bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cdon suppresses vascular smooth muscle calcification via repression of the Wnt/Runx2 Axis
Authors: Ahn Byeong-Yun , Jeong Yideul , Kim Sunghee , Zhang Yan , Kim Su Woo , Leem Young-Eun , Kang Jong-Sun 
Published: January 2023

AbstractOsteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) is a risk factor associated with vascular diseases. Wnt signaling is one of the major mechanisms implicated in the osteogenic conversion of VSMCs. Since Cdon has a negative effect on Wnt signaling in distinct cellular processes, we sought to investigate the role of Cdon in vascular calcification. The expression of Cdon was significantly downregulated in VSMCs of the aortas of patients with atherosclerosis and aortic stenosis. Consistently, calcification models, including vitamin D3 (VD3)-injected mice and VSMCs cultured with calcifying media, exhibited reduced Cdon expression. Cdon ablation mice (cKO) exhibited exacerbated aortic stiffness and calcification in response to VD3 compared to the controls. Cdon depletion induced the osteogenic conversion of VSMCs accompanied by cellular senescence. The Cdon-deficient aortas showed a significant alteration in gene expression related to cell proliferation and differentiation together with Wnt signaling regulators. Consistently, Cdon depletion or overexpression in VSMCs elevated or attenuated Wnt-reporter activities, respectively. The deletion mutant of the second immunoglobulin domain (Ig2) in the Cdon ectodomain failed to suppress Wnt signaling and osteogenic conversion of VSMCs. Furthermore, treatment with purified recombinant proteins of the entire ectodomain or Ig2 domain of Cdon displayed suppressive effects on Wnt signaling and VSMC calcification. Our results demonstrate a protective role of Cdon in VSMC calcification by suppressing Wnt signaling. The Ig2 domain of Cdon has the potential as a therapeutic tool to prevent vascular calcification.
Hsa_circ_0021727 (circ-CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway
Authors: Meng Fan , Zhang Xiaokang , Wang Yanting , Lin Jie , Tang Yulin , Zhang Guisheng , Qiu Binqiang , Zeng Xingdu , Liu Weiyou , He Xin 
Published: January 2023

Abstract
Esophageal squamous cell carcinoma (ESCC) is characterized by high morbidity and mortality. Circular RNAs (circRNAs) play an important role in tumor progression. We discovered an aberrantly expressed circRNA (hsa_circ_0021727) in patients with ESCC. However, the mechanism of action of hsa_circ_0021727 in tumors is unclear. The present study aimed to investigate the biological role of hsa_circ_0021727 and its mechanism in ESCC progression. We screened for the expression of hsa_circ_0021727 in ESCC patients. Patients with ESCC with high expression of hsa_circ_0021727 had shorter survival than those with low expression. Hsa_circ_0021727 promoted the proliferation, invasion, and migration of ESCC cells. However, miR-23b-5p inhibited this ability of hsa_circ_0021727. MiR-23b-5p acts by targeting TAK1-binding protein 1 (TAB1). Upregulation of TAB1 can activate the nuclear factor kappa B (NFκB) pathway. Hsa_circ_0021727 promoted ESCC progression by activating TAB1/NFκB pathway by sponging miR-23b-5p. In addition, in vivo experiments also confirmed that hsa_circ_0021727 could promote the proliferation, invasion, and migration of ESCC cells. In short, hsa_circ_0021727 promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway. These findings might provide potential targets to treat ESCC.
Dynamics of the fcc-to-bcc phase transition in single-crystalline PdCu alloy nanoparticles
Authors: Jiang Yingying , Duchamp Martial , Ang Shi Jun , Yan Hongwei , Tan Teck Leong , Mirsaidov Utkur 
Published: January 2023

AbstractTwo most common crystal structures in metals and metal alloys are body-centered cubic (bcc) and face-centered cubic (fcc) structures. The phase transitions between these structures play an important role in the production of durable and functional metal alloys. Despite their technological significance, the details of such phase transitions are largely unknown because of the challenges associated with probing these processes. Here, we describe the nanoscopic details of an fcc-to-bcc phase transition in PdCu alloy nanoparticles (NPs) using in situ heating transmission electron microscopy. Our observations reveal that the bcc phase always nucleates from the edge of the fcc NP, and then propagates across the NP by forming a distinct few-atoms-wide coherent bcc–fcc interface. Notably, this interface acts as an intermediate precursor phase for the nucleation of a bcc phase. These insights into the fcc-to-bcc phase transition are important for understanding solid − solid phase transitions in general and can help to tailor the functional properties of metals and their alloys.
Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation
Authors: Irazoki Andrea , Gordaliza-Alaguero Isabel , Frank Emma , Giakoumakis Nikolaos Nikiforos , Seco Jordi , Palacín Manuel , Gumà Anna , Sylow Lykke , Sebastián David , Zorzano Antonio 
Published: January 2023

AbstractSome forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics in mitigating such processes and their impact on muscle fitness remain unaddressed. Here we report that opposite mitochondrial morphologies induce distinct inflammatory signatures, caused by differential activation of DNA sensors TLR9 or cGAS. In the context of mitochondrial fragmentation, we demonstrate that mitochondria-endosome contacts mediated by the endosomal protein Rab5C are required in TLR9 activation in cells. Skeletal muscle mitochondrial fragmentation promotes TLR9-dependent inflammation, muscle atrophy, reduced physical performance and enhanced IL6 response to exercise, which improved upon chronic anti-inflammatory treatment. Taken together, our data demonstrate that mitochondrial dynamics is key in preventing sterile inflammatory responses, which precede the development of muscle atrophy and impaired physical performance. Thus, we propose the targeting of mitochondrial dynamics as an approach to treating disorders characterized by chronic inflammation and mitochondrial dysfunction.
Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters
Authors: Matamoros Marcos , Ng Xue Wen , Brettmann Joshua B. , Piston David W. , Nichols Colin G. 
Published: January 2023

AbstractThe K+ channel selectivity filter (SF) is defined by TxGYG amino acid sequences that generate four identical K+ binding sites (S1-S4). Only two sites (S3, S4) are present in the non-selective bacterial NaK channel, but a four-site K+-selective SF is obtained by mutating the wild-type TVGDGN SF sequence to a canonical K+ channel TVGYGD sequence (NaK2K mutant). Using single molecule FRET (smFRET), we show that the SF of NaK2K, but not of non-selective NaK, is ion-dependent, with the constricted SF configuration stabilized in high K+ conditions. Patch-clamp electrophysiology and non-canonical fluorescent amino acid incorporation show that NaK2K selectivity is reduced by crosslinking to limit SF conformational movement. Finally, the eukaryotic K+ channel TREK2 SF exhibits essentially identical smFRET-reported ion-dependent conformations as in prokaryotic K+ channels. Our results establish the generality of K+-induced SF conformational stability across the K+ channel superfamily, and introduce an approach to study manipulation of channel selectivity.
Hospital crowdedness evaluation and in-hospital resource allocation based on image recognition technology
Authors: Deng Lijia , Cheng Fan , Gao Xiang , Yu Wenya , Shi Jianwei , Zhou Liang , Zhang Lulu , Li Meina , Wang Zhaoxin , Zhang Yu-Dong , Lv Yipeng 
Published: January 2023

AbstractHow to allocate the existing medical resources reasonably, alleviate hospital congestion and improve the patient experience are problems faced by all hospitals. At present, the combination of artificial intelligence and the medical field is mainly in the field of disease diagnosis, but lacks successful application in medical management. We distinguish each area of the emergency department by the division of medical links. In the spatial dimension, in this study, the waitlist number in real-time is got by processing videos using image recognition via a convolutional neural network. The congestion rate based on psychology and architecture is defined for measuring crowdedness. In the time dimension, diagnosis time and time-consuming after diagnosis are calculated from visit records. Factors related to congestion are analyzed. A total of 4717 visit records from the emergency department and 1130 videos from five areas are collected in the study. Of these, the waiting list of the pediatric waiting area is the largest, including 10,436 (person-time) people, and its average congestion rate is 2.75, which is the highest in all areas. The utilization rate of pharmacy is low, with an average of only 3.8 people using it at the one time. Its average congestion rate is only 0.16, and there is obvious space waste. It has been found that the length of diagnosis time and the length of time after diagnosis are related to age, the number of diagnoses and disease type. The most common disease type comes from respiratory problems, accounting for 54.3%. This emergency department has congestion and waste of medical resources. People can use artificial intelligence to investigate the congestion in hospitals effectively. Using artificial intelligence methods and traditional statistics methods can lead to better research on healthcare resource allocation issues in hospitals.
Response of woody vegetation to bush thinning on freehold farmlands in north-central Namibia
Authors: Nghikembua Matti T. , Marker Laurie L. , Brewer Bruce , Leinonen Arvo , Mehtätalo Lauri , Appiah Mark , Pappinen Ari 
Published: January 2023

AbstractBush encroachment affects much of the Namibian woodland landscape, causing significant loss of open savannah habitat and farm profits. Thinning of the trees/shrubs is recommended; however, research is required to identify the overall efficacy and effects of this method on the woodland habitat. We aimed to examine the effect of the thinning strategy applied on the vegetation structure of encroaching tree/shrub species, as well as the sighting lines of the habitat. Vegetation surveys were done on three freehold farms in north-central Namibia. The study utilised a combination of a blocked and split-plot study design: each block consisted of a pair of thinned and non-thinned plots with multiple subplots. Thinned plots had been manually thinned, with a post-thinning age of three years or more. Results revealed that tree/shrub abundance differed between species; thinned areas had the least abundance and overall species-treatment interactions were significant. Thinning caused a significant reduction in overall tree/shrub densities, settling within the recommended range for the area. Thinning also significantly reduced the average tree/shrub height, canopy area, medium-sized trees/shrubs, and increased sighting lines. This confirms a bush encroachment mitigation strategy that favours grass cover, and wildlife that rely on longer sighting lines for safety or when hunting.
Monitoring of plant-induced electrical signal of pepper plants (Capsicum annuum L.) according to urea fertilizer application
Authors: Kim Han Na , Seok Yeong Ju , Park Gyung Min , Vyavahare Govind , Park Jin Hee 
Published: January 2023

AbstractPlant-induced electrical signals (PIES) can be non-destructively monitored by inserting electrodes into plant stems, which reflect plant nutrient and water uptake. The main objective of this study was to evaluate the growth of pepper plants with different urea applications (low fertilizer: N0, Control: N1, and high fertilizer: N2) in soil by monitoring PIES. The PIES value was found to be low in the low urea treatment group while the two times higher urea applied pepper had the highest PIES value. The nutritional content of the stem, leaves and soil did not correlate with PIES because of dilution effect by high biomass with high urea application, but principal component analysis showed that the PIES was positively associated with pepper biomass and soil EC. The high fertilizer did not affect chlorophyll and proline contents in pepper leaves. The assessment of plant growth by PIES has advantages because non-destructive, real time and remote monitoring is possible. Therefore, PIES monitoring of different plants grown under various cultivation environments is useful method to evaluate plant activity and growth.
Enzyme-independent catabolism of cysteine with pyridoxal-5′-phosphate
Authors: Mulay Prajakatta , Chen Cindy , Krishna Vijay 
Published: January 2023

AbstractPyridoxal-5′-phosphate (PLP) is a versatile cofactor that assists in different types of enzymatic reactions. PLP has also been reported to react with substrates and catalyze some of these reactions independent of enzymes. One such catalytic reaction is the breakdown of cysteine to produce hydrogen sulfide (H2S) in the presence of multivalent metal ions. However, the enzyme-independent catalytic activity of PLP in catabolizing cysteine in the absence of multivalent ions is unknown. In this study, we show that PLP reacts with cysteine to form a thiazolidine product, which is supported by quantum chemical calculations of the absorption spectrum. The reaction of PLP with cysteine is dependent on ionic strength and pH. The thiazolidine product slowly decomposes to produce H2S and the PLP regenerates to its active form with longer reaction times (> 24 h), suggesting that PLP can act as a catalyst. We propose an enzyme-independent plausible reaction mechanism for PLP catalyzed cysteine breakdown to produce H2S, which proceeds through the formation of thiazolidine ring intermediates that later hydrolyzes slowly to regenerate the PLP. This work demonstrates that PLP catalyzes cysteine breakdown in the absence of enzymes, base, and multivalent metal ions to produce H2S.
Transcriptional activity mediated by β-CATENIN and TCF/LEF family members is completely dispensable for survival and propagation of multiple human colorectal cancer cell lines
Authors: Fröhlich Janna , Rose Katja , Hecht Andreas 
Published: January 2023

AbstractUnrestrained transcriptional activity of β-CATENIN and its binding partner TCF7L2 frequently underlies colorectal tumor initiation and is considered an obligatory oncogenic driver throughout intestinal carcinogenesis. Yet, theTCF7L2gene carries inactivating mutations in about 10% of colorectal tumors and is non-essential in colorectal cancer (CRC) cell lines. To determine whether CRC cells acquire TCF7L2-independence through cancer-specific compensation by other T-cell factor (TCF)/lymphoid enhancer-binding factor (LEF) family members, or rather lose addiction to β-CATENIN/TCF7L2-driven gene expression altogether, we generated multiple CRC cell lines entirely negative for TCF/LEF or β-CATENIN expression. Survival of these cells and the ability to propagate them demonstrate their complete β-CATENIN- and TCF/LEF-independence. Nonetheless, one β-CATENIN-deficient cell line eventually became senescent, and absence of TCF/LEF proteins and β-CATENIN consistently impaired CRC cell proliferation, reminiscent of mitogenic effects of WNT/β-CATENIN signaling in the healthy intestine. Despite this common phenotype, β-CATENIN-deficient cells exhibited highly cell-line-specific gene expression changes with little overlap between β-CATENIN- and TCF7L2-dependent transcriptomes. Apparently, β-CATENIN and TCF7L2 independently control sizeable fractions of their target genes. The observed divergence of β-CATENIN and TCF7L2 transcriptional programs, and the finding that neither β-CATENIN nor TCF/LEF activity is strictly required for CRC cell survival has important implications when evaluating these factors as potential drug targets.
Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives
Authors: Escala Nerea , Pineda Laura M. , Ng Michelle G. , Coronado Lorena M. , Spadafora Carmenza , del Olmo Esther 
Published: January 2023

AbstractMalaria cases and deaths keep being excessively high every year. Some inroads gained in the last two decades have been eroded especially due to the surge of resistance to most antimalarials. The search for new molecules that can replace the ones currently in use cannot stop. In this report, the synthesis of benzimidazole derivatives guided by structure–activity parameters is presented. Thirty-six molecules obtained are analyzed according to their activity against P. falciparum HB3 strain based on the type of substituent on rings A and B, their electron donor/withdrawing, as well as their dimension/spatial properties. There is a preference for electron donating groups on ring A, such as Me in position 5, or better, 5, 6-diMe. Ring B must be of the pyridine type such as picolinamide, other modifications are generally not favorable. Two molecules, 1 and 33 displayed antiplasmodial activity in the high nanomolar range against the chloroquine sensitive strain, with selectivity indexes above 10. Activity results of 1, 12 and 16 on a chloroquine resistance strain indicated an activity close to chloroquine for compound 1. Analysis of some of their effect on the parasites seem to suggest that 1 and 33 affect only the parasite and use a route other than interference with hemozoin biocrystallization, the route used by chloroquine and most antimalarials.
Specific AAV2/PHP.eB-mediated gene transduction of CA2 pyramidal cells via injection into the lateral ventricle
Authors: Okamoto Kazuki , Kamikubo Yuji , Yamauchi Kenta , Okamoto Shinichiro , Takahashi Megumu , Ishida Yoko , Koike Masato , Ikegaya Yuji , Sakurai Takashi , Hioki Hiroyuki 
Published: January 2023

AbstractGiven its limited accessibility, the CA2 area has been less investigated compared to other subregions of the hippocampus. While the development of transgenic mice expressing Cre recombinase in the CA2 has revealed unique features of this area, the use of mouse lines has several limitations, such as lack of specificity. Therefore, a specific gene delivery system is required. Here, we confirmed that the AAV-PHP.eB capsid preferably infected CA2 pyramidal cells following retro-orbital injection and demonstrated that the specificity was substantially higher after injection into the lateral ventricle. In addition, a tropism for the CA2 area was observed in organotypic slice cultures. Combined injection into the lateral ventricle and stereotaxic injection into the CA2 area specifically introduced the transgene into CA2 pyramidal cells, enabling us to perform targeted patch-clamp recordings and optogenetic manipulation. These results suggest that AAV-PHP.eB is a versatile tool for specific gene transduction in CA2 pyramidal cells.
New magneto-polaron resonances in a monolayer of a transition metal dichalcogenide
Authors: Trallero-Giner Carlos , Santiago-Pérez Darío G. , Fomin Vladimir M. 
Published: January 2023

AbstractTransition metal dichalcogenide (TMD) semiconductors are two-dimensional materials with great potential for the future of nano-optics and nano-optoelectronics as well as the rich and exciting development of basic research. The influence of an external magnetic field on a TMD monolayer raises a new question: to unveil the behavior of the magneto-polaron resonances (MPRs) associated with the phonon symmetry inherent in the system. It is shown that the renormalized Landau energy levels are modified by the interplay of the long-range Pekar–Fröhlich (PF) and short-range deformation potential (DP) interactions. This leads to a new series of MPRs involving the optical phonons at the center of the Brillouin zone. The coupling of the two Landau levels with the LO and $$A_1$$

A
1

optical phonon modes provokes resonant splittings of double avoided-crossing levels giving rise to three excitation branches. This effect appears as bigger energy gaps at the anticrossing points in the renormalized Landau levels. To explore the interplay between the MPRs, the electron-phonon interactions (PF and DP) and the couplings between adjacent Landau levels, a full Green’s function treatment for the evaluation of the energy and its life-time broadening is developed. A generalization of the two-level approach is performed for the description of the new MPR branches. The obtained results are a guideline for the magneto-optical experiments in TMDs, where three MPR peaks should be observable.
Enhanced angiogenic properties of umbilical cord blood primed by OP9 stromal cells ameliorates neurological deficits in cerebral infarction mouse model
Authors: Yoshida Yasunori , Takeda Yuki , Yamahara Kenichi , Yamamoto Hanae , Takagi Toshinori , Kuramoto Yoji , Nakano-Doi Akiko , Nakagomi Takayuki , Soma Toshihiro , Matsuyama Tomohiro , Doe Nobutaka , Yoshimura Shinichi 
Published: January 2023

AbstractUmbilical cord blood (UCB) transplantation shows proangiogenic effects and contributes to symptom amelioration in animal models of cerebral infarction. However, the effect of specific cell types within a heterogeneous UCB population are still controversial. OP9 is a stromal cell line used as feeder cells to promote the hematoendothelial differentiation of embryonic stem cells. Hence, we investigated the changes in angiogenic properties, underlying mechanisms, and impact on behavioral deficiencies caused by cerebral infarction in UCB co-cultured with OP9 for up to 24 h. In the network formation assay, only OP9 pre-conditioned UCB formed network structures. Single-cell RNA sequencing and flow cytometry analysis showed a prominent phenotypic shift toward M2 in the monocytic fraction of OP9 pre-conditioned UCB. Further, OP9 pre-conditioned UCB transplantation in mice models of cerebral infarction facilitated angiogenesis in the peri-infarct lesions and ameliorated the associated symptoms. In this study, we developed a strong, fast, and feasible method to augment the M2, tissue-protecting, pro-angiogenic features of UCB using OP9. The ameliorative effect of OP9-pre-conditioned UCB in vivo could be partly due to promotion of innate angiogenesis in peri-infarct lesions.
Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies
Authors: Calapre Leslie , Giardina Tindaro , Beasley Aaron B. , Reid Anna L. , Stewart Colin , Amanuel Benhur , Meniawy Tarek M. , Gray Elin S. 
Published: January 2023

AbstractPlasma circulating tumour DNA (ctDNA) has been suggested to be a viable biomarker of response to treatment in patients with high grade serous ovarian carcinoma (HGSOC). TP53 mutations are present in more than 90% of HGSOCs but somatic variants are distributed across all exonic regions of the gene, requiring next generation sequencing (NGS) technologies for mutational analysis. In this study, we compared the suitability of the Accel (Swift) and Oncomine (ThermoFisher) panels for identification of TP53 mutations in ctDNA of HGSOC patients (N = 10). Only 6 patients (60%) were found to have TP53 mutations using the ACCEL panel but the addition of molecular tags in the Oncomine panel improved ctDNA detection with at least one mutation detected in all cases (100%). Orthogonal validation of the 14 somatic variants found by Oncomine, using droplet digital PCR, confirmed 79% (11/14) of the identified mutations. Overall, the Oncomine panel with unique molecular identifiers (UMI) appears more useful for ctDNA analysis in HGSOC.