bluuebunny/crossref_metadata_2025_split huggingface dataset:
BTN3A1 promotes tumor progression and radiation resistance in esophageal squamous cell carcinoma by regulating ULK1-mediated autophagy
Authors: Yang Wenjing , Cheng Bo , Chen Pengxiang , Sun Xiaozheng , Wen Zhihua , Cheng Yufeng 
Published: November 2022

AbstractRadiotherapy is one of the most effective treatments for esophageal squamous cell carcinoma (ESCC); however, radioresistance is a clinical problem that must urgently be solved. Here, we found that butyrophilin subfamily 3 member A1 (BTN3A1) is upregulated in ESCC tumor tissues compared with nontumor tissues. We also evaluated BTN3A1 expression in patients with ESCC receiving adjuvant radiotherapy. The results demonstrated that BTN3A1 upregulation predicts a poor prognosis for ESCC patients. BTN3A1 overexpression promotes ESCC cell proliferation in vitro and in vivo. Moreover, BTN3A1 knockdown sensitized ESCC cells to radiation. We further explored the mode of death involved in BTN3A1-mediated radioresistance. Previous studies have shown that apoptosis, autophagy, necrosis, pyroptosis and ferroptosis are important for the survival of ESCC cells. We performed an RT-PCR array and western blotting (WB) to identify the mode of death and revealed for the first time that BTN3A1 promotes cell radioresistance by activating autophagy. In addition, by performing immunoprecipitation and mass spectrometry analyses, we found that BTN3A1 regulated the expression of UNC-51-like autophagy activating kinase 1(ULK1) and promoted its phosphorylation to subsequently initiate autophagy. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay results indicated that BTN3A1 is a novel direct target of hypoxia inducible factor-1α (HIF-1α). HIF-1α, a transcription factor, promotes BTN3A1 transcription upon irradiation. Overall, the present study is the first to show that BTN3A1 plays a key role in radioresistance and that targeting BTN3A1 might be a promising strategy to improve radiotherapy efficacy in patients with ESCC.
Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling
Authors: Brownfield Douglas G. , de Arce Alex Diaz , Ghelfi Elisa , Gillich Astrid , Desai Tushar J. , Krasnow Mark A. 
Published: November 2022

AbstractThe lung’s gas exchange surface is comprised of alveolar AT1 and AT2 cells that are corrupted in several common and deadly diseases. They arise from a bipotent progenitor whose differentiation is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling. Fgfr2 is expressed in the developing progenitors in mouse then restricts to nascent AT2 cells and remains on throughout life. Its ligands are expressed in surrounding mesenchyme and can, in the absence of exogenous mechanical cues, induce progenitors to form alveolospheres with intermingled AT2 and AT1 cells. FGF signaling directly and cell autonomously specifies AT2 fate; progenitors lacking Fgfr2 in vitro and in vivo exclusively acquire AT1 fate. Fgfr2 loss in AT2 cells perinatally results in reprogramming to AT1 identity, whereas loss or inhibition later in life triggers AT2 apoptosis and compensatory regeneration. We propose that Fgfr2 signaling selects AT2 fate during development, induces a cell non-autonomous AT1 differentiation signal, then continuously maintains AT2 identity and survival throughout life.
Impact of hydronium ions on the Pd-catalyzed furfural hydrogenation
Authors: Yu Iris K. M. , Deng Fuli , Chen Xi , Cheng Guanhua , Liu Yue , Zhang Wei , Lercher Johannes A. 
Published: November 2022

AbstractIn aqueous mediums, the chemical environment for catalytic reactions is not only comprised of water molecules but also of corresponding ionized species, i.e., hydronium ions, which can impact the mechanism and kinetics of a reaction. Here we show that in aqueous-phase hydrogenation of furfural on Pd/C, increasing the hydronium ion activities by five orders of magnitude (from pH 7 to pH 1.6) leads to an increase of less than one order of magnitude in the reaction rate. Instead of a proton-coupled electron transfer pathway, our results show that a Langmuir-Hinshelwood mechanism describes the rate-limiting hydrogen addition step, where hydrogen atom adsorbed on Pd is transferred to the carbonyl C atom of the reactant. As such, the strength of hydrogen binding on Pd, which decreases with increasing hydronium ion concentration (i.e., 2 kJ molH2−1 per unit pH), is a decisive factor in hydrogenation kinetics (rate constant +270%). In comparison, furfural adsorption on Pd is pH-independent, maintaining a tilted geometry that favors hydrogen attack at the carbonyl group over the furan ring.
Long noncoding RNA DIO3OS induces glycolytic-dominant metabolic reprogramming to promote aromatase inhibitor resistance in breast cancer
Authors: Chen Xueman , Luo Rong , Zhang Yunmei , Ye Shuying , Zeng Xin , Liu Jiang , Huang Di , Liu Yujie , Liu Qiang , Luo Man-Li , Song Erwei 
Published: November 2022

AbstractAromatase inhibition is an efficient endocrine therapy to block ectopic estrogen production for postmenopausal estrogen receptor (ER)-positive breast cancer patients, but many develop resistance. Here, we show that aromatase inhibitor (AI)-resistant breast tumors display features of enhanced aerobic glycolysis with upregulation of long noncoding RNA (lncRNA) DIO3OS, which correlates with poor prognosis of breast cancer patients on AI therapies. Long-term estrogen deprivation induces DIO3OS expression in ER-positive breast tumor cells, which further enhances aerobic glycolysis and promotes estrogen-independent cell proliferation in vitro and in vivo. Mechanistically, DIO3OS interacts with polypyrimidine tract binding protein 1 (PTBP1) and stabilizes the mRNA of lactate dehydrogenase A (LDHA) by protecting the integrity of its 3’UTR, and subsequently upregulates LDHA expression and activates glycolytic metabolism in AI-resistant breast cancer cells. Our findings highlight the role of lncRNA in regulating the key enzyme of glycolytic metabolism in response to endocrine therapies and the potential of targeting DIO3OS to reverse AI resistance in ER-positive breast cancer.
SENP1 prevents steatohepatitis by suppressing RIPK1-driven apoptosis and inflammation
Authors: Yan Lingjie , Zhang Tao , Wang Kai , Chen Zezhao , Yang Yuanxin , Shan Bing , Sun Qi , Zhang Mengmeng , Zhang Yichi , Zhong Yedan , Liu Nan , Gu Jinyang , Xu Daichao 
Published: November 2022

AbstractActivation of RIPK1-driven cell death and inflammation play important roles in the progression of nonalcoholic steatohepatitis (NASH). However, the mechanism underlying RIPK1 activation in NASH remains unclear. Here we identified SENP1, a SUMO-specific protease, as a key endogenous inhibitor of RIPK1. SENP1 is progressively reduced in proportion to NASH severity in patients. Hepatocyte-specific SENP1-knockout mice develop spontaneous NASH-related phenotypes in a RIPK1 kinase-dependent manner. We demonstrate that SENP1 deficiency sensitizes cells to RIPK1 kinase-dependent apoptosis by promoting RIPK1 activation following TNFα stimulation. Mechanistically, SENP1 deSUMOylates RIPK1 in TNF-R1 signaling complex (TNF-RSC), keeping RIPK1 in check. Loss of SENP1 leads to SUMOylation of RIPK1, which re-orchestrates TNF-RSC and modulates the ubiquitination patterns and activity of RIPK1. Notably, genetic inhibition of RIPK1 effectively reverses disease progression in hepatocyte-specific SENP1-knockout male mice with high-fat-diet-induced nonalcoholic fatty liver. We propose that deSUMOylation of RIPK1 by SENP1 provides a pathophysiologically relevant cell death-restricting checkpoint that modulates RIPK1 activation in the pathogenesis of nonalcoholic steatohepatitis.
Predicting neoadjuvant chemotherapy benefit using deep learning from stromal histology in breast cancer
Authors: Li Fengling , Yang Yongquan , Wei Yani , Zhao Yuanyuan , Fu Jing , Xiao Xiuli , Zheng Zhongxi , Bu Hong 
Published: November 2022

AbstractNeoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced breast cancer. However, not all patients benefit from NAC; some even obtain worse outcomes after therapy. Hence, predictors of treatment benefit are crucial for guiding clinical decision-making. Here, we investigated the predictive potential of breast cancer stromal histology via a deep learning (DL)-based approach and proposed the tumor-associated stroma score (TS-score) for predicting pathological complete response (pCR) to NAC with a multicenter dataset. The TS-score was demonstrated to be an independent predictor of pCR, and it not only outperformed the baseline variables and stromal tumor-infiltrating lymphocytes (sTILs) but also significantly improved the prediction performance of the baseline variable-based model. Furthermore, we discovered that unlike lymphocytes, collagen and fibroblasts in the stroma were likely associated with a poor response to NAC. The TS-score has the potential to better stratify breast cancer patients in NAC settings.
Designing high-TC superconductors with BCS-inspired screening, density functional theory, and deep-learning
Authors: Choudhary Kamal , Garrity Kevin 
Published: November 2022

AbstractWe develop a multi-step workflow for the discovery of conventional superconductors, starting with a Bardeen–Cooper–Schrieffer inspired pre-screening of 1736 materials with high Debye temperature and electronic density of states. Next, we perform electron-phonon coupling calculations for 1058 of them to establish a large and systematic database of BCS superconducting properties. Using the McMillan-Allen-Dynes formula, we identify 105 dynamically stable materials with transition temperatures,TC ≥ 5 K. Additionally, we analyze trends in our dataset and individual materials including MoN, VC, VTe, KB6, Ru3NbC, V3Pt, ScN, LaN2, RuO2, and TaC. We demonstrate that deep-learning(DL) models can predict superconductor properties faster than direct first-principles computations. Notably, we find that by predicting the Eliashberg function as an intermediate quantity, we can improve model performance versus a direct DL prediction ofTC. We apply the trained models on the crystallographic open database and pre-screen candidates for further DFT calculations.
Computational modeling of complex bioenergetic mechanisms that modulate CD4+ T cell effector and regulatory functions
Authors: Baker Ryan , Hontecillas Raquel , Tubau-Juni Nuria , Leber Andrew J. , Kale Shiv , Bassaganya-Riera Josep 
Published: November 2022

AbstractWe built a computational model of complex mechanisms at the intersection of immunity and metabolism that regulate CD4+ T cell effector and regulatory functions by using coupled ordinary differential equations. The model provides an improved understanding of how CD4+ T cells are shaping the immune response during Clostridioides difficile infection (CDI), and how they may be targeted pharmacologically to produce a more robust regulatory (Treg) response, which is associated with improved disease outcomes during CDI and other diseases. LANCL2 activation during CDI decreased the effector response, increased regulatory response, and elicited metabolic changes that favored Treg. Interestingly, LANCL2 activation provided greater immune and metabolic modulation compared to the addition of exogenous IL-2. Additionally, we identified gluconeogenesis via PEPCK-M as potentially responsible for increased immunosuppressive behavior in Treg cells. The model can perturb immune signaling and metabolism within a CD4+ T cell and obtain clinically relevant outcomes that help identify novel drug targets for infectious, autoimmune, metabolic, and neurodegenerative diseases.
Long-range connections are crucial for synchronization transition in a computational model of Drosophila brain dynamics
Authors: Qiu Shuihan , Sun Kaijia , Di Zengru 
Published: November 2022

AbstractThe synchronization transition type has been the focus of attention in recent years because it is associated with many functional characteristics of the brain. In this paper, the synchronization transition in neural networks with sleep-related biological drives in Drosophila is investigated. An electrical synaptic neural network is established to research the difference between the synchronization transition of the network during sleep and wake, in which neurons regularly spike during sleep and chaotically spike during wake. The synchronization transition curves are calculated mainly using the global instantaneous order parametersS. The underlying mechanisms and types of synchronization transition during sleep are different from those during wake. During sleep, regardless of the network structure, a frustrated (discontinuous) transition can be observed. Moreover, the phenomenon of quasi periodic partial synchronization is observed in ring-shaped regular network with and without random long-range connections. As the network becomes dense, the synchronization of the network only needs to slightly increase the coupling strengthg. While during wake, the synchronization transition of the neural network is very dependent on the network structure, and three mechanisms of synchronization transition have emerged: discontinuous synchronization (explosive synchronization and frustrated synchronization), and continuous synchronization. The random long-range connections is the main topological factor that plays an important role in the resulting synchronization transition. Furthermore, similarities and differences are found by comparing synchronization transition research for the Hodgkin-Huxley neural network in the beta-band and gammma-band, which can further improve the synchronization phase transition research of biologically motivated neural networks. A complete research framework can also be used to study coupled nervous systems, which can be extended to general coupled dynamic systems.
Co-administration of FVIII with IVIG reduces immune response to FVIII in hemophilia A mice
Authors: Afraz Sajjad , Stevic Ivan , Matino Davide , Wen Jianping , Atkinson Helen , Chan Anthony K. C. , Hortelano Gonzalo 
Published: November 2022

AbstractHemophilia A is an X-linked recessive congenital bleeding disorder. Exogenous infusion of FVIII is the treatment of choice, and the development of immunoglobulins against FVIII (inhibitors) remains the major challenge in clinical management of the disease. Here, we investigated the effect of co-administration of FVIII with intravenous immunoglobulin (IVIG) on the development of inhibitors in previously untreated hemophilia A mice. A group of hemophilia A mice (C57BL/6FVIII−/−) received weekly injections of recombinant human FVIII (rFVIII) for twelve consecutive weeks while a second group received co-injections of rFVIII + IVIG. An in-house enzyme-linked immunosorbent assay (ELISA) was designed to detect antibodies to rFVIII. Every mouse in the first group developed antibodies to rFVIII. In contrast, mice treated with rFVIII + IVIG showed significantly lower antibody titers. Interestingly, when co-administration of IVIG was discontinued after 12 weeks in some mice (rFVIII continued), these mice experienced an increase in antibody titer. In contrast, mice that continued to receive rFVIII + IVIG retained significantly lower titers. In conclusion, prophylactic rFVIII co-administration with IVIG modulated the immune response to FVIII and resulted in decreased anti-FVIII antibody titer. These findings suggest that co-injection therapy with IVIG could potentially be effective in the management of hemophilia A patients at risk of inhibitor development.
Synthesis and characterization of Ni0.5Al0.5Fe2O4 nanoparticles for potent antifungal activity against dry rot of ginger (Fusarium oxysporum)
Authors: Sharma Sushma , Kumari Poonam , Thakur Priyanka , Brar Gaganpreet Singh , Bouqellah Nahla A. , Hesham Abd El-Latif 
Published: November 2022

AbstractCurrent study signifies the use of nanoparticles as alternative in plant disease management to avoid harmful effect of pesticide and fungicide residue. Synthesis of nanoparticles (Ni0.5Al0.5Fe2O4) by hydrothermal method and studied their X-ray diffraction analysis (XRD), Raman spectra, and UV spectra and further successfully evaluated for antifungal activity against a soil and seed borne pathogenic fungus (Fusarium oxysporum).Among various pests, fungal pathogens are the main cause of crop destruction and we developed nanoparticles (Ni0.5Al0.5Fe2O4) which is successfully evaluated for antimycotic activity against dry rot (F. oxysporum) of ginger which causes 50–70% losses in the ginger plant. In vitro and in vivo analysis designated that the nanoparticles (Ni0.5Al0.5Fe2O4) has shown an excellent antifungal activity against F. oxysporum at 0.5 mg/ml concentration. Similarly, no disease incidence was recorded when Ni0.5Al0.5Fe2O4 nanoparticles used at 0.5 mg/ml concentration under in vivo conditions. In plants various environmental stresses (biotic and abiotic) leads to excessive production of reactive oxygen species (ROS) causing progressive oxidative damage and ultimately leads to cell death. The role of ROS in nanoparticles (Ni0.5Al0.5Fe2O4) represents by reduction in the growth inhibition of F. oxysporum. We speculated in light of these results that the cytotoxic effect of Ni0.5Al0.5Fe2O4 nanoparticles on F. oxysporum may be mediated through ROS. We can suggest the role of nanoparticles (Ni0.5Al0.5Fe2O4) gives a promising result as a fungicidal activity and could be a novel family of future new generation fungicide.
Results of the performance test for quality assessment of personal radiation dosimetry services including the influence of the dosimeter readout frequency
Authors: Feng Chen-Ju , Wu Chin-Hui , Huang Yi-Hui , Chu Chien-Hau , Lien Ke-Yu , Wang Yu-Chieh , Lee Shen-Hao , Hsu Shih-Ming 
Published: November 2022

AbstractThis study was to determine the significance of factors considered for the measurement accuracy of personal dosimeter in dosimetry services such as dosimetry service, irradiation category, years of use and readout frequency. The investigation included management information questionnaire, on-site visit and blind test. The blind test with random selected personal badge was used in inter-comparison of eight dosimetry services, and the test results followed ANSI/HPS N13.11 criteria. This study also analyzed the measurement deviations if they felt in the criteria of ICRP 75 or not. One-way ANOVA tests were used to analyze the significant difference of the measurement deviations in different dosimetry services, irradiation categories, and years of use. Simple linear-regression test was performed for the significance of the prediction model between measurement deviations and readout frequencies. All visited dosimetry services followed the proper statue of basic management and passed the performance check of the tolerance level. The average deviations corresponding to category I, category II deep dose, and category II shallow dose were 6.08%, 9.49%, and 10.41% respectively. There had significant differences of measurement deviation in different dosimetry services (p < 0.0001) and irradiation categories (p = 0.016) but no significant difference in years of use (p = 0.498). There was no significance in the linear-regression model between measurement deviation and badge readout frequencies. Based on the regular calibration of the personal dosimeter, the deviation of the measured value is mainly affected by different dosimetry services and irradiation categories; and there shows no significant influence by years of use and readout frequency.
First theoretical framework for highly efficient photovoltaic parameters by structural modification with benzothiophene-incorporated acceptors in dithiophene based chromophores
Authors: Khalid Muhammad , Ahmed Rameez , shafiq Iqra , Arshad Muhammad , Asghar Muhammad Adnan , Munawar Khurram Shahzad , Imran Muhammad , Braga Ataualpa A. C. 
Published: November 2022

AbstractNow a days, researchers are constantly doing efforts to upgrade the performance of solar based devices with the aim of increasing the role of photovoltaic materials in modern hi-tech optoelectronic applications. Realizing the recent energy conditions across the globe, research is diverted from fullerene to non-fullerene electron acceptor moieties in this era, considering their remarkable contribution in organic solar cells (OSCs). Therefore, we designed seven novel non-fullerene fused ring electron acceptor chromophores (MD2–MD8) from DOC2C6-2F by structural tailoring with different acceptors at end-capped units. DFT study was performed at B3LYP functional to discover the opto-electronic characteristics of the newly tailored chromophores. Various analysis such as frontier molecular orbitals (FMOs), transition density matrix (TDM), density of states (DOS), binding energy (Eb), reorganization energy, open circuit voltage (Voc) was carried out to comprehend the photovoltaic response of MD2–MD8. Decrease in band gaps (1.940–1.571 eV) with wider absorption spectrum (725.690–939.844 nm in chloroform) along with greater charge transfer rate from HOMO towards LUMO were examined in derivatives as compared to MR1 (Egap = 1.976 eV, λmax = 738.221 nm) except MD7. Further, in all derivatives, smaller values of Eb (0.252–0.279 eV) were examined than that of reference (0.296 eV). These lower binding energy values of MD2–MD8 indicated the higher rate of excitation dissociation with lager charger transfer rate than MR1, which further supported by DOS and TDM analyses. Additionally, least reorganization energy in the aforesaid compounds for hole with electron was also inspected. Moreover, Voc a good photovoltaic response was noted for all studied compounds which indicated that these compounds are suitable to synthesize OSCs in future.
Identification of potential microRNA diagnostic panels and uncovering regulatory mechanisms in breast cancer pathogenesis
Authors: Sharifi Zahra , Talkhabi Mahmood , Taleahmad Sara 
Published: November 2022

AbstractEarly diagnosis of breast cancer (BC), as the most common cancer among women, increases the survival rate and effectiveness of treatment. MicroRNAs (miRNAs) control various cell behaviors, and their dysregulation is widely involved in pathophysiological processes such as BC development and progress. In this study, we aimed to identify potential miRNA biomarkers for early diagnosis of BC. We also proposed a consensus-based strategy to analyze the miRNA expression data to gain a deeper insight into the regulatory roles of miRNAs in BC initiation. Two microarray datasets (GSE106817 and GSE113486) were analyzed to explore the differentially expressed miRNAs (DEMs) in serum of BC patients and healthy controls. Utilizing multiple bioinformatics tools, six serum-based miRNA biomarkers (miR-92a-3p, miR-23b-3p, miR-191-5p, miR-141-3p, miR-590-5p and miR-190a-5p) were identified for BC diagnosis. We applied our consensus and integration approach to construct a comprehensive BC-specific miRNA-TF co-regulatory network. Using different combination of these miRNA biomarkers, two novel diagnostic models, consisting of miR-92a-3p, miR-23b-3p, miR-191-5p (model 1) and miR-92a-3p, miR-23b-3p, miR-141-3p, and miR-590-5p (model 2), were obtained from bioinformatics analysis. Validation analysis was carried out for the considered models on two microarray datasets (GSE73002 and GSE41922). The model based on similar network topology features, comprising miR-92a-3p, miR-23b-3p and miR-191-5p was the most promising model in the diagnosis of BC patients from healthy controls with 0.89 sensitivity, 0.96 specificity and area under the curve (AUC) of 0.98. These findings elucidate the regulatory mechanisms underlying BC and represent novel biomarkers for early BC diagnosis.