bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through its DNA binding domain but not transcription activation domain
Authors: Qi Huihui , Luo Li , Lu Caijing , Chen Runze , Zhou Xianyao , Zhang Xiaohui , Jia Yichang 
Published: February 2023

AbstractVocalization is an essential medium for social signaling in birds and mammals. Periaqueductal gray (PAG) a conserved midbrain structure is believed to be responsible for innate vocalizations, but its molecular regulation remains largely unknown. Here, through a mouse forward genetic screening we identified one of the key Wnt/β-catenin effectors TCF7L2/TCF4 controls ultrasonic vocalization (USV) production and syllable complexity during maternal deprivation and sexual encounter. Early developmental expression of TCF7L2 in PAG excitatory neurons is necessary for the complex trait, while TCF7L2 loss reduces neuronal gene expressions and synaptic transmission in PAG. TCF7L2-mediated vocal control is independent of its β-catenin-binding domain but dependent of its DNA binding ability. Patient mutations associated with developmental disorders, including autism spectrum disorders, disrupt the transcriptional repression effect of TCF7L2, while mice carrying those mutations display severe USV impairments. Therefore, we conclude that TCF7L2 orchestrates gene expression in midbrain to control vocal production through its DNA binding but not transcription activation domain.
VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU
Authors: Su Benyu , Lim David , Qi Chenyang , Zhang Zhongwei , Wang Junxiao , Zhang Fengmei , Dong Chao , Feng Zhihui 
Published: February 2023

AbstractCell cycle checkpoint kinases play a pivotal role in protecting against replicative stress. In this study, valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was found to promote breast cancer MCF-7 cells to traverse into G2/M phase for catastrophic injury by promoting PPP2R2A (the B-regulatory subunit of Phosphatase PP2A) to facilitate the dephosphorylation of Chk1 at Ser317 and Ser345. By contrast, VPA protected normal 16HBE cells from HU toxicity through decreasing PPP2R2A expression and increasing Chk1 phosphorylation. The effect of VPA on PPP2R2A was at the post-transcription level through HDAC1/2. The in vitro results were affirmed in vivo. Patients with lower PPP2R2A expression and higher pChk1 expression showed significantly worse survival. PPP2R2A D197 and N181 are essential for PPP2R2A-Chk1 signaling and VPA-mediated bidirectional effect on augmenting HU-induced tumor cell death and protecting normal cells.
Anionic phospholipids control mechanisms of GPCR-G protein recognition
Authors: Thakur Naveen , Ray Arka P. , Sharp Liam , Jin Beining , Duong Alexander , Pour Niloofar Gopal , Obeng Samuel , Wijesekara Anuradha V. , Gao Zhan-Guo , McCurdy Christopher R. , Jacobson Kenneth A. , Lyman Edward , Eddy Matthew T. 
Published: February 2023

AbstractG protein-coupled receptors (GPCRs) are embedded in phospholipids that strongly influence drug-stimulated signaling. Anionic lipids are particularly important for GPCR signaling complex formation, but a mechanism for this role is not understood. Using NMR spectroscopy, we explore the impact of anionic lipids on the function-related conformational equilibria of the human A2Aadenosine receptor (A2AAR) in bilayers containing defined mixtures of zwitterionic and anionic phospholipids. Anionic lipids prime the receptor to form complexes with G proteins through a conformational selection process. Without anionic lipids, signaling complex formation proceeds through a less favorable induced fit mechanism. In computational models, anionic lipids mimic interactions between a G protein and positively charged residues in A2AAR at the receptor intracellular surface, stabilizing a pre-activated receptor conformation. Replacing these residues strikingly alters the receptor response to anionic lipids in experiments. High sequence conservation of the same residues among all GPCRs supports a general role for lipid-receptor charge complementarity in signaling.
Remodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice
Authors: Zhang Shengchang , Liu Ying , Jing Weiqiang , Chai Qihao , Tang Chunwei , Li Ziyang , Man Zhentao , Chen Chen , Zhang Jing , Sun Peng , Zhang Rui , Yang Zhenmei , Han Maosen , Wang Yan , Wei Xia , Li Jun , Li Wei , Abdalla Mohnad , Yu Gongchang , Shi Bin , Zhang Yuankai , Zhao Kun , Jiang Xinyi 
Published: February 2023

AbstractMassive intra-articular infiltration of proinflammatory macrophages is a prominent feature of rheumatoid arthritis (RA) lesions, which are thought to underlie articular immune dysfunction, severe synovitis and ultimately joint erosion. Here we report an efferocytosis-informed nanoimitator (EINI) for in situ targeted reprogramming of synovial inflammatory macrophages (SIMs) that thwarts their autoimmune attack and reestablishes articular immune homeostasis, which mitigates RA. The EINI consists of a drug-based core with an oxidative stress-responsive phosphatidylserine (PtdSer) corona and a shell composed of a P-selectin-blocking motif, low molecular weight heparin (LMWH). When systemically administered, the LMWH on the EINI first binds to P-selectin overexpressed on the endothelium in subsynovial capillaries, which functions as an antagonist, disrupting neutrophil synovial trafficking. Due to the strong dysregulation of the synovial microvasculature, the EINI is subsequently enriched in the joint synovium where the shell is disassembled upon the reactive oxygen species stimulation, and PtdSer corona is then exposed. In an efferocytosis-like manner, the PtdSer-coroneted core is in turn phagocytosed by SIMs, which synergistically terminate SIM-initiated pathological cascades and serially reestablish intra-articular immune homeostasis, conferring a chondroprotective effect. These findings demonstrate that SIMs can be precisely remodeled via the efferocytosis-mimetic strategy, which holds potential for RA treatment.
Synthesis of precisely functionalizable curved nanographenes via graphitization-induced regioselective chlorination in a mechanochemical Scholl Reaction
Authors: Stanojkovic Jovana , William Ronny , Zhang Zhongbo , Fernández Israel , Zhou Jingsong , Webster Richard D. , Stuparu Mihaiela C. 
Published: February 2023

AbstractWhile the synthesis of nanographenes has advanced greatly in the past few years, development of their atomically precise functionalization strategies remains rare. The ability to modify the carbon scaffold translates to controlling, adjusting, and adapting molecular properties. Towards this end, here, we show that mechanochemistry is capable of transforming graphitization precursors directly into chlorinated curved nanographenes through a Scholl reaction. The halogenation occurs in a regioselective, high-yielding, and general manner. Density Functional Theory (DFT) calculations suggest that graphitization activates specific edge-positions for chlorination. The chlorine atoms allow for precise chemical modification of the nanographenes through a Suzuki or a nucleophilic aromatic substitution reaction. The edge modification enables modulation of material properties. Among the molecules prepared, corannulene-coronene hybrids and laterally fully π-extended helicenes, heptabenzo[5]superhelicenes, are particularly noteworthy.
Wet oxidation and catalytic wet oxidation of pharmaceutical sludge
Authors: Zeng Xu , Liu Jun , Zhao Jianfu 
Published: February 2023

AbstractIn this work, wet oxidation and catalytic wet oxidation of pharmaceutical sludge using homogeneous and heterogeneous catalysts were investigated. The results indicate that wet oxidation is a promising method for the highly efficient degradation of pharmaceutical sludge. Under optimal conditions, the highest removal efficiencies of volatile suspended solids (VSS) 86.8% and chemical oxygen demand (COD) 62.5% were achieved at 260 °C for 60 min with an initial oxygen pressure of 1.0 MPa. NaOH exhibited excellent acceleration performance on the VSS removal. The highest VSS removal efficiency of 95.2% was obtained at 260 °C for 60 min with an initial oxygen pressure of 1.0 MPa and 10 g·L−1 of NaOH. By using a Cu–Ce/γ-Al2O3 catalyst, the highest removal rates of VSS 87.3% and COD 72.6% were achieved at 260 °C for 60 min with an initial oxygen pressure of 1.0 MPa and 10 g·L−1 of catalyst. The wet oxidation reaction can be maintained itself owing to the exothermic heat. The produced low-molecular-weight carboxylic acids have potential commercial utilization as organic carbon sources in the biological wastewater treatment processes. The inorganic residues can be utilized for the building materials production. These results implied that the catalytic wet oxidation is a promising method for the volume reduction and resource utilization of pharmaceutical sludge.
Protective effects of isorhamnetin against H2O2-induced oxidative damage in HaCaT cells and comprehensive analysis of key genes
Authors: Hu Wen , Zhang Jingzhan , Wang Hongjuan , Guan Mengmeng , Dai Leheng , Li Jun , Kang Xiaojing 
Published: February 2023

AbstractIsorhamnetin (ISO) is a methylated flavonol present in the leaves, flowers, and fruits of many plants with antitumour, anti-inflammatory, antioxidant, and anti-apoptotic properties. ISO has been suggested as the active substance in Vernonia anthelmintica (L.) to treat vitiligo. However, the mechanisms underlying its effects remain unclear. In this study, human keratinocytes (HaCaT cells) were pre-treated with or without ISO and then stimulated with hydrogen peroxide (H2O2) to generate oxidative damage. Pre-treatment with ISO increased HaCaT cell viability, reduced malondialdehyde content, and enhanced superoxide dismutase activity, resulting in a reduction in the loss of mitochondrial membrane potential, improved cell morphological damage, and apoptosis inhibition. Furthermore, we identified 51 significantly dysregulated differentially expressed genes (DEGs) of HaCaT cells treated with ISO using RNA-sequencing. Enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases indicated that the protective effect of ISO could be related to its effects on the Wnt signalling pathway. Our study provides novel insights into key gene regulation in the progression of oxidative damage and the mechanisms of action of ISO.
Multiple plasma membrane reporters discern LHFPL5 region that blocks trafficking to the plasma membrane
Authors: Soler David C. , Ballesteros Angela , Sloan Andrew E. , McCormick Thomas S. , Stepanyan Ruben 
Published: February 2023

AbstractThe mechano-electrical transduction (MET) channel of the inner ear receptor cells, termed hair cells, is a protein complex that enables our senses of hearing and balance. Hair cell MET requires an elaborate interplay of multiple proteins that form the MET channel. One of the MET complex components is the transmembrane protein LHFPL5, which is required for hair cell MET and hearing. LHFPL5 is thought to form a multi-protein complex with other MET channel proteins, such as PCDH15, TMIE, and TMC1. Despite localizing to the plasma membrane of stereocilia, the mechanosensing organelles of hair cells, LHFPL5 requires its binding partner within the MET complex, PCDH15, to localize to the stereocilia tips in hair cells and to the plasma membrane in heterologous cells. Using the Aquaporin 3-tGFP reporter (AGR) for plasma membrane localization, we found that a region within extracellular loop 1, which interacts with PCDH15, precludes the trafficking of AGR reporter to the plasma membrane in heterologous cell lines. Our results suggest that the presence of protein partners may mask endoplasmic reticulum retention regions or enable the proper folding and trafficking of the MET complex components, to facilitate expression of the MET complex at the stereocilia membrane.
Left ventricular hypertrophy detection using electrocardiographic signal
Authors: Liu Cheng-Wei , Wu Fu-Hsing , Hu Yu-Lun , Pan Ren-Hao , Lin Chuen-Horng , Chen Yung-Fu , Tseng Guo-Shiang , Chan Yung-Kuan , Wang Ching-Lin 
Published: February 2023

AbstractLeft ventricular hypertrophy (LVH) indicates subclinical organ damage, associating with the incidence of cardiovascular diseases. From the medical perspective, electrocardiogram (ECG) is a low-cost, non-invasive, and easily reproducible tool that is often used as a preliminary diagnosis for the detection of heart disease. Nowadays, there are many criteria for assessing LVH by ECG. These criteria usually include that voltage combination of RS peaks in multi-lead ECG must be greater than one or more thresholds for diagnosis. We developed a system for detecting LVH using ECG signals by two steps: firstly, the R-peak and S-valley amplitudes of the 12-lead ECG were extracted to automatically obtain a total of 24 features and ECG beats of each case (LVH or non-LVH) were segmented; secondly, a back propagation neural network (BPN) was trained using a dataset with these features. Echocardiography (ECHO) was used as the gold standard for diagnosing LVH. The number of LVH cases (of a Taiwanese population) identified was 173. As each ECG sequence generally included 8 to 13 cycles (heartbeats) due to differences in heart rate, etc., we identified 1466 ECG cycles of LVH patients after beat segmentation. Results showed that our BPN model for detecting LVH reached the testing accuracy, precision, sensitivity, and specificity of 0.961, 0.958, 0.966 and 0.956, respectively. Detection performances of our BPN model, on the whole, outperform 7 methods using ECG criteria and many ECG-based artificial intelligence (AI) models reported previously for detecting LVH.
A multicenter, randomized, open-labelled, non-inferiority trial of sustained-release sarpogrelate versus clopidogrel after femoropopliteal artery intervention
Authors: Han Ahram , Lee Taeseung , Lee Joongyub , Song Suk-Won , Lee Sang-Su , Jung In Mok , Kang Jin Mo , Gwon Jun Gyo , Yun Woo-Sung , Cho Yong-Pil , Ko Hyunmin , Park Yang-Jin , Min Seung-Kee 
Published: February 2023

AbstractOptimal antiplatelet therapy after endovascular therapy (EVT) for peripheral artery disease is controversial. This trial aimed to evaluate whether sarpogrelate plus aspirin was non-inferior for preventing early restenosis after femoropopliteal (FP) EVT compared to clopidogrel plus aspirin. In this open-label, prospective randomized trial, 272 patients were enrolled after successful EVT for FP lesions. Patients in each group received aspirin 100 mg and clopidogrel 75 mg or sarpogrelate 300 mg orally once per day for 6 months. The primary outcome was target lesion restenosis at 6 months, tested for noninferiority. Patient characteristics and EVT patterns were similar, except for increased inflow procedures in the sarpogrelate group and increased outflow procedures in the clopidogrel group. The sarpogrelate group showed a tendency of less restenosis at 6 months than the clopidogrel group (13.0% vs. 19.1%, difference 6.1 percentage points, 95% CI for noninferiority − 0.047 to 0.169). Secondary endpoints related to safety outcomes were rare in both groups. Risks of target lesion restenosis of the two intervention arm were uniform across most major subgroups except for those with coronary artery disease. In conclusion, Sarpogrelate plus aspirin is non-inferior to clopidogrel plus aspirin in preventing early restenosis after FP EVT. Larger multi-ethnic trials are required to generalize these findings. Trial registration: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02959606; 09/11/2016).
Perfect intrinsic squeezing at the superradiant phase transition critical point
Authors: Hayashida Kenji , Makihara Takuma , Marquez Peraca Nicolas , Fallas Padilla Diego , Pu Han , Kono Junichiro , Bamba Motoaki 
Published: February 2023

AbstractSome of the most exotic properties of the quantum vacuum are predicted in ultrastrongly coupled photon–atom systems; one such property is quantum squeezing leading to suppressed quantum fluctuations of photons and atoms. This squeezing is unique because (1) it is realized in the ground state of the system and does not require external driving, and (2) the squeezing can be perfect in the sense that quantum fluctuations of certain observables are completely suppressed. Specifically, we investigate the ground state of the Dicke model, which describes atoms collectively coupled to a single photonic mode, and we found that the photon–atom fluctuation vanishes at the onset of the superradiant phase transition in the thermodynamic limit of an infinite number of atoms. Moreover, when a finite number of atoms is considered, the variance of the fluctuation around the critical point asymptotically converges to zero, as the number of atoms is increased. In contrast to the squeezed states of flying photons obtained using standard generation protocols with external driving, the squeezing obtained in the ground state of the ultrastrongly coupled photon–atom systems is resilient against unpredictable noise.
Gender differences in prevalence of hepatitis C virus infection in Egypt: a systematic review and meta-analysis
Authors: Abdel-Gawad Muhammad , Nour Mohamed , El-Raey Fathiya , Nagdy Hanaa , Almansoury Yahya , El-Kassas Mohamed 
Published: February 2023

AbstractEgypt is the country with the highest known hepatitis C virus (HCV) prevalence worldwide. The origin of gender differences in HCV prevalence is not usually well understood. This systematic review and meta-analysis aimed to review and evaluate the gender differences in HCV infection rates amongst Egyptians. Such data would be important to support prevention and control programs aiming to minimize HCV-related morbidity and mortality. PubMed, Scopus, and Web of Science (WOS) were searched for relevant articles published from 1st January 2011 to 13th December 2021, using the search terms (HCV OR “hepatitis C” OR hepacivirus) AND (prevalence OR seroprevalence OR epidemiology OR incidence OR magnitude). At first, retrieved articles were screened, and then relevant data were extracted and analyzed. Descriptive statistics were used for data analysis. Out of 616 studies from databases, only 30 were included after the full-text screening, with 193,621 included participants: 97,597 male and 96,024 female. The overall seroprevalence of HCV antibodies in all included studies was 0.02 (CI − 0.23 to 0.28), with no significant difference between males and females. However, HCV RNA positivity was significantly more prevalent in males than females in adults and the general population (after excluding high-risk groups). In children, no statistically significant differences between males and females were found in the seroprevalence of HCV antibodies nor in the prevalence of PCR positivity. HCV RNA positivity is significantly higher in males than females in adults, while there are no gender differences in children.
Ab-GALFA, A bioassay for insect gall formation using the model plant Arabidopsis thaliana
Authors: Hirano Tomoko , Okamoto Ayaka , Oda Yoshihisa , Sakamoto Tomoaki , Takeda Seiji , Matsuura Takakazu , Ikeda Yoko , Higaki Takumi , Kimura Seisuke , Sato Masa H. 
Published: February 2023

AbstractInsect galls are abnormal plant organs formed by gall-inducing insects to provide shelter and nutrients for themselves. Although insect galls are spatialized complex structures with unique shapes and functions, the molecular mechanism of the gall formation and the screening system for the gall inducing effectors remains unknown. Here, we demonstrate that an extract of a gall-inducing aphid, Schlechtendalia chinensis, induces an abnormal structure in the root-tip region of Arabidopsis seedlings. The abnormal structure is composed of stem-like cells, vascular, and protective tissues, as observed in typical insect galls. Furthermore, we confirm similarities in the gene expression profiles between the aphid-treated seedlings and the early developmental stages of Rhus javanica galls formed by S. chinensis. Based on the results, we propose a model system for analyzing the molecular mechanisms of gall formation: the Arabidopsis-based Gall-Forming Assay (Ab-GALFA). Ab-GALFA could be used not only as a model to elucidate the mechanisms underlying gall formation, but also as a bioassay system to isolate insect effector molecules of gall-induction.
How scan parameter choice affects deep learning-based coronary artery disease assessment from computed tomography
Authors: Denzinger Felix , Wels Michael , Breininger Katharina , Taubmann Oliver , Mühlberg Alexander , Allmendinger Thomas , Gülsün Mehmet A. , Schöbinger Max , André Florian , Buss Sebastian J. , Görich Johannes , Sühling Michael , Maier Andreas 
Published: February 2023

AbstractRecently, algorithms capable of assessing the severity of Coronary Artery Disease (CAD) in form of the Coronary Artery Disease-Reporting and Data System (CAD-RADS) grade from Coronary Computed Tomography Angiography (CCTA) scans using Deep Learning (DL) were proposed. Before considering to apply these algorithms in clinical practice, their robustness regarding different commonly used Computed Tomography (CT)-specific image formation parameters—including denoising strength, slab combination, and reconstruction kernel—needs to be evaluated. For this study, we reconstructed a data set of 500 patient CCTA scans under seven image formation parameter configurations. We select one default configuration and evaluate how varying individual parameters impacts the performance and stability of a typical algorithm for automated CAD assessment from CCTA. This algorithm consists of multiple preprocessing and a DL prediction step. We evaluate the influence of the parameter changes on the entire pipeline and additionally on only the DL step by propagating the centerline extraction results of the default configuration to all others. We consider the standard deviation of the CAD severity prediction grade difference between the default and variation configurations to assess the stability w.r.t. parameter changes. For the full pipeline we observe slight instability (± 0.226 CAD-RADS) for all variations. Predictions are more stable with centerlines propagated from the default to the variation configurations (± 0.122 CAD-RADS), especially for differing denoising strengths (± 0.046 CAD-RADS). However, stacking slabs with sharp boundaries instead of mixing slabs in overlapping regions (called true stack ± 0.313 CAD-RADS) and increasing the sharpness of the reconstruction kernel (± 0.150 CAD-RADS) leads to unstable predictions. Regarding the clinically relevant tasks of excluding CAD (called rule-out; AUC default 0.957, min 0.937) and excluding obstructive CAD (called hold-out; AUC default 0.971, min 0.964) the performance remains on a high level for all variations. Concluding, an influence of reconstruction parameters on the predictions is observed. Especially, scans reconstructed with the true stack parameter need to be treated with caution when using a DL-based method. Also, reconstruction kernels which are underrepresented in the training data increase the prediction uncertainty.