bluuebunny/crossref_metadata_2025 huggingface dataset:
Pb-rich Cu grain boundary sites for selective CO-to-n-propanol electroconversion
Authors: Niu Wenzhe , Chen Zheng , Guo Wen , Mao Wei , Liu Yi , Guo Yunna , Chen Jingzhao , Huang Rui , Kang Lin , Ma Yiwen , Yan Qisheng , Ye Jinyu , Cui Chunyu , Zhang Liqiang , Wang Peng , Xu Xin , Zhang Bo
Published: August 2023

Electrochemical carbon monoxide (CO) reduction to high-energy-density fuels provides a potential way for chemical production and intermittent energy storage. As a valuable C3 species, n-propanol still suffers from a relatively low Faradaic efficiency (FE), sluggish conversion rate and poor stability. Herein, we introduce an “atomic size misfit” strategy to modulate active sites, and report a facile synthesis of a Pb-doped Cu catalyst with numerous atomic Pb-concentrated grain boundaries. Operando spectroscopy studies demonstrate that these Pb-rich Cu-grain boundary sites exhibit stable low coordination and can achieve a stronger CO adsorption for a higher surface CO coverage. Using this Pb-Cu catalyst, we achieve a CO-to-n-propanol FE (FEpropanol) of 47 ± 3% and a half-cell energy conversion efficiency (EE) of 25% in a flow cell. When applied in a membrane electrode assembly (MEA) device, a stable FEpropanol above 30% and the corresponding full-cell EE of over 16% are maintained for over 100 h with the n-propanol partial current above 300 mA (5 cm2 electrode). Furthermore, operando X-ray absorption spectroscopy and theoretical studies reveal that the structurally-flexible Pb-Cu surface can adaptively stabilize the key intermediates, which strengthens the *CO binding while maintaining the C–C coupling ability, thus promoting the CO-to-n-propanol conversion.
Multicolor lifetime imaging and its application to HIV-1 uptake
Authors: Starling Tobias , Carlon-Andres Irene , Iliopoulou Maro , Kraemer Benedikt , Loidolt-Krueger Maria , Williamson David J. , Padilla-Parra Sergi
Published: August 2023

Simultaneous imaging of nine fluorescent proteins is demonstrated in a single acquisition using fluorescence lifetime imaging microscopy combined with pulsed interleaved excitation of three laser lines. Multicolor imaging employing genetically encodable fluorescent proteins permits spatio-temporal live cell imaging of multiple cues. Here, we show that multicolor lifetime imaging allows visualization of quadruple labelled human immunodeficiency viruses on host cells that in turn are also labelled with genetically encodable fluorescent proteins. This strategy permits to simultaneously visualize different sub-cellular organelles (mitochondria, cytoskeleton, and nucleus) during the process of virus entry with the potential of imaging up to nine different spectral channels in living cells.
Rapid transition from primary to secondary crust building on the Moon explained by mantle overturn
Authors: Prissel Tabb C. , Zhang Nan , Jackson Colin R. M. , Li Haoyuan
Published: August 2023

Geochronology indicates a rapid transition (tens of Myrs) from primary to secondary crust building on the Moon. The processes responsible for initiating secondary magmatism, however, remain in debate. Here we test the hypothesis that the earliest secondary crust (Mg-suite) formed as a direct consequence of density-driven mantle overturn, and advance 3D mantle convection models to quantify the resulting extent of lower mantle melting. Our modeling demonstrates that overturn of thin ilmenite-bearing cumulates ≤ 100 km triggers a rapid and short-lived episode of lower mantle melting which explains the key volume, geochronological, and spatial characteristics of early secondary crust building without contributions from other energy sources, namely KREEP (potassium, rare earth elements, phosphorus, radiogenic U, Th). Observations of globally distributed Mg-suite eliminate degree-1 overturn scenarios. We propose that gravitational instabilities in magma ocean cumulate piles are major driving forces for the onset of mantle convection and secondary crust building on differentiated bodies.
Nonlinearity of the cloud response postpones climate penalty of mitigating air pollution in polluted regions
Authors: Jia Hailing , Quaas Johannes
Published: August 2023

Aerosol–cloud interactions contribute substantially to uncertainties in anthropogenic forcing, in which the sensitivity of cloud droplet number concentration (Nd) to aerosol plays a central role. Here we use satellite observations to show that the aerosol–Ndrelation (in log–log space) is not linear as commonly assumed. Instead, theNdsensitivity decreases at large aerosol concentrations due to the transition from aerosol-limited to updraft-limited regime, making the widely used linear method problematic. A sigmoidal transition is shown to adequately fit the data. When using this revised relationship, the additional warming that arises from air pollution mitigation is delayed by two to three decades in heavily polluted locations, compared to the linear relationship. This cloud-mediated climate penalty will manifest markedly starting around 2025 in China and 2050 in India after applying the strongest air quality policy, underlining the urgency of mitigating greenhouse gas emissions.
Improved fluoroscopy-guided biopsies in the diagnosis of indeterminate biliary strictures: a multi-center retrospective study
Authors: Xiong Zhe , Wang Kuangjing , Zhang Huahui , Fang Ying , Li Fengdong , Huang Jin
Published: August 2023

To evaluate the diagnostic accuracy of improved fluoroscopy-guided biopsies for indeterminate biliary strictures (IBDS). A multi-center retrospective study was performed. Patients with IBDS who underwent digital single-operator cholangioscopy (DSOC) and improved fluoroscopy-guided biopsies procedures were included. The individual sensitivity, specificity, and accuracy were analyzed. A total of 67 patients were enrolled in this multi-center retrospective study. The DSOC and improved fluoroscopy-guided biopsies procedures were successfully performed in all cases (100%). The sensitivity, specificity, and accuracy values were 83.3%, 89.5%, and 85.1% for DSOC visual impression; 95.8%, 94.7%, and 95.5% for improved fluoroscopy-guided biopsies procedures, respectively. The sensitivity and accuracy of improved fluoroscopy-guided biopsies were significantly higher compared with DSOC visual impression. Four patients (6.0%, 4/67) occurred adverse events after the procedures. Improved fluoroscopy-guided biopsies had a high diagnostic accuracy of IBDS diagnosis.
Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19
Authors: Bark Lovisa , Larsson Ing-Marie , Wallin Ewa , Simrén Joel , Zetterberg Henrik , Lipcsey Miklos , Frithiof Robert , Rostami Elham , Hultström Michael
Published: August 2023

A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3–6 months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Elevated GFAp at follow-up 3–6 months after ICU discharge was associated to the development of mild cognitive dysfunction (p = 0.01), especially in women (p = 0.005). Patients who experienced different dimensions of fatigue at follow-up had significantly lower GFAp in both the ICU and at follow-up, specifically in general fatigue (p = 0.009), physical fatigue (p = 0.004), mental fatigue (p = 0.001), and reduced motivation (p = 0.001). Women showed a more pronounced decrease in GFAp compared to men, except for in mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL concentration at follow-up was lower in patients who experienced reduced motivation (p = 0.004). Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19.

Trial registration The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).
The effects of the NMDAR co-agonist d-serine on the structure and function of optic tectal neurons in the developing visual system
Authors: Chorghay Zahraa , Li Vanessa J. , Schohl Anne , Ghosh Arna , Ruthazer Edward S.
Published: August 2023

The N-methyl-d-aspartate type glutamate receptor (NMDAR) is a molecular coincidence detector which converts correlated patterns of neuronal activity into cues for the structural and functional refinement of developing circuits in the brain. d-serine is an endogenous co-agonist of the NMDAR. We investigated the effects of potent enhancement of NMDAR-mediated currents by chronic administration of saturating levels of d-serine on the developing Xenopus retinotectal circuit. Chronic exposure to the NMDAR co-agonist d-serine resulted in structural and functional changes in the optic tectum. In immature tectal neurons, d-serine administration led to more compact and less dynamic tectal dendritic arbors, and increased synapse density. Calcium imaging to examine retinotopy of tectal neurons revealed that animals raised in d-serine had more compact visual receptive fields. These findings provide insight into how the availability of endogenous NMDAR co-agonists like d-serine at glutamatergic synapses can regulate the refinement of circuits in the developing brain.
Distinction between rhinitis alone and rhinitis with asthma using interactomics
Authors: Aguilar Daniel , Lemonnier Nathanaël , Melén Erik , Bustamante Mariona , Gruzieva Olena , Guerra Stefano , Keil Thomas , Koppelman Gerard H. , Celedón Juan C. , Antó Josep M. , Bousquet Jean
Published: August 2023

The concept of “one-airway-one-disease”, coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma. We observed significant differences in the topology of the interactomes and in the pathways associated to each phenotype. In rhinitis alone, identified pathways included cell cycle, cytokine signalling, developmental biology, immune system, metabolism of proteins and signal transduction. In rhinitis and asthma multimorbidity, most pathways were related to signal transduction. The remaining few were related to cytokine signalling, immune system or developmental biology. Toll-like receptors and IL-17-mediated signalling were identified in rhinitis alone, while IL-33 was identified in rhinitis in multimorbidity. On the other hand, few pathways were associated with both phenotypes, most being associated with signal transduction pathways including estrogen-stimulated signalling. The only immune system pathway was FceRI-mediated MAPK activation. In conclusion, our findings suggest that rhinitis alone and rhinitis and asthma multimorbidity should be considered as two distinct diseases.
Clinical significance of the expression of FOXP3 and TIGIT in Merkel cell carcinoma
Authors: Iwasaki Takeshi , Hayashi Kazuhiko , Matsushita Michiko , Nonaka Daisuke , Matsumoto Takamasa , Taniguchi Midori , Kuwamoto Satoshi , Umekita Yoshihisa , Oda Yoshinao
Published: August 2023

The pathogenesis of 80% of Merkel cell carcinoma (MCC) cases is associated with Merkel cell polyomavirus (MCPyV). Forkhead helix transcription factor P3 (FOXP3) and the T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)–CD155 pathway, which are targets for immunotherapy, were assessed as prognostic factors of MCC. We analyzed mRNA expression data of 111 patients with MCC and performed immunohistochemical analysis to detect the expression of programmed death ligand 1 (PD-L1), CD8, FOXP3, TIGIT, and CD155 in 65 cases of MCC. In CD8 and FOXP3 immunostaining, the number of expressing-infiltrating cells was determined by dividing the region into tumor center and invasive front areas. FOXP3 expression was evaluated separately in cells with high and low intensities. Aberrant TIGIT expression and weak CD155 staining were observed in MCC cells. CD8- and FOXP3-positive cell infiltrations were higher in the invasive front than in the tumor center. Multivariate Cox hazard analysis revealed that high infiltration of cells with low-intensity FOXP3 expression in the invasive front is a favorable prognostic factor (p = 0.025). Thus, targeting TIGIT–CD155 signaling and FOXP3 as well as PD-L1 may be a therapeutic strategy for MCC.
Soluble HLA-G (sHLA-G) measurement might be useful as an early diagnostic biomarker and screening test for gastric cancer
Authors: Mejía-Guarnizo Lidy Vannessa , Monroy-Camacho Paula Stefanny , Rincón-Rodríguez Daniel Esteban , Rincón-Riveros Andrés , Martinez-Vargas Daniel Augusto , Huertas-Caro Carlos Alexander , Oliveros-Wilches Ricardo , Sanchez-Pedraza Ricardo , Nuñez-Lemus Marcela , Cristancho-Lievano Carlos Felipe , Castellanos-Moreno Adriana Milena , Martinez-Correa Lina María , Rodríguez-García Josefa Antonia
Published: August 2023

Gastric cancer (GC) is the fifth most frequent malignancy worldwide and has a high mortality rate related to late diagnosis. Although the gold standard for the GC diagnosis is endoscopy with biopsy, nonetheless, it is not cost-effective and is invasive for the patient. The Human leukocyte antigen G (HLA-G) molecule is a checkpoint of the immune response. Its overexpression in cancer is associated with immune evasion, metastasis, poor prognosis, and lower overall survival. We evaluate the plasma levels of soluble HLA-G, (sHLA-G) in patients with GC and benign gastric pathologies using an ELISA test. A higher concentration of sHLA-G in patients with GC than in those with benign pathologies, higher levels of plasma sHLA-G in women with GC compared with men and significant differences in the sHLA-G levels between the benign gastric pathologies evaluated, was our main findings. As no significant differences were found between the GC assessed stages in our study population, we suggest that sHLA-G is not an adequate marker for staging GC, but it does have diagnostic potential. In addition to providing information on the potential of sHLA-G as a diagnostic marker for GC, our study demonstrate that HLA-G molecules can be found in the membrane of exosomes, which highlights the need to perform studies with a larger number of samples to explore the functional implications of HLA-G positive exosomes in the context of gastric cancer, and to determine the clinical significance and possible applications of these findings in the development of non-invasive diagnostic methods.
Using heterogeneous sources of data and interpretability of prediction models to explain the characteristics of careless respondents in survey data
Authors: Kopitar Leon , Stiglic Gregor
Published: August 2023

Prior to further processing, completed questionnaires must be screened for the presence of careless respondents. Different people will respond to surveys in different ways. Some take the easy path and fill out the survey carelessly. The proportion of careless respondents determines the survey’s quality. As a result, identifying careless respondents is critical for the quality of obtained results. This study aims to explore the characteristics of careless respondents in survey data and evaluate the predictive power and interpretability of different types of data and indices of careless responding. The research question focuses on understanding the behavior of careless respondents and determining the effectiveness of various data sources in predicting their responses. Data from a three-month web-based survey on participants’ personality traits such as honesty-humility, emotionality, extraversion, agreeableness, conscientiousness and openness to experience was used in this study. Data for this study was taken from Schroeders et al.. The gradient boosting machine-based prediction model uses data from the answers, time spent for answering, demographic information on the respondents as well as some indices of careless responding from all three types of data. Prediction models were evaluated with tenfold cross-validation repeated a hundred times. Prediction models were compared based on balanced accuracy. Models’ explanations were provided with Shapley values. Compared with existing work, data fusion from multiple types of information had no noticeable effect on the performance of the gradient boosting machine model. Variables such as “I would never take a bribe, even if it was a lot”, average longstring, and total intra-individual response variability were found to be useful in distinguishing careless respondents. However, variables like “I would be tempted to use counterfeit money if I could get away with it” and intra-individual response variability of the first section of a survey showed limited effectiveness. Additionally, this study indicated that, whereas the psychometric synonym score has an immediate effect and is designed with the goal of identifying careless respondents when combined with other variables, it is not necessarily the optimal choice for fitting a gradient boosting machine model.
Effect of temperature on the dynamic parameters of silty clay in a seasonally frozen region
Authors: Guo Haotian , Lin Yuli , Sun Chao , Mao Xin , Li Jinfeng
Published: August 2023

The effect of temperature on the dynamic parameters of silty clay in a seasonally frozen region was assessed using a GDS dynamic triaxial test system. The strength parameters, dynamic elastic modulus, damping ratio, and other dynamic parameters of the soil samples were analyzed under different temperature conditions. The results demonstrated that the shear strength parameters (internal friction angle and cohesion) of the silty clay under a dynamic load increased significantly with decreasing temperature, and the internal friction angle increased sharply below 0 °C. The dynamic elastic modulus increased as the temperature decreased and changed significantly in the ice-water phase change region. The slope of the dynamic stress–strain curve of the soil sample increased significantly with decreasing temperature. As the temperature decreased, the damping ratio reduced, and the ability of the soil to absorb seismic waves declines. The research results provide new data and information to guide construction projects in seasonally frozen region.
Identification of LncPVT1 and CircPVT1 as prognostic biomarkers in human colorectal polyps
Authors: RezaSoltani Mahsa , Forouzesh Flora , Salehi Zahra , Zabihi Mohammad-Reza , Rejali Leili , Nazemalhosseini-Mojarad Ehsan
Published: August 2023

LncPVT1 and CircPVT1 are isoforms for the PVT1 gene and are associated with cancer progression and carcinogenesis. Our study investigated the expression of LncPVT1 and CircPVT1 in colon adenoma polyps. 40 tissues of colorectal polyps and 40 normal-adjacent tissues (NATs) were taken. The expression of LncPVT1 and CircPVT1 was evaluated through qRael-Time PCR. The relation between expression and features of clinicopathological was explored. The ceRNA network was constructed by LncPVT1 and CircPVT1 and predicted miRNAs and miRNAs targets. Further, hub nodes in this network were determined using the cytoHubba package. Over-expressed LncPVT1 and CircPVT1 were differentiated in polyp and NATs. The expression level of LncPVT1 and CircPVT1 were significantly higher in adenoma polyps than in hyperplastic polyps. The area under the curve of the ROC estimate for the LncPVT1 and CircPVT1 was 0.74 and 0.77, respectively. A positive correlation was observed between the LncPVT1 expression and CircPVT1. Three miRNAs, including hsa-miR-484, hsa-miR-24-3p, hsa-miR-423-5p, and CircPVT1, were detected as ceRNA hub nodes. In this study, expression profiles of LncPVT1 and CircPVT1 were significantly higher in precancerous polyps. In addition, based on our in silico analysis, LncPVT1, CircPVT1/miR-484, miR-24-3p, miR-423-5p/PLAGL2 axis might be involved in colon cancer development. LncPVT1 and CircPVT1 can be prescribed as warning problems as potential prognostic biomarkers in patients with pre-CRC colon polyps.
Different levels of autophagy induced by transient serum starvation regulate metabolism and differentiation of porcine skeletal muscle satellite cells
Authors: Wang Yi , Gao Juan , Fan Bojun , Hu Yuemin , Yang Yuefei , Wu Yajie , Li Feng , Ju Huiming
Published: August 2023

This study aimed to investigate the effects of different levels of autophagy induced by transient serum starvation on the metabolism, lipid metabolism, and differentiation of porcine skeletal muscle satellite cells (SMSCs) to preliminary elucidate the role and function of autophagy in the regulatory network of skeletal muscle development. Different levels of autophagy were induced by controlling the serum concentration in the culture system for 24 h. Apoptosis, membrane potential, reactive oxygen species (ROS), ATP, and myogenic and lipogenic differentiation markers were monitored to determine if autophagy affected the metabolism and differentiation of SMSCs. Autophagy was induced in SMSCs via serum starvation (5%, 15%), as evidenced by decreased p62 and mTOR phosphorylation levels and increased LC3B lipidation and AMPK phosphorylation levels. Transmission electron microscopy revealed the presence of autophagosomes, and the rates of morphologically abnormal nuclei and mitochondria gradually increased with the decrease in serum concentration, the number of autophagic lysosomes also increased, indicating that 5% serum starvation induced severe autophagy, while 15% serum starvation induced mild autophagy. Compared with the control group and 15% serum-starved SMSCs, SMSCs undergoing 5% serum starvation had the highest intracellular ATP and ROS levels, the highest percentage of apoptotic cells, and the lowest membrane potential. The 15% serum-starved SMSCs had the highest membrane potential, but the percentage of apoptotic cells did not change significantly compared with the control group. The levels of the myogenic markers MyoD1 and MHC were significantly higher in 15% serum-starved SMSCs than in serum-sufficient SMSCs and the lowest in the 5% serum-starved SMSCs. The lipid contents (measured by Oil Red O staining and quantification of triglycerides) and lipogenic markers Peroxisome Proliferators-activated Receptors γ and Lipoprotein Lipase were also significantly higher in SMSCs undergoing 15% serum starvation than in the control group, and the lowest in the 5% serum-starved SMSCs. Different levels of starvation stress induce different levels of autophagy. Mild autophagy induced by moderate serum starvation promotes the metabolism and differentiation of SMSCs, while severe autophagy renders SMSCs more apoptotic, abnormal metabolism and suppresses SMSC differentiation into adipocytes or myocytes, and reduces lipid metabolisms. Our study suggests that autophagy plays a role in skeletal muscle development and may help design strategies for improving meat production traits in domestic pigs.
Insights into the microRNA landscape of Rhodnius prolixus, a vector of Chagas disease
Authors: Santiago Paula Beatriz , da Silva Bentes Kaio Luís , da Silva Waldeyr Mendes Cordeiro , Praça Yanna Reis , Charneau Sébastien , Chaouch Soraya , Grellier Philippe , dos Santos Silva Ferraz Marcos Antônio , Bastos Izabela Marques Dourado , de Santana Jaime Martins , de Araújo Carla Nunes
Published: August 2023

The growing interest in microRNAs (miRNAs) over recent years has led to their characterization in numerous organisms. However, there is currently a lack of data available on miRNAs from triatomine bugs (Reduviidae: Triatominae), which are the vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. A comprehensive understanding of the molecular biology of vectors provides new insights into insect-host interactions and insect control approaches, which are key methods to prevent disease incidence in endemic areas. In this work, we describe the miRNome profiles from gut, hemolymph, and salivary gland tissues of the Rhodnius prolixus triatomine. Small RNA sequencing data revealed abundant expression of miRNAs, along with tRNA- and rRNA-derived fragments. Fifty-two mature miRNAs, previously reported in Ecdysozoa, were identified, including 39 ubiquitously expressed in the three tissues. Additionally, 112, 73, and 78 novel miRNAs were predicted in the gut, hemolymph, and salivary glands, respectively. In silico prediction showed that the top eight most highly expressed miRNAs from salivary glands potentially target human blood-expressed genes, suggesting that R. prolixus may modulate the host’s gene expression at the bite site. This study provides the first characterization of miRNAs in a Triatominae species, shedding light on the role of these crucial regulatory molecules.
3DPAFIPN as a halogenated dicyanobenzene-based photosensitizer catalyzed gram-scale photosynthesis of pyrano[2,3-d]pyrimidine scaffolds
Authors: Mohamadpour Farzaneh
Published: August 2023

Utilizing the Knoevenagel–Michael tandem cyclocondensation reaction of barbituric acid/1,3-dimethylbarbituric acid, malononitrile, and aryl aldehydes, a sustainable methodology for the photosynthesis of pyrano[2,3-d]pyrimidine scaffolds has been devised. The present study expounds on the development of a green radical synthetic approach toward this class of compounds. In this study, a novel halogenated dicyanobenzene-based photosensitizer was utilized in an aqueous solution, exposed to air at room temperature, and activated by a blue LED as a renewable energy source for the purpose of generating energy. The primary aim of this endeavor is to employ a recently developed, easily obtainable, and affordably priced halogenated cyanoarene-based donor–acceptor (D–A). The 3DPAFIPN [2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile]} photocatalyst, as a thermally activated delayed fluorescence (TADF), is capable of inducing single electron transfer (SET) upon irradiation with visible light, thereby offering a facile and efficient approach with a high degree of effectiveness, energy efficiency, and eco-friendliness. The aforementioned phenomenon facilitates the exploration of the temporal changes that have occurred in the interactions between the surroundings and chemical constituents. The present study aimed to investigate the turnover number (TON) and turnover frequency (TOF) for pyrano[2,3-d]pyrimidine scaffolds. Additionally, it has been demonstrated that gram-scale cyclization is a viable method for utilization in industrial applications.
Calcineurin-mediated dephosphorylation enhances the stability and transactivation of c-Myc
Authors: Masaki Takahiro , Habara Makoto , Hanaki Shunsuke , Sato Yuki , Tomiyasu Haruki , Miki Yosei , Shimada Midori
Published: August 2023

c-Myc, a transcription factor, induces cell proliferation and is often aberrantly or highly expressed in cancers. However, molecular mechanisms underlying this aberrantly high expression remain unclear. Here, we found that intracellular Ca2+ concentration regulates c-Myc oncoprotein stability. We identified that calcineurin, a Ca2+-dependent protein phosphatase, is a positive regulator of c-Myc expression. Calcineurin depletion suppresses c-Myc targeted gene expression and c-Myc degradation. Calcineurin directly dephosphorylates Thr58 and Ser62 in c-Myc, which inhibit binding to the ubiquitin ligase Fbxw7. Mutations within the autoinhibitory domain of calcineurin, most frequently observed in cancer, may increase phosphatase activity, increasing c-Myc transcriptional activity in turn. Notably, calcineurin inhibition with FK506 decreased c-Myc expression with enhanced Thr58 and Ser62 phosphorylation in a mouse xenograft model. Thus, calcineurin can stabilize c-Myc, promoting tumor progression. Therefore, we propose that Ca2+ signaling dysfunction affects cancer-cell proliferation via increased c-Myc stability and that calcineurin inhibition could be a new therapeutic target of c-Myc-overexpressing cancers.
High-accuracy morphological identification of bone marrow cells using deep learning-based Morphogo system
Authors: Lv Zhanwu , Cao Xinyi , Jin Xinyi , Xu Shuangqing , Deng Huangling
Published: August 2023

Accurate identification and classification of bone marrow (BM) nucleated cell morphology are crucial for the diagnosis of hematological diseases. However, the subjective and time-consuming nature of manual identification by pathologists hinders prompt diagnosis and patient treatment. To address this issue, we developed Morphogo, a convolutional neural network-based system for morphological examination. Morphogo was trained using a vast dataset of over 2.8 million BM nucleated cell images. Its performance was evaluated using 508 BM cases that were categorized into five groups based on the degree of morphological abnormalities, comprising a total of 385,207 BM nucleated cells. The results demonstrated Morphogo’s ability to identify over 25 different types of BM nucleated cells, achieving a sensitivity of 80.95%, specificity of 99.48%, positive predictive value of 76.49%, negative predictive value of 99.44%, and an overall accuracy of 99.01%. In most groups, Morphogo cell analysis and Pathologists' proofreading showed high intragroup correlation coefficients for granulocytes, erythrocytes, lymphocytes, monocytes, and plasma cells. These findings further validate the practical applicability of the Morphogo system in clinical practice and emphasize its value in assisting pathologists in diagnosing blood disorders.
The DECON pilot project investigates predictive markers for successful bariatric surgery
Authors: Seifert Gabriel , Fagnocchi Luca , Edozie Michael , Herrmann Stephan , Baumann Hannah , Panzeri Ilaria , Mewes Stephanie , Aicher David , Runkel Mira , Lässle Claudia , Fink Jodok , Marjanovic Goran , Fichtner-Feigl Stephan , Pospisilik J. Andrew
Published: August 2023

Obesity is a chronic, multifactorial disease which is linked to a number of adverse endocrinological and metabolic conditions. Currently, bariatric surgery is one of the most effective treatments for individuals diagnosed with severe obesity. However, the current indications for bariatric surgery are based on inadequate metrics (i.e., BMI) which do not account for the complexity of the disease, nor the heterogeneity among the patient population. Moreover, there is a lack of understanding with respect to the biological underpinnings that influence successful and sustained weight loss post-bariatric surgery. Studies have implicated age and pre-surgery body weight as two factors that are associated with favorable patient outcomes. Still, there is an urgent medical need to identify other potential factors that could improve the specificity of candidate selection and better inform the treatment plan of patients with obesity. In this report, we present and describe the cohort of the DECON pilot project, a multicenter study which aims to identify predictive biomarkers of successful weight loss after bariatric surgery.
Bile acids modulate reinstatement of cocaine conditioned place preference and accumbal dopamine dynamics without compromising appetitive learning
Authors: Zanella Daniele , Smith Nicholas K. , Hardaway J. Andrew , Buchanan Anna Marie , Mullins Clarence H. , Galli Aurelio , Carter Angela M.
Published: August 2023

Psychostimulants target the dopamine transporter (DAT) to elicit their psychomotor actions. Bile acids (BAs) can also bind to DAT and reduce behavioral responses to cocaine, suggesting a potential therapeutic application of BAs in psychostimulant use disorder. Here, we investigate the potential of BAs to decrease drug-primed reinstatement when administered during an abstinence phase. To do this, after successful development of cocaine-associated contextual place preference (cocaine CPP), cocaine administration was terminated, and animals treated with vehicle or obeticholic acid (OCA). When preference for the cocaine-associated context was extinguished, mice were challenged with a single priming dose of cocaine, and reinstatement of cocaine-associated contextual preference was measured. Animals treated with OCA demonstrate a significantly lower reinstatement for cocaine CPP. OCA also impairs the ability of cocaine to reduce the clearance rate of electrically stimulated dopamine release and diminishes the area under the curve (AUC) observed with amperometry. Furthermore, the AUC of the amperometric signal positively correlates with the reinstatement index. Using operant feeding devices, we demonstrate that OCA has no effect on contextual learning or motivation for natural rewards. These data highlight OCA as a potential therapeutic for cocaine use disorder.
Differences in spinal posture and mobility between adults with obesity and normal weight individuals
Authors: Bayartai Munkh-Erdene , Luomajoki Hannu , Tringali Gabriella , De Micheli Roberta , Abbruzzese Laura , Sartorio Alessandro
Published: August 2023

The aim of this study was to cross-sectionally investigate the relationships between obesity and spinal posture as well as mobility by comparing the spinal parameters between adults with obesity and normal-weight individuals. The spinal parameters were measured in 71 adults with obesity and 142 normal-weight individuals using a radiation-free back scan, the Idiag M360. Differences in spinal posture and movements between the two groups were determined using a two-way analysis of variance. Adults with obesity had greater thoracic kyphosis [difference between groups (Δ) = 6.1°, 95% CI 3.3°–8.9°, p < 0.0001] and thoracic lateral flexion (Δ = 14.5°, 95% CI 5.1°–23.8°, p = 0.002), as well as smaller thoracic flexion (Δ = 3.5°, 95% CI 0.2°–6.9°, p = 0.03), thoracic extension (Δ = 4.1°, 95% CI 1.1°–7.1°, p = 0.008), lumbar flexion (Δ = 10.4°, 95% CI 7.7°–13.5°, p < 0.0001), lumbar extension (Δ = 4.8°, 95% CI 2.2°–7.4°, p = 0.0003) and lumbar lateral flexion (Δ = 12.8°, 95% CI 9.8°–15.7°, p = < 0.0001) compared to those with normal weight. These findings provide relevant information about the characteristics of the spine in adults with obesity to be taken into careful consideration in the prescription of adapted physical activities within integrated multidisciplinary pathways of metabolic rehabilitation.
Modeling strength characteristics of basalt fiber reinforced concrete using multiple explainable machine learning with a graphical user interface
Authors: Kulasooriya W. K. V. J. B. , Ranasinghe R. S. S. , Perera Udara Sachinthana , Thisovithan P. , Ekanayake I. U. , Meddage D. P. P.
Published: August 2023

This study investigated the importance of applying explainable artificial intelligence (XAI) on different machine learning (ML) models developed to predict the strength characteristics of basalt-fiber reinforced concrete (BFRC). Even though ML is widely adopted in strength prediction in concrete, the black-box nature of predictions hinders the interpretation of results. Among several attempts to overcome this limitation by using explainable AI, researchers have employed only a single explanation method. In this study, we used three tree-based ML models (Decision tree, Gradient Boosting tree, and Light Gradient Boosting Machine) to predict the mechanical strength characteristics (compressive strength, flexural strength, and tensile strength) of basal fiber reinforced concrete (BFRC). For the first time, we employed two explanation methods (Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME)) to provide explanations for all models. These explainable methods reveal the underlying decision-making criteria of complex machine learning models, improving the end user's trust. The comparison highlights that tree-based models obtained good accuracy in predicting strength characteristics yet, their explanations were different either by the magnitude of feature importance or the order of importance. This disagreement pushes towards complicated decision-making based on ML predictions which further stresses (1) extending XAI-based research in concrete strength predictions, and (2) involving domain experts to evaluate XAI results. The study concludes with the development of a “user-friendly computer application” which enables quick strength prediction of basalt fiber reinforced concrete (BFRC).
Tetramethylalloxazines as efficient singlet oxygen photosensitizers and potential redox-sensitive agents
Authors: Golczak Anna , Prukała Dorota , Sikorska Ewa , Gierszewski Mateusz , Cherkas Volodymyr , Kwiatek Dorota , Kubiak Adam , Varma Naisargi , Pędziński Tomasz , Murphree Shaun , Cibulka Radek , Mrówczyńska Lucyna , Kolanowski Jacek Lukasz , Sikorski Marek
Published: August 2023

Tetramethylalloxazines (TMeAll) have been found to have a high quantum yield of singlet oxygen generation when used as photosensitizers. Their electronic structure and transition energies (S0 → Si, S0 → Ti, T1 → Ti) were calculated using DFT and TD-DFT methods and compared to experimental absorption spectra. Generally, TMeAll display an energy diagram similar to other derivatives belonging to the alloxazine class of compounds, namely π,π* transitions are accompanied by closely located n,π* transitions. Photophysical data such as quantum yields of fluorescence, fluorescence lifetimes, and nonradiative rate constants were also studied in methanol (MeOH), acetonitrile (ACN), and 1,2-dichloroethane (DCE). The transient absorption spectra were also analyzed. To assess cytotoxicity of new compounds, a hemolytic assay was performed using human red blood cells (RBC) in vitro. Subsequently, fluorescence lifetime imaging experiments (FLIM) were performed on RBC under physiological and oxidative stress conditions alone or in the presence of TMeAll allowing for pinpointing changes caused by those compounds on the intracellular environment of these cells.
A proposal for leaky integrate-and-fire neurons by domain walls in antiferromagnetic insulators
Authors: Brehm Verena , Austefjord Johannes W. , Lepadatu Serban , Qaiumzadeh Alireza
Published: August 2023

Brain-inspired neuromorphic computing is a promising path towards next generation analogue computers that are fundamentally different compared to the conventional von Neumann architecture. One model for neuromorphic computing that can mimic the human brain behavior are spiking neural networks (SNNs), of which one of the most successful is the leaky integrate-and-fire (LIF) model. Since conventional complementary metal-oxide-semiconductor (CMOS) devices are not meant for modelling neural networks and are energy inefficient in network applications, recently the focus shifted towards spintronic-based neural networks. In this work, using the advantage of antiferromagnetic insulators, we propose a non-volatile magnonic neuron that could be the building block of a LIF spiking neuronal network. In our proposal, an antiferromagnetic domain wall in the presence of a magnetic anisotropy gradient mimics a biological neuron with leaky, integrating, and firing properties. This single neuron is controlled by polarized antiferromagnetic magnons, activated by either a magnetic field pulse or a spin transfer torque mechanism, and has properties similar to biological neurons, namely latency, refraction, bursting and inhibition. We argue that this proposed single neuron, based on antiferromagnetic domain walls, is faster and has more functionalities compared to previously proposed neurons based on ferromagnetic systems.
Causal relationship between endometriosis with infertility and ankylosing spondylitis
Authors: Wang Jian-xiong , Shen Yue , Wang Xi-le , Ma Lin-li , Xu Sheng-qian
Published: August 2023

Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = − 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.
A multicenter study on two-stage transfer learning model for duct-dependent CHDs screening in fetal echocardiography
Authors: Tang Jiajie , Liang Yongen , Jiang Yuxuan , Liu Jinrong , Zhang Rui , Huang Danping , Pang Chengcheng , Huang Chen , Luo Dongni , Zhou Xue , Li Ruizhuo , Zhang Kanghui , Xie Bingbing , Hu Lianting , Zhu Fanfan , Xia Huimin , Lu Long , Wang Hongying
Published: August 2023

Duct-dependent congenital heart diseases (CHDs) are a serious form of CHD with a low detection rate, especially in underdeveloped countries and areas. Although existing studies have developed models for fetal heart structure identification, there is a lack of comprehensive evaluation of the long axis of the aorta. In this study, a total of 6698 images and 48 videos are collected to develop and test a two-stage deep transfer learning model named DDCHD-DenseNet for screening critical duct-dependent CHDs. The model achieves a sensitivity of 0.973, 0.843, 0.769, and 0.759, and a specificity of 0.985, 0.967, 0.956, and 0.759, respectively, on the four multicenter test sets. It is expected to be employed as a potential automatic screening tool for hierarchical care and computer-aided diagnosis. Our two-stage strategy effectively improves the robustness of the model and can be extended to screen for other fetal heart development defects.
IF1 promotes oligomeric assemblies of sluggish ATP synthase and outlines the heterogeneity of the mitochondrial membrane potential
Authors: Romero-Carramiñana Inés , Esparza-Moltó Pau B. , Domínguez-Zorita Sonia , Nuevo-Tapioles Cristina , Cuezva José M.
Published: August 2023

The coexistence of two pools of ATP synthase in mitochondria has been largely neglected despite in vitro indications for the existence of reversible active/inactive state transitions in the F1-domain of the enzyme. Herein, using cells and mitochondria from mouse tissues, we demonstrate the existence in vivo of two pools of ATP synthase: one active, the other IF1-bound inactive. IF1 is required for oligomerization and inactivation of ATP synthase and for proper cristae formation. Immunoelectron microscopy shows the co-distribution of IF1 and ATP synthase, placing the inactive “sluggish” ATP synthase preferentially at cristae tips. The intramitochondrial distribution of IF1 correlates with cristae microdomains of high membrane potential, partially explaining its heterogeneous distribution. These findings support that IF1 is the in vivo regulator of the active/inactive state transitions of the ATP synthase and suggest that local regulation of IF1-ATP synthase interactions is essential to activate the sluggish ATP synthase.
Glyphosate ban will have economic impacts on European agriculture but effects are heterogenous and uncertain
Authors: Finger Robert , Möhring Niklas , Kudsk Per
Published: August 2023

Glyphosate is the most widely used pesticide in Europe. However, due to its potential effects on human health, its renewal is currently under discussion in European policy. Here, we synthesize the existing evidence on potential farm-level economic impacts of a potential glyphosate ban in European agriculture using a literature review. We identified 19 studies published until 2022. We find that where glyphosate is currently used (30% and 50% of the acreage with annual and perennial tree crops respectively), such a ban can have large economic impacts. However, the range of impacts reported in the literature is substantial. Economic losses arising from a glyphosate ban estimated in peer reviewed studies range from 3 Euro/hectare in silage maize to up to 553 Euro/hectare in grapevine production. While potential losses are largest, in absolute terms (in Euro/hectare), for high-value perennial crops such as fruits and grapevines losses are similar in perennial and arable crops if expressed in relative terms (i.e. in % of per hectare profits). We currently lack assessments of economic implications of a glyphosate ban for most countries and farming systems. Thus, the overall economic implications at the European level are largely unknown.
A novel DNA-quantum dot nanostructure electrochemiluminescence aptamer sensor by chain reaction amplification for rapid detection of trace Cd2+
Authors: Wang Runze , Zhao Yu , Jie Guifen
Published: August 2023

This work proposes a new enzyme-free electrochemiluminescence sensing platform based on a novel DNA-QD nanostructure and hybridization chain reaction amplification for the trace detection of Cd2+.
Synthetic lipo-polylysine with anti-cancer activity
Authors: Yi Xuan , Wan Pengqi , Shen Wei , Zhang Xiaonong , Zhang Peng , Xiao Chunsheng
Published: August 2023

A cationic lipo-polylysine C12-PLL13 can interact with negatively charged tumor cell membrane and induce cell necrosis by triggering membrane perforation and disintegration, offering a distinct therapeutic mechanism from traditional antitumor drugs.
A diketopyrrolopyrrole-based small molecule with an extended conjugated skeleton and J-aggregation behavior for 808 nm laser triggered phototheranostics
Authors: Liu Jiawei , Zhang Xinmin , Fu Mingxuan , Wang Xiaoyuan , Gao Yicong , Xu Xingpeng , Xiao Tangxin , Wang Qi , Fan Quli
Published: August 2023

A conjugated small molecule based on DPP architecture with J-aggregation behavior was designed and synthesized as a proof-of-concept example for 808 nm laser-triggered phototheranostics.
Self-assembled peptide nanosheets functionalized with Fe3O4 nanoparticles with enhanced nanozymatic activity for sensitive colorimetric detection and selective adsorption of Hg2+
Authors: Luan Xin , Zhu Danzhu , He Peng , Han Ping , Wei Gang
Published: August 2023

The combination of peptide nanosheets and magnetic Fe3O4 nanozymes promotes colorimetric detection and selective adsorption of Hg2+.
Mapping the metabolic characteristics of probiotic-fermentedGanoderma lucidumand its protective mechanism against Cd-induced nephrotoxicity
Authors: Dai Zhen , Li Gaoheng , Wang Xixi , Gao Bo , Gao Xiuwei , Strappe Padraig , Zhou Zhongkai
Published: August 2023

An animal model of Cd-induced kidney damage was designed to investigate the nephroprotective potential of the probiotic-fermentedGanoderma lucidum(FGL)viametabonomic analysis.
A super-high brightness and excellent colour quality laser-driven white light source enables miniaturized endoscopy
Authors: Li Shuxing , Huang Linhui , Guo Yunqin , Wang Le , Xie Rong-Jun
Published: August 2023

A laser-driven white light source promises intrinsic advantages for miniaturized endoscopic illumination.