bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and functional characterization of the catalytic domain of a cell-wall anchored bacterial lytic polysaccharide monooxygenase from Streptomyces coelicolor
Authors: Votvik Amanda K. , Røhr Åsmund K. , Bissaro Bastien , Stepnov Anton A. , Sørlie Morten , Eijsink Vincent G. H. , Forsberg Zarah
Published: April 2023

Bacterial lytic polysaccharide monooxygenases (LPMOs) are known to oxidize the most abundant and recalcitrant polymers in Nature, namely cellulose and chitin. The genome of the model actinomycete Streptomyces coelicolor A3(2) encodes seven putative LPMOs, of which, upon phylogenetic analysis, four group with typical chitin-oxidizing LPMOs, two with typical cellulose-active LPMOs, and one which stands out by being part of a subclade of non-characterized enzymes. The latter enzyme, called ScLPMO10D, and most of the enzymes found in this subclade are unique, not only because of variation in the catalytic domain, but also as their C-terminus contains a cell wall sorting signal (CWSS), which flags the LPMO for covalent anchoring to the cell wall. Here, we have produced a truncated version of ScLPMO10D without the CWSS and determined its crystal structure, EPR spectrum, and various functional properties. While showing several structural and functional features typical for bacterial cellulose active LPMOs, ScLPMO10D is only active on chitin. Comparison with two known chitin-oxidizing LPMOs of different taxa revealed interesting functional differences related to copper reactivity. This study contributes to our understanding of the biological roles of LPMOs and provides a foundation for structural and functional comparison of phylogenetically distant LPMOs with similar substrate specificities.
Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors
Authors: Bapat Aditi S. , O’Connor Christine H. , Schwertfeger Kathryn L.
Published: April 2023

Interactions between tumor cells and the tumor microenvironment are critical for tumor growth, progression, and response to therapy. Effective targeting of oncogenic signaling pathways in tumors requires an understanding of how these therapies impact both tumor cells and cells within the tumor microenvironment. One such pathway is the janus kinase (JAK)/signal transducer and activator or transcription (STAT) pathway, which is activated in both breast cancer cells and in tumor associated macrophages. This study demonstrates that exposure of macrophages to JAK inhibitors leads to activation of NF-κB signaling, which results in increased expression of genes known to be associated with therapeutic resistance. Furthermore, inhibition of the NF-κB pathway improves the ability of ruxolitinib to reduce mammary tumor growth in vivo. Thus, the impact of the tumor microenvironment is an important consideration in studying breast cancer and understanding such mechanisms of resistance is critical to development of effective targeted therapies.
Microfluidic platform for the reproduction of hypoxic vascular microenvironments
Authors: Takahashi Naoyuki , Yoshino Daisuke , Sugahara Ryuji , Hirose Satomi , Sone Kazuki , Rieu Jean-Paul , Funamoto Kenichi
Published: April 2023

Vascular endothelial cells (ECs) respond to mechanical stimuli caused by blood flow to maintain vascular homeostasis. Although the oxygen level in vascular microenvironment is lower than the atmospheric one, the cellular dynamics of ECs under hypoxic and flow exposure are not fully understood. Here, we describe a microfluidic platform for the reproduction hypoxic vascular microenvironments. Simultaneous application of hypoxic stress and fluid shear stress to the cultured cells was achieved by integrating a microfluidic device and a flow channel that adjusted the initial oxygen concentration in a cell culture medium. An EC monolayer was then formed on the media channel in the device, and the ECs were observed after exposure to hypoxic and flow conditions. The migration velocity of the ECs immediately increased after flow exposure, especially in the direction opposite to the flow direction, and gradually decreased, resulting in the lowest value under the hypoxic and flow exposure condition. The ECs after 6-h simultaneous exposure to hypoxic stress and fluid shear stress were generally aligned and elongated in the flow direction, with enhanced VE-cadherin expression and actin filament assembly. Thus, the developed microfluidic platform is useful for investigating the dynamics of ECs in vascular microenvironments.
The evaluation of the role of diabetes health literacy and health locus of control on quality of life among type 2 diabetes using the Path analysis
Authors: Jafari Alireza , Zadehahmad Zohreh , Armanmehr Vajihe , Talebi Mahdi , Tehrani Hadi
Published: April 2023

Quality of life (QOL) in patients with diabetes is affected by multiple factors, and this study aimed to determine the effect of health locus of control points (HLOC) and diabetes health literacy (DHL) on QOL in Iranian patients with type 2 diabetes. This cross-sectional study was conducted between October 2021 and February 2022 among 564 people with type 2 diabetes. Patients were selected using proportional stratified sampling and simple random sampling methods. Data were collected using three questionnaires: (1) Multidimensional Health Locus of Control scale (form C), (2) World Health Organization Quality of Life Scale, and (3) Diabetes Health Literacy Scale. Data were analyzed by software’s of SPSSV22and AMOSV24. There was a positive and significant correlation between DHL and QOL. There was a positive and significant correlation between the subscales of internal HLOC, and doctors HLOC with QOL. According to the Path analysis results, all variables showed 58.93% of the direct effects and 41.07% of indirect effects of the final model. Numerate health literacy, informational health literacy, communicative health literacy, internal HLOC, other powerful people HLOC, chance HLOC, and doctors HLOC were able to predicted 49% variance of diabetes QOL (R2 = 0.49). The subscales of communicative health literacy, informational health literacy, internal HLOC, doctors HLOC, and chance HLOC had the greatest impact on QOL of people with diabetes. Based on the results of Path analysis, diabetes health literacy and HLOC play an effective role in QOL of diabetic. Therefore, there is a need to design and implement programs to improve the health literacy of patients as well as HLOC to improve QOL of patients.
Measurements of tendon length changes during stretch–shortening cycles in rat soleus
Authors: Fukutani Atsuki , Hashizume Satoru , Isaka Tadao
Published: April 2023

The muscle force attained during concentric contractions is augmented by a preceding eccentric contraction (the stretch–shortening cycle (SSC) effect). At present, tendon elongation is considered the primary mechanism. However, we recently found that the magnitude of the SSC effect was not different, even after removing the Achilles tendon. To resolve these discrepant results, direct measurement of changes in Achille tendon length is required. Therefore, this study aimed to elucidate the influence of tendon elongation on the SSC effect by directly measuring the changes in Achilles tendon length. The rat soleus was subjected to pure concentric contractions (pure shortening trials) and concentric contractions with a preceding eccentric contraction (SSC trials). During these contractions, the Achilles tendon length was visualized using a video camera. The muscle force attained during the concentric contraction phase in the SSC trial was significantly larger than that in the pure shortening trial (p = 0.022), indicating the existence of the SSC effect. However, the changes in Achilles tendon length were not different between trials (i.e., the magnitude of tendon shortening attained during the shortening phase was 0.20 ± 0.14 mm for the SSC trial vs. 0.17 ± 0.09 mm for the pure shortening trial), indicating that the observed SSC effect is difficult to be explained by the elastic energy stored in tendons or muscle–tendon interaction. In conclusion, the effect of tendon elongation on the SSC effect should be reconsidered, and other factors may contribute to the SSC effect.
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

The 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

Salinity 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

Organoids 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

Nail 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

Coronavirus 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

Organelles 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

Various 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

Tribological 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

Depression 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

C–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

Expansion 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

This 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

Iodine-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

Changes 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.
Study of the competition between Colletotrichum godetiae and C. nymphaeae, two pathogenic species in olive
Authors: Garcia-Lopez M. Teresa , Serrano M. Socorro , Camiletti Boris X. , Gordon Ana , Estudillo Cristina , Trapero Antonio , Diez Concepcion M. , Moral Juan
Published: April 2023

Olive anthracnose, a critical olive fruit disease that adversely impacts oil quality, is caused by Colletotrichum species. A dominant Colletotrichum species and several secondary species have been identified in each olive-growing region. This study surveys the interspecific competition between C. godetiae, dominant in Spain, and C. nymphaeae, prevalent in Portugal, to shed light on the cause of this disparity. When Petri-dishes of Potato Dextrose Agar (PDA) and diluted PDA were co-inoculated with spore mixes produced by both species, C. godetiae displaced C. nymphaeae, even if the percentage of spores in the initial spore mix inoculation was just 5 and 95%, respectively. The C. godetiae and C. nymphaeae species showed similar fruit virulence in separate inoculations in both cultivars, the Portuguese cv. Galega Vulgar and the Spanish cv. Hojiblanca, and no cultivar specialization was observed. However, when olive fruits were co-inoculated, the C. godetiae species showed a higher competitive ability and partially displaced the C. nymphaeae species. Furthermore, both Colletotrichum species showed a similar leaf survival rate. Lastly, C. godetiae was more resistant to metallic copper than C. nymphaeae. The work developed here allows a deeper understanding of the competition between C. godetiae and C. nymphaeae, which could lead to developing strategies for more efficient disease risk assessment.
In silico study of HASDI (high-affinity selective DNA intercalator) as a new agent capable of highly selective recognition of the DNA sequence
Authors: Zaremba Andrii A. , Zaremba Polina Yu. , Zahorodnia Svitlana D.
Published: April 2023

Cancer as an acquired genetic disease is based on changes both in the genome itself and in transcription processes. Accordingly, it is at the DNA level that it makes sense to search for and design agents capable of effective and selective anticancer action. In this study, we used an iterative approach based on a molecular dynamics simulation to design a highly selective DNA-intercalating agent called HASDI. To confirm its selective affinity to DNA, we conducted two simulation experiments: HASDI in a complex with a DNA fragment of the EBNA1 gene (it targets 16 nucleotide pairs of this gene) and HASDI in a complex with a random DNA fragment of the KCNH2 gene. The molecular dynamics simulation was carried out in the GROMACS 2019 package. The binding energy was calculated by gmx_MMPBSA 1.5.2. The further analysis was performed using the built-in utilities of GROMACS, gmx_MMPBSA and also XMGRACE and Pymol 1.8. As a result, we determined that the EBNA1-50nt/HASDI complex was stable throughout the whole simulation trajectory. HASDI, due to the presence of a linker modified depending on a specific pair of nitrogenous bases, formed an average of 32 hydrogen bonds with a sequence of 16 nucleotide pairs. Phenazine rings were stably intercalated every 2 base pairs. The root-mean-square deviation of HASDI in such a complex fluctuated around the value of 6.5 Å and had no tendency to increase. The calculated value of the binding free energy was − 235.3 ± 7.77 kcal/mol. The KCNH2-50nt/HASDI complex, as an example of the intercalation of the designed structure into a random part of the human genome, maintained the stability of its position at a level comparable to the EBNA1-50nt/HASDI complex. The phenazine rings were constantly intercalated in their original positions, and the root-mean-square deviation fluctuated around one value, although it had a tendency to chaotic changes. At the same time, this complex was characterized by 17–19 hydrogen bonds, on average, and the binding free energy was − 193.47 ± 14.09 kcal/mol. Moreover, the DNA duplex had local single-nucleotide melting in the region of the 4th linker. According to a significant decrease in the number of hydrogen bonds, a decrease in energy gain, as well as a decrease in the stability of the DNA duplex characteristic of the KCNH2-50nt/HASDI complex compared to the target EBNA1-50nt/HASDI complex, the molecule we designed can be considered a potentially selective DNA polyintercalating agent capable of relatively accurate recognition of 16 base pairs.
Control of magnetic states and spin interactions in bilayer CrCl3 with strain and electric fields: an ab initio study
Authors: Ebrahimian Ali , Dyrdał Anna , Qaiumzadeh Alireza
Published: April 2023

Using ab initio density functional theory, we demonstrated the possibility of controlling the magnetic ground-state properties of bilayer CrCl$$_{3}$$

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by means of mechanical strains and electric fields. In principle, we investigated the influence of these two fields on parameters describing the spin Hamiltonian of the system. The obtained results show that biaxial strains change the magnetic ground state between ferromagnetic and antiferromagnetic phases. The mechanical strain also affects the direction and amplitude of the magnetic anisotropy energy (MAE). Importantly, the direction and amplitude of the Dzyaloshinskii–Moriya vectors are also highly tunable under external strain and electric fields. The competition between nearest-neighbor exchange interactions, MAE, and Dzyaloshinskii–Moriya interactions can lead to the stabilization of various exotic spin textures and novel magnetic excitations. The high tunability of magnetic properties by external fields makes bilayer CrCl$$_{3}$$

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a promising candidate for application in the emerging field of two-dimensional quantum spintronics and magnonics.
Long noncoding RNA SNHG6 silencing sensitized esophageal cancer cells to 5-FU via EZH2/STAT pathway
Authors: Tan Ran , Liu Jia , Wang Jiang , Zhang Wei , He Meng , Zhang Yueli
Published: April 2023

Chemotherapy was the main treatment method for esophageal cancer (EC) patients. However, chemotherapy resistance due to multiple factors is a major barrier to EC treatment. For investigating how small nucleolar RNA host gene 6 (SNHG6) affected the 5-fluorouracil (5-FU) resistance in EC as well as its possible molecular mechanism. This work conducted cell viability assay, clone formation, scratch assays together with cell apoptosis for evaluating the roles of SNHG6 and enhancer of zeste homolog 2 (EZH2, the histone-lysine N-methyltransferase). Relevant molecular mechanism was identified by RT-qPCR analysis together with Western-blot (WB) assays. Our data showed that SNHG6 expression increased in EC cells. SNHG6 promotes colony formation and migration, whereas suppresses EC cell apoptosis. SNHG6 silencing markedly promoted 5-FU-mediated suppression on KYSE150 and KYSE450 cells. Additional mechanism studies showed that SNHG6 modulating STAT3 and H3K27me3 via promoting EZH2 level. Similar to the function of SNHG6, abnormal expression of EZH2 promotes the malignancy of EC and intensifies its resistance to 5-FU. In addition, overexpression of EZH2 abolished the role of SNHG6 silencing in 5-FU sensitivity in EC cells. SNHG6 overexpression promoted malignancy of EC and increased EC cell resistance to 5-FU. Besides, further molecular mechanism studies provided a novel regulatory pathways that SNHG6 knockdown promoted EC cell sensitivity to 5-FU by modulating STAT3 and H3K27me3 via promoting EZH2 expression.
Hidden chamber discovery in the underground Hellenistic necropolis of Neapolis by muography
Authors: Tioukov Valeri , Morishima Kunihiro , Leggieri Carlo , Capriuoli Federico , Kitagawa Nobuko , Kuno Mitsuaki , Manabe Yuta , Nishio Akira , Alexandrov Andrey , Gentile Valerio , Iuliano Antonio , De Lellis Giovanni
Published: April 2023

We report in this paper the muography of an archaeological site located in the highly populated “Sanità” district in the center of Naples, ten meters below the current street level. Several detectors capable of detecting muons - high energy charged particles produced by cosmic rays in the upper layers of atmosphere - were installed underground at the depth of 18 m, to measure the muon flux over several weeks. By measuring the differential flux with our detectors in a wide angular range, we have produced a radiographic image of the upper layers. Despite the architectural complexity of the site, we have clearly observed the known structures as well as a few unknown ones. One of the observed new structures is compatible with the existence of a hidden, currently inaccessible, burial chamber.
Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study
Authors: Yamagata Hiroki , Hayashi Aiko , Yoshida Yoich , Koshizaka Masaya , Onishi Shunichiro , Yoshida Tomohiko , Hiwasa Takaki , Takemoto Minoru
Published: April 2023

In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is integral to cholesterol metabolism, have also been observed. PCSK9 was also reported to be associated with insulin secretion and diabetes mellitus (DM). Therefore, we aimed to examine the clinical significance of PCSK9 antibodies (PCSK9-Abs) levels. We measured blood PCSK9-Abs and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with DM (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. The primary endpoint of this study was to examine whether PCSK9-Abs can be a prognostic marker for overall mortality among the patients with diabetes. The secondary endpoint was to examine the relationship between PCSK9-Abs and clinical parameters. Although both PCSK9-Abs and PCSK9 protein levels were significantly higher in the DM group than in the HD group (p < 0.008), PCSK9-Abs and PCSK9 protein levels showed no correlation in either group. Mortality was significantly associated with higher PCSK9-Ab levels, but unrelated to PCSK9 protein levels. After investigating for potential confounding factors, higher PCSK9-Ab levels were still associated with increased mortality among the patients with DM. PCSK9-Abs may be a novel prognostic marker for overall mortality in patients with diabetes, and further studies are warranted to verify its usefulness.
Sound source localization based on residual network and channel attention module
Authors: Hu Fucai , Song Xiaohui , He Ruhan , Yu Yongsheng
Published: April 2023

This paper presents a sound source localization (SSL) model based on residual network and channel attention mechanism. The method takes the combination of log-Mel spectrogram and generalized cross-correlation phase transform (GCC-PHAT) as the input features, and extracts the time–frequency information by using the residual structure and channel attention mechanism, thus obtaining a better localizing performance. The residual blocks are introduced to extract deeper features, which can stack more layers for high-level features and avoid gradient vanishing or exploding at the same time. The attention mechanism is taken into account for the feature extraction stage in the proposed SSL model, which can focus on the most important information on the input features. We use the signals collected by microphone array to explore the performance of the model under different features, and find the most suitable input features of the proposed method. We compare our method with other models on public dataset. Experience results show a quite substantial improvement of sound source localizing performance.
A database of heterogeneous faces for studying naturalistic expressions
Authors: Long Houqiu , Peluso Natalie , Baker Chris I. , Japee Shruti , Taubert Jessica
Published: April 2023

Facial expressions are thought to be complex visual signals, critical for communication between social agents. Most prior work aimed at understanding how facial expressions are recognized has relied on stimulus databases featuring posed facial expressions, designed to represent putative emotional categories (such as ‘happy’ and ‘angry’). Here we use an alternative selection strategy to develop the Wild Faces Database (WFD); a set of one thousand images capturing a diverse range of ambient facial behaviors from outside of the laboratory. We characterized the perceived emotional content in these images using a standard categorization task in which participants were asked to classify the apparent facial expression in each image. In addition, participants were asked to indicate the intensity and genuineness of each expression. While modal scores indicate that the WFD captures a range of different emotional expressions, in comparing the WFD to images taken from other, more conventional databases, we found that participants responded more variably and less specifically to the wild-type faces, perhaps indicating that natural expressions are more multiplexed than a categorical model would predict. We argue that this variability can be employed to explore latent dimensions in our mental representation of facial expressions. Further, images in the WFD were rated as less intense and more genuine than images taken from other databases, suggesting a greater degree of authenticity among WFD images. The strong positive correlation between intensity and genuineness scores demonstrating that even the high arousal states captured in the WFD were perceived as authentic. Collectively, these findings highlight the potential utility of the WFD as a new resource for bridging the gap between the laboratory and real world in studies of expression recognition.
Clinical characteristics and risk factors of patients with eosinophilic fasciitis associated with pleural effusion
Authors: Chen Zhifeng , Wasti Binaya , Shang Yulin , Jia Aijun , Xiang Xudong , Ouyang Ruoyun
Published: April 2023

To investigate the risk factors of eosinophilic fasciitis (EF) associated with pleural effusion (PE). A retrospective analysis was performed on 22 patients with EF diagnosed by skin biopsy in our hospital, and they were divided into EF-PE and EF according to chest computed tomography examination. The clinical characteristics, clinical manifestations, comorbidities and laboratory test indicators of the two groups were collected and compared, and the risk factors for occurring PE in patients with EF were determined by multivariate logistic regression analysis. Among 22 patients with EF, 8 had PE. The age, course of disease, incidence of fever, weight loss, cough and shortness of breath, pulmonary infection, hypothyroidism, hydronephrosis and kidney stone, swelling rate of small vascular endothelial cells, consolidation shadows, C-reactive protein and thyroid stimulating hormone in EF-PE group were higher than those in EF group, while free triiodothyronine and thyroxine were lower than those in EF group. Age, fever, shortness of breath, C-reactive protein, ESR, thyroid stimulating hormone, pulmonary infection, hypothyroidism, hydronephrosis, kidney stones, swollen small vascular endothelial cells and chest CT consolidation shadows were identified as risk factors for happening PE in patients with EF, while free triiodothyronine and free thyroxine were identified as protective factors against PE in patients with EF. The incidence of EF-PE was 36.36% in this study. Advanced age, high C-reactive protein, ESR, thyroid stimulating hormone, incidence of fever, shortness of breath, pulmonary infection, hydronephrosis, kidney stones, swollen small vascular endothelial cells, chest CT consolidation shadows, and low free triiodothyronine and thyroxine suggest that patients with EF are significantly at increased risk of PE.