, forage grass cultivation replaced maize-soybean cultivation was suggested as an ecological restoration model to enhance soil C sequestration potential, owing to its role in increasing OC stock of aggregation and aggregate stability, in the karst region of southwest China.
Machine learning models development for shear strength prediction of reinforced concrete beam: a comparative study
Authors: Yaseen Zaher Mundher 
Published: January 2023

AbstractFiber reinforced polymer (FPR) bars have been widely used as a substitutional material of steel reinforcement in reinforced concrete elements in corrosion areas. Shear resistance of FRP reinforced concrete element can be affected by concrete properties and transverse FRP stirrups. Hence, studying the shear strength (Vs) mechanism is one of the highly essential for pre-design procedure for reinforced concrete elements. This research examines the ability of three machine learning (ML) models called M5-Tree (M5), extreme learning machine (ELM), and random forest (RF) in predictingVsof 112 shear tests of FRP reinforced concrete beam with transverse reinforcement. For generating the prediction matrix of the developed ML models, statistical correlation analysis was conducted to generate the suitable inputs models forVsprediction. Statistical evaluation and graphical approaches were used to evaluate the efficiency of the proposed models. The results revealed that all the proposed models performed in general well for all the input combinations. However, ELM-M1 and M5-Tree-M5 models exhibited less accuracy performance in comparison with the other developed models. The study showed that the best prediction performance was revealed by M5 tree model using nine input parameters, with coefficient of determination (R2) and root mean square error (RMSE) equal to 0.9313 and 35.5083 KN, respectively. The comparison results also indicated that ELM and RF were performed significant results with a less slight performance than M5 model. The study outcome contributes to basic knowledge of investigating the impact of stirrups onVsof FRP reinforced concrete beam with the potential of applying different computer aid models.
Deep 3D reconstruction of synchrotron X-ray computed tomography for intact lungs
Authors: Shin Seungjoo , Kim Min Woo , Jin Kyong Hwan , Yi Kwang Moo , Kohmura Yoshiki , Ishikawa Tetsuya , Je Jung Ho , Park Jaesik 
Published: January 2023

AbstractSynchrotron X-rays can be used to obtain highly detailed images of parts of the lung. However, micro-motion artifacts induced by such as cardiac motion impede quantitative visualization of the alveoli in the lungs. This paper proposes a method that applies a neural network for synchrotron X-ray Computed Tomography (CT) data to reconstruct the high-quality 3D structure of alveoli in intact mouse lungs at expiration, without needing ground-truth data. Our approach reconstructs the spatial sequence of CT images by using a deep-image prior with interpolated input latent variables, and in this way significantly enhances the images of alveolar structure compared with the prior art. The approach successfully visualizes 3D alveolar units of intact mouse lungs at expiration and enables us to measure the diameter of the alveoli. We believe that our approach helps to accurately visualize other living organs hampered by micro-motion.
Carbon black-containing self-healing adhesive hydrogels for endoscopic tattooing
Authors: Kwon Hyung Jun , Shin Hyun Ho , Hyun Da Han , Yoon Ghilsuk , Park Jun Seok , Ryu Ji Hyun 
Published: February 2023

AbstractEndoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing.
PRMT5 is a therapeutic target in choroidal neovascularization
Authors: Muniyandi Anbukkarasi , Martin Matthew , Sishtla Kamakshi , Motolani Aishat , Sun Mengyao , Jensen Nathan R. , Qi Xiaoping , Boulton Michael E. , Prabhu Lakshmi , Lu Tao , Corson Timothy W. 
Published: January 2023

AbstractOcular neovascular diseases including neovascular age-related macular degeneration (nvAMD) are widespread causes of blindness. Patients’ non-responsiveness to currently used biologics that target vascular endothelial growth factor (VEGF) poses an unmet need for novel therapies. Here, we identify protein arginine methyltransferase 5 (PRMT5) as a novel therapeutic target for nvAMD. PRMT5 is a well-known epigenetic enzyme. We previously showed that PRMT5 methylates and activates a proangiogenic and proinflammatory transcription factor, the nuclear factor kappa B (NF-κB), which has a master role in tumor progression, notably in pancreatic ductal adenocarcinoma and colorectal cancer. We identified a potent and specific small molecule inhibitor of PRMT5, PR5-LL-CM01, that dampens the methylation and activation of NF-κB. Here for the first time, we assessed the antiangiogenic activity of PR5-LL-CM01 in ocular cells. Immunostaining of human nvAMD sections revealed that PRMT5 is highly expressed in the retinal pigment epithelium (RPE)/choroid where neovascularization occurs, while mouse eyes with laser induced choroidal neovascularization (L-CNV) showed PRMT5 is overexpressed in the retinal ganglion cell layer and in the RPE/choroid. Importantly, inhibition of PRMT5 by PR5-LL-CM01 or shRNA knockdown of PRMT5 in human retinal endothelial cells (HRECs) and induced pluripotent stem cell (iPSC)-derived choroidal endothelial cells (iCEC2) reduced NF-κB activity and the expression of its target genes, such as tumor necrosis factor α (TNF-α) and VEGF-A. In addition to inhibiting angiogenic properties of proliferation and tube formation, PR5-LL-CM01 blocked cell cycle progression at G1/S-phase in a dose-dependent manner in these cells. Thus, we provide the first evidence that inhibition of PRMT5 impedes angiogenesis in ocular endothelial cells, suggesting PRMT5 as a potential therapeutic target to ameliorate ocular neovascularization.
Effects of wounds in the cell membrane on cell division
Authors: Tanvir Md. Istiaq Obaidi , Yumura Shigehiko 
Published: February 2023

AbstractCells are consistently subjected to wounding by physical or chemical damages from the external environment. We previously showed that a local wound of the cell membrane modulates the polarity of cell migration and the wounded cells escape from the wound site in Dictyostelium. Here, we examined effects of wounds on dividing cells. When the cell membrane at the cleavage furrow during cytokinesis was locally wounded using laserporation, furrow constriction was significantly accelerated. Neither myosin II nor cortexillins contributed to the acceleration, because the acceleration was not hindered in mutant cells deficient in these proteins. When the cell membrane outside the furrow was wounded, the furrow constriction was not accelerated. Instead, the wounded-daughter half became smaller and the unwounded half became larger, resulting in an asymmetrical cell division. These phenomena occurred independently of wound repair. When cells in anaphase were wounded at the presumptive polar region, about 30% of the wounded cells changed the orientation of the division axis. From these observations, we concluded that dividing cells also escape from the wound site. The wound experiments on dividing cells also provide new insights into the mechanism of cytokinesis and cell polarity establishment.