bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer
Authors: Zhu Shimiao , Yang Zhao , Zhang Zheng , Zhang Hongli , Li Songyang , Wu Tao , Chen Xuanrong , Guo Jianing , Wang Aixiang , Tian Hao , Yu Jianpeng , Zhang Changwen , Su Lei , Shang Zhiqun , Quan Changyi , Niu Yuanjie 
Published: March 2023

AbstractEnabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC. In vivo, upregulated HOXB3 contributed to CRPC xenografts progression and abiraterone resistance. To uncover the mechanism of HOXB3 driving tumor progression, we performed RNA-sequencing in HOXB3 negative (HOXB3-) and HOXB3 high (HOXB3 + ) staining CRPC tumors and determined that HOXB3 activation was associated with the expression of WNT3A and enriched WNT pathway genes. Furthermore, extra WNT3A and APC deficiency led HOXB3 to be isolated from destruction-complex, translocated to nuclei, and then transcriptionally regulated multiple WNT pathway genes. What’s more, we also observed that the suppression of HOXB3 could reduce cell proliferation in APC-downregulated CRPC cells and sensitize APC-deficient CRPC xenografts to abiraterone again. Together, our data indicated that HOXB3 served as a downstream transcription factor of WNT pathway and defined a subgroup of CRPC resistant to antiandrogen which would benefit from HOXB3-targeted therapy.
Structural insights into the human niacin receptor HCA2-Gi signalling complex
Authors: Yang Yang , Kang Hye Jin , Gao Ruogu , Wang Jingjing , Han Gye Won , DiBerto Jeffrey F. , Wu Lijie , Tong Jiahui , Qu Lu , Wu Yiran , Pileski Ryan , Li Xuemei , Zhang Xuejun Cai , Zhao Suwen , Kenakin Terry , Wang Quan , Stevens Raymond C. , Peng Wei , Roth Bryan L. , Rao Zihe , Liu Zhi-Jie 
Published: March 2023

AbstractThe hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-Gi signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors.
Enhanced Ca2+-channeling complex formation at the ER-mitochondria interface underlies the pathogenesis of alcohol-associated liver disease
Authors: Thoudam Themis , Chanda Dipanjan , Lee Jung Yi , Jung Min-Kyo , Sinam Ibotombi Singh , Kim Byung-Gyu , Park Bo-Yoon , Kwon Woong Hee , Kim Hyo-Jeong , Kim Myeongjin , Lim Chae Won , Lee Hoyul , Huh Yang Hoon , Miller Caroline A. , Saxena Romil , Skill Nicholas J. , Huda Nazmul , Kusumanchi Praveen , Ma Jing , Yang Zhihong , Kim Min-Ji , Mun Ji Young , Harris Robert A. , Jeon Jae-Han , Liangpunsakul Suthat , Lee In-Kyu 
Published: March 2023

AbstractCa2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 mutation or genetic ablation of PDK4 prevents alcohol-induced MCC complex formation and subsequent mitochondrial Ca2+ accumulation and dysfunction. Finally, ectopic induction of MAM formation reverses the protective effect of PDK4 deficiency in alcohol-induced liver injury. Together, our study defines a mediatory role of PDK4 in promoting mitochondrial dysfunction in ALD.
Mitochondrial ATP synthase as a direct molecular target of chromium(III) to ameliorate hyperglycaemia stress
Authors: Wang Haibo , Hu Ligang , Li Hongyan , Lai Yau-Tsz , Wei Xueying , Xu Xiaohan , Cao Zhenkun , Cao Huiming , Wan Qianya , Chang Yuen-Yan , Xu Aimin , Zhou Qunfang , Jiang Guibin , He Ming-Liang , Sun Hongzhe 
Published: March 2023

AbstractChromium(III) is extensively used as a supplement for muscle development and the treatment of diabetes mellitus. However, its mode of action, essentiality, and physiological/pharmacological effects have been a subject of scientific debate for over half a century owing to the failure in identifying the molecular targets of Cr(III). Herein, by integrating fluorescence imaging with a proteomic approach, we visualized the Cr(III) proteome being mainly localized in the mitochondria, and subsequently identified and validated eight Cr(III)-binding proteins, which are predominately associated with ATP synthesis. We show that Cr(III) binds to ATP synthase at its beta subunit via the catalytic residues of Thr213/Glu242 and the nucleotide in the active site. Such a binding suppresses ATP synthase activity, leading to the activation of AMPK, improving glucose metabolism, and rescuing mitochondria from hyperglycaemia-induced fragmentation. The mode of action of Cr(III) in cells also holds true in type II diabetic male mice. Through this study, we resolve the long-standing question of how Cr(III) ameliorates hyperglycaemia stress at the molecular level, opening a new horizon for further exploration of the pharmacological effects of Cr(III).
Diversity of platinum-sites at platinum/fullerene interface accelerates alkaline hydrogen evolution
Authors: Chen Jiayi , Aliasgar Mohammed , Zamudio Fernando Buendia , Zhang Tianyu , Zhao Yilin , Lian Xu , Wen Lan , Yang Haozhou , Sun Wenping , Kozlov Sergey M. , Chen Wei , Wang Lei 
Published: March 2023

AbstractMembrane-based alkaline water electrolyser is promising for cost-effective green hydrogen production. One of its key technological obstacles is the development of active catalyst-materials for alkaline hydrogen-evolution-reaction (HER). Here, we show that the activity of platinum towards alkaline HER can be significantly enhanced by anchoring platinum-clusters onto two-dimensional fullerene nanosheets. The unusually large lattice distance (~0.8 nm) of the fullerene nanosheets and the ultra-small size of the platinum-clusters (~2 nm) leads to strong confinement of platinum clusters accompanied by pronounced charge redistributions at the intimate platinum/fullerene interface. As a result, the platinum-fullerene composite exhibits 12 times higher intrinsic activity for alkaline HER than the state-of-the-art platinum/carbon black catalyst. Detailed kinetic and computational investigations revealed the origin of the enhanced activity to be the diverse binding properties of the platinum-sites at the interface of platinum/fullerene, which generates highly active sites for all elementary steps in alkaline HER, particularly the sluggish Volmer step. Furthermore, encouraging energy efficiency of 74% and stability were achieved for alkaline water electrolyser assembled using platinum-fullerene composite under industrially relevant testing conditions.
Structural basis of the substrate recognition and inhibition mechanism of Plasmodium falciparum nucleoside transporter PfENT1
Authors: Wang Chen , Yu Leiye , Zhang Jiying , Zhou Yanxia , Sun Bo , Xiao Qingjie , Zhang Minhua , Liu Huayi , Li Jinhong , Li Jialu , Luo Yunzi , Xu Jie , Lian Zhong , Lin Jingwen , Wang Xiang , Zhang Peng , Guo Li , Ren Ruobing , Deng Dong 
Published: March 2023

AbstractBy lacking de novo purine biosynthesis enzymes, Plasmodium falciparum requires purine nucleoside uptake from host cells. The indispensable nucleoside transporter ENT1 of P. falciparum facilitates nucleoside uptake in the asexual blood stage. Specific inhibitors of PfENT1 prevent the proliferation of P. falciparum at submicromolar concentrations. However, the substrate recognition and inhibitory mechanism of PfENT1 are still elusive. Here, we report cryo-EM structures of PfENT1 in apo, inosine-bound, and inhibitor-bound states. Together with in vitro binding and uptake assays, we identify that inosine is the primary substrate of PfENT1 and that the inosine-binding site is located in the central cavity of PfENT1. The endofacial inhibitor GSK4 occupies the orthosteric site of PfENT1 and explores the allosteric site to block the conformational change of PfENT1. Furthermore, we propose a general “rocker switch” alternating access cycle for ENT transporters. Understanding the substrate recognition and inhibitory mechanisms of PfENT1 will greatly facilitate future efforts in the rational design of antimalarial drugs.
mRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5
Authors: Andreano Emanuele , Paciello Ida , Pierleoni Giulio , Maccari Giuseppe , Antonelli Giada , Abbiento Valentina , Pileri Piero , Benincasa Linda , Giglioli Ginevra , Piccini Giulia , De Santi Concetta , Sala Claudia , Medini Duccio , Montomoli Emanuele , Maes Piet , Rappuoli Rino 
Published: March 2023

AbstractSevere acute respiratory syndrome 2 Omicron BA.4 and BA.5 are characterized by high transmissibility and ability to escape natural and vaccine induced immunity. Here we test the neutralizing activity of 482 human monoclonal antibodies isolated from people who received two or three mRNA vaccine doses or from people vaccinated after infection. The BA.4 and BA.5 variants are neutralized only by approximately 15% of antibodies. Remarkably, the antibodies isolated after three vaccine doses target mainly the receptor binding domain Class 1/2, while antibodies isolated after infection recognize mostly the receptor binding domain Class 3 epitope region and the N-terminal domain. Different B cell germlines are used by the analyzed cohorts. The observation that mRNA vaccination and hybrid immunity elicit a different immunity against the same antigen is intriguing and its understanding may help to design the next generation of therapeutics and vaccines against coronavirus disease 2019.
Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins
Authors: Agam Ganesh , Gebhardt Christian , Popara Milana , Mächtel Rebecca , Folz Julian , Ambrose Benjamin , Chamachi Neharika , Chung Sang Yoon , Craggs Timothy D. , de Boer Marijn , Grohmann Dina , Ha Taekjip , Hartmann Andreas , Hendrix Jelle , Hirschfeld Verena , Hübner Christian G. , Hugel Thorsten , Kammerer Dominik , Kang Hyun-Seo , Kapanidis Achillefs N. , Krainer Georg , Kramm Kevin , Lemke Edward A. , Lerner Eitan , Margeat Emmanuel , Martens Kirsten , Michaelis Jens , Mitra Jaba , Moya Muñoz Gabriel G. , Quast Robert B. , Robb Nicole C. , Sattler Michael , Schlierf Michael , Schneider Jonathan , Schröder Tim , Sefer Anna , Tan Piau Siong , Thurn Johann , Tinnefeld Philip , van Noort John , Weiss Shimon , Wendler Nicolas , Zijlstra Niels , Barth Anders , Seidel Claus A. M. , Lamb Don C. , Cordes Thorben 
Published: March 2023

AbstractSingle-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro and in vivo. We performed an international blind study involving 19 laboratories to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics. Using two protein systems with distinct conformational changes and dynamics, we obtained an uncertainty of the FRET efficiency ≤0.06, corresponding to an interdye distance precision of ≤2 Å and accuracy of ≤5 Å. We further discuss the limits for detecting fluctuations in this distance range and how to identify dye perturbations. Our work demonstrates the ability of smFRET experiments to simultaneously measure distances and avoid the averaging of conformational dynamics for realistic protein systems, highlighting its importance in the expanding toolbox of integrative structural biology.
Applying T-classifier, binary classifiers, upon high-throughput TCR sequencing output to identify cytomegalovirus exposure history
Authors: Zhou Kaiyue , Huo Jiaxin , Gao Caixia , Wang Xu , Xu Pengfei , Hou Jiahuan , Guo Wenying , Sun Tao , Da Lin 
Published: March 2023

AbstractWith the continuous development of information technology and the running speed of computers, the development of informatization has led to the generation of increasingly more medical data. Solving unmet needs such as employing the constantly developing artificial intelligence technology to medical data and providing support for the medical industry is a hot research topic. Cytomegalovirus (CMV) is a kind of virus that exists widely in nature with strict species specificity, and the infection rate among Chinese adults is more than 95%. Therefore, the detection of CMV is of great importance since the vast majority of infected patients are in a state of invisible infection after the infection, except for a few patients with clinical symptoms. In this study, we present a new method to detect CMV infection status by analyzing high-throughput sequencing results of T cell receptor beta chains (TCRβ). Based on the high-throughput sequencing data of 640 subjects from cohort 1, Fisher’s exact test was performed to evaluate the relationship between TCRβ sequences and CMV status. Furthermore, the number of subjects with these correlated sequences to different degrees in cohort 1 and cohort 2 were measured to build binary classifier models to identify whether the subject was CMV positive or negative. We select four binary classification algorithms: logistic regression (LR), support vector machine (SVM), random forest (RF), and linear discriminant analysis (LDA) for side-by-side comparison. According to the performance of different algorithms corresponding to different thresholds, four optimal binary classification algorithm models are obtained. The logistic regression algorithm performs best when Fisher's exact test threshold is 10−5, and the sensitivity and specificity are 87.5% and 96.88%, respectively. The RF algorithm performs better at the threshold of 10−5, with a sensitivity of 87.5% and a specificity of 90.63%. The SVM algorithm also achieves high accuracy at the threshold value of 10−5, with a sensitivity of 85.42% and specificity of 96.88%. The LDA algorithm achieves high accuracy with 95.83% sensitivity and 90.63% specificity when the threshold value is 10−4. This is probably because the two-dimensional distribution of CMV data samples is linearly separable, and linear division models such as LDA are more effective, while the division effect of nonlinear separable algorithms such as random forest is relatively inaccurate. This new finding may be a potential diagnostic method for CMV and may even be applicable to other viruses, such as the infectious history detection of the new coronavirus.
Graphene nanoparticles as data generating digital materials in industry 4.0
Authors: Ali Muhammad A. , Irfan Muhammad S. , Khan Tayyab , Khalid Muhammad Y. , Umer Rehan 
Published: March 2023

AbstractOne of the potential applications of 2D materials is to enhance multi-functionality of structures and components used in aerospace, automotive, civil and defense industries. These multi-functional attributes include sensing, energy storage, EMI shielding and property enhancement. In this article, we have explored the potential of using graphene and its variants as data generating sensory elements in Industry 4.0. We have presented a complete roadmap to cover three emerging technologies i.e. advance materials, artificial intelligence and block-chain technology. The utility of 2D materials such as graphene nanoparticles is yet to be explored as an interface for digitalization of a modern smart factory i.e. “factory-of-the-future”. In this article, we have explored how 2D material enhanced composites can act as an interface between physical and cyber spaces. An overview of employing graphene-based smart embedded sensors at various stages of composites manufacturing processes and their application in real-time structural health monitoring is presented. The technical challenges associated with interfacing graphene-based sensing networks with digital space are discussed. Additionally, an overview of the integration of associated tools such as artificial intelligence, machine learning and block-chain technology with graphene-based devices and structures is also presented.
Face masks negatively skew theory of mind judgements
Authors: Leos-Mendoza Héctor , Gold Ian , Pérez-Gay Juárez Fernanda 
Published: March 2023

AbstractFace masks obscure a significant portion of the face, reducing the amount of information available to gauge the mental states of others—that is, to exercise the Theory of Mind (ToM) capacity. In three experiments, we assessed the effect of face masks on ToM judgements, measuring recognition accuracy, perceived valence, and perceived arousal in various sets of facial expressions comprising 45 different mental states. Significant effects of face masks were found in all three variables. Judgements of all expressions are less accurate when masked, but, while judgements of negative expressions do not show consistent changes in valence or arousal, positive expressions are perceived to be less positive and less intense. In addition, we identified face muscles associated with changes in perceived valence and arousal, shedding light on the mechanisms through which masks impact ToM judgements, which might be relevant for mitigation strategies. We discuss the implications of these findings in the context of the recent pandemic.
Developmental enamel defects and their relationship with caries in adolescents aged 18 years
Authors: Olczak-Kowalczyk Dorota , Krämer Norbert , Gozdowski Dariusz , Turska-Szybka Anna 
Published: March 2023

AbstractRandomly selected 1,611 individuals aged 18 years formed a nationally representative sample from all provinces of Poland. Developmental defects of the enamel (DDE) and caries were assessed using the modified DDE index, molar incisor hypomineralisation (MIH) Treatment Need Index (MIH-TNI), FDI and WHO criteria by 22 trained and calibrated dentists. T-test was used for comparing group means. A simple and multiple logistic regression tests were used to assess the relationship between DDE and caries severity expressed as DMFT (p < 0.05). The prevalence of DDE was 13.7%. Demarcated opacities (DEO) were the most frequent (9.65%); 4% had diffuse opacities (DIO) and 1.5% had hypoplasia. MIH was diagnosed in 0.6% patients. The prevalence of caries was 93.2%, with mean DMFT of 6.50 ± 4.22. The DMFT value was 7.52 ± 4.77 in the group of patients with demarcated opacities (DEO); 7.85 ± 4.74 with diffuse opacities (DIO) and 7.56 ± 4.57 with enamel hypoplasia, respectively. There was a significant relationship between caries severity and DDE (p < 0.001), DEO (p = 0.001) and DIO (p = 0.038), and between DDE and DMFT index (p < 0.001). The results obtained in the study proved the significant relationship between DDE and DMFT in 18-year-olds, the assessment of which was the aim of the study.
Investigation of optimal gestational weight gain for twin pregnancy in Southwest China: a retrospective study
Authors: Gao Li , Lei Cuirong , Zhou Shuwei , Liao Qianqian , Mei Lingwei , Zhong Qimei , Lan Xia , Chen Ya , Wang Lan 
Published: March 2023

AbstractThere is a lack of data on gestational weight gain (GWG) in twin pregnancies. We divided all the participants into two subgroups: the optimal outcome subgroup and the adverse outcome subgroup. They were also stratified according to prepregnancy body mass index (BMI): underweight (< 18.5 kg/m2), normal weight (18.5–23.9 kg/m2), overweight (24–27.9 kg/m2), and obese (≥ 28 kg/m2). We used 2 steps to confirm the optimal range of GWG. The first step was proposing the optimal range of GWG using a statistical-based method (the interquartile range of GWG in the optimal outcome subgroup). The second step was confirming the proposed optimal range of GWG via compared the incidence of pregnancy complications in groups below or above the optimal GWG and analyzed the relationship between weekly GWG and pregnancy complications to validated the rationality of optimal weekly GWG through logistic regression. The optimal GWG calculated in our study was lower than that recommended by the Institute of Medicine. Except for the obese group, in the other 3 BMI groups, the overall disease incidence within the recommendation was lower than that outside the recommendation. Insufficient weekly GWG increased the risk of gestational diabetes mellitus, premature rupture of membranes, preterm birth and fetal growth restriction. Excessive weekly GWG increased the risk of gestational hypertension and preeclampsia. The association varied with prepregnancy BMI. In conclusion, we provide preliminary Chinese GWG optimal range which derived from twin-pregnant women with optimal outcomes(16–21.5 kg for underweight, 15–21.1 kg for normal weight, 13–20 kg for overweight), except for obesity, due to the limited sample size.
Arabic gum ameliorates systemic modulation in Alloxan monohydrate-induced diabetic rats
Authors: Ibrahim Rasha Mohammed , Abdelhafez Hemmat Mansour , EL-Shamy Sawsan Abd EL-Maksoud , Eid Fatma Ahmed , Mashaal Alya 
Published: March 2023

AbstractMedicinal plants are considered an alternative therapy for diabetes mellitus as they regulate glucose levels. Moreover, a variety of plants offer a rich source of bioactive compounds that have potent pharmacological effects without any negative side effects. The present study aimed to clarify the effects of Arabic gum/Gum Acacia (GA) on the biochemical, histopathological, and immunohistochemical changes observed in diabetic rats. Further, the anti-inflammatory activity of GA in response to diabetes, through inflammatory mediators analysis. Male rats were divided into four groups: untreated control, diabetic, Arabic gum-treated, and Arabic gum-treated diabetic rats. Diabetes was induced using alloxan. Animals were sacrificed after 7 and 21 days of treatment with Arabic gum. Body weight, blood and pancreas tissue samples were collected for analysis. Alloxan injection significantly decreased body weight, increased glucose levels, decreased insulin levels, and caused depletion of islets of Langerhans and β-cell damage in the pancreas. Arabic gum treatment of diabetic rats significantly increased body weight, decreased serum glucose levels, increased insulin levels, exerts anti-inflammatory effect, and improved the pancreas tissue structure. Arabic gum has beneficial pharmacological effects in diabetic rats; therefore, it might be employed as diabetic therapy to reduce the hyperglycemic damage and may be applicable for many autoimmune and inflammatory diseases treatment. Further, the new bioactive substances, such as medications made from plants, have larger safety margins, and can be used for a longer period of time.