bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-terminal acetylation can stabilize proteins independent of their ubiquitination
Authors: van de Kooij Bert , de Vries Evert , Rooswinkel Rogier W. , Janssen George M. C. , Kok Frédérique K. , van Veelen Peter A. , Borst Jannie 
Published: April 2023

AbstractThe majority of proteins in mammalian cells are modified by covalent attachment of an acetyl-group to the N-terminus (Nt-acetylation). Paradoxically, Nt-acetylation has been suggested to inhibit as well as to promote substrate degradation. Contrasting these findings, proteome-wide stability measurements failed to detect any correlation between Nt-acetylation status and protein stability. Accordingly, by analysis of protein stability datasets, we found that predicted Nt-acetylation positively correlates with protein stability in case of GFP, but this correlation does not hold for the entire proteome. To further resolve this conundrum, we systematically changed the Nt-acetylation and ubiquitination status of model substrates and assessed their stability. For wild-type Bcl-B, which is heavily modified by proteasome-targeting lysine ubiquitination, Nt-acetylation did not correlate with protein stability. For a lysine-less Bcl-B mutant, however, Nt-acetylation correlated with increased protein stability, likely due to prohibition of ubiquitin conjugation to the acetylated N-terminus. In case of GFP, Nt-acetylation correlated with increased protein stability, as predicted, but our data suggest that Nt-acetylation does not affect GFP ubiquitination. Similarly, in case of the naturally lysine-less protein p16, Nt-acetylation correlated with protein stability, regardless of ubiquitination on its N-terminus or on an introduced lysine residue. A direct effect of Nt-acetylation on p16 stability was supported by studies in NatB-deficient cells. Together, our studies argue that Nt-acetylation can stabilize proteins in human cells in a substrate-specific manner, by competition with N-terminal ubiquitination, but also by other mechanisms that are independent of protein ubiquitination status.
Exogenous application of selenium and nano-selenium alleviates salt stress and improves secondary metabolites in lemon verbena under salinity stress
Authors: Ghanbari Fardin , Bag-Nazari Majid , Azizi Afsaneh 
Published: April 2023

AbstractSalinity stress is one of the most serious abiotic factors that affects the growth, performance, and secondary compounds of medicinal plants. The aim of this study was to determine the effect of foliar application of selenium and nano-selenium separately on growth, essential oils, physiological parameters, and some secondary metabolites of Lemon verbena under salinity stress. The results showed that selenium and nano-selenium significantly increased growth parameters, photosynthetic pigments, and relative water content. Compared to the control, a higher accumulation of osmolytes (i.e., proline, soluble sugars, and total protein) and higher antioxidant activity were observed in the selenium-treated plants. In addition, selenium alleviated the adversary effect of oxidative stress, resulting from salinity, by reducing leaf electrolyte leakage, malondialdehyde, and H2O2accumulation. Furthermore, selenium and nano-selenium enhanced the biosynthesis of secondary metabolites such as essential oils, total phenolic content, and flavonoid compounds under non-stress and salinity conditions. They also reduced Na+accumulation in the root and shoot of the salinity-treated plants. Hence it can be concluded that exogenous application of selenium and nano-selenium separately can mitigate the negative effects of salinity by improving the quantitative and qualitative performance of lemon verbena plants under salinity stress.
Drug cytotoxicity screening using human intestinal organoids propagated with extensive cost-reduction strategies
Authors: Takahashi Yu , Inoue Yu , Sato Shintaro , Okabe Takayoshi , Kojima Hirotatsu , Kiyono Hiroshi , Shimizu Makoto , Yamauchi Yoshio , Sato Ryuichiro 
Published: April 2023

AbstractOrganoids are regarded as physiologically relevant cell models and useful for compound screening for drug development; however, their applications are currently limited because of the high cost of their culture. We previously succeeded in reducing the cost of human intestinal organoid culture using conditioned medium (CM) of L cells co-expressing Wnt3a, R-spondin1, and Noggin. Here, we further reduced the cost by replacing recombinant hepatocyte growth factor with CM. Moreover, we showed that embedding organoids in collagen gel, a more inexpensive matrix than Matrigel, maintains organoid proliferation and marker gene expression similarly when using Matrigel. The combination of these replacements also enabled the organoid-oriented monolayer cell culture. Furthermore, screening thousands of compounds using organoids expanded with the refined method identified several compounds with more selective cytotoxicity against organoid-derived cells than Caco-2 cells. The mechanism of action of one of these compounds, YC-1, was further elucidated. We showed that YC-1 induces apoptosis through the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, the mechanism of which was distinct from cell death caused by other hit compounds. Our cost-cutting methodology enables large-scale intestinal organoid culture and subsequent compound screening, which could expand the application of intestinal organoids in various research fields.
DeepNAPSI multi-reader nail psoriasis prediction using deep learning
Authors: Folle Lukas , Fenzl Pauline , Fagni Filippo , Thies Mareike , Christlein Vincent , Meder Christine , Simon David , Minopoulou Ioanna , Sticherling Michael , Schett Georg , Maier Andreas , Kleyer Arnd 
Published: April 2023

AbstractNail psoriasis occurs in about every second psoriasis patient. Both, finger and toe nails can be affected and also severely destroyed. Furthermore, nail psoriasis is associated with a more severe course of the disease and the development of psoriatic arthritis. User independent quantification of nail psoriasis, however, is challenging due to the heterogeneous involvement of matrix and nail bed. For this purpose, the nail psoriasis severity index (NAPSI) has been developed. Experts grade pathological changes of each nail of the patient leading to a maximum score of 80 for all nails of the hands. Application in clinical practice, however, is not feasible due to the time-intensive manual grading process especially if more nails are involved. In this work we aimed to automatically quantify the modified NAPSI (mNAPSI) of patients using neuronal networks retrospectively. First, we performed photographs of the hands of patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis. In a second step, we collected and annotated the mNAPSI scores of 1154 nail photos. Followingly, we extracted each nail automatically using an automatic key-point-detection system. The agreement among the three readers with a Cronbach’s alpha of 94% was very high. With the nail images individually available, we trained a transformer-based neural network (BEiT) to predict the mNAPSI score. The network reached a good performance with an area-under-receiver-operator-curve of 88% and an area-under precision-recall-curve (PR-AUC) of 63%. We could compare the results with the human annotations and achieved a very high positive Pearson correlation of 90% by aggregating the predictions of the network on the test set to the patient-level. Lastly, we provided open access to the whole system enabling the use of the mNAPSI in clinical practice.
A COVID-19 medical image classification algorithm based on Transformer
Authors: Ren Keying , Hong Geng , Chen Xiaoyan , Wang Zichen 
Published: April 2023

AbstractCoronavirus 2019 (COVID-19) is a new acute respiratory disease that has spread rapidly throughout the world. This paper proposes a novel deep learning network based on ResNet-50 merged transformer named RMT-Net. On the backbone of ResNet-50, it uses Transformer to capture long-distance feature information, adopts convolutional neural networks and depth-wise convolution to obtain local features, reduce the computational cost and acceleration the detection process. The RMT-Net includes four stage blocks to realize the feature extraction of different receptive fields. In the first three stages, the global self-attention method is adopted to capture the important feature information and construct the relationship between tokens. In the fourth stage, the residual blocks are used to extract the details of feature. Finally, a global average pooling layer and a fully connected layer perform classification tasks. Training, verification and testing are carried out on self-built datasets. The RMT-Net model is compared with ResNet-50, VGGNet-16, i-CapsNet and MGMADS-3. The experimental results show that the RMT-Net model has a Test_ acc of 97.65% on the X-ray image dataset, 99.12% on the CT image dataset, which both higher than the other four models. The size of RMT-Net model is only 38.5 M, and the detection speed of X-ray image and CT image is 5.46 ms and 4.12 ms per image, respectively. It is proved that the model can detect and classify COVID-19 with higher accuracy and efficiency.
Spatial subcellular organelle networks in single cells
Authors: Venkatesan Mythreye , Zhang Nicholas , Marteau Benoit , Yajima Yukina , De Zarate Garcia Nerea Ortiz , Fang Zhou , Hu Thomas , Cai Shuangyi , Ford Adam , Olszewski Harrison , Borst Andrew , Coskun Ahmet F. 
Published: April 2023

AbstractOrganelles play important roles in human health and disease, such as maintaining homeostasis, regulating growth and aging, and generating energy. Organelle diversity in cells not only exists between cell types but also between individual cells. Therefore, studying the distribution of organelles at the single-cell level is important to understand cellular function. Mesenchymal stem cells are multipotent cells that have been explored as a therapeutic method for treating a variety of diseases. Studying how organelles are structured in these cells can answer questions about their characteristics and potential. Herein, rapid multiplexed immunofluorescence (RapMIF) was performed to understand the spatial organization of 10 organelle proteins and the interactions between them in the bone marrow (BM) and umbilical cord (UC) mesenchymal stem cells (MSCs). Spatial correlations, colocalization, clustering, statistical tests, texture, and morphological analyses were conducted at the single cell level, shedding light onto the interrelations between the organelles and comparisons of the two MSC subtypes. Such analytics toolsets indicated that UC MSCs exhibited higher organelle expression and spatially spread distribution of mitochondria accompanied by several other organelles compared to BM MSCs. This data-driven single-cell approach provided by rapid subcellular proteomic imaging enables personalized stem cell therapeutics.
Repair of critical-sized bone defects in rabbit femurs using graphitic carbon nitride (g-C3N4) and graphene oxide (GO) nanomaterials
Authors: Sadek Ahmed Abdelrahiem , Abd-Elkareem Mahmoud , Abdelhamid Hani Nasser , Moustafa Samia , Hussein Kamal 
Published: April 2023

AbstractVarious biomaterials have been evaluated to enhance bone formation in critical-sized bone defects; however, the ideal scaffold is still missing. The objective of this study was to investigate the in vitro and in vivo regenerative capacity of graphitic carbon nitride (g-C3N4) and graphene oxide (GO) nanomaterials to stimulate critical-sized bone defect regeneration. The in vitro cytotoxicity and hemocompatibility of g-C3N4and GO were evaluated, and their potential to induce the in vitro osteogenesis of human fetal osteoblast (hFOB) cells was assessed using qPCR. Then, bone defect in femoral condyles was created in rabbits and left empty as control or filled with either g-C3N4or GO. The osteogenesis of the different implanted scaffolds was evaluated after 4, 8, and 12 weeks of surgery using X-ray, computed tomography (CT), macro/microscopic examinations, and qPCR analysis of osteocalcin (OC) and osteopontin (OP) expressions. Both materials displayed good cell viability and hemocompatibility with enhanced collagen type-I (Col-I), OC, and OP expressions of the hFOB cells. Compared to the control group, the bone healing process in g-C3N4and GO groups was promoted in vivo. Moreover, complete healing of the bone defect was observed radiologically and grossly in g-C3N4implanted group. Additionally, g-C3N4implanted group showed higher percentages of osteoid tissue, mature collagen, biodegradation, and expressions of OC and OP. In conclusion, our results revealed that g-C3N4and GO nanomaterials could induce osteogenesis in critical-sized bone defects.
Tribological behaviors of laser textured surface under different lubrication conditions for rotary compressor
Authors: Ding Shaopeng , Wei Huijun , Yang Ouxiang , Deng Liying , Mu Di 
Published: April 2023

AbstractTribological behaviors of laser textured surface with elliptical dimples were experimentally compared with that of the smooth one under different lubrication conditions, including the poor-oil, rich-oil and dry lubrication. The lubrication regime was analyzed with the increasing operating load by ring-on-ring tribological tests. Finally, the performance impact of rolling piston rotary compressor with textures fabricated on the thrust surfaces was investigated. Results show that the tribological improvement strongly depends on lubrication condition. With the increase of applied loads under rich-oil and poor-oil lubrication, the effect of micro dimple promotes the critical load transforming lubrication regime, and expands the range of hydrodynamic lubrication, meanwhile maintains a similar minimum of friction coefficient as the smooth surface but enhances wear resistance. However, it is reverse to increase the friction coefficient and surface wear for the textured surfaces under dry lubrication. The compressor performance can be improved significantly by laser surface texturing with a 2% reduction of friction power consumption and a 2.5% enhancement of energy efficiency ratio.
Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide
Authors: Zhang Kun , Zhang Chaoguo , Teng Xiuli , Wang Ke , Chen Mingwei 
Published: April 2023

AbstractDepression affects people with multiple adverse outcomes, and the side effects of antidepressants are troubling for depression sufferers. Aromatic drugs have been widely used to relieve symptoms of depression with fewer side effects. Ligustilide (LIG) is the main component of volatile oil in angelica sinensis, exhibiting an excellent anti-depressive effect. However, the mechanisms of the anti-depressive effect of LIG remain unclear. Therefore, this study aimed to explore the mechanisms of LIG exerting an anti-depressive effect. We obtained 12,969 depression-related genes and 204 LIG targets by a network pharmacology approach, which were intersected to get 150 LIG anti-depressive targets. Then, we identified core targets by MCODE, including MAPK3, EGF, MAPK14, CCND1, IL6, CASP3, IL2, MYC, TLR4, AKT1, ESR1, TP53, HIF1A, SRC, STAT3, AR, IL1B, and CREBBP. Functional enrichment analysis of core targets showed a significant association with PI3K/AKT and MAPK signaling pathways. Molecular docking showed strong affinities of LIG with AKT1, MAPK14, and ESR1. Finally, we validated the interactions between these proteins and LIG by molecular dynamics (MD) simulations. In conclusion, this study successfully predicted that LIG exerted an anti-depressive effect through multiple targets, including AKT1, MAPK14, and ESR1, and the pathways of PI3K/AKT and MAPK. The study provides a new strategy to explore the molecular mechanisms of LIG in treating depression.
Development of a new HISCL automated CXCL9 immunoassay
Authors: Hasegawa Takehiro , Yoshida Maho , Watanabe Shunsuke , Kondo Takami , Asada Hideo , Nakagawa Atsushi , Tomii Keisuke , Kameda Masami , Otsuka Mitsuo , Kuronuma Koji , Chiba Hirofumi , Katayanagi Shinji , Miyazaki Yasunari , Mori Akio 
Published: April 2023

AbstractC–X–C motif chemokine ligand 9 (CXCL9), a candidate biomarker, reflects type 1 (T1) inflammation pathology. Here, we report the analytical performance and clinical characteristics of a new CXCL9 reagent for a fully automated immunoassay device. We evaluated the limits of blank, detection, and quantitation (LoQ) along with other efficacy parameters, and the ability of the assay to report patient health, COVID-19 status, and the presence of asthma and/or interstitial lung diseases (ILDs). The coefficient of variation for 5-day total precision using two instruments was 7% across two controls, serum, and plasma panels. LoQ of 2.2 pg/mL suggested the efficacy of the assay in detecting T1 inflammation in plasma or serum; no cross-reactivity or interference was observed. We identified high serum CXCL9 levels in samples from patients with acute COVID-19 infections (n = 57), chronic bird-related hypersensitivity pneumonitis (n = 61), asthma (n = 194), and ILDs (n = 84) compared to healthy individuals (< 39.0 pg/mL). Furthermore, CXCL9 levels increased with age in asthma patients, and an opposite trend was observed for T2 inflammatory factors. These results suggest the utility of the automated CXCL9 immunoassay for measuring CXCL9 in clinical samples and reflect its role in T1 inflammation.
Heat denaturation enables multicolor X10-STED microscopy
Authors: Saal Kim Ann , Shaib Ali H. , Mougios Nikolaos , Crzan Dagmar , Opazo Felipe , Rizzoli Silvio O. 
Published: April 2023

AbstractExpansion microscopy (ExM) improves imaging quality by physically enlarging the biological specimens. In principle, combining a large expansion factor with optical super-resolution should provide extremely high imaging precision. However, large expansion factors imply that the expanded specimens are dim and are therefore poorly suited for optical super-resolution. To solve this problem, we present a protocol that ensures the expansion of the samples up to 10-fold, in a single expansion step, through high-temperature homogenization (X10ht). The resulting gels exhibit a higher fluorescence intensity than gels homogenized using enzymatic digestion (based on proteinase K). This enables the sample analysis by multicolor stimulated emission depletion (STED) microscopy, for a final resolution of 6–8 nm in neuronal cell cultures or isolated vesicles. X10ht also enables the expansion of 100–200 µm thick brain samples, up to 6-fold. The better epitope preservation also enables the use of nanobodies as labeling probes and the implementation of post-expansion signal amplification. We conclude that X10ht is a promising tool for nanoscale resolution in biological samples.
Validity and reliability of the Apple Health app on iPhone for measuring gait parameters in children, adults, and seniors
Authors: Werner Christian , Hezel Natalie , Dongus Fabienne , Spielmann Jan , Mayer Jan , Becker Clemens , Bauer Jürgen M. 
Published: April 2023

AbstractThis study assessed the concurrent validity and test–retest-reliability of the Apple Health app on iPhone for measuring gait parameters in different age groups. Twenty-seven children, 28 adults and 28 seniors equipped with an iPhone completed a 6-min walk test (6MWT). Gait speed (GS), step length (SL), and double support time (DST) were extracted from the gait recordings of the Health app. Gait parameters were simultaneously collected with an inertial sensors system (APDM Mobility Lab) to assess concurrent validity. Test–retest reliability was assessed via a second iPhone-instrumented 6MWT 1 week later. Agreement of the Health App with the APDM Mobility Lab was good for GS in all age groups and for SL in adults/seniors, but poor to moderate for DST in all age groups and for SL in children. Consistency between repeated measurements was good to excellent for all gait parameters in adults/seniors, and moderate to good for GS and DST but poor for SL in children. The Health app on iPhone is reliable and valid for measuring GS and SL in adults and seniors. Careful interpretation is required when using the Health app in children and when measuring DST in general, as both have shown limited validity and/or reliability.
Dietary iodine attenuates allergic rhinitis by inducing ferroptosis in activated B cells
Authors: Nakamura Yutaka , Fuse Yozen , Komiyama Seiga , Nagatake Takahiro , Kunisawa Jun , Hase Koji 
Published: April 2023

AbstractIodine-containing formulations have been widely used to treat iodine deficiency and as antiseptics. Lecithin-bound iodine (LBI) has been approved to treat allergic diseases in Japan; however, its underlying mechanism remains unknown. In this study, we show that LBI ameliorated disease symptoms in an ovalbumin (OVA)-induced allergic rhinitis mouse model. LBI suppressed OVA-specific IgE production by attenuating germinal center (GC) reaction in the draining lymph nodes. The antiallergic effect of LBI is most likely attributed to increased serum iodine levels but not thyroid hormone levels. In vitro treatment of activated B cells with potassium iodide induced ferroptosis by increasing intracellular reactive oxygen species (ROS) and ferrous iron in a concentration-dependent manner. Accordingly, LBI diets increased ROS levels in GC B cells of the draining lymph nodes. This study suggests that iodine directly promotes ferroptosis in activated B cells and attenuates GC reactions, leading to the alleviation of allergic symptoms.
Rewiring of the 3D genome during acquisition of carboplatin resistance in a triple-negative breast cancer patient-derived xenograft
Authors: Dozmorov Mikhail G. , Marshall Maggie A. , Rashid Narmeen S. , Grible Jacqueline M. , Valentine Aaron , Olex Amy L. , Murthy Kavita , Chakraborty Abhijit , Reyna Joaquin , Figueroa Daniela Salgado , Hinojosa-Gonzalez Laura , Da-Inn Lee Erika , Baur Brittany A. , Roy Sushmita , Ay Ferhat , Harrell J. Chuck 
Published: April 2023

AbstractChanges in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (< 2 Mb) interactions, chromatin looping, formation of TAD, chromatin state switching into a more active state, and amplification of ATP-binding cassette transporters. Transcriptome changes suggested the role of long-noncoding RNAs in carboplatin resistance. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of aggressiveness-, metastasis- and other cancer-related pathways. Integrative analysis highlighted increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial energy metabolism. Our results suggest that 3D genome remodeling may be a key mechanism underlying carboplatin resistance.